Ship, Quarantine, or Discard: A Streamlined Process and Analytical Tool Yields Better Decisions on Resolving Temperature Excursions

Ship, Quarantine, or Discard: A Streamlined Process and Analytical Tool Yields Better Decisions on Resolving Temperature Excursions

Written by Modality Solutions

Posted on: September 23, 2021

temperature excursions, Ship, Quarantine, or Discard: A Streamlined Process and Analytical Tool Yields Better Decisions on Resolving Temperature Excursions, image of scientists working with analytic tools to resolve temp excursions

It’s estimated that seven out of ten pharmaceutical products in the US require temperature control during transportation1, a trend that’s escalated with the rapid growth in temperature-sensitive therapeutics like large molecule, protein-based biologics. With many biopharmaceutical products now requiring storage at consistent temperatures within the range of 2° to 8° Celsius—and some requiring a deep-frozen state of -60° Celsius or below—the integrity of the biopharmaceutical cold chain is more vital than ever.

When temperature excursions occur during the shipment and storage of controlled-temperature drug products or during clinical trials, the product’s stability, efficacy, and safety can be at risk. That makes it essential for pharmaceutical companies to make the most informed decisions about how to resolve temperature excursions and handle drug products exposed to such excursions. Our experience helping a leading biopharmaceutical company address this challenge demonstrates the value of a data-driven, analytical approach to identifying and mitigating cold chain temperature excursions.
 

The Challenge of Managing Temperature Excursions

Reducing the risks associated with temperature excursions during shipment and storage is essential to protecting controlled temperature drug products. But across a global, complex biopharmaceutical supply chain, the tasks of monitoring and reporting on temperature excursions, managing temperature excursion data, and mitigating temperature-related issues promptly are becoming much more challenging.

Speed is of the essence when it comes to detecting that a temperature excursion has occurred, identifying the root cause, and determining the best course of action to ensure a safe, efficacious product makes it to the patient on time. That’s especially true for personalized medicines, such as cell and gene therapies that use the patient’s biological material as the therapeutic. When the treatment is costly to produce and in scarce supply, quickly identifying and correcting temperature excursions is a must.

Minimizing the impact of temperature excursions a drug product is exposed to in transit—and taking fast action in the event they occur—requires an effective and efficient temperature excursion management process that includes these critical steps:

  • Identifying that an excursion event has occurred (using the correct temperature monitoring device, which will vary based on factors like location, resource availability, and technology)
  • Analyzing temperature excursion data
  • Using data to make an informed decision about whether to continue with the shipment, quarantine the affected product, or discard and replace it

Unfortunately, it’s common for various obstacles to jeopardize this process, including language barriers and other communication challenges among staff and time zone differences that cause delays in sharing and responding to temperature excursion notifications. The seemingly simple act of providing the necessary temperature excursion data to the staff member with the proper skill set to analyze it is often one of the most significant impediments. Using the results of that analysis to make an informed decision on whether to keep, quarantine, or discard and replace the affected shipment requires that the right person with the ability and authority to make that decision is notified quickly and equipped with actionable information.
 

How an Analytical Process and Tool Can Help

A major biopharmaceutical company was experiencing these very problems when addressing temperature excursions for its controlled temperature drugs. After struggling with the best way to manage temperature excursion data, the company asked Modality Solutions to assess the situation and recommend a solution based on our in-depth experience evaluating and optimizing the biopharmaceutical cold chain.

Our assessment revelated that the company’s existing process for managing and mitigating temperature excursions lacked the decision-making data or tools needed for a fast, effective response. Erring on the side of caution, in some cases the company discarded shipments affected by temperature excursions and replaced them with emergency shipments in the absence of actionable data. By assuming the worst-case scenario, the company lost time and money and wasted resources whenever a temperature excursion occurred. The staff investigated each excursion after the fact but in a reactive mode.

Modality Solutions developed a new process that provides two key improvements:

  • Making drug stability data readily available throughout the supply chain is now the basis for analyzing temperature excursions, informed by the excursion frequency, high and low temperatures experienced, number of freeze/thaw cycles the product can withstand, drug modality and molecular properties, primary and secondary packaging used, and other technical factors. Modality engineers drew on their extensive experience ensuring drug stability throughout the supply chain—along with stability testing of this company’s specific drug products—to recommend the stability data needed for fast, accurate analysis of temperature excursions. Rather than rely solely on labeled storage conditions, our engineers advised exposing the product to temperatures outside these conditions, in combination with vibration and shock, to evaluate drug stability in a more realistic environment.

Stability data illustrates how long a drug is permitted to be exposed to various temperatures compared to the length of time the drug was exposed to those temperature conditions in transit.

 

  • A new system guides the process of collecting, summarizing, and delivering actionable temperature excursion data to the right subject matter expert. This agile, streamlined process enables the company to make confident, informed decisions about handling affected shipments to ensure drug safety and efficacy, without delays or unnecessary costs. Modality engineers designed the data collection and analysis system. They also supported its initial deployment by performing root cause analysis on the temperature excursion, determining excursion impacts, and documenting the required data for regulatory purposes.

Excursion data depicts a temperature excursion event as a variance from the allowable storage temperature range.

 
As this experience demonstrated, the combination of robust data analysis tools and an efficient process makes it possible to deliver actionable information about temperature excursions to the right subject matter experts for effective analysis and quick decision-making. With the proper approach and tools in place, this biopharmaceutical company can respond to temperature excursions faster, reduce discarded shipments, and avoid repeat emergency shipments, saving over $1 million annually. The company also has greater confidence that the drug products it ships to patients will remain stable and safe throughout the cold chain.

1 https://www.shipabco.com/the-rules-for-shipping-pharmaceuticals-you-need-to-know/#:~:text=According%20to%20information%20from%20Shipwaves,temperature%20regulated%20shipping%20is%20important.

Why Cold Chain Engineering is Vital to Transporting Monoclonal Antibodies (mAbs) and Other Biologics

Why Cold Chain Engineering is Vital to Transporting Monoclonal Antibodies (mAbs) and Other Biologics

Written by Modality Solutions

Posted on: September 20, 2021

Transporting Monoclonal Antibodies, Why Cold Chain Engineering is Vital to Transporting Monoclonal Antibodies (mAbs) and Other Biologics, image of a women scientist in a lab

The global biologics market is forecast to reach $625 million by 20261, fueled by a rapid rise in therapeutics that leverage biological materials such as cells, genes, tissues, and blood products. Monoclonal antibodies (mAbs) are particularly in high demand, with the market for this class of drugs expected to expand at a compound annual growth rate of 14.4% through 2027.2

Biologics hold great promise for addressing previously untreatable diseases and are now used for a wide range of indications. But when it comes to transporting them safely and effectively, biologics pose more complex challenges than small molecule drugs. Cold chain engineering can address those challenges, ensuring that these high-value therapeutics remain stable, safe, and efficacious from manufacturer to patient.
 

The Unique Transport Risks of Biologics

As compared to chemically-derived small molecule drugs, large molecule, protein-based therapeutics are more costly to produce, more fragile, and at greater risk of instability when exposed to environmental risks in transport, including physical events like shock and vibration. Vibration has the potential to destroy the protein’s structure, while shock events can cause a portion of the large molecule to shear off. Confirming that a mAb or other biologic will remain stable throughout the cold chain is vital and typically requires complex bioassays (as compared to the simpler purity and identity tests used on chemically-derived drugs).

mAbs and other biologics also have controlled temperature requirements that must be maintained consistently throughout the cold chain. When exposed to extreme temperature excursions, these therapeutics are at risk of protein denaturation (a loss of structure due to unfolding), which can reduce their efficacy. High temperatures also can prompt chemical reactions like oxidation and deamidation, which impact drug formulation, or physical reactions such as aggregate or fragment generation, which can reduce the product’s efficacy or potency or trigger an adverse immune response in the patient.

Unlike small molecule drugs that involve a well-defined production process capable of yielding large quantities, mAbs and other biologics require a more complex production process that tends to yield smaller batches. Given that these materials are both costly to produce and available in scare quantities, maintaining drug product stability, safety, and efficacy throughout the cold chain is paramount.
 

Cold Chain Engineering Reduces the Risks

Cold chain engineering is essential to protecting fragile, temperature-sensitive, high-value mAbs and other biologics in transit. It’s an integrated, multi-disciplinary approach to designing and optimizing the biopharmaceutical cold chain, to reduce transport risks that can jeopardize a drug’s safety, stability, and efficacy.

Cold chain engineering involves four disciplines that share a common goal of providing practical solutions to drug transport challenges using scientific and mathematical principles:

  • Chemical engineering focuses on understanding how environmental factors like physical impact and heat transfer affect the formulation of a mAb or other biologic at the molecular level.
  • Mechanical engineering evaluates the effects of physical events such as shock and vibration on fragile, protein-based therapeutics.
  • Biomedical engineering assesses the drug’s biological mechanisms and the unique challenges posed by drug-device therapeutics to ensure they’re protected throughout the cold chain.
  • Packaging engineering involves evaluating and selecting the optimal thermal packaging solution for controlled-temperature biologics.

Since cold chain issues are inherently multi-faceted, a multi-disciplinary approach that leverages the right combination of engineering experts is essential to validating and optimizing the cold chain for mAbs and other biologics. From package design engineering and evaluation, to thermal shipper selection, to development of the validation master plans critical to a successful filing, cold chain engineering ensures that biologics stay safe, stable, and efficacious from the point of manufacture to the point of use.
 

Validating the Cold Chain Through Transport Simulation

One of the most critical functions of a cold chain engineering approach is to validate the cold chain process as part of the Common Technical Document (CTD) requirements of a Biologics License Application (BLA) filing. BLA documentation reviews and pre-approval inspections involve an evaluation of the process validation conducted for the drug product—including transport validation—along with any stability testing, thermal packaging qualification, and validation master planning completed.

Historically, drug transport validation was conducted using real-life shipments in the field. But these shipments can’t duplicate the extreme, concurrent environmental hazards a drug product is likely to face in transit. As a result, real-world shipment data does not provide enough information. Real-life shipments also can’t provide transport validation data on an expedited basis—a significant obstacle for a mAb or other biologic with a Fast Track, Breakthrough Therapy, Accelerated Approval, or Priority Review designation.

For a more accurate assessment of the concurrent environmental risks a biologic will be exposed in transit—with faster access to robust, repeatable test results—biopharmaceutical companies increasingly rely on transport simulation testing.
 

Biopharma industry best practice: Transport Simulation Testing and Cold Chain Engineering

Now recognized as an industry best practice, transport simulation tests for the five environmental hazards a drug may be exposed to in transit—temperature, vibration, shock, humidity, and pressure—concurrently and at the edges of the operating space, based on the expected conditions across the identified shipping lanes. Transport simulation testing yields the robust data regulators expect for BLA filings, helping ensure a smooth and successful approval process for mAbs and other biologics.

Modality Solutions is the leader in transport simulation, conducting simulation tests that are regularly accepted by the FDA and other agencies, across 200+ successful drug submissions. Through our ISO-certified Advantage Transport Simulation Lab™, Modality engineers have conducted transport simulation tests on mAbs, vaccines, cell-and-gene therapies, and other biologics, along with numerous small molecule drugs and drug-device combination products.

Whether you’re just getting started designing the cold chain for a new mAb or other biologic, preparing for a BLA filing, or looking to solve a cold chain problem with a biologic that’s already in the market, Modality Solutions can help. We have the in-house cold chain engineering expertise to optimize and enhance the cold chain for your biologic, ensuring it stays safe, stable, and efficacious.

References:

1. https://www.globenewswire.com/news-release/2019/10/10/1928253/0/en/Biologics-Market-To-Reach-USD-625-6-Million-By-2026-Reports-And-Data.html
2. https://www.businesswire.com/news/home/20201016005169/en/Global-Monoclonal-Antibodies-Market-to-Surpass-US-368.8-Billion-by-2027-Says-Coherent-Market-Insights-CMI

Modality Solutions Welcomes Sumika Stansbury to its Growing Cold Chain Engineering™ Team

Modality Solutions Welcomes Sumika Stansbury to its Growing Cold Chain Engineering™ Team

Written by Modality Solutions

Posted on: September 9, 2021

Sumika-Stansbury, Modality Solutions, image for press release

September 9, 2021: Modality Solutions announced that Sumika Stansbury has joined the company as a Consulting Engineer. Sumika will help biopharmaceutical companies prepare their drug products for the rigors of the cold chain by developing transport validation test protocols, reviewing test validation data, and writing the comprehensive technical reports they rely on for successful regulatory filings.

Her experience in chemical engineering, coupled with her strengths in team-building, project management, and client service, was a real differentiator,” said Modality Solutions President, Gary Hutchinson.

Click here to view the online press release announcement.

Learn more about Sumika and the Modality team.

Modality Solutions Named Inc. 5000 Fastest-Growing Company for Third Year in a Row in 2021

Modality Solutions Named Inc. 5000 Fastest-Growing Company for Third Year in a Row in 2021

Written by Modality Solutions

Posted on: August 18, 2021

In 2021, Inc. Magazine has again named Modality Solutions to the publication’s annual Inc. 5000 list, the most prestigious ranking of America’s successful, fast-growing private companies. This is the third consecutive year that Modality Solutions has been recognized by Inc. magazine.

“Our growth at Modality Solutions has been consistent year over year, and we’ve continued to see that into 2021,” said Gary Hutchinson, co-founder and President. “This is especially meaningful this year as our clients have continued to turn to us as a critical partner despite the ongoing global pandemic. Our ability to help our clients achieve regulatory success, including those working on emergency use authorizations or accelerated approval pathways, has allowed us to have very significant growth even amidst economic uncertainty.”

Also in 2021, the Houston-based firm was ranked the fastest growing engineering firm in the Inc Texas Regionals.

To view our full Inc. 5000 press release for 2021, click here.

See also:

Modality Solutions Recognized on Inc. Magazine’s List of Fastest-Growing Private Companies in Texas

Modality Solutions Featured on NBC’s Today Show for its work on COVID-19 Vaccines in its special report, Race for a Vaccine: Distributing Vaccines Across America

Modality Solutions Adds Matthew Coker to Its Consulting Engineer Team

Modality Solutions Adds Matthew Coker to Its Consulting Engineer Team

Written by Modality Solutions

Posted on: July 26, 2021

JULY 20, 2021: Modality Solutions is pleased to announce the addition of Matthew Coker to its growing engineering team. Matthew brings a technical emphasis on cellular and biomolecular engineering as it relates to regenerative medicine to his new position as a Modality Solutions consulting engineer.

“Matthew supports our goals of providing project managers and technical liaisons for our clients’ development teams as they move forward with new drug product transport simulation test design,” said Gary Hutchinson, Modality Solutions President and Co-Founder.

Learn more about Matthew and the Modality team

Read the full press release below:

Modality Solutions, a full-service cold chain biopharmaceutical engineering firm, is pleased to announce the addition of Matthew Coker to its growing engineering team. Matthew brings a technical emphasis on cellular and biomolecular engineering as it relates to regenerative medicine to his new position as a Modality Solutions consulting engineer.

According to Precedence Research, the regenerative medicine market size is expected to hit around $23.7 billion by 2027, growing at a compound annual growth rate of 16.1% from 2020 to 2027. Factors such as the increasing prevalence of chronic disorders and genetic disorders, the rising popularity of stem cells, and a growing number of trauma emergencies are driving the growth of the regenerative medicine market.

Matthew’s consulting engineer responsibilities include design and validation engineering services for the life sciences industry. He strategically creates the proper validation strategy for a client’s cold chain systems through risk and gap analysis. In addition, he designs and executes validation master plans by creating standard operating procedures and qualifying critical equipment and thermal packaging.

“Matthew joining our team of experts supports our goals of providing project managers and technical liaisons for our clients’ development teams as they move forward with new drug product transport simulation test design, risk assessment, and protocol development,” said Modality Solutions President Gary Hutchinson. “Matthew’s experience in biomedical engineering, coupled with cellular and biomolecular engineering knowledge, make him a valuable addition to our engineering team.”

Born and raised in Dallas, Texas, Matthew received his Bachelor of Science degree in Biomedical Engineering at the University of Texas at Austin, Cockrell School of Engineering. He also has a minor in Business Administration from the U of T McCombs School of Business.

As a UT College Scholar, Matthew worked on a sponsored project for Denver-based Innolitics. He helped create a deep learning model using a convolutional neural network to detect long nodules. In addition, Matthew participated in a COVID-19 Proning Monitor Project where a device to monitor the orientation of patients in the prone position to treat patients was developed. It included disease research, stakeholder interviews, market analysis, engineering requirements, and creating/implementing validation tests to ensure the device satisfied customer needs.

 

Jazz Pharmaceuticals Announces U.S. FDA Approval of Rylaze™ for the Treatment of Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Jazz Pharmaceuticals Announces U.S. FDA Approval of Rylaze™ for the Treatment of Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Written by Modality Solutions

Posted on:

DUBLIN, June 30, 2021 /PRNewswire/ — Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced the U.S. Food and Drug Administration (FDA) approval of Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in pediatric and adult patients one month and older. Rylaze was granted orphan drug designation for the treatment of ALL/LBL by FDA in June 2021. The Biologics Licensing Application (BLA) approval followed review under the Real-Time Oncology Review (RTOR) program, an initiative of FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients. Approval under U.S. FDA’s Real-Time Oncology Review program represents an important therapeutic advance for pediatric and adult patients who develop hypersensitivity to E. coli-derived asparaginase treatments. Rylaze is expected to become commercially available in the U.S. in mid-July, 2021. (source: Jazz Pharmaceuticals press release)

Modality Solutions works with biopharma innovators like Jazz Pharmaceuticals to ensure their cold chains are ready for regulatory filing success. Many of our client’s clinical trials are being conducted under special FDA designations, including as part of the Orphan Drug Development Program.

Read the full Rylaze press release

FDA Grants Priority Review to Agenus’ Balstilimab for Cervical Cancer After Chemotherapy

FDA Grants Priority Review to Agenus’ Balstilimab for Cervical Cancer After Chemotherapy

Written by Modality Solutions

Posted on:

LEXINGTON, Mass., June 17, 2021 (GLOBE NEWSWIRE) — Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents which includes checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, today announced that the U.S. Food and Drug Administration (FDA) has accepted Agenus’ Biologics License Application (BLA) for balstilimab, an anti-PD-1 antibody, for the treatment of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The FDA has granted Priority Review to this submission, a designation for drugs which, if approved, may provide significant improvements in the safety or effectiveness of the treatment of serious conditions. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of December 16, 2021. (source: Agenus press release)

Modality Solutions works with biopharma innovators like Agenus to ensure their cold chains are ready for regulatory filing success. The majority of our clients are working under FDA Expedited Review Program pathways, including Priority Review, Fast Track Designation, Breakthrough Designation, and Accelerated Approval.

Read the full Agenus press release

Cold-Chain Validation: Emerging Vaccines for COVID-19 and Beyond Require More Extensive Evaluation

Cold-Chain Validation: Emerging Vaccines for COVID-19 and Beyond Require More Extensive Evaluation

Written by Modality Solutions

Posted on: April 14, 2021

by Brian Gazaille, Gary M. Hutchinson and Daniel J. Littlefield
Friday, February 5, 2021 2:59 pm

In the wake of fast-track approvals for Pfizer’s and Moderna’s respective SARS-CoV-2 vaccines, now begins the largest immunization campaign in world history. Its success will depend not only on the products’ safety and efficacy, but also on several mass-distribution programs requiring significant cold-chain infrastructure. The public has become acutely aware of the Pfizer vaccine’s demanding cryostorage specifications, generating considerable anxiety about how mass distribution will happen. Behind the scenes, however, cold-chain engineering companies such as Modality Solutions have worked alongside drug developers to ensure that vaccines can be shipped efficiently without compromising drug-product safety and quality.

Arktek cryostorage containers holding Ebola vaccines for distribution in Sierra Leone; in 2015, cold-chain engineering company Modality Solutions supported clinical trials for Ebola vaccines in that country. (Photo Courtesy of Modality Solutions)

In December 2020, I spoke with Gary M. Hutchinson (president and cofounder) and Daniel J. Littlefield (principal, cofounder, and head of engineering) of Modality Solutions to learn about what resources SARS-CoV-2 vaccines will require during transport, what challenges new products will impose on existing cold-chain networks, and what lessons the biopharmaceutical industry can learn from the cold-chain industry’s experiences with vaccine storage and handling. Our conversation also traverses emerging distribution models and the need for drug manufacturers and cold-chain specialists to work in parallel to optimize vaccine formulations.
 

Early Involvement for Shipment Success

How would you characterize your company’s role in vaccine distribution?

Hutchinson: We specialize in transportation validation. We help clients formalize and understand hazards that are inherent to shipping a biologic, vaccine, or advanced therapy through a commercial supply chain. And significant risks abound. The biopharmaceutical industry settled on temperature risks early in its development, so the idea of cold chain became the most considered factor in drug-product shipment. But when therapies such as monoclonal antibodies (MAbs) emerged, researchers discovered that other hazards posed risks to drug-product efficacy and quality.

Subsequent testing revealed a unique intersection of engineering and logistics devoted to understanding transport risks and developing methods to evaluate them. As a cold-chain engineering company, we put that information in a coherent package to explain to regulatory agencies that a therapy can be shipped safely.

Although timelines have been abbreviated during the pandemic, drug companies usually engage us late in phase 2 or early in phase 3 clinical trials — the point at which a company becomes confident about moving into large-scale manufacturing. That stage also requires transitioning a therapy from a clinical formulation to one more appropriate for commercial distribution — for instance, from a deep-frozen to a standard frozen or refrigerated formulation. Our role begins during that transition. We help clients test their commercial formulations for large-scale distribution and assist with the associated packaging and logistics.

Littlefield: Although Modality focuses on validating distribution processes, we also support emergency-response clinical trials. For instance, the US National Institutes of Health (NIH) and World Health Organization (WHO) contracted us to assist with Ebola vaccine trials in the Democratic Republic of the Congo (DRC) in 2019 and Sierra Leone in 2015.
 

Risk Assessment and Preparedness

How do shipping conditions for emerging SARS-CoV-2 vaccines compare with those for existing vaccines, and how prepared are cold-chain networks to accommodate distinctive transport needs?

Littlefield: Although shipping conditions differ by product, vaccines requiring cold-chain transport usually are transported at temperatures above –20 °C. Smallpox vaccines often are shipped at –20 °C, as is Moderna’s recently approved SARS-CoV-2 vaccine.
Despite media coverage of requirements for Pfizer’s vaccine, which include cryostorage at –60 °C, such low-temperature specifications are atypical. However, because we worked with Ebola vaccines, which have similarly low temperature requirements, we noticed at the beginning of the race for a COVID-19 vaccine some striking parallels between formulation and distribution specifications for those vaccine types — similarities that only now are gaining attention.

Capabilities for providing an extreme temperature range exist, in part, because drug companies want to be conservative with fast-tracked products that have not had time for comprehensive data analysis.

Hutchinson: The public continues to wonder whether rapid development has compromised the safety profiles of COVID-19 vaccines. Now the public also is asking whether we can accomplish the distribution piece. We want to make people aware that such work has been happening all along.

Figure 1: The Advantage Transport multimodal simulation laboratory validates materials for vaccine transport by exposing products to environmental hazards such as changes in temperature, pressure, and humidity as well as shock and vibration events
(Photo courtesy of Modality Solutions).

Figure 1: The Advantage Transport multimodal simulation laboratory validates materials for vaccine transport by exposing products to environmental hazards such as changes in temperature, pressure, and humidity as well as shock and vibration events
(Photo courtesy of Modality Solutions).

Modality has been involved in the engineering work for ~40% of late-phase COVID-19 vaccines. We perform risk assessment at our transport simulation laboratory in Bloomington, IN, where we can replicate most any environment that COVID-19 vaccines and follow-on therapies might experience during transport (Figure 1). We test for temperature, shock, vibration, pressure, and humidity hazards, stressing our clients’ molecules to the edge of failure in worst-case conditions. Based on our simulations, our clients can compare their products’ pre- and post-shipment properties to develop appropriate specifications and identify potential liabilities. Then our clients can present those assessments to the US Food and Drug Administration (FDA) to support their claims about product safety and stability.

The biopharmaceutical industry has moved quickly through vaccine development, but it also has gathered enough data concerning stability at specified temperature ranges. Those numbers are not arbitrary; they are tested and reviewed extensively. And while scientists have been developing drug products, engineers and logisticians have been working in parallel to plan for massive distribution. Based on what we know about existing products, we are confident that COVID-19 vaccines will be safe during transport. Vaccine developers are placing substantial “guardrails” around distribution, and we continue to test beyond conservative ranges to ensure product efficacy, stability, and safety even in the case of failure.
 

Shipping Challenges and Opportunities

What are the most difficult parts of a cold-chain operation, and how do you mitigate problems?

Littlefield: Challenges increase as a drug product moves further down the process from manufacturing. The “last-mile” logistics of getting vaccines to patients can be difficult to manage. But product damage can occur whenever there is movement. A shipment can be dropped during loading, unloading, or delivery, and shock events can damage vaccine products and packaging. Vibration from truck or airline transport can be just as detrimental as a shock event. Thus, risk assessment is critical to cold-chain success, and we work hard to ensure that our simulations are demanding and realistic. Packages will experience hazards, and companies need to know whether their products will be viable despite whatever problems arise.

Packaging typically is qualified at a certain temperature for a specified duration — e.g., for 72 hours at –60 °C. A vaccine product will be fine as long as it is packed out, shipped, delivered, and moved to appropriate refrigeration conditions within that period. But delays occur. Will a product remain viable if it sits somewhere for two days beyond that 72-hour mark? It might, because that specification is based on worst-case conditions. For that reason, we force temperature excursions during simulation. We want clients to know whether a product can be used, for instance, if its packaging reaches –50 °C instead of staying at –60 °C. Drug developers sometimes perform similar tests at their facilities, including accelerated-aging studies, during which a product is stored, for example, at –20 °C for 30 days. Combining all those data can help drug developers to determine what conditions their vaccines can and cannot tolerate.

Hutchinson: When people think about cold-chain challenges, they usually reference Pfizer’s COVID-19 vaccine. Americans wonder, for instance, about how such a vaccine could be shipped to rural parts of the United States. However, Pfizer is leveraging advantages from having its own captured network. For distribution in the United States, nearly all COVID-19 vaccine developers have contracted through Operation Warp Speed to use US Army logistics teams and the McKesson wholesale distribution network. After initial distribution through those channels, doses somehow need to be sent to healthcare providers for administration. So Pfizer’s vaccine requires deep-freezing, but the company is using a direct distribution model, whereas other vaccines may have less demanding temperature specifications but depend on multiple transitions. Last-mile logistics involve several handoffs, each adding risk into the system for a potential temperature excursion or shock/vibration event. Tradeoffs exist for both distribution models.

How might the pandemic influence transport of vaccines for indications besides COVID-19?

Hutchinson: Impacts already are manifesting in the commercial airline network. Besides UPS and FedEx, commercial airlines were the biggest movers of pharmaceutical freight. But many flights have been grounded because people are unable or afraid to travel by air. Decreases in air traffic have removed a huge amount of capacity from the shipping network, and that problem will reverberate in many supply chains. The vaccine industry is no exception.

Shipment delays are another pandemic-induced challenge. Major supply-chain integrators such as UPS and FedEx have shut down key delivery services. That will disrupt pharmaceutical distribution. Delays will have escalated significantly during the 2020 holiday season. The importance of lifesaving medicine cannot be overstated, but pharmaceuticals ultimately account for a miniscule amount of shipment volume, and that makes it difficult for integrators to prioritize packages from the life sciences. How difficult would it be to find the one box of lifesaving medicine among the millions of boxes of Christmas gifts, for instance?

That problem brings us back to basic questions about whether to choose active or passive packaging systems for drug products. Active thermal systems do not use phase-change materials (PCMs) such as water/ice or dry ice. Instead, such systems use mechanical or electrical cooling systems combined with thermostatic controls to maintain proper product temperatures. The powers of active temperature control tend to be overestimated. Some active systems run on batteries, which eventually die. They can be recharged, of course, but doing that requires an extra handling step, introducing risk.

Passive thermal control relies on PCMs, making them simpler and more cost effective than active solutions. Passive shippers also enable cold-chain engineers and logisticians to build in a safety margin. For instance, packages qualified at –20 °C for 72 hours are proven to maintain those conditions in extreme heat. If a shipment bed is cool, then passive packaging can last longer than 72 hours.

Thus, passive systems hold significant advantages. People might not recognize such benefits because they think, “My freight has been delayed. Thank goodness that I am using an active shipper that can be plugged in to last in perpetuity.” However, many things need to go right for an active shipper to perform successfully, whereas passive shippers enable engineers to set design parameters around extreme temperature profiles. If a package is delayed but experiences mild temperatures, then it is likely to perform as expected.
 

Enabling Global Vaccine Distribution

What issues arise with shipment of biologics and vaccines to underresourced countries?
Littlefield: Such places need to develop sufficient infrastructure to support cold-chain operations. Most countries in sub-Saharan Africa still lack dry-ice capabilities. Countries affected by the Ebola virus — the DRC, Sierra Leone, Guinea, and Liberia — have developed some capability for cryostorage at –60 °C. Those countries will need either to construct additional capacity for the Pfizer vaccine or use Moderna’s product. Large vaccination programs are already in place for diseases such as diphtheria and polio, so those programs, which provide for –20 °C storage, could be adapted for Moderna’s vaccine. But large-scale implementation of vaccines requiring lower temperatures will be a challenge.

The NIH, US Agency for International Development (USAID), Bill and Melinda Gates Foundation, and World Health Organization (WHO) provide much support for cold-chain operations in developing countries. But the challenge is a bit like giving someone a guitar; doing that doesn’t make that person a musician. Giving clinicians a –60 °C freezer doesn’t make them cold-chain experts. My experience is that pharmacists and physicians in those countries are incredibly smart and talented but don’t yet have experience with cold-chain engineering. Developing adequate infrastructure will require a training component that until now has been neglected.
 

The Future of Vaccine Distribution

What is the COVID-19 pandemic teaching the biopharmaceutical industry about vaccine distribution, and how might distribution change in the future?

Hutchinson: Vaccines are “mission critical,” but distribution still relies on a business-to-consumer (B2C) commercial network. Biologics and vaccines have special requirements and great need for expedited service, yet we throw them into the same networks as every other shipment, introducing several hazards. Shipping companies try to protect against temperature excursions and shock/vibration events by overpackaging drug products using four-inch–wall polyurethane boxes that end up in landfills and gel ice made with nasty additives. Such tactics are inevitable when shipping drug products in networks that are not fit for purpose.

An idea that has emerged — one that I am trying to evangelize — is to build a distinctive life-sciences distribution network. Using a specialized network would be much more efficient than handing off a vaccine shipment to UPS or FedEx and hoping for the best. Of course, those carriers respect and support the biopharmaceutical industry, but transferring sensitive products with special requirements into a high-volume network can beget mistakes. Such problems will continue for as long as the biopharmaceutical industry remains a miniscule part of a huge network.

We need to try something different. The pandemic should be a wake-up call. And if another pandemic happens soon, it would be a shame if we did not learn anything from our current conditions and found ourselves lamenting the same problems as we have now because we did not make fundamental changes.

The vaccine industry will learn several lessons as Pfizer’s and Moderna’s vaccines are distributed widely and as more candidates advance through clinical trials. But genuine change will start within trade associations. Creating a distinctive life-sciences logistics network will be difficult because the companies comprising that industry are competitive. Large companies with sufficient volume and capacity will need to cooperate to establish a network.

A commercial opportunity exists in creating such a network. Integrators such as UPS use life-sciences–specific warehousing for storage but then throw all those packages into their general delivery network. Maybe vaccine developers could leverage an industry-specific network within a large integrated carrier. Amazon already has provided a model for creating our own captured network, and the biopharmaceutical industry ships enough product to make something like that work; it just needs to find a suitable shipping partner and then commit to shifting resources to specialized logistics.

Littlefield: The industry is learning that many activities that traditionally have been performed sequentially can be done in parallel. Until now, vaccine development has taken many years. Now we are witnessing vaccines move from discovery through commercial distribution in under a year. Part of that stems from acceleration on the part of research and development (R&D), but rapid development still requires appropriate checks on vaccine efficacy and stability. In terms of distribution, that means that transportation validation needs to be performed earlier and more effectively than it has in the past.

Hutchinson: Some companies already have learned that lesson and have aligned their development and manufacturing capabilities with their end products in mind. It is no accident that the Moderna vaccine can be stored at warmer, more conventional freezer temperatures and enjoy longer viability a refrigerated temperature than other formulations can. Decisions about those requirements were made early. Our goal, as a cold-chain engineering company, is to set up vaccine companies for success by engaging them relatively early in the clinical process to consider what challenges will come during commercial transport. Then we help them assemble datasets that they will need to minimize cold-chain risks going forward.

Brian Gazaille is associate editor at BioProcess International, part of Informa Connect; brian.gazaille@informa.com. Gary M. Hutchinson (ghutchinson@modality-solutions.com) is president and cofounder, and Daniel J. Littlefield (dlittlefield@modality-solutions.com) is principal, cofounder, and head of engineering at Modality Solutions; 2600 South Shore Boulevard, Suite 364, League City, TX 77573; https://www.modality-solutions.com.

Safe Transportation of COVID-19 Vaccines: Challenges and Solutions

Safe Transportation of COVID-19 Vaccines: Challenges and Solutions

Written by Modality Solutions

Posted on:

Gary Hutchinson
Daniel J. Littlefield

The race for safe, efficacious COVID-19 vaccines is on, with an estimated 66 vaccine candidates in the clinical trial phase and many more in the preclinical drug development phase worldwide.1 While there is great urgency to find effective preventative measures and therapeutics for SARS-CoV-2, the virus that causes COVID-19, the drug discovery and manufacturing development process is just one piece of the puzzle. Once a vaccine candidate has been deemed efficacious and safe, has received regulatory approval, and has been manufactured in the significant quantities needed, another hurdle remains: Transporting the vaccine in a manner that preserves its integrity.

The cold chain requirements for COVID-19 vaccines will present a myriad of challenges. Fortunately, the industry’s experience with other modern vaccines, combined with technology-based transport validation solutions, provides a roadmap for successfully transporting these vital drugs.
 

Understanding the Obstacles

The complexities of transporting a COVID-19 vaccine begin from the nature of these therapies and the challenges associated with any therapy developed on an accelerated timeline.

Traditional vaccines – like those designed to eradicate childhood diseases – use either an inactivated virus (as with polio, influenza, hepatitis A, and rabies) or an attenuated virus (as with measles, mumps, and chickenpox) to spur antibody development. Modern vaccines take a more sophisticated approach, using large, complex, fragile molecules to power the immune system to target and thwart a virus or other disease. The larger the molecule, the more susceptible it is to damage, notwithstanding the limited protection provided by the molecule’s lipid proteins.

As with other large molecules, a vaccine is particularly sensitive to shock and vibration – two hazards that can jeopardize drug safety and efficacy. Vibration (which involves repetitive, low-amplitude impact) can serve as an energy input into a large, three-dimensional molecule, with the potential to alter it chemically. Shock (which involves short-duration, high-amplitude impact) can shear off part of the molecule, reducing its efficacy or introducing particulates that can cause adverse events.

In addition to the complexities of any large molecule drug, COVID-19 vaccines will pose other logistical issues. Given the urgent need to stem the pandemic’s tide, these vaccines are being developed under the Coronavirus Treatment Acceleration Program (CTAP) specially created by the US Food & Drug Administration (FDA) to move new treatments to patients as quickly as possible. When vaccines and therapeutics move through the drug development and regulatory processes on an accelerated timeline, researchers tend to take a conservative approach, particularly when it comes to temperature tolerance.

Any biologic is sensitive to temperature, so tight temperature controls are always necessary to maintain their integrity. Because the first-round COVID-19 vaccine candidates were developed on a fast track, employing conservative formulation stability strategies, they will likely need to be stored in a deep-frozen state, typically defined as below -60°C. From a transportation standpoint, that usually means packing and shipping the vaccine in dry ice. By comparison, many established vaccines can be safely stored and transported at refrigerated temperatures of 2-8° C.

Another important consideration in transportation is a good understanding of the interaction of temperature, vibration, and shock. While any of these individually can cause product damage, they do not necessarily work independently of each other. This possible interaction emphasizes the importance of concurrent testing to investigate those transport activities which can result in any combination of significant vibration activity (e.g., long transportation lanes), temperature excursions, and multiple shock events (e.g., frequent manual handling or mode changes).

Controlling temperature and reducing the risk of vibration and shock throughout the cold chain is of the utmost importance when transporting modern vaccines and other therapeutics. While the safe transportation of COVID-19 vaccines will prove difficult, the industry’s experience with the Ebola outbreak in sub-Saharan Africa in 2015 demonstrates that it can be done effectively.

Much like COVID-19, the Ebola vaccine required storage in a deep-frozen state to avoid damage and preserve integrity. Once properly thawed and reconstituted, it could only be refrigerated for up to 12 hours prior to dosing. The associated transportation and distribution problems were successfully solved, demonstrating that supply chain networks can be designed, executed, and monitored amidst very formidable logistical obstacles. Though the COVID-19 pandemic is occurring on a much larger scale than the Ebola outbreak, the blueprint for its safe transport exists.
 

Testing the Cold Chain Strategy

Safe and rapid distribution of a vaccine is critical to stemming the tide of the coronavirus pandemic. But before an approved COVID-19 vaccine can be shipped to healthcare providers, regulators must be assured that the pharmaceutical company’s cold chain plan is sound and feasible. Among their requirements, regulators such as the FDA require pharmaceutical companies and other drug makers to perform transport validation studies on the final formulation of the drug, which typically happens concurrent with phase III clinical trials. Additionally, initial transport validation may be done on engineering batches or before a final formulation decision is made, enabling the company to appraise multiple candidate formulations early in the drug development process.

 

This is the point at which the scientists’ drug discovery and development work is handed off to engineers and logisticians to determine how to protect the drug throughout the cold chain. Through rigorous risk assessments, these professionals work to find the optimum intersection of the drug product and the supply chain, demonstrating to regulators that the drug can be transported to the point of use on a large scale, while maintaining its safety and efficacy.

While the regulations vary by country, any developer of a COVID-19 vaccine or therapy will be required to demonstrate that it will maintain a chain of custody throughout the supply chain by employing consistent, repeatable processes that preserve the vaccine’s integrity. Transport validation is the critical part of that requirement.

Historically, transport validation for vaccines and other therapies was done in real-world settings – placing packages filled with a drug product on trucks and planes and sending them across the globe. Over time, the industry discovered that real-world shipments testing has inherent limitations.

  • A real-world shipping test does not allow for testing multiple concurrent hazards. Yet, in the real world, each potential hazard does not occur in isolation.
  • In a real-world shipping test, the worst-case scenario will not occur. However, a valid assessment should test the “worst-case” edges of the intended operating space.
  • A real-world shipping test does not allow for controlling multiple variables in a way that makes the test both realistic and repeatable.
  • Due to such limitations, a real-world shipping test on a COVID-19 vaccine will not be able to guarantee that the drug will experience all possible hazards, at their peak, at the same time, or that the testing experience can be repeated under identical conditions.

Consider this example: A COVID-19 vaccine is driven by truck to an airport in Los Angeles, California, then flown from Los Angeles to Sydney, Australia, then driven to a clinic 15 miles away. That vaccine has endured a long flight, but it probably has not been subject to significant shock events since it was only dropped off and picked up a couple of times. If the same vaccine is driven by truck from Temecula,

California to San Diego, then flown to Louisville, Kentucky, where it takes a connecting flight to Columbus, Ohio and is then driven by truck to Marietta, Ohio, it has a greater chance of enduring shock because it has been picked up and dropped off more often. These two scenarios present very different risks, underscoring the fact that it is unlikely for real-world testing to simulate the many scenarios a drug might encounter in transit.
 

Transport Validation Goes High-Tech

Critical feedback from the FDA and other regulators has created an incentive for pharmaceutical and biotech companies to overcome these limitations by conducting transport validation using more rigorous methodologies. Over time, transport validation testing has evolved and advanced significantly with the help of technology. Today, the makers of COVID-19 vaccines and other biologics can use technology-based simulation approaches to test the drug’s physical and chemical integrity, based on the actual hazards that will occur in the field, to ensure there will be no risk of degradation during transit.

Degradation of a COVID-19 vaccine can result from two primary causes: A change in chemical stability (e.g., the chemical properties of the molecule are altered) or a change in physical stability (e.g., a portion of the molecule breaks off and turns into particulates, or the vaccine’s lipid protein “unravels” too much while deep-frozen and does not return to its original state once thawed for dosing).

A transport simulation study can determine if degradation occurs after concurrent exposure to the five potential hazards drugs may encounter in transit: temperature, shock, vibration, pressure, and humidity. Typically, the study is preceded by a risk assessment to determine which risks are the highest priority for this vaccine or other drug, which then informs the test design and implementation. Deep knowledge of the shipping lanes the vaccine will eventually travel through is also essential to ensuring the test reflects real-world conditions.

With a valid transport test designed, logisticians and engineers can use simulation technology to test all five hazards on a worst-case scenario basis, concurrently, in a controlled lab setting, under repeatable conditions. For instance, various temperature fluctuations can be tested, varying levels and duration of vibration can be simulated, and shock events (such as package drops) can be done at different frequencies. This controlled testing environment yields data that can help assure pharmaceutical companies and regulators that no matter what happens in transit in the real world, the integrity, efficacy, and safety profile of the COVID-19 vaccine will be maintained.

Transport simulation studies also prove useful in situations where the drug is in short supply (as is the case with the early COVID-19 vaccine candidates) or is expensive. Given the scale of the pandemic and the urgency of stemming its spread, every ounce of COVID-19 vaccine is essential to preserve; there is no room for waste. Conducting a controlled transport validation in which multiple hazards are tested at their peak, concurrently, reduces the total amount of vaccine material needed. Additionally, because COVID-19 vaccine development is in its early stages there are still knowledge gaps, making it even more important to obtain as much information about the material as efficiently as possible.

Beyond meeting the regulatory requirement to demonstrate product robustness under worst-case hazard conditions, the data obtained from transport validation helps guide pharmaceutical companies on how to move forward with their cold chain network. Ideally, the testing will find that the vaccine maintained its chemical and physical integrity when subjected to the rigors of worst-case concurrent hazards.

In the event that transport validation uncovers potential risks in the operating plan, the company now has the information to develop risk mitigation measures. Mitigation is especially critical under the Coronavirus Treatment Acceleration Program (CTAP). There simply may not be time or resources to change the formulation, so other measures may be more feasible, such as changes to the packaging design or materials.
 

Once the transportation plan is validated and accepted by regulators, it is important to establish a program of monitoring and controls to ensure the vaccine reaches the front lines with its safety and efficacy profile intact. In the early stages of COVID-19 vaccine distribution, monitoring and controls will prove essential until additional stability data is available to support a wider acceptable temperature range. While these early vaccines, and other mRNA-based vaccines, will require deep-frozen temperatures for initial storage and transportation, they will also require dilution and thawing before dosing. After preparation for dosing, the temperature requirements switch to refrigerated temperatures (2 to 8° C), but the vaccine can only be kept at this temperature for a maximum of 24 to 48 hours before dosing. These complex temperature requirements require significant monitoring and controls to confirm the proper temperature and storage duration.
 

Looking Ahead

While the earliest COVID-19 vaccine candidates will require the most restrictive temperature controls, the next generation vaccines will benefit from a larger body of knowledge about their stability boundaries, opening the door to some formulations that will be stable at refrigerated temperatures, which the supply chain has a greater capacity to handle. For example, viral vector-based vaccines have less restrictive temperature and duration requirements, making them stable for months and or even years at refrigerated temperatures. This temperature range is more suitable to long-term vaccination and therapy programs, which COVID-19 vaccines will inevitably progress to over time. The data provided by transport simulation studies and real-world shipping tests will be integral to providing vaccine developers with the insights to develop such formulations.

However, challenges still exist when transporting vaccines at refrigerated temperatures. It will be critical to test that the refrigerated drug will withstand the hazards of shipment and that the formulation remains unchanged, through consistent and repeatable transport validation. When testing is done under the controlled conditions of a lab environment, it is feasible to repeat the same conditions tested with an early, deep-frozen formulation and compare the results to the new refrigerator-stable drug. Such a head-to-head comparison provides greater assurance to regulators that the proper controls are in place for safe transport. In turn, the challenges of safely transporting and distributing COVID-19 vaccines will become more than surmountable, helping to speed the delivery of these vital preventive medicines to people globally.
 

Reference

1. Corum. J., Wee, S., & Zimmer, C. (2020, October 28), Coronavirus Vaccine Tracker, The New York Times.

Author Biographies

Gary Hutchinson, President of Modality Solutions, is an expert in controlled-environment logistics. He has deep expertise in understanding the environment and infrastructure, designing controls, and creating monitoring systems. Gary’s background in the life sciences field includes a focus on biologics, tissue heart valves, cardiac monitoring equipment, and perfusion systems. www.modality-solutions.com

Daniel Littlefield, Principal of Modality Solutions, is an expert in process improvement, risk assessment, safety, and security. Currently head of the organization’s engineering management activities, he has successfully led clinical trial operations and assessments worldwide. Daniel’s career includes a variety of technical and supervisory roles in research and operations. www.modality-solutions.com

Modality Solutions Recognized on Inc. Magazine’s List of Fastest-Growing Private Companies in Texas

Modality Solutions Recognized on Inc. Magazine’s List of Fastest-Growing Private Companies in Texas

Written by Modality Solutions

Posted on: April 7, 2021

Modality Solutions Recognized on Inc. Magazine’s List of Fastest-Growing Private Companies in Texas

Modality Solutions, a leading cold chain optimization firm, makes Inc. 5000 Regionals: Texas 2021 list with 64 percent two-year growth.

HOUSTON (PRWEB) APRIL 01, 2021

Modality Solutions, a leading biopharmaceutical cold chain validation engineering firm with expertise in regulatory requirements and transport simulation technology for life science applications, is pleased to announce it ranked No. 179 on the Inc. 5000 Regionals: Texas 2021 list.

Based on its 64 percent growth, Modality Solutions is one of 56 Houston companies to make the Texas regional list. It is one of three Houston engineering firms to be recognized as a fastest-growing company.

The 2021 Inc. 5000 Regionals are ranked according to percentage revenue growth when comparing 2017 and 2019. According to Inc., the companies that made the regional ranking set a high bar. When so many businesses lack clarity, these leaders are bound to be the first to get to tomorrow.

“It’s a distinct honor to be one of the most successful companies within the Texas economy’s most dynamic segment—its private businesses,” said Gary Hutchinson, President of Modality Solutions. “Our recognition on Inc. 5000 National and the Houston Business Journal fastest-growing lists two consecutive years is about providing value to our biopharmaceutical industry clients. Biotech, pharmaceutical, and medical device companies increasingly rely on us for our deep knowledge of multiple, complex cold chain regulations. Our engineering experience and regulatory knowledge help make sure our clients ensure patient safety from Phase II development to last-mile delivery.”

“This list proves the power of companies in Texas no matter the industry,” says Inc. editor-in-chief Scott Omelianuk. “The impressive revenues and growth rates prove the insight and diligence of CEOs and that these businesses are here to stay.”

View Modality Solutions company profile for Inc. 5000 Regionals: Texas 2021 at https://www.inc.com/profile/modality-solutions

For more information about Modality Solutions, visit https://www.modality-solutions.com

About Modality Solutions, LLC

Founded in 2011, Modality Solutions is the leading validation engineering, regulatory guidance expert, advanced testing, and cold chain optimization firm serving the biopharmaceutical cold chain industry. Its focus is on the successful and rapid regulatory approval of a drug company’s therapy and its cold chain optimization. The ISO 9001:2015 certified engineering firm specializes in integrating cold chain operations, developing transport validation strategies, supporting global regulatory applications, and global clinical trial operations. It conducts transport simulation testing with its unique Advantage Transport Simulation Laboratory™. Modality Solutions is recognized as a fastest-growing private company by both Inc. Magazine and the Houston Business Journal. For more information, visit https://www.modality-solutions.com

Engineering Angles: Solving the cold chain conundrum

Engineering Angles: Solving the cold chain conundrum

Written by Modality Solutions

Posted on:

A well-designed transport validation approach can mitigate potential distribution hazards

By Gary Hutchinson President, Modality Solutions
Dec 16, 2020

The pharma cold chain has never been more crucial or complex.

As the nature of the modalities in the product pipeline evolve, the logistics challenges escalate. Consider that an ever-increasing percentage of new pharmaceuticals are vaccines, cell and gene therapies, and other biologics — drugs with stringent temperature and transportation requirements. The FDA approved a record 22 new biologics in 2019, and 21 of them have cold chain requirements.

For pharma manufacturers with environmentally sensitive drugs like these in their portfolios, the cold chain is both a priority and a challenge. While regulatory compliance is always a key objective, protecting against environmental hazards throughout the distribution network is crucial to ensuring drug safety and efficacy and staying competitive. And with billions spent annually on pharma logistics — including transportation, specialized packaging, monitoring and controls — the financial stakes are high.

Current Good Distribution Practices (cGDPs) for the pharma supply chain are always a formidable task due to the distributed nature of modern controlled environment networks and the third-party contractor relationships involved. When developing a transportation plan for environmentally sensitive drugs, the task is further complicated by five potential hazards: temperature, shock, vibration, pressure and humidity. Together these hazards create a pharma cold chain conundrum, but one that can be solved with the right approach.

It starts with the right testing

When transporting pharma products that are based on proteins, tissues, genes or cells, the inevitable variations in equipment, material handling, personnel skills and experience make it difficult to validate the controlled environment logistics network to a high degree of confidence. In turn, careful consideration must be given to in-transit monitoring, procedural controls, visual indicators and stability testing. These areas have an increasing focus with technology advances making it possible to dynamically test the cumulative and significant hazards that can occur during transport.

Temperature variation is one hazard of particular concern for environmentally sensitive drugs. Even temporarily storing a thermal packaging system in a forced-air refrigeration cooler within the qualification time period can cause low temperatures and potential freezing of the drug product. In protein-based drugs, that raises the risk that the protein will degrade, become inactive, or suffer other issues that could impact safety or efficacy.

But it’s not only temperature shifts that can create problems. Vibration and shock events are inherent in the logistics network, often occur concurrently with temperature fluctuations, and are particularly troublesome for solution formulations of certain large proteins. Large molecules — like those used in many modern therapies (including many for COVID-19) — are susceptible to damage that can alter the protein chemically or physically.

Traditional testing approaches — essentially shipping the drug out in the real world — don’t allow for testing such hazards concurrently and at worst-case levels, leaving gaps in a manufacturer’s understanding of the cumulative effects. Dynamic transport simulations testing is an effective approach to closing those gaps, especially for drugs with cold chain requirements.

A well-designed transport validation approach starts with assessing the risks for each environmental hazard to each specific drug in your expected commercial supply chain, the expected shipping durations, and the expected range of variances that could occur, including temperature exposure. Then advanced simulation technology is used to test multiple hazards simultaneously, at the worst-case edges of the intended operating space, and assess their interaction in a controlled environment.

The data gleaned from dynamic transport validation testing is invaluable — enabling pharma manufacturers to confidently define the shipping conditions, handling procedures, and specialized packaging required to protect a drug’s integrity in transit. By making informed decisions about how to best design the cold chain for a particular drug, manufacturers can reduce the compliance, quality and financial risks associated with transportation and ensure the safety and efficacy of the final product.

Gary Hutchinson is president of Modality Solutions and a controlled-environment logistics expert.

Race For a Vaccine: Distributing Vaccines Across America

Race For a Vaccine: Distributing Vaccines Across America

Written by Modality Solutions

Posted on: December 7, 2020


Race For a Vaccine: Distributing Vaccines Across America
NBC Today Show News – November 30, 2020
Vicky Nguyen
NBC Investigative & Consumer Correspondent

NBC News featured Modality Solutions’ expert engineers and its Advantage Transport Simulation Laboratory in one of its continuing reports on a “Race for a Vaccine.” On Monday, November 30, 2020, Today Show hosts Savannah Guthrie and Hoda Kotb introduced the pressing cold chain logistics topic of “Distributing Vaccines Across America.” NBC Investigative & Consumer Correspondent Vicky Nguyen provided viewers with an inside look at the how, when, and where of the critical operations required to get the vaccine to the people who need it most.

Footage of our engineers in the simulation laboratory testing product showed how Modality Solutions puts actual vaccine-filled containers through tests like vibrations that mimic bumpy roads, extreme temperatures, dangerous drops, and changes in air pressure that simulate air travel, and more.

Bottom Line: Several vaccine trials are now near completion, but getting those vaccines from manufacturers to a clinic near you is a mega logistics operation, never done before on this scale.

Click here to read the transcript of the interview.

Modality Solutions is a Sponsor and Workshop Presenter at the Virtual BMWS20 – Biomanufacturing World Summit

Modality Solutions is a Sponsor and Workshop Presenter at the Virtual BMWS20 – Biomanufacturing World Summit

Written by Modality Solutions

Posted on: November 10, 2020

company-news-BMWS20

“Our sponsorship and workshop at the BMWS20 support our continued commitment to helping the global biopharmaceutical industry collaborate on new approaches to similar challenges,” said Modality Solutions President Gary M. Hutchinson. “It’s our mission to share our cold chain validation best practices that will help industry leaders understand the changing industry standards and how to integrate risk management processes with validation best practices to ensure compliance, quality, and product integrity.”

Modality Solutions is a sponsor and session panelist at the Biomanufacturing World Summit (BMWS20) Nov. 16-17, 2020 virtual conference.

Gary M. Hutchinson and Daniel J. Littlefield will present “Transport Simulation Testing of Your Therapy: A Better Approach Than ‘Real World’ Shipping Tests.”

During the session, attendees will take away valuable information, including:

  • Accelerated, sequential testing (e.g., ASTM, ISTA) is no longer acceptable by the FDA for drug product testing.
  • Real-world testing cannot test the “worst-case” edges of your operating space.
  • Real-world testing in the post-COVID-19 world will be difficult and expensive.

To view our BMWS20 sponsorship and workshop presentation press release, click here.

Agency Feedback Integrates Regulations, Industry Guidance, and Best Practices Across Global Cold Chain Jurisdictions

Agency Feedback Integrates Regulations, Industry Guidance, and Best Practices Across Global Cold Chain Jurisdictions

Written by Modality Solutions

Posted on: November 6, 2020

Cold-Chain-Jurisdictions, image of business hands reaching with gears to make it work.

By Gary Hutchinson, President, Modality Solutions
 
In 2021, Modality Solutions will be facilitating a review of practical approaches for cold chain compliance by jurisdiction. We will align current regulations, guidance documents, and agency feedback across therapies to offer risk-appropriate techniques. We will share regulatory responses from our extensive database developed from almost 200 interactions with global regulators with our clients on over 95 different therapies, including biologics since 2017. Here is why we are taking this approach.
 
A practical, manageable approach to a secure and robust cold chain is only possible to understand at the intersection of regulations, industry best practice standards, and supplier capabilities. This integration of willing regulators, innovators, and supplier partners must cooperate to ensure prompt, efficient, and compliant logistics networks to distribute therapies worldwide. The need for regulations, industry standards, and service providers to support the cold chain process has grown as fast as the technology platforms for new therapies and new manufacturing and delivery systems have exploded.
 
However, too often, these relationships are seen only as antagonistic or transactional. Information requests and meetings with regulators (especially Type B and C) are a great wealth of practical knowledge that can immediately be applied across the biopharmaceutical cold chain.
 

Meeting the Challenge Requires Integration

The industry can only integrate cold chain requirements, starting with therapy development and extending to environmental control during transit, by establishing an effective cold chain strategy. Integrating a systematic process for the assessment, management, communication, and review of risks to the therapy’s quality across the cold chain is the best way to anticipate cold chain challenges.
 
Best-in-class organizations integrate quality risk management, primary packaging studies, chemical and physical stability studies, drug product formulation testing, packaging design, and monitors and controls. Framing this activity as only a product development activity does not allow downstream cold chain management considerations to be included in the product design discussion. A holistic view provides the most significant opportunity for defining any subsequent commercial cold chain alternatives (e.g., shipper design, networks, and monitoring) that align with country-specific regulatory requirements.
 

Regulatory Considerations

Regulators have presented a growing series of country-specific guidelines and regulations (over thirty-five and counting) governing temperature control in storage and shipping. Too often, sponsors, innovators, and their suppliers define compliance by a gap analysis of the standards that apply to the cold chain and the measures taken to ensure temperature control during shipping and storage.
 
A switch from gap analysis to a holistic and integrated approach across multiple jurisdictions is now required.
 
The sponsor takes primary responsibility for ensuring that the therapy is fit for use. However, these innovators increasingly require strong partnerships with partners and suppliers coordinated with regulators, especially in fast-track accelerated review programs. Increasingly, manufacturers of cold chain products do have direct control over their products’ storage and handling. From the start of production through shipment from their main supply warehouse until they reach the first point of shipment and then distributed point-of-use with healthcare professionals, third-parties manage all aspects of the cold chain.
 
However, while accountable, drug sponsors can only have an indirect influence on cold chain compliance. The sponsor may indicate how the products should be stored and handled based on evidence from clinical studies and basic knowledge about therapeutic drug physical and chemical stability properties and requirements. An effective cold chain strategy must also recognize when the responsibility lies with a supply chain partner.
 
Specific compliance requirements for establishing an effective cold chain structure and governance strategy are based upon a combination of regulatory requirements defined by the corresponding regulatory body such as FDA, EMA, WHO, Health Canada, etc. However, industry best practice guidance from organizations such as the International Safe Transit Association (ISTA), United States Pharmacopeia (USP), International Air Transport Association (IATA), International Committee on harmonization (ICH), and the Parenteral Drug Association (PDA) offers essential information on the details and considerations required.
 
Too often, sponsors and their partners ask a series of generic questions are to audit compliance with cold chain standards:

  • Is the packaging used formally qualified for the product being shipped?
  • Is the equipment used to control the temperature levels suitable or formally calibrated?
  • Is the package used during transportation to ensure temperature uniformity within the container?
  • Is a temperature profile study required?

A deeper understanding of the science, risks, processes, and engineering behind these questions must be our first aim. Only then can the most critical question – “Why?” – can be answered, allowing “Is?” to be bypassed altogether and move directly to “How?”.
 

Cold Chain Management Trends

As life-saving drug therapies’ value and criticality escalate, regulatory requirements are moving toward tighter control over every facet of the cold chain. Even with the differences in formal requirements across different jurisdictions, regulators, innovators, and supplier partners gravitate to the most conservative approach because appropriate risk-appropriate techniques are not adequately explained during interactions with agencies. Training will continue to be an issue as logistics network partners have to balance these conservative requirements forced on the network by incomplete interactions with regulatory partners and their partners’ desired practice. Formal and informal regulation complicating today’s global supply chain means success is, at best, a moving target. Collaboration among all partners and consistent engineering first principles approach with regulators provide the foundation for future compliance risk reduction and approval success.
 

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Modality Solutions a Sponsor and Cold Chain Panelist at the Bio Supply Management Alliance (BSMA) 2020 Conference

Modality Solutions a Sponsor and Cold Chain Panelist at the Bio Supply Management Alliance (BSMA) 2020 Conference

Written by Modality Solutions

Posted on: November 5, 2020

BSMA---Company-News image

“As the global biopharmaceutical industry assesses the long-term impact the COVID-19 virus has on the cold chain for their life-saving products,” said President Gary Hutchinson. “We are committed to helping the industry to reimagine the biopharmaceutical cold chain logistics network and explore shared-use strategies and revise the current industry approach. We need to evaluate the risk in the overreliance on a current general B2C delivery network and implement industry-wide reforms.”
 
Modality Solutions was a sponsor and session panelist at the Bio Supply Management Alliance (BSMA) October 22-23, 2020 virtual conference.
 
The panel discussion topic “Reimagination of the Decimated Transportation Network After the COVID-19 Pandemic Attack” featured a diverse group of industry leaders, including President Gary Hutchinson. Moderator, Joel Glende, BSMA Executive Vice President Manufacturing & Academia Member Engagement led a lively discussion between the five panelists.
 
The building block themes of the life sciences supply chain conference were:

  • Ensuring supply of materials APIs and services from global suppliers
  • Building the NextGen supply chain for life sciences – the Ilumina Journey
  • Preparedness for the distribution of emerging vaccines for COVID-19
  • Transportation network readiness for COVID-19 vaccines
  • Digital transformation of life sciences for resilience and agility
  • Virtual audits of drug manufacturers and their global suppliers

 
BSMA is known for its driving innovation in the life sciences supply chain, it brought together experts in the global healthcare industry for this valuable conference.
 

To view our BSMA 2020 sponsorship and participation press release, click here.

 

Modality Solutions Makes 2020 Houston Business Journal Fast 100 List Second Consecutive Year

Modality Solutions Makes 2020 Houston Business Journal Fast 100 List Second Consecutive Year

Written by Modality Solutions

Posted on: October 8, 2020

Modality Solutions is pleased to be recognized for the second year in a row for our sustained managed growth in the Houston region,” said President Gary Hutchinson. “Our mission is to help our clients successfully launch new therapies and assist them in preparing for regulatory reviews. And I’m proud to say our team is made up of the brightest engineering professionals in biopharmaceutical cold chain logistics.

Modality solutions reported a two-year (2017-2019) revenue growth of 65 percent. It moved up from No. 90 on the Fast 100 2019 list to No. 62 on the 2020 list.

“Amid the challenging business environment of COVID-19, the Houston Business Journal is proud to once again recognize the fastest-growing private companies in Houston,” said Bob Charlet, Publisher. The rankings were revealed during a live online broadcast September 18.

 

To view our formal Fast 100 press release, click here.

 

Modality Solutions Focuses on Supply Chain Validation and Cell Therapy Clinical Trials at SBE Conference

Modality Solutions Focuses on Supply Chain Validation and Cell Therapy Clinical Trials at SBE Conference

Written by Modality Solutions

Posted on:

Modality Solutions presented at the Society of Biological Engineers (SBE), part of AICHE (American Institute of Chemical Engineers) virtual “3rd Cell Therapies and Immunotherapy Conference.” The conference focused on gene and cell therapies and other immunotherapies. It included cutting edge developments on gene therapy manufacture, microenvironment engineering of tumors, and the use of CAR-NK therapies led by the Houston-based MD Anderson Cancer Network.

Rob Battista, a Senior Engineer with Modality Solutions, focused on supply chain validation for CAR-T cell therapies. While Modality Solutions Principal, Dan Littlefield, focused on best practices to apply to cell therapy clinical trials in developing countries.

Rob has extensive experience in distribution validation for biologics and gene therapies. He shared his gene therapy expertise with the conference by focusing on risk assessment and transport simulation. According to Rob, supply chain hazards have the potential to affect patient safety and therapy efficacy via:

  • Damage to the quality of the therapy
  • Supply chain errors causing delayed or missed dosing of patients
  • Quality violations during shipment
  • And the loss of patient-specific material

For transport simulation, Rob advocated concurrent exposure of therapies to applicable parameters at the edges of the supply chain’s multi-dimensional operating space (e.g., temperature, pressure, shock, vibration). After exposure to realistic and concurrent simulation, the commonly analyzed quality parameters include cell count, cell viability, post-thaw proliferation, and phenotype purity assays.

Dan is a thought leader and recognized expert in cold chain engineering support for emergency response clinical trials, including work with NIH, CDC, BARDA, and WHO. He focused on the practical aspects of the challenges associated with clinical trial logistics in developing countries, such as the importance of risk assessment, equipment qualification, and the use of roleplaying scenarios in emergency response training.

Dan outlined as part of the risk assessment the importance of evaluating existing controls for hazard prevention impacting product storage. In his example, he explained that a set of controls with a common failure mode are not independent layers of protection. Modality Solutions considers these important details every time they conduct a risk assessment and have successfully conducted more than 100 risk assessments for many clients’ logistics processes under many circumstances.

The use of emergency response scenarios as part of training is an excellent example of how the breadth of Modality Solutions’ team experience applies to every aspect of their work product. Dan’s experience in defense and law enforcement, along with his work as a hazmat technical expert with DuPont, allow him to develop topical and engaging scenarios where staff roleplay the incident from initial investigation, troubleshooting, response, and mitigation. President Gary Hutchinson noted that he uses a comparable scenario-based training to assist clients in preparing for regulatory reviews.

Regarding the conference itself, Rob said, “I want to thank the SBE for the opportunity to present alongside all the other esteemed researchers. I found the work on centrifugal reactors used for mAbs adapted for cell therapies to be especially interesting.” Dan shared he also appreciated the opportunity, and noted, “I think Rob and I are a bit downstream for this audience, but we always encourage everyone in the discovery chain to consider how to get the therapy to the patient, since it’ll matter eventually.”

 

 

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Modality Solutions Makes Inc. 5000 List of America’s Fastest-Growing Companies 2nd Consecutive Year

Modality Solutions Makes Inc. 5000 List of America’s Fastest-Growing Companies 2nd Consecutive Year

Written by Modality Solutions

Posted on: August 27, 2020

“Modality Solutions is pleased to be recognized for the second year in a row within the American economy’s most dynamic segment—its independent small businesses,” said President Gary Hutchinson. “Our primary goal is to continue to help clients successfully launch new therapies while we continue on our track record of successful outcomes for our clients. It’s great to join the ranks of companies like Intuit, Zappos, Under Armour, Microsoft, Patagonia, and many other well-known brands that gained their first national exposure as honorees on the Inc. 5000.”

Modality Solutions reported a three-year (2016-2019) revenue growth of 71 percent. The Houston-based firm is one of four engineering firms from the metro area and one of 11 in the State of Texas.

“The companies on this year’s Inc. 5000 come from nearly every realm of business,” says Inc. editor-in-chief Scott Omelianuk. “From health and software to media and hospitality, the 2020 list proves that no matter the sector, incredible growth is based on the foundations of tenacity and opportunism.”

To view our formal Inc. 5000 press release, click here.

Monjuvi® Brings New Optimism for Refractory Diffuse Large B-cell Lymphoma (DLBCL) to Patients Worldwide

Monjuvi® Brings New Optimism for Refractory Diffuse Large B-cell Lymphoma (DLBCL) to Patients Worldwide

Written by Modality Solutions

Posted on: August 23, 2020

cold chain validation strategy, image of MorphoSys logo over a backdrop

On July 31st, 2020 the FDA has approved tafasitamab-cxix, officially named Monjuvi®, in combination with Lenalidomide as a second-line treatment for adult patients with relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) for our client MorphoSys. We are very proud of their fantastic accomplishment and excited about our small role in their success.
 
Monjuvi, in combination with Lenalidomide, addresses a high unmet medical need and qualified for the FDA’s Fast Track, Priority Review, and Breakthrough Therapy designations. These designations make the filing process, including cold chain validation, more challenging than other filings because of the compressed timelines and competing priorities for both material and intellectual capital across the organization.
 
Modality Solutions incorporated existing stability and engineering studies into a comprehensive cold chain validation strategy that was shared with regulators early in the approval process. Once the strategy was agreed upon, our focus shifted to creating data on drug product quality during transport.
 
Transport simulation testing provides the fastest and most effective approach to cold chain validation of drug product available. After five days of continuous stressing of drug candidate Monjuvi at the edges of safe operating space, MorphoSys could begin analytical testing of the stressed drug product immediately afterward.
 
This proven approach was shared up-front with their regulatory partners, and the drug product quality data was accepted without comment. This focused and accelerated pathway to approval has again been shown to be an industry best practice for biologics in general and monoclonal antibodies in particular.
 
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwidei, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow, or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter.ii In the United States each year approximately 10,000 patients are diagnosed with relapsed or refractory DLBCL who are not eligible for ASCT.iii
 
FDA Breakthrough Therapy designation is intended to expedite development and review of drug candidates. It is granted if preliminary clinical evidence indicates that the drug candidate may demonstrate substantial improvement over existing therapies in the treatment of a serious or life-threatening disease. The Biologics License Application (BLA) for Monjuvi was granted Priority Review and approved under the FDA’s Accelerated Approval program.
 

 
In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize Monjuvi globally. Monjuvi will be co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.
 
MorphoSys (NASDAQ:MOR) is a commercial-stage biopharmaceutical company dedicated to the discovery, development, and commercialization of exceptional, innovative therapies for patients suffering from cancer. Headquartered near Munich, Germany, the MorphoSys group includes a fully owned U.S. subsidiary MorphoSys U.S. Inc.iv
 

References

i. Sarkozy C, et al. Management of relapsed/refractory DLBCL. Best Practice Research & Clinical Haematology. 2018 31:209-16. doi.org/10.1016/j.beha.2018.07.014.

ii. Skrabek P, et al. Emerging therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma. Current Oncology. 2019 26(4): 253-265. doi.org/10.3747/co.26.5421.

iii. DRG Epidemiology data.

iv. www.morphosys.com

New Simulated Transport Methodologies White Paper Announced

New Simulated Transport Methodologies White Paper Announced

Written by Modality Solutions

Posted on: August 12, 2020

Modality Solutions new white paper details how simulated transport is a valuable technique for determining the physical stability of drug product protein solutions, including vaccines, monoclonal antibodies, antibody-drug conjugates (ADCs), and gene therapies. Large molecule drug products may be susceptible to degradation when exposed to common transport hazards. Simulation testing exposes the product to the concurrent combination of these hazards at worst-case edges of your operating space in the global supply chain. Unlike ASTM-based testing, the hazards are applied with realistic durations and intensities that reflect the supply chain’s risks.

The white paper explains:

  • The simulation testing concurrently exposes the product to the five major transport hazards affecting drug product quality: shock, vibration, temperature, pressure, and humidity at the edges of your operating space.
  • Analytical results from samples exposed to worst-case transportation hazards demonstrate product robustness during simulated shipping.
  • Non-accelerated profiles are selected because they reflect the energy levels and intensities in the supply chain. The goal is not to accelerate the testing, but to replicate all the hazards in transit.


“An understanding of these methodologies is vital to ensure the simulated transport hazards reflect the actual cold chain for each therapy. “If correctly planned and executed to be included in the BLA, analytical results from samples exposed to concurrent transport simulation are considered industry best practice.”

— Modality Solutions President, Gary Hutchinson.

 

Click here to view the Simulated Transport Methodologies White Paper press release.

Is Your Supply Chain Prepared for the Coronavirus Vaccine?

Is Your Supply Chain Prepared for the Coronavirus Vaccine?

Written by Modality Solutions

Posted on: July 27, 2020

Cold Chain COVID-19, Is Your Supply Chain Prepared for the Coronavirus Vaccine?, image of a drone with the COVID-19 vaccine and hands reaching for it

You need a strategy to address the inevitable cold chain challenges caused by worldwide COVID-19 vaccine deliveries
 

Scientists are working round the clock to develop a COVID-19 vaccine. There are 23 vaccines in human clinical trials against the virus, SARS-CoV-2, according to the World Health Organization, with more set to begin testing soon.

“At the end of the day, you have to prioritize efficacy and then resolve the challenges around the logistics of the trial or logistics of manufacturing large quantities of vaccine,” said Pascal Soriot, AstraZeneca’s CEO, in a briefing with reporters.i

Developing a vaccine is only the first hurdle. Nearly 6 billion people will need an estimated two doses.ii One thing in common for most of the vaccine candidates that are the front runners in Phase 2 and 3 development are either genetic vaccines, viral vectored, or protein-based. As such, they will be highly unstable and susceptible to environmental hazards occurring during transportation. Ebola vaccine currently available is viral vectored and has to be stored below -60℃. If this is an indication of what is to come, the safe distribution of so many doses globally (see the chart below) will require a coordinated, robust, and reliable cold chain supply chain infrastructure that will take time to implement given the already existing supply chain shortages.

Stakeholders are to start designing their vaccine distribution cold chain immediately to guarantee timely and safe delivery of this much-coveted vaccine the entire world is anticipating.

Preventing failure entails first ensuring that raw ingredients maintain safe temperatures during transportation and storage. Then manufacturers must design a cold chain system that ensures the finished vaccine will withstand such environmental hazards as temperature fluctuations, shock, vibration, humidity, or pressure throughout storage, packaging, domestic and international shipping, distribution, and last-mile delivery.

There are many issues to consider, and some are unique to COVID-19. To minimize the risk that supply chain gaps may cause losses of valuable vaccines, two primary areas must be addressed:
 

  1. Packaging component shortages and manufacturing scale-up.
  2. Transportation and the vaccine supply chain.

 
The COVID-19 pandemic has caused shortages of ingredients and supplies. Sand used to manufacture glass vials is one example. Manufacturers must take extra care to minimize shipping damage not only to raw materials but also to supplies.

The pandemic is pressuring manufacturing capacity, too. Manufacturers are looking to design facilities that can pivot to other vaccines as some formulations fail. Their cold chains, therefore, must be flexible to accommodate changing requirements.

Most COVID-19 vaccine frontrunners use cell or gene therapy, which requires cryogenic temperatures during transportation and storageiii. The few protein-based formulations can use the conventional 2°C to 8°C) cold chain. Regardless of the vaccines’ exact temperature requirements, however, they all are highly sensitive to environmental hazards.

Simulation technology is a powerful tool vaccine developers can use to ensure the physical and chemical integrity of COVID-19 vaccines until it reaches the patient. Transport simulation can evaluate risks very early on and provide actionable data for mitigation. Whether this means using a qualified thermal shipper or adjusting the vaccine cold chain to achieve a better stability in-transit, the sooner you can prepare for safe door-to-door shipping, the sooner much-needed vaccines can be delivered to patients throughout the world.

Regulatory agencies have accepted simulation results for product and packaging validation. Unlike real-world testing, it lets organizations virtually test their supply chain strategy and cold chain processes under multiple conditions simultaneously, thus enhancing their supply chain’s resiliency and prepare for a successful regulatory approval in less time.

Early preparation is key. Evaluate existing resources and perform a risk assessment. Select and test thermal or cryogenic packaging, monitoring devices, and vials while vaccines are still being developed. This process enables packaging performance to be validated in conditions that match those of the proposed shipping lanes and transportation modes. Preparing early better ensures that packaging supplies are available when commercialization starts.

Simulation technology provides data that is a powerful time-saving tool for vaccine developers and an assurance of the physical and chemical integrity of COVID-19 vaccines. Contact Modality Solutions to learn how simulation testing can help you safeguard your cold chain.

 

Contact Us

Endnotes

i: Source:STATNEWS.COM

ii: https://www.supplychaindive.com/news/coronavirus-vaccine-supply-chain/579835/

iii: https://www.who.int/publications/m/item/draft-landscape-of-Covid-19-candidate-vaccines

NBC News Report “The Race to Get a Vaccine Delivered”

NBC News Report “The Race to Get a Vaccine Delivered”

Written by Modality Solutions

Posted on: July 8, 2020

cold chain logistics, NBC featuring Modality Solutions


Vaccine Delivery – Massive Mission
The Race to Get a Vaccine Delivered
NBC Nightly News – June 13, 2020
Kevin Tibbles

Modality Solutions is in the business of cold chain logistics. We knew it was only a matter of time before the COVID-19 24/7 news coverage would identify a significant piece to the puzzle: getting a vaccine to the people who need it most. On Saturday, June 13, 2020, NBC weekend anchor, Jose Diaz-Balart, introduced the topic. “Vaccine Delivery—a Massive Mission. Here is an inside look on what it is going to take to get a billion COVID-19 vaccines from drug-making factories to your doctor’s office, the health of so many Americans depends on them doing it right.”

Reporting from Chicago O’Hare’s Airport, NBC’s Kevin Tibbles interviews Chris Gonsowski, Vice President of DHL Global Forwarding. Chris explained in layman’s terms how drug products require refrigeration, and how the logistics of delivering to the corner pharmacy are daunting. Ben Hubbard, CEO of Parsyl, explained how if there is a break in the cold chain, the vaccine can lose its potency.

Bottom line: it is projected, 8,000 fully loaded 747 cargo planes will be needed to deliver one billion doses of COVID-19 vaccine to the U.S. market.

Click here to read the transcript of the interview.

How Transport Simulation Testing Benefits Fast-Track Approval Timeline

How Transport Simulation Testing Benefits Fast-Track Approval Timeline

Written by Modality Solutions

Posted on: June 18, 2020

How Transport Simulation Testing Benefits Fast-Track Approval Timeline, image of animated shipping process across the globe.

Abstract:

FDA Fast-Track designation compresses approximately eight years of development and validation activities into roughly 18 months. To meet this accelerated timeline, we recommend performing transportation simulation testing for cold chain validation as early as possible. Simulation testing provides robust, repeatable, and reliable results in four days or less for most proposed shipping lanes. Real-world shipments cannot be assured proper control of testing parameters and cannot be used afterward for root cause analysis if drug product formulation stability issues are uncovered.
 

Introduction

More than 30 countries have adopted or amended Good Distribution Practices for pharmaceuticals in the past decade.i While the specifics vary, they all advise some degree of environmental or condition monitoring and tracking to ensure therapeutics and diagnostics are handled in a way that ensures their safety and efficacy.

U.S. Pharmacopeia Good Storage and Distribution Practices for Drug Products Chapter 1079 advises operational and performance testing for products, as well as temperature profiling studies for transportation and warehouses. iiASTM D4169, “Standard Practices for Performance Testing of Shipping Containers and Systems” addresses packaging durability for each shipping mode.iii

The EU’s Guidelines on Good Distribution Practice of medicinal products for human use (2013/C 343/01) are based on Article 84 and Article 85b(3) of Directive 2001/83/EC. Chapter 9 of that document calls for a risk-based approach for transportation that demonstrates that “medicines have not been exposed to conditions that may compromise their quality and integrity.”iv

Health Canada recommends using temperature monitoring devices where appropriate. It notes, “Temperature excursions outside of their respective labeled storage conditions for brief periods may be acceptable provided stability data and scientific/technical justification exist demonstrating that product quality is not affected.”v

To follow any of these guidelines, pharmaceutical manufacturers need transportation testing that simulates the temperature, humidity, pressure, vibration, and shock a biopharmaceutical product may experience during transit and storage. Unless those conditions are tested concurrently, the simulation won’t truly reflect real-world hazards. And if these hazards are not tested in a controlled laboratory testing, there is no guarantee that the “edges” of the operating space have been tested.
 

Fast Track Speeds Everything, So Plan Transportation Testing Early

Fast-Track designation is granted to approximately 60% of drug formulation approved last year, so early transportation simulation testing is vital. Compressing the usual seven to eight-year timeline into 18 months requires biopharmaceutical companies to work even more efficiently. For product and package testing, that means simulating worst-case shipping conditions to meet this accelerated timeline while obtaining reliable results.
 

 

Is Your Testing Solution Comprehensive?

The drug product’s stability specifications are the starting point. Modality Solutions tests at the edge of the operating space using worst-case conditions for all five major environmental hazards concurrently to determine how long the product can be exposed to combinations of temperature, humidity, pressure, vibration, and shock before the drug product formulation’s physical or chemical integrity is affected. This “edge of the operating space” testing strategy cannot be executed with ‘real-world’ shipping studies, which ensure you cannot thoroughly test the test your drug product stability in shipping studies alone.

We also perform a functionality test on the selected thermal packaging to simulate the maximum time the product could be in transit, and formulation integrity is not compromised from the point of manufacture to the distributor, pharmacy, or end-user. Based on test results, the thermal packaging solutions selected could be confirmed or optimized.

Notably, Modality Solutions tests products and packaging against multiple hazards simultaneously to ensure the actual risks and worst-cases exposures during transportation are investigated. Results obtained are more realistic, than is possible when testing each parameter separately and more reliable that real-world shipping studies.
 

Test Early and Be Ready for Fast-Track FDA Submission

Modality Solutions has performed simulation testing for more than 70 pharmaceutical products, presentations, and indications and provided the data to regulators to date. Each of those cold chain process validation submissions has been reviewed and approved by regulators around the world.

Performing thorough transportation simulation testing as early as possible ensures that if there are any surprises – such as formulations that are less stable than anticipated or packaging that is less robust than promised – pharmaceutical developers have time to address them. Consequently, regulatory submission packages can be complete, accurate, and well-documented.

At Modality Solutions, our team of experts is attuned to regulatory guidance around Good Distribution Practices, and we have the testing capabilities to simulate and evaluate the effects of environmental hazards throughout the supply chain. We offer robust transportation simulation testing as well as clinical trial cold chain monitoring, site compliance, safety review, end-user training, and project management. Our goal is to establish a collaborative relationship with our clients to deliver fast, successful, and scientifically sound supply chain cold chain solutions for clinical trials globally.

When you’re ready to test your products against even the harshest shipping conditions, contact us. Modality Solutions is here to help.
 

References

i A Global Review of Good Distribution Practices, IQPC, https://www.iqpc.com/media/8378/34072.pdf
ii U.S. Pharmacopeia Good Storage and Distribution Practices for Drug Products, chapter 1079, http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1079.html
iii Standard Practice for Performance Testing of Shipping Containers and Systems. ASTM, https://www.document-center.com/standards/show/ASTM-D4169
iv Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use(2013/C 343/01), European Commission https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2013:343:0001:0014:EN:PDF
v Guidelines for Temperature Control of Drug Products during Storage andTransportation (GUI-0069), HealthCanada,https://www.usp.org/sites/default/files/usp/document/workshops/guidelines_for_temperature_control_of_drug_products_during_storage_and_transportation_gui-0069_health_canada_2011.pdf

Prepare Your Post COVID-19 Clinical Trials in Four Steps  

Prepare Your Post COVID-19 Clinical Trials in Four Steps  

Written by Modality Solutions

Posted on: May 23, 2020

Prepare Your Post COVID-19 Clinical Trials in Four Steps, image of a doctor and patient with a clinical trial drug

Clinical trials around the world are being disrupted by the COVID-19 pandemic, leaving sponsors with no choice sometimes but to suspend some trials and delay others. This is creating a huge backlog in ongoing trials resulting in a rush to regulatory approval once the restrictions imposed by the pandemic are lifted. Are you prepared for the rebound and the long-term impacts on the global supply chain affecting your clinical trials?
 
By late March, Eli Lilly and Bristol Myers Squibb had delayed the start of new clinical trials to free up physicians to treat COVID-19 patients. Since then, Lilly, BMS, and many othersi – including GlaxoSmithKline, Janssen, and Sanofi – have temporarily suspended clinical trials because of the pandemic.
 
ClinicalTrials.gov shows 615 industry-funded studies currently are suspended, but there are many more funded by governments and academia. Overall, more than 1,000 clinical trials have been disrupted, according to GlobalData’s COVID-19 Dashboard on the Pharma Intelligence Center.
 
Most trials aren’t related to the SARS-CoV-2 virus and, therefore, take a lower priority. The FDAii continues to update guidance on strategies to conduct clinical trials during the COVID-19 crisis to help those companies cope with trials under pandemic conditions. The most recent guidance was added to its comprehensive listiii on May 12.
 
The pandemic has introduced concerns that many ongoing trials cannot overcome immediately. For example, some sponsors are unable to activate trial sites because of countries’ strict lock-down measures. Other trial sites are unavailable because their resources are being used for COVID-19 trials. Physicians have been redeployed, too. At Yale Cancer Center, for example, even oncologists were diverted to the intensive care unit, according to Wirediv magazine.
 
Supply chain stresses have been created by state stay-at-home orders that made it difficult-to-impossible for companies and their laboratories to receive shipments. In a May conference call, Luminex noted that $2 million worth of its flow cytometry products used for developing diagnostics and drugs couldn’t be delivered to scientific labs because no one was there to receive them.
 
There are indications that clinical trials are restarting as regions begin to loosen restrictions.
Concurrent planning and rapid response to challenges will determine who the winners are and which much needed pharmaceutical products will emerge first on the market.
 
The imperative of a new supply chain cold chain model for clinical trials is key to success. Sponsors must embrace the need for agility and collaboration with not only local regulatory agencies but now local health authorities to comply with each region’s unique COVID-19 safety regulations.

 

1. Modify your Supply Chain Protocol to include contingencies for emergencies.
Conduct periodic risk assessments to identify the vulnerabilities in your supply chain and develop plans to mitigate the risks associated with the identified vulnerabilities and integratcontingencies for emergenciesThis step will enable sponsors to strengthen their supply chain and lower the risk for drug supply disruptions for clinical trials.v
 
2. Amend Risk Assessments to account for the impact of COVID-19 measures.
Sponsors must consider both the risk of COVID-19 potentially affecting study participants directly in case of infection, and whether COVID-19 related measures such as social distancing or availability of personal protection gear will affect trial conduct. Conducting comprehensive ongoing risk assessments during clinical trials to monitor any COVID-19 related adjustments are recommended.
 
3. Plan for Clinical Trial Protocol deviations and include data collection standards into your protocol.
Regulators globally have promised more flexibility than in the past. For example, new FDA guidance specifies that changes to a protocol or investigational plan meant “to minimize or eliminate immediate hazards or to protect the life and well-being of research participants (e.g., to limit exposure to COVID-19)” may be implemented without IRB approval or before filing an IND/IDE amendment—but are required to be reported afterwards.vi
 
4. Track changes in regulations and monitor guidelines in all regions of your clinical trials.
Every locality has unique and changing COVID-19 guidelines. Sponsors will need to track for changes by local health authorities and regulators in every locality where they are conducting clinical trials. Regions vary in level of travel restrictions, social distancing, lockdown, and quarantine rules, as well as testing and contact tracing.
 

Our team of pharmaceutical cold chain clinical trial operations experts stay on top of regulation changes and regional health authority guidelines to ensure the safety of your team and the patients involved. We offer end-to-end clinical trial cold chain monitoring, site compliance, safety review, end-user training, and project management. Our goal is to establish a collaborative relationship with our clients to deliver fast, successful, and scientifically sound supply chain cold chain solutions for clinical trials globally.
 
When you’re ready to brave this new, ever-changing environment, contact us. Modality Solutions is here to help.
 

Schedule a Free Consult

 

References
i https://www.biopharmadive.com/news/coronavirus-clinical-trial-disruption-biotech-pharma/574609/

ii https://www.fda.gov/drugs/coronavirus-covid-19-drugs/clinical-trial-conduct-during-covid-19-pandemic

iii https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders

iv https://www.wired.com/story/covid-19-stalls-clinical-trials-for-everything-but-covid-19/

v https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-supply-chain-update

vi https://www.fda.gov/media/136238/downloadFDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency Guidance for Industry, Investigators, and Institutional Review Boards March 2020 Updated on May 14, 2020

COVID-19 and the Race to Get a Vaccine Through FDA’s Supercharged Fast Track Approval Named Coronavirus Treatment Acceleration Program (CTAP)

COVID-19 and the Race to Get a Vaccine Through FDA’s Supercharged Fast Track Approval Named Coronavirus Treatment Acceleration Program (CTAP)

Written by Modality Solutions

Posted on: April 24, 2020

The Coronavirus Treatment Acceleration Program launched by the FDA in response to COVID-19, is a Supercharged Fast-Track Approval process that reduces the Fast-Track Approval timeline from 18 months to as soon as possible in order to get treatment to the patients as fast as possible.

Can the pharmaceutical supply chain adapt to the hyperspeed of CTAP approvals?

A vaccine traditionally takes 7-8 years to develop from the laboratory tables to the patient. The COVID-19 pandemic is inducing a rush of clinical trials for existing drugs and biologics to see if they can be potentially used against the virus, as well as initiating novel approaches, including mRNA, DNA vaccine, and vectors to be tested through clinical trials.

“The list of biopharmaceutical companies rapidly developing vaccines is growing in response to the novel Coronavirus (COVID-19) pandemic. Moderna Therapeutics has a messenger RNA (mRNA) in Phase I trials, Inovio Pharmaceuticals’ DNA vaccine entered human trials the first week of April, while others including Novovax, which is developing a vaccine based on its recombinant protein nanoparticle platform.” (1)

Innovators are doing their part, and so is the FDA. Breakthrough Therapy Designation or Fast-Track Approval was implemented by the FDA for accelerating treatment development for serious conditions such as the Coronavirus pandemic. This pandemic prompted the FDA to further supercharge the process by creating the Coronavirus Treatment Acceleration Program (CTAP). The FDA intends to use all of the regulatory flexibility granted to it by Congress to ensure the most efficient and timely development of vaccines to fight COVID-19.

  • The FDA will generally respond within a day to requests from developers and scientists to develop or evaluate new drug and biologic therapies.
  • Provide ultra-rapid, interactive input on most development plans.
  • Provide ultra-rapid protocol review – within 24 hours of submission, in some cases.
  • Complete review of single-patient expanded access requests around-the-clock, generally within 3 hours. (2)

Supply Chain challenges for COVID-19 vaccines and therapies

The vaccines or treatments aimed at treating high patient populations globally to control a pandemic will require millions if not billions of doses. Most of the leading COVID-19 vaccine candidates are using novel approaches, including mRNA, DNA vaccine, and vectors that are highly sensitive to environmental hazards occurring during transportation such as temperature, shock, and vibration.

Is your current supply chain ready for the volume, global distribution, and speed of new therapy approvals? Early implementors will rise to the challenge.

Not ready to address supply chain challenges yet? Line up your Supply Chain experts for when you are ready.

Modality Solutions has successfully worked with clinical trial supply chain issues for the Ebola vaccine, and we have the testing capabilities to evaluate the effects of environmental hazards throughout the supply chain. We also have the expertise of integrating existing or creating new supply chain protocols for therapies developed to treat the Coronavirus.

 

To learn more about our services click the button below:

Learn More

References

Novel R&D approaches and the need for flexibility make single-use key in tackling COVID-19

https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap

Modality Solutions Leans into Medical Device Growth Through Engineering

Modality Solutions Leans into Medical Device Growth Through Engineering

Written by Modality Solutions

Posted on: April 20, 2020

Supply & Demand Chain Executive’s Associate Editor, Brielle Jaekel, included Modality Solutions in her March 30, 2020 article titled: Logistics is Looking to Senior Management, Board for 2020 Direction.

Jaekel shares, “Modality Solutions is growing its engineering team with the addition of Carson Dickey, who will focus on combination medical device qualification and validation in the biopharmaceutical cold chain to capitalize on the growing United States market. The pharma engineering firm states that it believes it is advancing innovative forms of treatment in the market, and it believes that packaging is fundamental in keeping up safety standards. 

Dickey will act as a significant part of this focus, as he will design and validate thermal packaging for environmentally sensitive products. He has experience in designing polymeric medical device technologies and integrating antimicrobial properties in devices as well as testing plans.” 

About Supply & Demand Chain Executive (SDCE)
For over 10 years Supply & Demand Chain Executive (SDCE) has been the only magazine in the Supply Chain industry covering the entire global supply chain that focuses on ROI, professional development and change management, all in a solutions-based format. It is a business technology magazine for supply chain executives at manufacturing and non-manufacturing companies and organizations, as well as public sector agencies, covering solutions and services for improving supply chain operations and efficiencies.

Click here to read the entire article.

Ebola Clinical Trial Liaison Dr. Jean-Jacque Muyembe Honored

Ebola Clinical Trial Liaison Dr. Jean-Jacque Muyembe Honored

Written by Modality Solutions

Posted on: March 25, 2020

 

Modality Solutions has been actively involved in NIH clinical trials for an Ebola vaccine since 2015. Our key partner in the Democratic Republic of Congo is Dr. Jean-Jacques Muyembe. He was interviewed in the DRC by Monica Villamizar of the PBS News Hour on January 16, 2020.

Click here to read the transcript of the interview.

 

 

In addition, Dr. Muyembe was named to Nature’s 10. This year’s Nature, Vol. 576, annual list was made up of ten people who mattered in science for 2019. His Nature’s 10 feature was titled “Jean-Jacque Muyembe Tamfum – Ebola fighter. The co-discoverer of Ebola faces his tenth battle with the virus in the DRC – his toughest yet.” The article covers his initial investigation of an unidentified ailment (later named Ebola) in 1976 deep in the jungles of what now is the DRC to how a 680-person, controlled clinical trial in 2019 led by his team, and supported by Modality Solutions, showed a 90% survival rate for those treated with antibody-based drugs shortly after infection.

Click here to read the Nature feature on Dr. Muyembe.

Dan Littlefield Video Interview on DRC Ebola Clinical Trials

Dan Littlefield Video Interview on DRC Ebola Clinical Trials

Written by Modality Solutions

Posted on:

Co-founder and principal Dan Littlefield spoke on Modality Solutions’ involvement in the Ebola clinical trials with Executive Platforms for its popular EP Thought Leader Series. Most recently Dan worked with the NIH to help fight Ebola in the Democratic Republic of Congo.
 
Dan talks about some of the challenges of working in a conflict environment, and how Modality Solutions’ experience designing and implementing cold chain solutions to assure patient safety and drug efficacy contributed to the success of the Ebola virus clinical trial. “Our work in the Congo, along with our earlier work in Sierra Leone, Liberia, and Guinea, has been effective in ensuring clinical trial successes by applying effective engineering tools to daunting logistical problems. We’ve been fortunate to work with many great people in our efforts,” said Dan Littlefield.
 
You can watch the interview below:
 

 
Source: https://epthoughtleaders.com/engineering-cold-chain-solutions-to-support-ebola-clinical-trials-a-conversation-with-dan-littlefield-of-modality-solutions/

Carson Dickey Joins Engineering Team

Carson Dickey Joins Engineering Team

Written by Modality Solutions

Posted on: March 16, 2020

Modality Solutions is pleased to announce the addition of Carson Dickey to its growing engineering team. Carson’s primary focus is on combination medical device qualification and validation in the biopharmaceutical cold chain. He provides design and validation engineering services by conducting thermal packaging design and qualification for environmentally sensitive products.

“Carson joining our team of experts supports our goals for providing transport simulation test design, risk assessment, and protocol development as it relates to the combination medical device sector,” said Modality Solutions President, Gary Hutchinson.

Raised in Plano, Texas, Carson attended Texas A&M University where he received his Master of Engineering in Biomedical Engineering with a certification in Quality Engineering for Regulated Technologies. As a Bioinnovation Design Fellow, he participated in the design, prototype fabrication, design verification testing, and development of testing protocols and procedures for cutting-edge medical devices.

Click here to view the online press release announcement.

How Artificial Intelligence Is Improving the Pharma Supply Chain

How Artificial Intelligence Is Improving the Pharma Supply Chain

Written by Modality Solutions

Posted on: March 9, 2020

Artificial Intelligence Is Improving the Pharma Supply Chain, image of a blue AI graphic

Artificial intelligence (AI) will transform the pharmaceutical cold chain — not in the distant, hypothetical future, but in the next few years. As the president of a company that has been actively involved in the creation of an application that will utilize machine learning to generate predictive data on environmental hazards in the biopharmaceutical cold chain cycle, I’ve seen firsthand the promise of this technology.

When coupled with machine learning and predictive analytics, the AI transformation goes much deeper than smarter search functions. It holds the potential to address some of the biggest challenges in pharmaceutical cold chain management. Here are some examples:
 
Analytical decision-making: Most companies capture only a fraction of their data’s potential value. By aggregating and analyzing data from multiple sources — a drug order and weather data along a delivery route, for example — AI-based systems can provide complete visibility with predictive data throughout the cold chain. Before your cold chain starts, you can predict hurdles and properly allocate resources.

Analytical decision-making relies on companies having actionable data and real-time visibility throughout the cold chain. Just-in-time delivery of uncompromised drug product relies on predictive data analytics. With the help of analytical decision-making, cold chain logistics and overall drug cost, patient risk, and gaps in the pharmaceutical pipeline will be significantly reduced.

For example, BenevolentAI in the United Kingdom is using a platform of computational and experimental technologies and processes to draw on vast quantities of mined and inferred biomedical data to improve and accelerate every step of the drug discovery process.
 
Supply chain management (SCM): A 2013 study by McKinsey & Company detailed a severe lack of agility in pharmaceutical supply chains. It noted that replenishment times from manufacturer to distribution centers averaged 75 days for pharmaceuticals but 30 days for other industries, and reported the need for better transparency around costs, logistics, warehousing and inventory. Assuring drug efficacy, patient identity and chain of custody integrated with supply chain agility is where the true value of AI lies for the drug industry.

DataRobot is an example where the agile pharmaceutical supply chain can be implemented with an AI platform powered by open-source algorithms that are able to model automation by using historical drug delivery data. Supply chain managers can build a model that accurately predicts whether a given drug order could be consolidated with another upcoming order to the same location or department.
 
Inventory management: Biomarkers are making personalized medicine mainstream. Consequently, pharmaceutical companies must stock many more therapeutics but in much lower quantities. AI-based inventory management can determine which product is most likely to be needed (and how often), track exactly when it’s delivered to a patient, and provide delivery time and delays or incidents that might trigger replacement shipment within hours.

OptumRx increasingly uses AI/ML to manage data it collects in a healthcare setting. Since becoming operational, the AI/ML system is able to continuously improve itself by analyzing data and outcomes, all without additional intervention. Early results indicate that AI/ML is adding agility to the cold chain already by reducing the number of shortages or excess inventory of drug products needed.
 
Warehouse automation: Integrating AI into warehouse automation tools speeds communications and reduces errors in “pick and pack” settings. At its simplest, AI predicts which items will be stored the longest and positions them accordingly. With this approach, Lineage Logistics, a cold-chain food supplier, increased productivity by 20%. In another example, AI positions high-volume items so they are easily accessible while still reducing congestion.

 

FDA Embraces AI and Big Data

Historically, pharmaceutical companies have been slow to adapt to disruptive technologies because of the important oversight role played by the FDA. However, the FDA realizes AI’s potential to learn and improve performance. It already has approved AI to detect diabetic retinopathy and potential strokes in patients, and updated regulations are expected soon to help streamline the implementation of this important tool.

 

Gain a Competitive Edge

For pharmaceutical companies looking to implement AI into their cold chain, here are some steps to take to become an early adopter:

  1. Prepare your data, and ensure you own it. You need a strong pipeline of clean data and a mature logistics ecosystem with historical data on temperature, environmental conditions and packaging, as well as any other data you collect during your cold chain. If you don’t have clean data stored, start collecting it now. If you think you have the data, verify that you own it. Some vendors claim ownership of the thermal data their systems generate and don’t allow it to be manipulated by third-party software. In that case, it can’t be combined with other data sources for AI analysis. Either negotiate ownership or change vendors.
  2. Define your area of need: Where do you need a competitive edge? Start small with one factor that makes a measurable impact on your cold chain. That may be inventory control, packaging optimization, logistics, regulatory strategy or patient compliance. Track metrics and tie them to business value.
  3. Assemble the right people and verify your internal capabilities. Implementing or supporting an AI/machine learning strategy requires skills that IT personnel typically lack. Consider upskilling your IT team or adding an AI skills requirement for your next new hires.

AI is at a turning point. In the next decade, it is expected to contribute a massive amount of money to the global economy. In the life sciences market alone, AI is valued at $902.1 million and is expected to grow at a rate of 21.1% through 2024. As part of this growth, I believe AI will also make significant contributions to the pharmaceutical supply chain.

This article was authored by Gary Hutchison, President of Modality Solutions and Forbes Technology Council Member. It first appeared on January 31, 2020 on Forbes.com. Click here to view it online.

How Biosimilars’ Early Stability Testing Can Accelerate FDA Approval and Commercialization

How Biosimilars’ Early Stability Testing Can Accelerate FDA Approval and Commercialization

Written by Modality Solutions

Posted on: February 17, 2020

How Biosimilars’ Early Stability Testing Can Accelerate FDA Approval and Commercialization, image of a dna strand

Biosimilars have been a point of contention within the pharmaceutical industry for the past 30 years. Initially, debate raged around whether biosimilars could, in fact, be substituted for reference drugs. That early skepticism has been resolved, but issues remain. To put that in perspective, the global biosimilars market was valued at $10 billion in 2018 and is projected to grow at a CAGR of 27% between 2019 and 2025, to $69 billion globallyi. The U.S. portion of that market is expected to grow even faster, at 38%. Such rapid growth is spurred by the global drive to reduce healthcare costs, followed by the growing incidence of chronic diseases, and the expiration of biologics patents. Biosimilar developers are looking for strategies to bring biosimilars to market faster and to grow market share.

Understanding how the biosimilar behaves during shipping when exposed to temperature, vibration, shock, humidity, and pressure excursions, is a key element in speeding time to FDA approval and on to commercial drug sales.

In guidance publications, the FDA recommends “an appropriate physicochemical and functional comparison of the stability of the proposed biosimilar.” They further suggest that accelerated and stress stability studies, or forced degradation studies, should be used to establish degradation profiles and provide a direct comparison of the proposed biosimilar product with the reference product.  These comparative studies should be conducted under multiple stress conditions (e.g., high temperature, freeze-thaw, light exposure, and agitation) that can cause incremental product degradation over a defined time period.

The FDA addressed more issues in February with two guidance. The first reiterated its stance that biosimilars have no clinically meaningful differences from their reference drugsii. The second guidance clarified Biologic License Application (BLA) policies for expanding indicationsiii. It aims to speed licensing.

Too often, biosimilar manufacturers postpone stability testing for the distribution of drug products until the product is nearly ready to ship. Then, when they learn exactly how sensitive their products are to temperature, vibration, shock, and pressure, they scramble to find solutions.

Performing shipping qualifications for biosimilars as early as possible alerts manufacturers to specific sensitivities so they can be remediated either during product design or through a combination of packaging solutions.

Acting early minimizes delays.
 

Proactive Shipping Qualification and Drug Stability Studies speed FDA approval and allow a faster path to commercialization.

Establish a Validation Master Plan for your cold supply chain and make it an integral part of your BLA submission. It assures the FDA that you can control conditions – and, therefore, product quality – from the manufacturer to the pharmacy. Just as importantly, it helps you deliver biosimilars to patients without unnecessary regulatory delays.

  • Clearly define all your risks upfront.
  • Understand environmental hazard challenges other than temperature and how they could affect biosimilarity after interactions with the primary container or packaging.
  • Understand the interactions between multiple hazards.
  • How do these interactions impact drug product quality?
  • How does temperature and shock/vibration contribute to particulate formation?
  • Identify the shock/vibration and pressure impact on CCI and sterility.
  • Consider using simulation studies to conduct drug product operational qualification.
  • Test your biosimilar in controlled versus uncontrolled environments.
  • Complete a full range of testing for hazards in your ‘design space’ (all shipping lanes).
  • Clearly identify hazards other than temperature.
  • Execute a risk assessment and prepare a mitigation plan for your biosimilar cold supply chain.
  • Justify your approach for operational qualification and performance qualification.

 
Conduct a biosimilars-specific risk assessment and add mitigation strategy into a validation master plan for your cold supply chain. It should include an analysis of specific product risks based upon environmental conditions as well as lanes, carriers, and transportation modes. Documenting these risks and mitigation strategies provides clear justification for your approach. With this information, manufacturers can design more robust logistics safeguards that incorporate, for example, specialized packaging, labeling, and monitoring solutions, as well as careful attention to risks associated with certain carriers, lanes, routes, and modes of transportation.

This validation master plan for the cold chain should be an integral part of your BLA submission. It assures the FDA that you can control conditions – and, therefore, product quality – from the manufacturer to the pharmacy. Just as importantly, it helps you deliver biosimilars to patients without unnecessary delays.
 

To learn more about using pharmacovigilance shipping studies to speed biosimilars’ commercialization time, contact Modality Solutions by clicking the button below:

Contact

 

References

i https://www.gminsights.com/industry-analysis/biosimilars-market

ii https://www.fda.gov/regulatory-information/search-fda-guidance-documents/promotional-labeling-and-advertising-considerations-prescription-biological-reference-and-biosimilar

iii https://www.fda.gov/regulatory-information/search-fda-guidance-documents/biosimilars-and-interchangeable-biosimilars-licensure-fewer-all-conditions-use-which-reference

Modality Solutions Announces ISO 9001:2015 Certification

Modality Solutions Announces ISO 9001:2015 Certification

Written by Modality Solutions

Posted on:

We are pleased to announce we achieved our ISO 9001:2015 registration by certification body Intertek on December 10, 2019. The scope of Modality Solutions’ ISO 9001:2015 Quality Management System certification covers consulting, design and engineering services and testing for supply chain logistics related to transport-sensitive food and drug products.

Quality Manager, Hannah Anderson, spearheaded the year-long process. In preparation for the audits, she reviewed and revised all existing Standard Operating Procedures (SOPs) and created ten new SOPs. Anderson trained staff on the new standards, conducted internal audits, and managed the Intertek audits at the Modality Solutions corporate office in Houston and the company’s Advantage Transport Simulation Laboratory™ in Bloomington, Indiana.

ISO 9001:2015 specifies requirements for a Quality Management System when an organization:
needs to demonstrate its ability to consistently provide products and services that meet customer and applicable statutory as well as regulatory requirements aims to enhance customer satisfaction through the assurance of conformity to customer and applicable statutory and regulatory requirements.

With our ISO 9001:2015 certification, our clients are confident in knowing the services we provide will meet or exceed the requirements of this internationally recognized quality management standard,” said Gary Hutchinson, President of Modality Solutions. “By demonstrating our ongoing commitment to our quality management systems, both GDP and ISO 9001:2015, we will continue to implement improvements towards increased efficiency and maximum client satisfaction.

To view the complete online press release, click here.

Modality Solutions Reports 2019 Strongest Year Ever Driven by Awards & Certification

Modality Solutions Reports 2019 Strongest Year Ever Driven by Awards & Certification

Written by Modality Solutions

Posted on: January 22, 2020

We are pleased to announce our 2019 milestone highlights include recognition by both Inc. 5000 and the Houston Business Journal as a fastest growing company. We also achieved ISO 9001:2015 certification–with the scope of the accreditation covering consulting, design and engineering services and testing for supply chain logistics related to transport-sensitive drug products. Also, we received the distinction of being one of the “Best Entrepreneurial Companies in America” by Entrepreneur magazine on its 2019 Entrepreneur 360™ List.

Our Co-founder and President, Gary Hutchinson, was accepted into Forbes Technology Council, an invitation-only community for world-class CIOs, CTOs, and technology executives. Gary was vetted and selected by a review committee based on the depth and diversity of his experience. 

The biopharmaceutical industry also benefited from our first live webinar on September 19. Principals Dan Littlefield and Gary covered a step-by-step cold chain validation process to help pharmaceutical companies meet and exceed increasingly stringent regulatory expectations, including monoclonal antibodies, antibody-drug conjugates, and cell therapies. And, we were a Silver Sponsor and cold chain validation workshop presenter at the Biomanufacturing World Summit (BMWS19) Conference in San Diego from November 11-12.

“2019 was a stellar year for us, with ISO 9001:2015 certification, recognition by Inc. and Entrepreneur magazines, participation in the Forbes Tech Council, and continuing to partner with our clients to validate safe, and effective cold chains,” said Gary. “As we continue our mission into the next decade, our vision for the future is to continue to expand with our team of experienced engineers our ongoing role to promote safe, effective and validated cold chain for a whole range of therapies.” 

To view the complete online press release, click here.

The Promise of Antibody-Drug Conjugates (ADC) Comes with Additional Cold Chain Challenges

The Promise of Antibody-Drug Conjugates (ADC) Comes with Additional Cold Chain Challenges

Written by Modality Solutions

Posted on: January 21, 2020

2020 saw a resurgence of antibody-drug conjugates (ADCs) with seven new approvals and close to 100 investigational ADCs currently in pre-clinical and clinical trialsi. In January 2020, ADC Therapeutics announced an overall response rate that exceeded expectations for its Phase II clinical trials, clearing a big hurdle toward its first ADC pipelineii. On April 22, 2020, the US Food and Drug Administration (FDA) granted an accelerated approval to Trodelvy™ (sacituzumab govitecan-hziy) for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior treatments for metastatic diseaseiii. And on August 5, 2020™, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin-blmf (BLENREP) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agentiv.

Those therapeutics are just a few examples of ADC therapies that are benefitting from the accelerated approval pathway the FDA granted this class of drug. Faster approvals coupled with increasing drug prices is expected to propel ADCs to a $7.5 billion market by 2025 – a compound annual growth rate of 17.7% for the next five yearsv.

ADCs are designed to harness the targeting ability of monoclonal antibodies. Their three-component system is composed of a cytotoxic anticancer agent with a biodegradable linker to a monoclonal antibodyvi. The benefits of ADC therapy are the focused and targeted application of cytotoxic anticancer agents that maximize efficacy by discriminating between cancer and normal tissue, thus minimizing the damage to the surrounding healthy tissue.

Accelerated paths to approval and the unique challenges of ADC development and manufacturing cause additional cold supply chain hurdles. The starting point for any ADC manufacturing is the development of the parent mAb. Typically, mAbs destined for ADC production need additional optimization for robustness against the more demanding process conditions inherent in ADC processes. Recent studies indicate that ADC stability may be governed by properties stemming from both the antibody and the linker-toxin chemistry vii.

For example, the ADC trastuzumab emtansine (T-DM1) was subjected to several stress conditions including temperature, mechanical agitation, and repeated freeze and thaw. The stability assessment of the ADC compared to the parent monoclonal antibody showed clearly that T-DM1 is relatively less stable than its parent mAb. This was attributed to the presence of the drug-linker that is attached to the mAbviii.

The FDA published a regulator’s perspective on the challenges of ADC development in June 2018, specifically referring to the necessity of stability testing for the intermediates drug and linker as well as the final ADC drug product. The same perspective suggested freeze and thaw studies be included in stability testingix.

Cold chain supply optimization depends on starting early to establish environmental monitoring needs for candidate mAbs as well as the linker/drug used in the ADC. Testing candidate mAbs for manufacturing robustness should be done in parallel with testing the effects of environmental hazards on the monoclonal antibody as it moves through the supply chain.

Specifically, stability data in relation to temperature, shock, vibration, and humidity during transport and storage should be evaluated as well as linker/drug intermediates stability testing, including freeze-thaw studies. Armed with this information, the ADC product could be modified for robustness to lower the supply chain risk. Early cold chain optimization is also an opportunity to eliminate penalties associated with delays in the supply chain during clinical trials and the FDA approval timeline.

Modality Solutions has been involved in providing optimized cold chain solutions for three of the ADCs currently on the market. We are your trusted partner, whether you are a CRO or biopharmaceutical innovator within North America or globally.

 

More on This Topic:

On-Demand Webinar: Cold Chain Validation Best Practices Including Immunotherapy Webinar

White Paper: The Challenges of Cold Chain Validation for Regenerative Medicine

Blog: Apheresis collection for CAR T-Cell Therapy requires greater agility in the cold chain

 

References

i https://www.adcreview.com/the-review/antibody-drug-conjugates/what-are-antibody-drug-conjugates/

ii https://endpts.com/adc-therapeutics-clears-a-big-hurdle-toward-its-first-bla-as-pivotal-phii-delivers-upbeat-orr-results/

iii https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-triple-negative-breast-cancer-has-spread-not-responded-other-treatments

iv https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma

v https://www.ihealthcareanalyst.com/global-antibody-drug-conjugates-market/

vi https://www.adcreview.com/the-review/antibody-drug-conjugates/how-do-adcs-work/

vii https://www.ncbi.nlm.nih.gov/pubmed/26869406

viii https://www.sciencedirect.com/science/article/abs/pii/S0731708517327838via%3Dihub

ix https://cdn.ymaws.com/www.casss.org/resource/resmgr/mwdg/MWDG_0617_Shapiro_Marjorie.pdf, pg 57.

Modality Solutions Included in the 2020 Company Focus & Industry Reference Guide

Modality Solutions Included in the 2020 Company Focus & Industry Reference Guide

Written by Modality Solutions

Posted on: January 14, 2020

Modality Solutions was included in the 2020 Company Focus & Industry Reference Guide published by Pharmaceutical Outsourcing™ The Journal of Pharmaceutical & Biopharmaceutical Contract Services.  Modality Solutions was included in the guide in the Pharmaceutical Cold Chain Management Solutions section.

According to Editor-in-Chief, Mike Auerbach, in the Pharmaceutical Outsourcing Vol. 20 Issue 5, November 2019, “The pharmaceutical contract manufacturing, development and services sector of the industry continues to grow in size and importance. A quick look at the most recent research and market outlook reports all point to strong growth in every sector of the contract services market in the coming years.”

Pharmaceutical Outsourcing is the leading review of business and technology for the pharmaceutical industry throughout North America. It is dedicated to pharmaceutical and biopharmaceutical contract services, and the publication has regular sections on contract manufacturing, contract research, contract packaging, formulation/development services, contract analytical testing, APIs, stability testing, clinical research, and other areas.

https://www.pharmoutsourcing.com/

The New Reality of Accelerated Paths to Commercialization and Its Impact on Cold Chain Supply

The New Reality of Accelerated Paths to Commercialization and Its Impact on Cold Chain Supply

Written by Modality Solutions

Posted on: December 18, 2019

Commercialization impact on cold chain, The New Reality of Fast and Furious Commercialization and its Impact on Cold Chain Supply, image of man pressing hex graphic display with icons

With five FDA programs speeding drugs through approval to commercialization, the pace of scale-up is accelerating, shortening time to market by months or even years. To make the most of these expedited programs, drug developers should evaluate their entire process to eliminate bottlenecks and non-value-added tasks. This evaluation should include logistics, where planning temperature-control strategies as early as possible in the development process helps avoid delays and get medications to patients more quickly.
 

Emerging Trends in Regulatory Approvals

To put the trend toward speedy approvals in context, 200 of the 367 novel drugs approved by the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) between 2011 and 2018 used one or more of its programs. Of those 200, 12 percent received the Accelerated Approval designation. The remainder were expedited under Fast Track, Breakthrough Therapy, Regenerative Medicine Advanced Therapy, or Priority Review designations. In 2020 68% of novel drugs approved were designated one or more expedited category.

A growing percentage of those drugs require cold-chain or controlled room temperature shipping and handling. Specifically, in 2018, 44 percent of the FDA-approved drugs required controlled temperature handling, and the percentage increases each year. The 2019 Biopharma Cold Chain Sourcebook estimates that by 2023, approvals for temperature-controlled pharmaceuticals will increase 59 percent from 2017 figures.

Biologics are the main reason for this increase. Today’s novel therapeutics often are developed by innovative small to mid-sized biopharmaceutical companies that thrive on rapid development. To deliver therapeutics as quickly as possible, they often include rare and orphan diseases applications in their portfolios in the hopes of qualifying for expedited approval designations.

That’s an effective strategy, but it doesn’t follow the strategic template used for blockbuster drugs.
 

Biologics and Cell & Gene Therapy

Cell and gene therapy advancement through expedited approval is a lot more challenging, especially when it comes to supply chain and cold chain.

Cell and gene therapy both use the body’s own cells and genetic information to target and fight disease. Patients’ own (autologous) cells or the healthy donor’s (allogenic) cells or genetic material are extracted, then altered to create a personalized therapy and re-injected into the patient. The supply chain is a complex and unique closed loop, patient to patient, time sensitive and requires a just-in-time delivery process.

Biological material collected for autologous and allogeneic therapies must be shipped under stringent temperature controls, most likely cryogenic temperature. Shipment is under extremely tight timelines, and a critical chain of identity and custody must be maintained from patient to manufacturing and back to the patient.

To maximize the potential of today’s small-batch, personalized medicines, biopharmaceutical companies need managers who understand the newer, faster pace and start planning early. By planning early, they can deliver potentially-life-saving therapeutics to patients as quickly and effectively as possible.
 

Strategies to Anticipate Your Cold Chain Needs

Participating in one of the FDA’s expedited programs is only one step to commercializing and delivering innovative therapeutics quickly. There are additional steps drug developers can take to further speed the process. Consider these points:
 

1. Map Your Cold Chain Supply Early

Begin discussing your controlled temperature challenges during the drug development stage. Identify drug stability issues that may be affected by temperature, light exposure, shock, or vibration. Then research packaging solutions and data monitoring systems that meet the requirements of the data required by the regulators from your planned launch regions and the World Health Organization’s (WHO’s) Good Distribution Practices (GDP) and your own logistics team. By beginning early, you can find cost-effective solutions for all transportation options and speed time to market.

Use development time to create more stable formulations with formulation exposure to environmental hazards with simulated transportation. This simplifies packaging and logistics needs, and can reduce logistics expenses. Confirming formulation robustness can also can expand the market for novel and existing therapeutics (especially in the developing world, where refrigeration is unreliable).

At the same time, use the development time to identify potential cost savings throughout the cold supply chain. This may mean more efficient routes or logistics partners, or new or improved technologies that support delivery methods that were unthinkable until recently. For example, UPS and CVS deployed drones for the first time in November for last mile delivery, and Merck is testing drones for disaster response. Earlier, improved reefers and condition monitors have made maritime and rail shipping as reliable and economical for pharmaceuticals as they have been for more durable goods.
 

For Cell and Gene Therapy (CGT)

Develop and test an integrated closed loop cell therapy supply network starting with treatment centers where initial cell/DNA collections start, to manufacturers, couriers, distribution centers, and clinical trial sites and back to the treatment center and patient. Create a process map for scheduling collections and coordinating logistics between providers, and all sites involved in the supply chain.
 

 

2. Adopt GMP and Continuous Manufacturing

Develop your products with good manufacturing processes (GMP) and continuous manufacturing (CM) in mind from the beginning. Designing processes for scale up from their inception minimizes the need to rework formulations and resubmit regulatory data when ingredients change. Likewise, CM enhances flexibility in batch-saving ways thanks to continuous optimization. Both strategies decrease development time from preclinical to commercial stages.
 

For Gene and Cell Therapy

Implement, test and standardize closed-system processing and cryopreservation at collection sites to enable industrialization of advanced therapies through starting material standardization for manufacture and ultimately able to introduce GMP.

 

3. Speed Global Access to Individualized Therapies

Developing a global regulatory cold chain strategy rather than a country-by-country approach is another time-saver. Once the markets are identified, determine their regulatory commonalities and differences. Then design the studies to meet the most rigorous regulatory requirements of those countries. (Note that even regions with similar requirements, like the U.S. and EU, are not perfectly aligned.) Developing a multi-nation strategy during the drug development process is faster and more cost effective than waiting until after commercialization in your primary markets.
 

Early Planning Matters

Accelerated drug approval pathways are making significant impacts on patient health as well as the health of the companies that develop them. Those gains can be unwittingly sabotaged, however, when drug developers neglect the big picture.

Planning early for GMP, scalable and continuous manufacturing, global regulatory requirements, and temperature-controlled logistics, helps companies advance with certainty. Planning early helps minimize delays and setbacks and makes the most of the opportunities afforded by the FDA’s expedited drug programs.

To learn how Modality Solutions can help you with the big picture, contact us.

Modality Solutions In the News: The New York Times

Modality Solutions In the News: The New York Times

Written by Modality Solutions

Posted on: December 9, 2019

Although Modality Solutions LLC is not mentioned in this New York Times, August 12, 2019 article on a possible cure for Ebola, we were asked to assist with this study because of our reputation of expertise in the field and previous collaboration with BARDA, CDC, and NIH during the 2015 – 2016 Ebola outbreak in West Africa. The Mitchell Group (TMG) and Leidos Biomed, working with the US National Institute of Health (NIH) and World Health Organization (WHO) requested our assistance for storage and transport of time and temperature-sensitive products (TTSPs) such as the investigational drugs, biological specimens, and laboratory reagents. In February and March 2019, our Subject Matter Experts (SMEs) traveled to the eastern provinces of the Democratic Republic of Congo (DRC) to evaluate and address cold chain management deficiencies. During their time in country, they provided cold chain training to local staff, conducted site assessments, and qualified critical equipment for the study.

 

Click Here to Download the Article.

Modality Solutions In the News: Wall Street Journal

Modality Solutions In the News: Wall Street Journal

Written by Modality Solutions

Posted on:

A Wall Street Journal, October 30, 2019 article announced one of the most important breakthroughs since the use of penicillin, a cure for Ebola. Although Modality Solutions is not mentioned in this article, it is important to note our involvement in the clinical trial phase that ultimately led to the successful development of a cure for Ebola. Modality Solutions was asked to assist with this clinical study because of our reputation and expertise in the field, as well as previous collaborations with BARDA, CDC, and NIH during the 2015 – 2016 Ebola outbreak in West Africa. The Mitchell Group (TMG) and Leidos Biomed, working with the US National Institute of Health (NIH) and World Health Organization (WHO) requested our assistance for optimizing storage and transport of time and temperature-sensitive products, such as the investigational drugs, biological specimens, and laboratory reagents involved in the clinical trial. In February and March 2019, our Subject Matter Experts (SMEs) traveled to the eastern provinces of the Democratic Republic of Congo (DRC) to evaluate and address cold chain management deficiencies. During their time in country, they conducted four site assessments, qualified critical equipment for the study, and conducted training for cold chain compliance for the local staff.

 

Click Here to Download the Article.

Modality Solutions Announces Webinar On-Demand Replay

Modality Solutions Announces Webinar On-Demand Replay

Written by Modality Solutions

Posted on: November 25, 2019

Modality Solutions hosted a live webinar entitled, “Cold Chain Validation Best Practices Including CAR T-cell and ADC Immunotherapies” covering a step-by-step cold chain validation guide to meet and exceed increasingly stringent regulatory expectations including immunotherapy and regenerative medicine formulations. Targeting complex cold chain biopharmaceutical industry leaders, the webinar was very well received. Due to the high volume of interest in the topic, Modality Solutions is providing free on-demand replays of the 45-minute presentation. Click here to access the cold chain validation webinar.

With more than 35 international cold chain regulatory compliance guidance documents, global standards are becoming more comprehensive and increasingly complex,” said Modality Solutions President, Gary Hutchinson. “New therapies, accelerating costs, sustainable technologies, and emerging markets demand validated cold chain networks that consistently produce low-cost and high-quality outcomes for patients–with a minimal variation, delivering value to a company’s supply chain. Our webinar is positioned to help companies build their reputation of reliability with regulators.

To access the free on-demand replay of “Cold Chain Validation Best Practices Including Immunotherapy,” go to https://modality-solutions.securechkout.com/cold-chain-validation-best-practices-webinar

To view the online press release, click here

Modality Solutions is Silver Sponsor & Workshop Presenter at BMWS19

Modality Solutions is Silver Sponsor & Workshop Presenter at BMWS19

Written by Modality Solutions

Posted on: November 4, 2019

Our sponsorship and workshop at the BMWS19 support our continued commitment to helping the global biopharmaceutical industry grow and evolve,” said Modality Solutions President Gary M. Hutchinson. “Today, more than ever, with complex regenerative medicine therapies, the biopharmaceutical industry is faced with the pressure to focus on the patient as they improve the quality, efficacy, and compliance of their life-saving products. It’s our mission to share our cold chain validation best practices that will help industry leaders understand the changing industry standards and how to integrate risk management processes with validation best practices to ensure compliance, quality, and product integrity.

Modality Solutions will present “Cold Chain Validation Best Practices Including Immunotherapy” on Monday, November 11, at 2:35 p.m. PT in Breakout Room 3. During the session, attendees will take away valuable information including:
 

  • Review of recent FDA feedback on immunotherapy submissions
  • Understanding damage boundaries for therapies
  • Defining your operating space for transportation hazards
  • Putting it all together: Cold chain validation strategies for monoclonal antibodies, antibody-drug conjugates, and cell therapies

 
The Biomanufacturing World Summit brings together pharmaceutical executives, cutting-edge technology providers, and media partners for North America’s premier biologics event. The 2-day conference will focus on the patient as biopharmaceutical companies strive to improve the quality, efficacy, cost, and compliance of their life-saving products.

To view our BMWS19 sponsorship and presentation release, click here.

Modality Solutions Makes Houston Business Journal’s Fast 100 List

Modality Solutions Makes Houston Business Journal’s Fast 100 List

Written by Modality Solutions

Posted on: October 21, 2019

It’s a distinct honor to make the Houston Business Journal’s Fast 100 list,” said co-founder and president, Gary M. Hutchinson. “Modality Solutions is redefining what it means to be a cold chain engineering firm in the biopharmaceutical industry sector, and we are pleased to make the Houston area our home. The community is vibrant and provides us with an exceptional business environment and talent pool for us to grow our business.

The Fast 100 has become the hallmark of entrepreneurial success for the Houston area. For 2019, revenue growth was based on companywide revenue from the fiscal year 2016 to the fiscal year 2018. To qualify, companies had to be Houston area-based, privately held, be for-profit, and have earned at least $1 million in revenue in the last fiscal year. Modality Solutions made its first appearance on the Houston Business Journal’s Fast 100 list with reported two-year revenue growth of 56 percent.

According to Editor-in-Chief, Giselle Rodriguez Greenwood in the publication’s Sept. 27-Oct. 3 issue featuring the honorees, “Congratulations to all 2019 Fast 100 and Innovation Award honorees. Your perseverance and hard work are what defines our city.

To view our formal Fast 100 press release, click here.

Modality Solutions Makes Inc. 5000 List of America’s Fastest-Growing Companies

Modality Solutions Makes Inc. 5000 List of America’s Fastest-Growing Companies

Written by Modality Solutions

Posted on: October 2, 2019

Modality Solutions is pleased to gain recognition within the American economy’s most dynamic segment—its independent small businesses,” said President Gary Hutchinson. “Our primary goal is to continue to strive for excellence while we continue on our track of sustained growth. It’s great to join the ranks of companies like Microsoft, Dell, Pandora, Zillow, and many other well-known brands who gained their first national exposure as honorees on the Inc. 5000.

The Inc. 5000 is a list of the fastest-growing private companies in the nation. Started in 1982, this prestigious list has become the hallmark of entrepreneurial success. For 2019 companies were ranked according to percentage revenue growth when comparing 2015 and 2018. Ranked No. 3094, Modality Solutions achieved its first national recognition as an honoree on this year’s list with three-year revenue growth of 120 percent. Based on this growth, we also ranked No. 47 in our industry category of the nation’s top Inc. 5000 engineering companies.

The companies on this year’s Inc. 5000 have followed so many different paths to success,” says Inc. editor in chief James Ledbetter. “There’s no single course you can follow, or investment you can take that will guarantee this kind of spectacular growth. But what they have in common is persistence and seizing opportunities.

To view our formal Inc. 5000 press release, click here.

Robert Battista Promoted to Senior Consulting Engineer

Robert Battista Promoted to Senior Consulting Engineer

Written by Modality Solutions

Posted on: September 11, 2019

Modality Solutions is pleased to announce it has promoted Robert Battista to Senior Consulting Engineer. As a member of the engineering team, Robert has added the responsibility of onboarding and mentoring new engineers. He continues to work directly with clients to strategically create the proper validation of their cold chain systems through risk and gap analysis and subsequent mitigation plans. He then implements the validation master plan through the creation of standard operating procedures, qualification of critical equipment, validation of processes, and in-person training for essential personnel.
 
Robert has shown exceptional talent and commitment to our mission of being the ‘called upon’ cold chain experts to make sure conflict-zone DRC medical facilities are operational and functioning to deliver life-saving Ebola treatment to patients,” said co-founder and CTO, Daniel J. Littlefield. “After training our clients in both the U.S. and abroad, we are also looking forward to utilizing his leadership for onboarding and development of our new engineers.
 
Raised in West Seneca, New York, Robert attended The Ohio State University where he received a Bachelor of Science degree in chemical engineering with a minor in physical geography.
 
Click here to view the online press release announcement.

Orphan Drugs: A Lifeline for Patients with Rare Diseases Can Bring Cold Chain Challenges

Orphan Drugs: A Lifeline for Patients with Rare Diseases Can Bring Cold Chain Challenges

Written by Modality Solutions

Posted on: August 14, 2019

Orphan-Drugs, baby getting a shot from a doctor

The Orphan Drug Act of 1983 (ODA) defined orphan drugs as a drug intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. (1) Prior to these legislative acts, only 38 drugs had been approved to treat rare diseases, but since the ODA was passed, there have been more 841 orphan drug designations issued by the end of 2017 in the U.S. alone. (2)
 
The ODA also enables sponsors to apply to the Food and Drug Administration (FDA) for orphan status for investigational drugs. Incentives such as tax credits and subsidies for clinical trials, reduced or waived regulatory fees, seven years of market exclusivity following product approval are clear differentiators for orphan drugs.
 
The market for rare disease products is continuously growing, expecting to reach $176 billion by 2020, with a CAGR of 10.5% just for orphan drugs – this is twice the growth rate of the overall prescription drug market (5.3% CAGR from 2014-2020). Thirty million people in the U.S. and 350 million people worldwide suffer from a rare disease, while 95% of rare diseases lack a single FDA approved treatment. (2)
 
It takes an average of at least ten years for a new mainstream medicine to complete the journey from initial discovery to the marketplace. Clinical trials alone for prescription drugs takes six to seven years in general. The average cost to research and development for a successful drug is estimated to be $2.6 billion. (3) Since the Orphan Drug Modernization Plan, effective June 29, 2017, the U.S. Food and Drug Administration unveiled a strategic plan to completely eliminate the agency’s existing orphan designation backlog and ensure continued timely response to all new requests for designation with firm deadlines. (4) Since the modernization plan, many large pharmaceutical entities shifted focus to orphan drugs development with a set of advantages like lower developmental costs due to government incentives, smaller-scale clinical trial requirements, fast-track designations, and accelerated approval are some of the incentives.
 
However, these opportunities also bring challenges to an “orphan drug” development program:

  • Identifying and setting up investigative sites for studies.
  • Recruiting for clinical trials in a limited patient population.
  • Navigating the requirements for shipping, packaging, and distribution of drug studies across multiple countries and jurisdictions with unique customs and regulatory requirements.
  • Understanding the variability in the orphan medicinal expression.
  • Comprehending the severity and the course of diseases that may not be well known.
  • Managing small and geographically dispersed populations. (5)

 

Cold Chain challenges in orphan drug development

Beyond the challenges of a widely dispersed patient population, smaller dose quantities, and complex regulations, more than 50% of the orphan drug market are biologics and need to be temperature controlled to maintain stability and drug efficacy. (6) Supply chain integrity of orphan drugs is crucial as the drug regulatory agencies of the world have increased their vigilance of the orphan drugs pharmaceutical supply chain. In the U.S., the FDA demands robust data collection for rare disease products with regard to their clinical effectiveness. Commonly manufacturers don’t engage the cold chain logistics partners early enough in the process to identify efficiencies that could speed up therapy for small patient populations. Monitoring for temperature and location is increasingly important in complex formulations, and even more so in orphan drugs products, where the loss of product can be costly, and time-consuming to both the supply chain and the patient. Orphan drugs require an integrated, specialized supply chain that aligns with the manufacturer’s commercialization strategy, regulatory mandates, stringent temperature needs, and often unique logistics’ challenges.
 

Our goal is to improve patient access to orphan medicinal products by creating a robust and compliant cold chain supply management system.

 
As an established expert in supply chain logistics with a global reach, our team has a significant opportunity to provide cost-effective solutions to the growing orphan drug market. We understand the regulatory requirements, validation strategies, and implementation know-how during packaging, shipment, and delivery in order to assure drug product efficacy from manufacturer to the patient’s hands.
 
Modality Solutions can guarantee quality cold chain supply management of your orphan drug through:

  1. Flexible cold chain design. Flexible design in your cold chain logistics network will ensure a supply chain that can respond to unique demand requests and incorporate alternative methods for supply chain compliance to account for shortages of resources. Maintaining dosing site storage flexibility in case patients are not available is often overlooked both for storage capacity and validation perspective. Allow for the packaging design and drug delivery to be modified for self-administration.
  2. Augment your in-house expertise. Modality Solutions will provide additional personnel on-site while preparing for approval saving on the cost and the challenge of an in-house hire. Often the orphan drug developer has fewer resources available to complete all the tasks leading up to submission. Additional support is often needed to assure the level of attention needed to handle the complexities around the submission. To compound this problem, the pace at which orphan drugs are approved is quicker because of their special designation. While the work required to bring to market is less, it does not offset the increased pace. The process goes from around six months to two months per review cycle.
  3. Agility in validation practices. Orphan drug approval timelines are compressed from six to two months for each cycle. Meeting each marker and timeline requirement is a challenge. However, Modality Solutions has the agility and resources for a rapid and comprehensive validation master plan.
  4. Best in the industry passive thermal packaging selection. We have rapidly selected and qualified numerous thermal packaging solutions with supplier-supplied data and have independently tested most thermal packaging on the market. We have provided cost-effective and compliant thermal packaging solutions for more than 75 temperature-controlled drug products ranging from cryopreserved deep-frozen technologies to cost-effective controlled-room temperature (CRT) passive packaging.
  5. Our Advantage Transport Simulation Laboratory™ studies the effects of transport stress on your orphan drug product. This simulation technology provides insights into the various circumstances to be considered during the implementation of early access programs (EAPs) such as drug formulation and packaging choices and offers key recommendations for their successful implementation. When working with Modality Solutions your orphan drug product will be tested for not only temperature and humidity hazards, but also pressure, shock, and vibration. Regulatory expectations and especially the high value of orphan medicinal products are driving leading companies to incorporate all these transport hazards as part of their CMC filing.
  6. Robust cold chain protocols. Orphan drugs are typically shipped in small amounts, via parcel networks rather than active containers or on small pallets. With parcel shipments, there is less control and more exposure to severe conditions compared to shipping pallet loads. Orphan drug treatments typically are done at small specialized clinics, rather than a hospital setting, and lack the critical logistics infrastructure. The unique and limited availability of orphan drugs makes the design and validation of your cold chain, especially risk-averse. The unforeseen exposure of parcel shipments and the lack of predictability for receiving sites necessitates a very robust packaging design and reliable continuous monitoring system to ensure drug integrity and security all the way to the patient’s hands.
  7. Shipping lane optimization and selection. Tight temperature control to match limited stability data has to be maintained in challenging real-world conditions. We have been consistently providing best-in-class logistics solutions in some of the most challenging emerging markets in the world. This expertise is required to guarantee supply chain integrity for all climates.
  8. International regulatory expertise. Modality Solutions team of engineers have implemented regulatory requirements for orphan drugs across the globe. Orphan drug regulations are fragmented between different countries. Some are relatively new such as Brazil’s ANVISA resolutions for orphan drugs which were recently adopted in 2018. In the United States, orphan drugs are investigated on an accelerated path due to their special status. This accelerated pathway can cause challenges with many non-US regulatory agencies who will not allow the orphan drug to be sold in their country because of the abbreviated clinical trials. Our experts in regulatory affairs will navigate through the international inconsistencies and assist you with the standard submission for global regulatory agencies.

 
You can rely on Modality Solutions to provide fully compliant cold chain logistics support for all temperature, shock, vibration, atmospheric pressure-sensitive orphan drug therapies while maintaining product availability and efficacy from manufacturer to the patient’s doorsteps in the most challenging climates.
 
References
1. Orphan Drug Act of 1983: http://www.ecfr.gov/cgi-bin/textidx?c=ecfr&SID=51cf70689d51f0ea4147c0a8ac649321&rgn=div5&view=text&node=21:5.0.1.1.6&idno=21
2. Orphan Drugs in the United States (Part one) Growth Trends in Rare Disease Treatments Institute Report October 17, 2018 https://www.iqvia.com/institute/reports/orphan-drugs-in-the-united-states-growth-trends-in-rare-disease-treatments
3. Biopharmaceutical Research & Development http://phrma-docs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf
4. Orphan Drug Modernization Plan | FDA https://www.fda.gov/industry/…orphan…drugs-and…/orphan-drug-modernization-plan
5. Redfearn, Suz. “Tufts: Facing Many Challenges, Orphan Drugs Take 18% Longer to Develop.” Center Watch Weekly. 14 May 2018. Web. https://www.centerwatch.com/cwweekly/2018/05/14/tufts-facing-many-challenges-orphan-drugs-take-18-longer-to-develop/
6. Orphan drug: Development trends and strategies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996062/

Rachel Sawyer Joins Engineering Team

Rachel Sawyer Joins Engineering Team

Written by Modality Solutions

Posted on: July 10, 2019

Modality Solutions is pleased to announce it has hired Rachel Sawyer as a consulting engineer. As a member of the engineering team, Rachel works to ensure proper design and use of cold chain systems. She conducts supply chain risk assessments and writes Standard Operating Procedures for cold chain related processes that meet regulatory requirements. She is responsible for drafting protocols and reports for testing and validation of processes, as well as reviews data packages and conducts in-person cold chain consulting services.

Rachel is based in Houston at corporate headquarters,” said President Gary Hutchinson. “But she will also travel to Bloomington, Indiana to design and conduct distribution and thermal studies in our Advantage Transportation Simulation Laboratory.

Raised in Cincinnati, Sawyer attended The Ohio State University where she received her B.S. in Chemical Engineering with a biological focus, and she was a Green Engineering Scholars graduate. Her coursework included: transport phenomena, separation processes, thermodynamics, kinetics, and reactor design.

Click here to view the online press release announcement.

Drones in Your Biopharmaceutical Supply Chain– Are You Ready? 

Drones in Your Biopharmaceutical Supply Chain– Are You Ready? 

Written by Modality Solutions

Posted on: July 3, 2019

Drones in Biopharmaceutical Supply Chain, Image of drones holding boxes flying over the valley

Today drug product delivery via drone is no longer a fringe technology – it’s here to stay. Over the past decade, drones have been the subject of experiment for use in broadening the capability of supply chain professionals to deliver life-saving vaccines and temperature sensitive drug therapies. (1)  Drones are transforming the pharmaceutical supply chain transportation model at a swift tempo, enabling the safe delivery of life-saving vaccines and medical supplies to areas impacted by natural disaster or an epidemic outbreak in record time, where poor infrastructure and instability can limit patient access. (2)  The impact of this new technology on the supply chain industry, including the biopharmaceutical cold chain, is monumental.

However, the innovation and implementation of drone technology are outpacing international aviation regulatory bodies ability to enact current oversight. (3)  NASA has taken the first step in attempting to develop a protocol, but determining and enforcing the rules is in the jurisdiction of the FAA. (4)  The FAA released recent drone-related regulations in 2016 (Small UAS Rule – Part 107). Unfortunately, Part 107 does not address regulations specific to drone delivery, nor does it define rules for pilotless flight. (1)  The regulations include operational limitations for drones, including specifying maximum weight (25 kg), flight altitude (400 ft), and a stipulation that they may be operated only during daylight hours.  The constraint raising the largest barricade to unleash the potential of drones is the requirement to maintain the visual line of sight (VLOS), preventing UAVs from performing long-distance tasks outside the sight of an observer. (1)

Drones in the Cold Chain – a Game Changer

Adopting drone delivery technology will open new markets and service areas previously considered not cost effective or too risky, such as engagement in humanitarian logistics, emergency, and disaster response. Drone delivery can speed up laboratory test results, blood supply, and organ transplant shipping and service to rural areas around the world previously thought unmanageable. Integrating drone technology fortifies your existing supply chain and widens your access to a larger patient population. Using drones to deliver drug products causes a paradigm shift from operating within a predictive model to operating within a responsive model of drug delivery logistics, especially for the last mile delivery to the patient.(7)

General benefits of drone delivery include:

  • Drones are fast – drug product can travel from warehouse or pharmacy to patient in 30 minutes. Some drones travel at a speed of 100 kilometers per hour at low altitude.
  • Drones are efficient – Experts believe that drones have the potential to reduce costs within the last mile and increase efficiency simultaneously. (5)
  • Drones are sustainable – Battery operated machinery minimizes environmental impact.
  • Drones are humanitarian – They are ideal for delivering medicine and healthcare supplies to remote, underdeveloped, or dangerous locations due to war and/or epidemic outbreak.
  • Drones are urban – Drones are ideal for delivering to areas that are overpopulated, traffic ridden, and too time-consuming to reach, such as large cities with dense population.
  • Drones are innovative – Adding drones to your supply chain sets you apart as an innovator among your peers, many of whom (age 30-49 demographic) believe the pharmaceutical/medical market will benefit most from drone delivery. (5)

 

Successful Drone Delivery in the Real World

The future of drone deliveries may lie in the hands of regulators. Less crowded air space and fewer regulations are ideal for successful drone delivery implementations. Zipline’s success story in a less developed country with challenging geography is a good example. California – based Zipline has built the swiftest and reliable delivery drone, capable of reaching speeds of up to 100 kilometers per hour, for the biopharmaceutical supply chain for humanitarian outreach. Motivated by suboptimal logistics infrastructure and rudimentary, vulnerable, and expensive drug product storage facilities in Rwanda, Zipline recognized an opportunity to improve the delivery of life-saving blood. They responded to the challenge by organizing a project with UPS and GAVI to collaboratively establish and test a drone delivery program.

The project team fabricated launch and landing stations capable of transporting up to 150 emergency deliveries per day to 21 transfusing stations in the western region of the country. Upon receipt of an order for blood, the orders were immediately packaged and sent to the patient. With flying at over 100 kilometers per hour, the life-saving blood and medical supplies are delivered within thirty minutes to the patient from the sky via parachute, which was once a 5-hour round-trip truck drive. (6)  Zipline accredits the speed of their drones to their ability to maintain a proper cold chain network.

Early public acceptance of drone delivery networks in urban areas will revolve around hospitals. And once drones can safely and reliably carry blood and medical supplies, that will pave the way to other kinds of drone deliveries. (9) Last October Swiss Post launched a medical transport network in Lugano, Switzerland, using drones made by another Bay Area company, Matternet. So far, the drones have made 350 deliveries, about 5 to 15 per day. (9)

In the US, Matternet is partnering with the city of Palo Alto on a proposal to shuttle blood to Stanford hospitals. Flirtey, a drone manufacturer in Reno, NV is focusing on using its aircraft for last-mile delivery of defibrillators — devices the company thinks could save hundreds of thousands of lives in America each year, by increasing the chance of survival from out-of-hospital cardiac arrest. (9) Beyond the blood and medical supply deliveries, drones could transform another key component of healthcare — lab tests. Timely test results help doctors diagnose infections and reduce guesswork in prescribing medications. Some of those decisions have life-or-death implications.(9)

Globally, last summer, UNICEF worked with local governments in the African country of Malawi to launch a drone corridor for companies, universities, and nonprofits to fly test missions there. UNICEF also invited groups to transport vaccines in Vanuatu, the South Pacific nation made up of roughly 80 islands east of Australia. The drone corridors run on a barter system, says Chris Fabian, who leads UNICEF’s venture capital arm. (13)

Modality Solutions – Boots on the Ground in Africa

Modality Solutions has extensive hands-on experience managing cold chain logistics hurdles and validating a supply chain in a Zone IV ICH stability zone with its own set of unique challenges not faced by typical supply chains. Primarily, the availability of resources needed to make a shipment as documented in the validation master plan. A refrigerated truck, dry ice, or even a basic polystyrene shipper available one day might not be available the next. Creating standard operating procedures by itself becomes a challenge because there are few things about the supply chain that are standard. Supply chains in these areas are most successful when they are most adaptable. When they have many different options to compensate for when one is not available.

In addition, many areas in these zones have additional hurdles like underdeveloped infrastructure, making it difficult to even get from one location to another. When there are only dirt roads going through a thick brush or arid desert, the supply chain depends on that road being traversable on that day. If it is blocked for whatever reason, there often is no other option. In these areas, there are wet seasons of the year during which the roads are nearly impossible to traverse. In these cases, locals sometimes favor delivering via motorcycle courier instead of a truck because they can drive on the mud roads.

Modality Solutions has experience managing clinical trials for candidate vaccines and treatments for the Ebola virus throughout Western Africa. We are very knowledgeable of the challenges of delivering cold chain therapies in Zone III and IV ICH stability zones. Every member of our team works to maximize clinical trial performance, data integrity, and patient safety. Our cold chain and engineering expertise enabled our in-country, “boots on the ground” team of engineers, project managers, and principals to develop procedures adapted to the specific materials, equipment, and transportation capabilities unique to Western Africa.

Furthermore, the development of these procedures required personnel to travel to relevant facilities and ensure that the requirements of the SOPs were not exceeding the capabilities of equipment and personnel at each site. Our team trained local staff on the SOPs to determine whether the procedures aligned with site capability.

We are the experts in challenging cold chain clinical trial monitoring and logistics and provide operational and technical support to the Ebola vaccination project in Sierra Leone, as well as providing assessments of multiple sites for the NIH vaccine projects in the Caribbean. We understand the challenges faced by health care staff in underdeveloped areas of the world and always maintain a presence throughout the duration of a project, staying close until we know the job is done. Modality Solutions is familiar with the challenges and has the experience and resources to take any existing supply chain logistics plan, validate and integrate it for drone delivery applications.

Operational and Performance Qualification of Drone Deliveries

Completing an operational qualification for an airborne drone presents additional challenges in operational qualification (OQ) and performance qualification (PQ):

  • Direct exposure to environmental hazards. Using drone delivery exposes the packaging directly to the outdoor environment for significant periods, which impacts temperature, humidity, shock, and vibration.
  • Chain of control and package integrity. Unauthorized access by people or wildlife must be prevented. Easy access to drug product and anti-tampering measures must be validated in extreme hazard conditions.
  • Drone equipment and electronics need to be tested and validated for extraordinary circumstances and unusual weather patterns. When navigating undeveloped land, there are a large number of extraordinary circumstances that could occur to interrupt the PQ. For instance, a drone might stand up to gusts of winds but might not survive a mid-air collision with an object or wildlife. High humidity in the environment could be disrupting the electronics, sandstorms that interfere with radio signals, or even the drone parts melting from the solar irradiation. The OQ and the PQs in these circumstances would need a test design for those unique environmental hazards and determining if a drone delivery could complete with a high degree of confidence.

 

Are you ready? Why go it alone? Predictive drug delivery is on its way

New drug delivery technology requires supply chains to be proactive rather than reactive. Predictive analytics leverage historical and current performance data in order to make predictions on future performance, creating intelligent supply chains capable of swift adaptation and agile decision-making processes, as it is no longer adequate to react to issues after the fact – we must anticipate future performance in order to make intelligent decisions. (8)  Cargo drones promise to make systems responsive rather than predictive. (8)  With our novel technologies, a proven track record of successful collaborations enabling over 75 new drug approvals, and access to industry influencers, we are prepared to transform your drug delivery operations to a predictive, agile, integrated cold chain.

There are several areas of impact specific to cold chain logistics to consider before integrating drone delivery with your current operations. Updating your Validation Master Plan using these guidelines will give you a head start:

  • Implement authentication systems to maintain secure and accurate delivery that includes protocols for replacement or compromised shipments.
  • Include protocols that have been tested and validated for the impact of exposure to various weather and environmental hazards: light, wind, humidity, shock, and vibration.
  • Create transparency in the supply chain through strategic planning by redefining chain of custody requirements, encouraging compliance with procedures while discouraging theft and improper handling through training and real-time monitoring of product movement. (8)

The decisions you make regarding cold chain operations can make life-saving drugs potentially deadly if the cold chain is disrupted. (8)  Avoid failures in infrastructure, decision making, coordination, and planning by partnering with the experts at Modality Solutions. With our Advantage Transport Simulation Laboratory™, a proven track record of successful collaborations enabling over 75 new drug approvals, expertise in Validation Master Planning, and access to industry influencers, we are prepared to transform your drug delivery operations to a predictive, agile, integrated cold chain for drone delivery system.

Expertise in Biopharmaceutical Cold Chain Management Systems Leads to Regulatory Compliance and Consistent Process Controls.
References
1. Lin, Pharm. D, Connie A, et al. Drone delivery of medications: Review of the landscape and legal considerations. American Journal of Health-System Pharmacy. 2018, Vol. 75, 3, pp. 153–158.
2. Pharma Logistics IQ. What is drone delivery, and how is it changing the pharmaceutical supply chain? Pharma Logistics IQ. [Online] April 12, 2019. [Cited: June 18, 2019.] https://www.pharmalogisticsiq.com/logistics/articles/what-is-drone-delivery-and-how-is-it-changing-the-pharmaceutical-supply-chain.
3. Heck, Andrew J. and McClanahan, Christopher J. Safety Concerns Prompt New FAA Regulations for Drones. The National Law Review. [Online] April 18, 2019. [Cited: June 17, 2019.] https://www.natlawreview.com/article/safety-concerns-prompt-new-faa-regulations-drones.
4. NASA. FAQs: NASA’s Drone Traffic Management Research in Reno and Corpus Christi. www.nasa.gov. [Online] May 28, 2019. [Cited: June 17, 2019.] https://www.nasa.gov/feature/ames/faqs-nasa-s-drone-traffic-management-research-in-reno-and-corpus-christi.
5. Connolly, Kate Bertrand. Eyes on the Skies: The Dream of Drone Delivery Starts to Take Flight. [ed.] Lisa McTigue Pierce, Daphne Allen and Rick Lingle. Packaging Digest. 2016, Vol. 53, 3.
6. Zipline. zipline. [Online] [Cited: June 18, 2019.] https://flyzipline.com/impact/.
7. Stefanovic, Nevad. Proactive Supply Chain Performance Management with Predictive Analytics. The Scientific World Journal. [Online] October 15, 2014. [Cited: June 18, 2019.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214046/.
8. Morain, Tony. Direct Relief, Merck and Partners Test Temperature-Controlled Autonomous Drone Delivery System for Medicines in Puerto Rico. www.directrelief.org. [Online] August 24, 2018. [Cited: June 18, 2019.] Researchers estimate that most deaths from Hurricane Maria in September 2017, were caused by loss of access to medicines and health care, not by wind or water. As people were displaced from their homes, health centers lost power for weeks, and travel was.
9. LANDHUIS, Esther. Medical Cargo Could Be The Gateway For Routine Drone Deliveries, March 10, 2018, 9:01 AM radio broadcast[cited: July 01, 2019] https://www.npr.org/sections/health-shots/2018/03/10/592059175/medical-cargo-could-be-the-gateway-for-routine-drone-deliveries

Apheresis Collection for CAR T-Cell Therapy Requires Agility in the Cold Chain

Apheresis Collection for CAR T-Cell Therapy Requires Agility in the Cold Chain

Written by Modality Solutions

Posted on: May 31, 2019

Autologous cell therapy, Apheresis Collection for CAR T-Cell Therapy Requires Agility in the Cold Chain, image of cell

Innovations in Cancer Immunotherapy

Autologous cell therapy (ACT) is a therapeutic intervention that uses an individual’s cells, which are cultured and expanded outside the body, and reintroduced into the donor. Advantages of this approach include the minimization of risks from systemic immunological reactions, bio-incompatibility, and disease transmission associated with cells not cultivated from the patient. We intend to review the promising CAR T-Cell Therapy that uses apheresis collection to start the ACT process and address the potential risks your cold chain supply management faces.

Because of the inability to categorically define the nature and expression of biomolecules and factors that are present, the apheresis collection for CAR T-Cell therapy are inherently fragile and are highly sensitive to variations in manufacturing and cold supply chain procedures. Carefully controlling every aspect of how apheresis is handled is the best way to ensure that the full potential of this exciting innovation in immunotherapy is realized. Standardization of immunotherapy manufacturing, storage conditions, and cryopreservation are a stepwise approach and should allow the field to deliver efficient, competitive, and approved new therapeutic options for patients with still-unmet medical needs.

Supply chain risks include extrinsic cold chain factors, such as temperature, CO2 ingress, humidity, shock, and vibration occurring during transportation from collection site to manufacturer and storage conditions which may influence the metabolic activity of the cells and therefore the function, specificity, and efficacy of the patient’s treatment.

 

CAR T-Cell Therapy

With the 2017 FDA approval of Kymriah (Merck) for the treatment of children with acute lymphoblastic leukemia (ALL), and Yescarta (Kite Pharma) for adults with advanced lymphomas, adoptive cell transfer (ACT), a specialized type of immunotherapy, has emerged as the front line in cancer treatment. [1]

With ACT, the patient’s own T cells are the major component of healing since they have the unique ability to initiate the immune system’s response to destroy cancer cells. A type of ACT making breakthroughs in targeted treatment is the chimeric antigen receptor T-Cell Therapy (CAR T-Cell). [2]

T cells are collected via autologous cell therapy, a complicated and multi-step process. The autologous cell therapy collection process has enabled breakthroughs in the treatment of cancer, but has also created challenges for regulatory officials, clinical workers, and supply chain professionals. [1] The collection takes place in a variety of clinical settings typically governed by local procedures. The time from T-cell harvest to infusion of CAR T-Cells varies from a few days to weeks [4]. CAR T-Cell Therapy is personalized medicine at its most elemental: a patient receives an exclusive treatment based upon their unique T cells.

To begin with, a patient typically undergoes blood cell collection or apheresis or a tumor cell collection. Blood cell collection is then assigned a unique identifier used throughout the manufacturing, distribution, and infusion process to ensure the patient receives the correct treatment. [3]

The apheresis sample is sent directly to the drug manufacturer, where the manufacturing process begins immediately. This collection could be shipped refrigerated and in some cases are cryogenically preserved at time of collection. In either case, strict temperature controls and monitoring are recommended to ensure high-quality starting material for downstream manufacturing processes. Qualified shipping containers, proper monitoring techniques, and validated procedural controls are key to ensuring bio-viability and patient safety. The process for receipt, storage, and distribution of the finished product is vital to success.
The typical process for a cancer-related autologous cell therapy

Figure 1: The typical process for a cancer-related autologous cell therapy [3]

 

Best Practices

Given the potential risks, personalized therapies require both a reliable and traceable chain of custody and chain of identity. Cancer patients undergoing immunotherapy have typically failed traditional methods of treatment, and their lives are literally in the hands of everyone involved – from the clinician collecting the sample to the material handler receiving the finished drug product into inventory.

Since the suitability of the patient’s harvest cells determine the reliability of cell assays the best practice is to cryopreserve the cells immediately after collection. Passive (non‐programmable), rate freezing has the advantages of lower cost, simplicity, and speed, and most importantly, facilitates the immediate cryopreservation of stem cell products avoiding potential pre‐freeze storage risks. [5]

The technology encompassing autologous cell therapy collection, storage, and processing has continued to evolve and merits a thorough review of current quality control expectations. FDA guidelines on who is qualified to pack the cells for initial shipment or the number of clinical investigators who should handle them upon return for patient infusion are evolving. Cryopreservation at time of collection needs adequate equipment and technical proficiency to monitor the frozen cells from collection site all the way to treatment application site to ensure reliable results and treatment efficacy.

 

Agility and Alignment

Do you have an appropriate monitoring strategy? Have you optimized your monitoring and procedural controls and your qualification approach? Are you ready to provide the option of immediate cryopreservation to a patient whose cells are collected and ready for manufacturing their specialized immunotherapy treatment?

Your quality and service level agreements with partners are critical to your success.

By using simple measures such as standardization of documentation, including cold chain transportation validation with shock and vibration simulation validation master plans, sample handling protocols, and summary reports, you minimize the opportunity for error.

 

More on This Topic:

On-Demand Webinar: Cold Chain Validation Best Practices Including Immunotherapy Webinar

White Paper: The Challenges of Cold Chain Validation for Regenerative Medicine

Blog: The cold chain challenges of today’s promising antibody-drug conjugates (ADCs)

 

References
1. Dana Farber Cancer Institute. Cellular Therapies Program. Dana Farber Cancer Institute. [Online] [Cited: May 11, 2019.] https://www.dana-farber.org/cellular-therapies-program/car-t-cell-therapy/faq-about-car-t-cell-therapy/.
2. US Department of Health and Human Services. NCI Dictionary of Cancer Terms. National Cancer Institute. [Online] [Cited: May 13, 2019.] https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adoptive-cellular-therapy.
3. O’Donnell, Dan. The Cell Therapy Supply Chain: Logistical Considerations for Autologous Immunotherapies. BioProcess International. [Online] [Cited: March 25, 2019.] https://bioprocessintl.com/manufacturing/cell-therapies/the-cell-therapy-supply-chain-logistical-considerations-for-autologous-immunotherapies/.
4. Leukemia & Lymphoma Society. Facts About Chimeric Antigen Receptor (CAR) T-Cell Therapy. Leukemia and Lymphoma Society. [Online] [Cited: May 13, 2019.] Revised June 2018. https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FSHP1_CART_Factsheet_June2018_FINAL.pdf.
5. Watts, Michael, and Lynch, Davis J. British Journal of Haematology. Wiley Online Library. [Online] [Cited: May 21, 2019.] Immediate Cryopreservation is supported as a best practice at the beginning of autologous cell therapy smaple collection. https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14378.
6. Modality Solutions. The Challenging Supply Chain & Logistics of Immunotherapy Drugs. Modality-Solutions.com. [Online] [Cited: March 25, 2019.] https://www.modality-solutions.com/the-challenging-supply-chain-logistics-of-immunotherapy-drugs/.

Regenerative Medicine – A Catalyst for Modern Targeted Cancer Therapy

Regenerative Medicine – A Catalyst for Modern Targeted Cancer Therapy

Written by Modality Solutions

Posted on: April 24, 2019

Regenerative Medicine, Doctor in lab coat holding graphic saying "Regenerative Medicine"

For thousands of years, tissue regeneration has been a topic of interest among the scientific world. The ancient civilizations of India and Greece were pioneering medical techniques that still impact the field today. Cleansing and debridement of wounds were commonplace, and there are reliable records from India dating back 1000 years describing skin grafting for facial reconstructions. The human regeneration potential was well-known also by the Greeks as early as the 8th Century BCE, as demonstrated by the myth of Prometheus: As punishment for offending Zeus, he was sentenced to 30,000 years of torture: Each day an eagle destroyed his liver, which then completely regenerated itself overnight to enable the process again the next morning. From these ancient origins we enter the modern era of regenerative medicine. [1][2]
 
Regenerative medicine is a major advancement in medical treatment used to replace or regenerate human tissue and organs that is based upon stem cell technology and tissue engineering. [3] No other cell in the body has the natural ability to repair damaged cells, generate new cell types or divide as rapidly as stem cells. [4]. Over the years, tissue engineering has gained momentum as a far-reaching scientific discipline – researchers have steadfastly pursued the development of new life-saving therapies. The field has grown from surgical implants such as artificial hips and bio-material scaffolds that support skin grafting to the discovery that launched it into a modern medical miracle: cell therapy. Cell therapy enabled major organ transplants, accelerating the innovation of bone marrow transplants for the treatment of leukemia, and invigorated cell biologists to investigate the possibility of creating, growing, and harvesting tissue in a laboratory setting. [5]
 
The positive impact that the versatility of stem cells has provided to modern medicine, particularly in the field of anticancer drug screening, regenerative medicine, immunotherapy, and targeted cancer treatment cannot be understated. Because of their unique properties, such as migration toward cancer cells, secretion of bioactive factors, and immunosuppression, stem cells promote tumor targeting and circumvent obstacles that have traditionally impeded gene therapy strategies. Monoclonal Antibodies (mAbs) which employ stem cells, function as novel delivery platforms by targeting both primary and metastatic cancer. [6]
 
Cancer stem cells are known to be responsible for tumor development, metastasis, and relapse after conventional therapies. Emergent therapeutic strategies in cancer have been focusing on the use of mAbs to stimulate an immune response against tumors, and since the inception of mAbs as cancer fighters, researchers are identifying and characterizing the stem cells of different tumor types. [7] Since mAbs should be able to facilitate earlier diagnosis by targeting specific antigens altered in cancer stem cells through molecular imaging, enable efficient destruction of tumor initiating cells, and improve clinical outcome for patients undergoing treatment. [4]
 
Monoclonal antibodies are an important part of cancer treatment and have opened the door for many innovations in the field of immunotherapy. Immunotherapies are a new type of cancer treatment that use extracted and genetically modified elements of a patient’s own cells to boost their immune system’s ability to work harder and smarter to attack and remove cancer cells. [8] [9]
 
The global immunotherapy market is expected to grow to USD 385.46 Billion by 2025 at a CAGR (compound annual growth rate) of 14.27% during the forecast period from 2018-2025. Major drivers that fuel the growth of the market are [10]:
 

  • Increasing adoption of targeted therapy over traditional therapy
  • Emergence of biosimilars
  • Increasing demand for monoclonal antibodies (mAbs)
  • High prevalence rate of lifestyle diseases
  • Fast track and orphan drug designations [10]

 
An emerging innovation in immunotherapy treatment has changed the supply chain so that it literally begins and ends with the patient.
 
The supply chain begins with the process of apheresis – the extraction of a patient’s T cells from their blood. Often apheresis will also involve a parallel process involving the extraction of the patient’s tumor cells. After the cells are collected and given a unique identifier, they are moved through the storage, manufacturing, and transportation network. [11]
 
A major challenge with scaling out the production of immunotherapy is the transition from a flexible process at a single academic institution to a highly controlled process that can be implemented across many collection, manufacturing, and treatment sites over a variety of geographic regions and climates. [8]
 
Several types of immunotherapy treat life-threatening diseases today – all are highly specialized to each patient and require documented collection, prompt storage, and precision handling – presenting new challenges to the supply chain industry. Currently, no FDA guidelines exist for managing the patient sample collection, transportation, manufacturing, storage, and distribution of immunotherapies. [11] We will delve into this topic with our discussion of the process of autologous therapy collection next month.
 
With this exciting new frontier comes additional regulatory challenges because the complex manufacturing processes and their intermediates pose – along with a complete range of environmentally controlled conditions ranging from controlled room temperature (CRT) to refrigerated to deep-frozen cryogenic packaging systems. Managing these intricacies will be a challenge for today’s biopharmaceutical cold chain professionals.
 
We are going to explore these regulatory challenges in a series of posts to share with our industry our observations after numerous interactions with the regulatory agencies on the best approach for cold chain process validation for immunotherapy products. We wanted to start at the beginning: defining your cold chain network. Since the logistics network for immunotherapy products are the most complex in the biopharmaceutical industry and relatively new to most regulators, a detailed process map is an important foundation for discussion.
 

  • It is important to ensure that the entire network from patient to processing center to manufacturing to packaging and labeling and finally distribution is clearly defined. The feedback we have seen on incomplete network diagrams are the following:
  • Include shipping to all sites appropriate to your distribution including clinical sites and consider worst case scenarios in your network design.
  • When transport simulation is used, please provide enough details about all identified hazards (i.e. temperature, shock, vibration, pressure, and humidity) to support a strong justification for the profiles used later to help demonstrate how the profiles relate to real world experience.
  • Note where changes to the configuration of the drug product material (e.g. boxes/pouches) relative to that used for shipment of the drug substance or intermediates and whether configuration changes might affect the results of studies.
  • Indicate when the shipping container was used in a previous step changes and identify any impacts or risks in this change.
  • Provide details on how the drug substance, intermediates and drug product are packaged and handled. Photographs of the packaging configurations in your network (e.g. the placement of product and diluent vials in a tray, the tray in the carton, and the carton in the sealed pouch) are very helpful to understanding the processes in the cold chain network.

 
Next up: choosing your quality attributes to assess for cryogenic shipping temperatures. We hope you check back next month as we take the next step in our exploration of the cold chain challenges of regenerative medicine.

 

References
1. University of Nebraska Medical Center. History of Regenerative Medicine. Mary and DIck Holland Regenerative Medicine Program. [Online] [Cited: April 7, 2019.] This web article references another publication: Regenerative Medicine: Gustav Steinhoff, first Edition 2011 XXIV, Springer Publications. https://www.unmc.edu.
2. Sampognaa, Gianluca et al. Regenerative medicine: Historical roots and potential strategies in modern medicine. Science Direct. [Online] September 2015. [Cited: April 8, 2019.] Open Access. https://www.sciencedirect.com/science/article/pii/S2213879X1500053X.
3. Regenerative Medicine: Historical Roots and Potential Strategies in Modern Medicine. Science Direct. [Online] [Cited: April 7, 2019.] https://www.sciencedirect.com.
4. Mayo Clinic Staff. Stem Cells: What they are and what they do. Mayo Cinic. [Online] April 2, 2019. [Cited: April 7, 2019.] http://www.mayoclinic.org.
5. Napoli E, et al. Adv Exp Med Biol. 2018. Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement. National Center for Biotechnology Information. [Online] [Cited: April 7, 2019.] http://ncbi.nlm.nih.gov.
6. Cheng-Liang Zhang, et al. Stem Cells in Cancer Therapy: Opportunities and Challenges. National Center for Biotechnology Information. [Online] Oncotarget, September 8, 2017. [Cited: April 7, 2019.] http://www.ncbi.nlm.nih.gov.
7. Okamoto OK, Perez JF. Targeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis. National Centre for Biotechnology Information. [Online] [Cited: April 7, 2019.] https://www.ncbi.nlm.nih.gov/pubmed/18598221.
8. Modality Solutions. The Challenging Supply Chain & Logistics of Immunotherapy Drugs. Modality-Solutions.com. [Online] [Cited: March 25, 2019.] https://www.modality-solutions.com/the-challenging-supply-chain-logistics-of-immunotherapy-drugs/.
9. American Cancer Society. What is Cancer Immunotherapy? www.Cancer.org. [Online] [Cited: March 11, 2019.] https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html.
10. MarketWatch. Global Immunotherapy Drugs Market to Grow at a CAGR over 14.27% from 2018 to 2025. MarketWatch. [Online] March 25, 2019. [Cited: April 8, 2019.] https://www.marketwatch.com/press-release/global-immunotherapy-drugs-market-to-grow-at-a-cagr-over-1427-from-2018-to-2025-2019-03-25?mod=mw_quote_news.
11. O’Donnell, Dan. The Cell Therapy Supply Chain: Logistical Considerations for Autologous Immunotherapies. BioProcess International. [Online] [Cited: March 25, 2019.] https://bioprocessintl.com/manufacturing/cell-therapies/the-cell-therapy-supply-chain-logistical-considerations-for-autologous-immunotherapies/.

Why Traditional Data Loggers May No Longer Meet FDA Regulations for Pharmaceutical Shipments

Why Traditional Data Loggers May No Longer Meet FDA Regulations for Pharmaceutical Shipments

Written by Modality Solutions

Posted on: March 20, 2019

FDA-Regulations

Temperature data loggers have been around for decades and were one of the first sensors in the biopharmaceutical cold chain. This technology provided temperature audit trails of shipments in transit, enabling partners in the cold chain to confirm whether the products remained within specification throughout transit and verifying the acceptability of the product for the next partner in the cold chain.
 
Unfortunately, most temperature data loggers utilized in the industry stopped developing at this limited functionality years ago and have not kept pace with the needs of the modern pharmaceutical cold chain. Increased need within the industry for visibility throughout the entire cold chain supply from manufacturer to end user is demanding data loggers to become more accessible and comprehensive. Data loggers are becoming a very important component in the entire cold chain process. However, the limitations of data loggers, even the misnamed ‘real time’ data loggers, become transparent.
 
Many data loggers are on the market today for temperature-controlled shipments of perishable biopharmaceutical products. Their latest advances allow real-time data monitoring capabilities, yet this technology can often fall short of reporting accurate data at all steps in the cold chain and impedes the ability of all partners in the biopharmaceutical cold chain from capturing the full visibility, scalability, and agility necessary to support the growth of the environmentally-sensitive biopharmaceutical therapy revolution underway.
 
The status quo technology requires significant manual input: data collection must start and stop through a data logger. If this operation is performed incorrectly, the shipment data may not be collected at all unless next-generation shadow monitoring is available. If the material handler activated the data logger at the initiation of transport, the receiving end completes the process by uploading the data and completing an ad hoc shipment review.
 
However, if the data logger is incorrectly placed by the material handler before the product is transported, the data collected would not be valid for the shipment per the qualification requirements of the shipping system. All these steps in the cold chain increase the likelihood of human error occurring along multiple cold chain touchpoints, potentially delaying the review process.
 
The focus has been on temperature logger technology, the hardware, and the data collection software that powers them, not on visualizing the data and proactively planning your cold chain. Status quo hardware and software are not empowering businesses to fully leverage the opportunities that the explosion of ‘big data’, ‘machine learning’ and artificial intelligence (AI) really presents, including predictive and prescriptive analytics and proactive response to prevent excursions from happening at all.
 

Is there a better way?

Most data loggers require the physical collection of data after a trip’s completion. Storage memory tracks temperature data captured at regular intervals, typically every 15, 30, or 60 minutes. After delivery, data is collected by connecting a USB cable from the logger to a PC or by other means and software reads and plots temperature (and possibly other environmental conditions) data, then the receiver must review the data to determine if product has been exposed to any deviations prescribed in the cold chain protocol and compliance.
 
Extracting data from loggers can take between 15 to 30 minutes per logger, and as previously described is a highly manual process. If the data shows a possible excursion with any variation from compliance and product quality, the products enter into a quality review process. The process review which follows may take up to 2 to 3 business days or longer depending on the type of product and length and severity of the temperature excursion. Without a complete data set, whether real-time or not, the biopharmaceutical cold chain is not able to ensure compliance. Visibility is worse than ad hoc: it is incomplete.
 
At the end of a shipment, loggers are typically discarded or returned to either the shipper or in some cases a third-party logistics provider. Even if they are designed to be reusable, without efficient reverse logistics processes in place, these data loggers may be just adding hazardous waste to the disposal stream.
 

 

Why do we need data loggers at all?

Less than a decade ago, the pharmaceutical industry believed it was not realistic to expect end-to-end visibility into shipment locations and statuses across an entire supply chain. Today, it’s not only possible and readily available, but there are cost-effective ways to achieve it. But is it enough?
 
At first, real-time data loggers were prohibitively expensive and used only for a portion of the supply chain, either for routes that have historically posed challenges, such as products moving into Brazil or Russia, or only for high-value shipments. Now, most continuous monitoring data loggers with data transmission available on the market are expensive because they require upfront investment before use. And even then, they fall short in providing 100% ‘real-time’ visibility over these important shipments, including the monitoring of environmental conditions (temperature, humidity, light) and product location.
 
Due to cost concerns, unreliable manual data retrieval, and additional waste attributed to shipments from discarded loggers, all partners in the cold chain, even traditionally well capitalized or funded biopharmaceutical innovators, have resisted pursuing ‘real-time’ data loggers as an option to connect all shipments across the cold chain, resulting in limited visibility only to projects or shipment routes.
 

Predictive analytics powered by big data

The fast-moving, constantly changing cold chain can be impacted at any moment by a variety of environmental factors. The greatest risk to a therapeutic product in transit is the impact of weather to both temperature control and on-time delivery. A late or damaged load has downstream effects that can lead to medicines and vaccines not reaching patients.
 
Today, the biopharmaceutical cold chain requires more than 100% visibility. While the focus continues on late and off-schedule shipments that threaten to disrupt operations, trigger a compliance event, and eventually challenge their regulatory reputation, a shift towards utilizing ‘big data’ and machine learning to drive predictive analytics for more proactive management practices is happening. This change away from data capture to forward-looking predictive analytics leads to more informed decision making, ensuring efficiency, and productivity across the supply chain.
 
Utilizing a wide range of weather data, a predictive analytics capability allows biomanufacturers and logistics partners required to follow US Food and Drug Administration (FDA) regulations to have instantaneous, ‘real-time’ visibility on 100% of the shipments in their supply chains, without a cumbersome data logger system in the way. Data logger solutions on the market today, including systems marketed as a ‘real time’ solution, are not equipped with the technology to provide live data during transport.
 
In a recent LogiPharma publication, [1] the majority of respondents, including 100 top decision makers in the pharmaceutical industry, cited innovating their distribution channels to remain competitive and improving end-to-end visibility as among their key challenges, and view Big Data (machine learning, artificial intelligence and advanced analytics) as likely having a considerable impact on the supply chain in the next five years. No data loggers and their partnered services currently on the market will get them the results envisioned.
 
Predictive data analytics is the future of efficient supply chain. manufacturers, wholesalers, distributors, and other partners are requiring greater visibility and proactive management to mitigate the issues that will jeopardize cold chain processes and impact their ability to comply with FDA regulations for pharmaceutical shipments. Previous track-and-trace methods powered by next-generation data loggers cannot meet end-to-end supply chain visibility required. Industry changes warrant developing and utilizing technology that provides predictive capabilities tied to ‘big data’ weather analysis in order to meet the need for an end-to-end, transparent and adaptive cold chain. Cold chain can be a differentiator when competing for market share, rather than a drain on resources.
 

It’s already possible.

Building an efficient and proactive cold chain goes beyond 100% continuously monitoring your assets. It requires the ability to foresee what will go wrong, where it will go wrong, when it will go wrong, and what needs to be done to avoid the risk in the first place.
 
To be proactive, the biopharmaceutical cold chain needs to leverage more than the power of real-time data loggers and the data they provide, not only to know how their shipment or goods are doing continuously but also to allow continuous risk monitoring and management.
 
Smart cold chain design involves data analytics using decision support tools and visual data. This involves looking at divergent and related data and combining them into actionable items. One is past trends in logistics patterns and two is in-depth analysis of future predicted data for the cold chain.
 

Prescribe, predict and forecast when optimizing your cold chain.

Utilizing complex data analysis will lead to efficient shipping lane selection, and appropriate monitoring during transport. However, measuring and monitoring excursions is useful but not cost effective or efficient. Preventing any excursions from occurring through accurate forecasting will allow shipment day and time management.
 

While continuous updated data is a vital aspect of cold chain in general, there is a need to integrate all aspects of cold chain supply process under one clear, reliable technology platform that will combine all parameters and provide automated solutions to optimal logistics.
Your partner in the cold chain analytics should add significant value and expertise, to the following attributes:

  • A track record of continually innovating solutions to surpass customer and industry needs
  • An extensive history with complex biopharmaceutical cold chains
  • Deep understanding of the complex algorithms necessary to tie ‘big data’ weather events to lane-specific, network-specific temperatures

 

REFERENCES
1. WBR Insights. Differentiated by Supply ChainA LogiPharma Report 2018. LogiPharma. London: WBR Digital, 2018.

Cold Chain Experts Modality Solutions Recognized as an Inc. Verified Company

Cold Chain Experts Modality Solutions Recognized as an Inc. Verified Company

Written by Modality Solutions

Posted on: March 13, 2019

Inc. editors independently reviewed Modality Solutions to validate its website functionality and content, social media links, and phone lines to confirm the firm is fully operational. An Inc. Verified Profile is meant to save possible new clients time by showcasing businesses that are part of the entrepreneurial ecosystem.

Both life sciences and healthcare industry sectors are increasingly challenged by operational and regulatory demands, corresponding higher risks for compliance, and pressures for improved value. Modality Solutions clients must have complete trust in the cold chain management company to provide accurate insight into thermal packaging, monitoring and controls, transport validation, controlled-environment logistics and clinical trials.

Becoming an Inc. Verified Company is prestigious and important. When a business needs to choose a consulting partner to validate its integrated cold chain, launch existing products into new markets, or improve its existing cold chain, the credibility and reputation of the organization they to choose to partner with is essential.

“The team at Modality Solutions is proud to join this highly respected ecosystem of global entrepreneurs verified by Inc. We are also looking forward to the review of our application for inclusion in the Inc. 5000 for 2019,” said President Gary Hutchinson.

Click here to view Modality Solutions Inc. Verified Profile.

Click here to view the Modality Solutions Inc. Verified Company press release.

 

Modality Solutions included in Pharmaceutical Outsourcing™ Industry Reference Guide

Modality Solutions included in Pharmaceutical Outsourcing™ Industry Reference Guide

Written by Modality Solutions

Posted on: January 28, 2019

Modaity_PR_Jan_2019

Modality Solutions was included in the Pharmaceutical OutsourcingThe Journal of Pharmaceutical & Biopharmaceutical Contract Services Vol. 19 Issue 6, November / December 2018. Pharmaceutical Outsourcing is the leading review of business and technology for the pharmaceutical industry throughout North America. The Journal is dedicated to pharmaceutical and biopharmaceutical contract services, and the publication has regular sections on contract manufacturing, contract research, contract packaging, formulation/development services, contract analytical testing, APIs, stability testing, clinical research, and other areas. Modality Solutions was included in the 2019 Company Focus & Industry Reference Guide under the Cold Chain Management Solutions heading.

 

Website: https://www.pharmoutsourcing.com/

Navigating the Immunotherapy Supply Chain: Advances in Transport Validation

Navigating the Immunotherapy Supply Chain: Advances in Transport Validation

Written by Modality Solutions

Posted on: January 16, 2019

Supply Chain Services

Immunotherapies are an increasingly complex set of treatments for a wide variety of diseases and medical conditions. The opportunities for immunotherapy drugs are expanding—but only if the supply chain provides enough stability to keep them safe and effective for patients throughout their journey.

The specific conditions of immunotherapy drugs in transport can present a number of challenges to the supply chain. At Modality Solutions, our experts in global cold chain validation have identified what hazards of immunotherapy drugs pose the greatest risks, and how advanced transport validation can help to mitigate these.

RELATED: Cold Chain Validation Best Practices Including Immunotherapy [WEBINAR]
 

Unique supply chain challenges for immunotherapies

Two of the more exciting immunotherapies are ADCs (Antibody Drug Conjugates) and CAR-T therapy (Chimeric Antigen Receptor T cell). CAR-T therapies are further divided into autologous (patient specific) and allogeneic (genetically similar but not patient specific) therapies. Because each treatment is individually created for a specific patient, tracking the therapy and patient identity is more important than ever.

Often, specifically for CAR-T cell therapies, the supply chain starts with the patient and ends with the patient. A unique closed loop supply chain has challenges not seen before. With autologous therapy, where collection of patient plasma is the basis for the immunotherapy, a separate blood cell supply chain needs to be established.

Most immunotherapies require deep frozen storage and transportation. Choosing your quality attributes to assess for cryogenic shipping temperatures and selecting the primary and secondary packaging that will keep the integrity of a unique, costly, and often irreplaceable therapy is a major undertaking.

Each of these added challenges demand a solid engineering basis for transport validation.
 

Identifying and mitigating risk

It is important to ensure that the entire network from patient to processing center to manufacturing to packaging and labeling and finally distribution is clearly defined, and risk assessment is performed throughout.

In order to begin assessing the immunotherapy supply chain for risk, pharmaceutical companies need a robust testing and optimization framework. At Modality Solutions, we call our proprietary testing framework the Hazard and Operability Study (HAZOP) technique, which is tailored for immunotherapy drugs to ensure high risks are identified and mitigated properly.

In a recent HAZOP analysis, Modality Solutions was able to uncover the greatest risks each of the shipping lanes represented to the cell cultures.

One of the findings was around the difficulty in maintaining the required thermal conditions throughout the closed loop supply chain. This was due to deep frozen temperatures required during transport from the patient and collection center to facilities worldwide to perform the genetic reengineering of cells, then efficiently returning the cells to the treatment center, and finally administering it to the right patient for treatment. Once the risks had been identified Modality Solutions moved on to the mitigating phase that included testing the packaging by exposing it to extreme conditions and simultaneous environmental hazards in order to create a risk mitigation plan..
 

Simulating environmental hazards faced in transport

Without the ability to test multiple concurrent environmental hazards at once, pharmaceutical companies face additional challenges in transport validation of the immunotherapy supply chain.

In another HAZOP case study, the FDA requested our client to conduct detailed concurrent traceability and multi-hazard environmental testing on the precursors to the immunotherapy: the monoclonal antibody, linker, and cytotoxin.

Our Advantage Transport Simulation Laboratory™ is able to simulate all major environmental hazards faced in shipping and distribution: shock, vibration, temperature, humidity, and pressure. In our lab, we exposed all products and respective packaging to simulated environmental conditions faced in the shipping lanes. This approach verified the quality of all three precursors after transport and ensured the capability of the packaging and components of the immunotherapy to withstand the environmental hazards faced before reaching the patient.

Building a Validation Master Plan

Several types of immunotherapies treat life-threatening diseases today. All are highly specialized to each patient and require documented collection, prompt storage, deep frozen temperatures, and precision handling, presenting new challenges to the supply chain industry never seen before. It is essential to understand every aspect of this complex supply chain and to build each of these risk components into a comprehensive Validation Master Plan (VMP) to create a robust and repeatable supply chain process with patient safety at its heart.

Along with HAZOP analysis and advanced transport simulation, Modality Solutions also offers help with Validation Master Plans (VMP) and technical documentation as part of our supply chain services to ensure transparency and quality management in the supply chain.

Contact us today to enlist the help of expert engineers for transport validation across the supply chain.

4 Challenges in Immunotherapy Drug Supply Chains and Logistics

4 Challenges in Immunotherapy Drug Supply Chains and Logistics

Written by Modality Solutions

Posted on: October 24, 2018

Supply Chain & Logistics, fintech icon on abstract financial technology background represent Blockchain and Fintech Investment

Immunotherapy, the process of strengthening a patient’s own immune system using pharmaceuticals, is rapidly increasing in popularity due to its effectiveness in many previously untreatable diseases. Commonly used to treat cancer, autoimmune diseases, and genetic disorders, these treatments have been incredibly successful for a wide variety of diseases.

However, with more advanced treatment comes a more complex supply chain. Shipping immunotherapy drugs presents unique challenges—most notably because these drugs are time sensitive and personalized for individual patients.

RELATED: Cold Chain Validation Best Practices Including Immunotherapy [WEBINAR]

So what challenges do we continue to face in the supply chain as the development of immunotherapy drugs rapidly evolves? And what opportunities are available to improve supply chain logistics? 
 

#1: The fragility of immunotherapies

One common type of immunotherapy uses monoclonal antibodies. Monoclonal antibodies are usually developed in an animal and then hybridized for use in a human’s immune system.

While these have been successful in treating COVID-19 and many other viruses and diseases, monoclonal antibodies increase fragility due to their size and complexity compared to conventional pharmaceuticals. They are particularly sensitive to shock and vibration and are easily denatured if exposed to temperatures outside of a very tight range.

As a result, additional precautions around shipping include cushioning packaging and extensive thermal insulation. Furthermore, the antibodies are studied against their shipping conditions in qualification studies, where they are exposed to conditions typically encountered during the logistics process.
 

#2: A unique starting point for T-cell therapies

Another challenge that companies face is the supply chain and logistics for T-cell therapies. In typical pharmaceutical manufacturing, the drug product is produced and manufactured in a plant and then stored and shipped to a determined location to be sold and used. However, for T-cell immunotherapy, the “supply chain” starts with the patient when their blood is drawn.

The blood is then shipped from a blood collection center to a specific lab where the cells are changed to be able to fight a specific disease, and then returned to the hospital to inject back into the patient. Shipping blood products is very challenging for several reasons. Blood products are sensitive to environmental factors such as temperature, shock, and vibration. They are perishable and must be shipped in accordance with Category B infectious substance federal regulations.
 

#3: The missing manufacturing link in the supply chain

Immunotherapy drugs are personalized for each patient based on their own antibodies, shifting the typical manufacturing step in the supply chain. The use of the immunotherapy process adds another challenge because it can be very time sensitive. The diseases being treated can progress rapidly, requiring an effective and efficient supply chain and logistics.

Immunotherapy products need packaging that protects them from the expected hazards during shipping, and the methods by which they are shipped is usually as fast as possible. These products also sometimes need to be stored in deep frozen temperatures, which by itself requires unique shipping solutions that utilize liquid nitrogen in membranes to maintain temperature.
 

#4: A limited supply

With T-cell therapies in particular, there is a limited supply, adding more risk to the process. Normally, if drug product is lost due to a problem in the supply chain & logistics for any reason, there is more supply available. With T-cell therapies, the supply is limited to the amount of blood that the patient can give, which is often even more limited with an ill patient.

Modality Solutions conducts risk assessments with immunotherapy supply chains and determines where the highest risk activities take place. If a shipment is lost, it can be a very long time before another batch can be made. The immunotherapy process is also extremely expensive as there is no scaling up that can be done due to the treatment being specific to the individual.
 

Maintaining control of the immunotherapy supply chain

Maintaining control of the supply chain & logistics for immunotherapies, where the allowed conditions are even more strict than normal, is very difficult. Immunotherapy drugs add risk due to the circumstances where these therapies are used.

Modality Solutions has assisted several clients that utilize monoclonal antibody treatments. For these clients, Modality Solutions writes a validation master plan (VMP), then conducts risk assessments utilizing HAZOP (Hazard and Operability Study) methodology and develops mitigation strategies in accordance with the plan.

The HAZOP methodology identifies what the risks to a supply chain are, and then analyzes them based on severity, likelihood of occurrence, and chance of detection. With immunotherapies, the overall severity of any errors is high, which is why the HAZOP methodology is better at identifying the risks that need to be mitigated.

Using these tools, Modality Solutions helps ensure safe shipment of immunotherapy treatment. Contact our team to learn more.

Cold Chain Industry Leader, Modality Solutions, is Silver Sponsor and Exhibitor at Biomanufacturing World Summit

Cold Chain Industry Leader, Modality Solutions, is Silver Sponsor and Exhibitor at Biomanufacturing World Summit

Written by Modality Solutions

Posted on: October 15, 2018

Silver Sponsor and exhibitor, Modality Solutions, joins a “who’s who” of pharmaceutical decision makers at the Executive Platform’s Biomanufacturing World Summit (BMWS18) in San Diego on October 29-30.

The BMWS18 brings together pharmaceutical executives, cutting-edge technology providers and media partners for its North America premier biologics event. President Gary Hutchinson and Principal Daniel Littlefield will attend the conference and participate in one-to-one meetings with other leaders in biopharmaceutical manufacturing and cold chain management.

BMWS18 participants learn about and discuss:

• Industry challenges and opportunities
• Quality as a culture, QbD, ICH guidelines
• Capacity management
• Supply chain management
• New processes and technologies
• Working with external partner

Modality Solutions is committed to helping biopharmaceutical companies explore cost-reduction strategies, understand changing industry standards, and initiate risk management processes to ensure compliance, quality and product integrity.

Click here to view the Modality Solutions BMWS18 press release.

The Design of Clinical Trials in Pharmaceutical Development

The Design of Clinical Trials in Pharmaceutical Development

Written by Modality Solutions

Posted on: September 25, 2018

Clinical Trials in Pharmaceutical Development, African woman walking down dirt road

Explore the Clinical Trial Design Including the Unique Cold Chain Logistics Challenges for Clinical Trials in Developing Countries

Clinical trial design is a defining step in the pharmaceutical development process that determines whether a candidate product will reach commercialization. An often-overlooked aspect of clinical trial design is the logistics of transporting the product. This may seem trivial due to the easy access to adequate storage facilities, packing materials, and shipping methods in developed countries. However, the storage and transportation of drug products while operating in emerging market countries presents problems with reliable power, availability of resources and services, and additional exposure to transport hazards. Although the challenges may be quite different, the theory and solutions to these problems are the same for both developed and developing countries.

Modality Solutions has worked on clinical trials in multiple countries in Western Africa, specifically related to candidate vaccines and treatments for the Ebola virus disease. Vaccines and treatments were shipped to a main hub in the country via jet aircraft followed by ground transport via car or truck. After the hub, these medicines were distributed to remote areas where even running water was not commonly available. The storage and transportation of these temperature-controlled drug products was no simple challenge. There was no access to dry ice, refrigerated trucks, or expensive packaging materials in the region.
 

Key Considerations for Operational Planning in Sub-Sahara Africa

Based on our cold chain and engineering experience, we developed procedures for the storage and distribution of vaccines, treatments, and patient samples (e.g., blood samples) within each country and for return to labs in the United States. These procedures needed to be adapted from standard procedures to account for the limited availability of materials and equipment in Western Africa. For example, due to inconsistent power supply within the region, many clinical sites relied on generators as the primary source of power. Secondary and tertiary generators were also used for backup power supply. Having extra generators, freezers and other types of equipment minimized potential downtime due to equipment failure.

Furthermore, the development of these procedures required personnel to travel to relevant facilities and ensure that the requirements of the SOPs were not exceeding the capabilities of equipment and personnel at each site. Considerations were made based on specific equipment available at each site and level of experience and knowledge of supporting staff. Additionally, Modality Solutions trained local staff on the SOPs and discussed if the procedures aligned with site capability. For example, the proximity of trained staff to a site affected the emergency response plans. At some of the more remote locations, personnel qualified to directly handle the product would not be able to arrive for a few hours. This changed the response to a power outage or freezer breakdown compared to sites where personnel could arrive in minutes.

The final procedures governed consistent performance of day-to-day operations at the facilities, maintenance plans for key equipment such as freezers and generators, monitoring and alarm systems for storage and transport, conditioning and packout of passive shippers, use of stock management systems, and emergency response plans. Documentation of routine maintenance and temperature storage along with archival of temperature data showed consistent adherence to operating procedures. Review of temperature data from storage and distribution proved the ability of the equipment and logistical design to maintain product temperature requirements.
 


 

Clinical Trial Distribution Design

The design of clinical trials in pharmaceutical development and the data generated is particularly sensitive to distribution because of the work that goes into evaluating product performance. If a drug product does not perform as expected, the investigation may need to address the formulation itself during on-going pharmaceutical development. Ensuring that the clinical trial logistics network adequately handles the clinical trial material assures us that any negative results are not caused by damaged product being used in the trial. Mishandling of product can not only effect results, but it can also be expensive to replace the product and more importantly, the clinical trial data that was lost. This is equally true for clinical trials in developing countries.

While the logistical problems of clinical trials between developed and developing countries may differ, the theory and solutions to these problems are the same. Minimizing the risk to transport hazard exposures such as temperature, shock, and vibration will result in ideal clinical trial data design and operation. Three strategies to minimize this risk are:

  1. Use centrally located distribution facilities
  2. Use robust packaging to protect drug products
  3. Prepare backup plans for temperature-controlled storage and distribution

Designing a logistical network which includes a centrally located distribution facility is advantageous to maintaining product quality. Using centrally located distribution facilities lowers the number of potential distribution hubs and shortens the duration of transport lanes. Minimizing the number of distribution hubs through the logistical network results in fewer exposure to shock events. Shorter lanes minimize the cost of transportation and exposure to transport hazards. Applying cost-saving strategies to transportation will allow for increased funding to be applied in the clinical trial design to increased capabilities of the storage facility:

  • Temperature control systems
  • Warehouse management or inventory control systems
  • Security
  • Infestation control
  • Backup power and backup equipment
  • Monitoring and alarm systems

 

Robust Thermal Packaging Protection

The use of robust packaging to protect drug products is even more important for clinical trial operation than during commercial transport. The data from a clinical trial is highly dependent on the assumption that the administered drug was of adequate quality. Damage to the drug product during transport could result in a negative response in a patient, potentially resulting in an unnecessary failure of the clinical trial. An unnecessary failure could cost a company millions of dollars and extremely delay a product’s commercial approval. Therefore, design, selection, and testing of packaging for clinical trials should exceed the typical requirements of commercial packaging.
 

Conclusion

Preparing for unexpected delays and equipment failure can save clinical trial product and data. All clinical trial operations should have response plans for emergency events that may affect storage and distribution. These events include, but are not limited to, power outages, equipment failure, and road closures/detours. Any of these could expose product to transport hazards that are more extreme and/or for a duration greater than expected. Response plans should include the use of backup refrigerators, freezers, generators, passive solutions, and/or alternate sites. Also key in emergency response is the proper use and installation of monitoring and alarm systems. Alarm systems may allow personnel to implement the correct response prior to damage or loss of product. A correct response to adverse events may save a clinical trial operating in a difficult environment.

Utilizing the above strategies will improve the design of clinical trials in pharmaceutical development and help to protect the quality of clinical material during distribution. This approach ensures that valid data is collected during the trial. Not doing so can greatly increase the cost of a clinical trial or even runs the risk of an adequate drug formulation failing in the clinical trial stage due to inadequate material handling.

To learn how Modality Solutions can help with your clinical trials, contact us or read more about our clinical trial operations services.
 

More on This Topic:

Video Interview: Modality’s Dan Littlefield discuss the challenges of working in a conflict environment on Ebola virus clinical trials.

White Paper: Cold Chain Process Validation Guide

Case Study: Leidos and FHI

Blog: https://www.modality-solutions.com/challenge-developing-clinical-trial-ebola-vaccine/

New Cold Chain Process Validation Guide Announced

New Cold Chain Process Validation Guide Announced

Written by Modality Solutions

Posted on:

Modality Solutions new guide helps biopharmaceutical companies meet cold chain regulatory requirements during process validation. You will receive valuable insights into validating your integrated cold chain while enhancing your regulatory reputation.
 

The paper:

• addresses economic and regulatory pressures, accelerating costs, technology changes, and the need to constantly adapt your business model.

• provides solutions that deliver value in your supply chain while enhancing your regulatory reputation.

• Explains the need to assure product handling, storage, transportation, and distribution are being performed appropriately for five key environmental hazards.

• Learn how to integrate your cold chain to ensure all processes are working together to achieve the common goal of delivering quality medicines to the patients who need them.

 
Click here to view the Cold Chain Process Validation Guide press release.

New Drug Product Formulation Testing White Paper Announced

New Drug Product Formulation Testing White Paper Announced

Written by Modality Solutions

Posted on:

Modality Solutions new white paper provides a new approach to transport simulation for drug products. The goal of the drug formulation simulation study is to concurrently expose drug product to all five environmental hazards – temperature, shock, vibration, humidity, and pressure – as they occur during real-world distribution.
 

The white paper examines the effectiveness of simulated transport studies. It uses a holistic methodology to testing the multiple hazards in cold chain transport. In doing so, the industry best practices of the following areas are explained:
 

• Hot and cold exposures to a single shipment

• Non-accelerated vibration

• Exposure to multiple pressures

• Parcel-based transport simulation testing

 

Regulatory expectations are driving leading companies to incorporate simulated transport testing into both their development and stability programs. Learn how Modality Solutions’ Advantage Transport Simulation Laboratory™ enables the study of transport stresses on early-stage drug formulations during the development process and verification of the robustness of the commercial drug product formulation.
 
Click here to view the Drug Product Formulation Testing White Paper press release.

 

Blockchain Applications in Pharmaceutical Serialization

Blockchain Applications in Pharmaceutical Serialization

Written by Modality Solutions

Posted on: June 15, 2018

Blockchain Applications

While blockchain is typically associated with bitcoin or other cryptocurrencies, it is actually a data format that is being implemented across industries. In the food supply industry, IBM has partnered with companies like Dole, Nestlé and Walmart in an effort to regulate food safety. IBM has also entered the jewelry market, as blockchaining enables consumers to track that their diamonds are being ethically sourced. Outside of industry, the United Nations and the World Identity Network announced an initiative known as “Blockchain for Humanity”, which will build a digital identity network for children without birth certificates.

In addition to these industries and organizations, life sciences companies are implementing this technology to increase security, prevent counterfeiting, and allow for better tracking of their products. A Health IT Analytics (2017) article reported that 22 percent of life science companies are presently using or experimenting with blockchain technology.1 A survey used in the same article indicates that more than 80 percent of those surveyed believe that blockchain usage will be widespread within five years. While it is difficult to fully understand the mathematics and networking behind blockchain, it is fairly easy to adopt and implement because the technology itself is open source. So, what is blockchain? And how can it possibly benefit the pharmaceutical serialization process?


Blockchain is a data format that uses previous entries in a sequence as part of the current entry. In a simplified sense, think of it like this:

If a serialization program gave a vial a serial number of “12345,” typically the next number would be “12346.” This is sequential serialization. With this process, a person could easily make counterfeits and give serial numbers that appear real. However, with blockchain serialization, the next number could potentially be, “45267” instead of “12346.” The first two numbers are the end of the first serial number, the third number is the “content” of the block, and the last two numbers are determined by an algorithm that is based on the rest of the numbers in the block. The number after that would be “67390.” Both of these steps used the same, incredibly simple, one-step algorithm to generate, and yet it is difficult to guess what the next number in the sequence would be. Because blockchain requires a person to not only know every serial number in sequence, but also the algorithm to determine the next set of numbers, it is near impossible to guess or create a valid serial number.

How does this benefit the pharmaceutical serialization process? Counterfeit pharmaceuticals rely on being able to guess serial numbers to create a product that seems legitimate. In 2012, it was revealed that counterfeit versions of Roche’s cancer drug Avastin had been circulating through the United States. Development of copying and printing technologies along with the ability of online pharmacies to conceal the source of their products enable counterfeiting.2 If someone has a single vial from a sequential serialization program, they can make a batch of serial numbers that are valid. Because the serial number is one of the only ways to verify a product, these counterfeits will make it to the patient. Blockchain prevents this by making it effectively impossible to guess a valid number.

There is actually another way blockchain technology can help with serialization. The other part of serialization that is important is creating traceability on where the product has been. Track and trace technologies, like serialization, have allowed pharmaceuticals to be followed down the supply chain. A few examples of blockchain being used for traceability exist transnationally. In April of 2017, IBM launched a partnership with Chinese supply chain management firm Easysight Supply Chain Management to introduce the Yijian Blockchain Technology Application System.3 Imperial Logistics has also made a notable stride, as they have partnered with One Network Enterprises to provide a serialization and authentication process for distribution.4 Drug pedigrees are another form of track and trace technology that record the details of drug distribution until it reaches the dispenser. The final regulations for pedigrees were drafted in the United States in 1999.5 More legislative action was taken toward pharmaceutical traceability in 2013, when US Congress enacted the Drug Supply Chain Security Act (DCSA). The Act outlines steps to build an electronic system to identify and trace drugs that are distributed throughout the United States.6 This system would also aim to improve detection and removal of counterfeit drugs from US supply chains.

The serialization system, although newer than pedigrees, is promising in protecting pharmaceuticals. Applying blockchain technology can help with the traceability function of serialization. Besides the serial numbers themselves, the data on what vials are going where can also be in blockchain format. Again, you begin with a special number at the beginning. Then, the block “contents” would say something like this:

“Vial 1 goes from Point A to Point C – confirmed by point C”
“Vial 3 goes from Point A to Point B – confirmed by point B”
“Vial 1 goes from Point C to Point B – confirmed by point B”
“Vial 2 Goes from Point C to Point A – confirmed by point A”

When looking at this list of contents, you can see every movement every vial makes and you can see who confirmed those movements. After so many lines of content, the ending number will be determined for the block. Again, this number will be a function of the beginning special number, but also the content itself. Once that number is determined, the next block of content begins.

Now think of how this works in practice. Say someone tried to change the data to say that vial 1 ended at point D instead. When that is changed and the block is recompiled, the ending number will change. This change will change every block afterwards, which will signal to everyone looking at the records that the data in the block is counterfeit.

Each transaction is signed by the people who made them. Then, the next part of blockchain data comes in to play. When a block is “closed” by the ending number and added to the chain, that block is then broadcasted to everyone on the network. If that block is not compatible with the previous block someone received, they will know there is a counterfeit record in the chain and can take steps to remediate it. The other way this is beneficial is that if someone receives extra vials, they can check the data in the block chain to see where those vials came from, where they should be, or if they are counterfeit product.

Until recently, encrypting serialization this way is not something that was even considered. However, with the rise of imitation and counterfeit products, as well as potential theft, patient safety is becoming a significant issue along with the potential economic harm that can come from bad product.

 

Sources:
1. https://healthitanalytics.com/news/83-of-life-science-execs-expect-healthcare-blockchain-in-5-years
2. https://www.reuters.com/article/us-drugs-counterfeits/fake-avastin-shows-very-little-protects-drug-supply-idUSBRE82B00120120312
3.https://www.pharmaceutical-technology.com/features/blockchain-pharma-opportunities-supply-chain/
4.https://www.onenetwork.com/2018/03/blockchain-serialization-authentication-medical-supply-chain/
5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617666/
6.https://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct/

The Impact of Setting the Temperature Control Unit (TCU) to a Cycled Setting

The Impact of Setting the Temperature Control Unit (TCU) to a Cycled Setting

Written by Modality Solutions

Posted on: May 21, 2018

The Impact of Setting the Temperature Control Unit (TCU) to a Cycled Setting

The growing importance of refrigerated trailers in the pharmaceutical industry

Refrigerated trailers in the pharmaceutical industry are important now more than ever. In the United States, 14 million tons of pharmaceutical products are shipped by truck every year.1 In Europe, however, most pharmaceuticals travel by air or sea. Cold chain spending worldwide is estimated to account for $15 billion in 2018 out of a $182 billion biopharma logistics market.2 It is interesting to note that in the United States specifically, data indicates that most prescription products are handled two or three times before reaching its point of selling. It is imperative, therefore, for appropriate measures and precautions to be taken between each travel point, especially for refrigerated pharmaceuticals. The use and transport of refrigerated pharmaceuticals is on the rise, as it is projected that by 2022, 30 of the top 50 selling drugs will require refrigeration.3 The expanding need for refrigerated trailers has led to an increased need to run tests to compare temperature cycles.
 
What is the impact of the cycled setting?

Cold chain transportation in refrigerated trailers present a number of challenges in pharmaceutical supply chains. These challenges include inadequate packaging, delays, and most notably, interrupted temperature and climate control.4 Regarding this final obstacle, we have results to share. While running a series of controlled tests for a client, the temperature control unit (TCU) was inadvertently set to cycle mode, allowing us to compare and contrast the results of a “continuous” versus “cycled” setting.
 
Most if not all carriers of temperature sensitive pharmaceutical products have clear instructions to set the temperature control unit (TCU) to run in “continuous” operation. Why? The fan and compressor unit remain active and operating at all times to minimize the temperature differentials within the trailer. But, the TCUs have an alternate setting for fuel saving. In this mode, the fan and compressor will cycle off when the set point temperature is achieved. The TCU will “wake up” when the thermostat temperature reads 3 to 5 degrees from the set point.
 
The temperature of the air passing thru the supply vent of the trailer is an indirect measurement of the mode of operation of the TCU. In continuous mode the extreme in temperature variation is plus or minus 3 degrees of the set point. In cycle mode, the lag time to activate the TCU can result in temperature spreads of over 5 degrees from the set point.
 
There is additional variance in the cycle mode because the fan operation also contributes to the overall distribution of temperatures within the trailer. The chart below is an example of cycle mode for a CRT at a cold exposure. The temperature variations violate both sides of the CRT limits.


 
Clearly, the cycle mode will not meet the tight tolerance for refrigerated (5C) shipments. Controlled room temperature (CRT) shipments are also placed in jeopardy depending on the specific definition of CRT. Similar conclusions can be made about the cycle mode for the hot exposure. The results are demonstrated in the chart below.


 
The chart below is an example of continuous mode for a refrigerated (5C) shipment at a cold exposure. The temperature variations are well within normal limits.


 
The chart below is an example of continuous mode for hot exposure. As seen by the graph the results were similar.


 
If the cycle mode is used at all, it should only be for frozen shipments when the setpoint is safely set well below the critical high temperature. The fuel savings between the two modes are less than $20 for a 24-hour period. These savings cannot justify the risk of wider trailer temperatures for either refrigerated or CRT pharmaceutical products.
 

Sources:
1. Basta, Lipowicz, 2018 Biopharma Cold Chain Sourcebook (Brooklyn: Healthcare Commerce Media Corp, 2018)., 51
2. Ibid, 63
3. Ibid, 23
4. https://unitedworldtransportation.com/4-common-cold-chain-logistics-problems-truckers-face-tips-solving/

Cold Chain Experts Modality Solutions Announce Its New Content-Rich Website Experience

Cold Chain Experts Modality Solutions Announce Its New Content-Rich Website Experience

Written by Modality Solutions

Posted on: April 18, 2018

Cold chain experts Modality Solutions is pleased to announce that its new website is designed to educate users on the varied ways to work with an established one-stop cold chain provider to best fit their specific needs.
 
HOUSTON, Tex. April 18, 2018 Modality Solutions LLC, a privately-held full service engineering firm that provides insight into cold chain thermal packaging, monitoring and controls, transport validation, and controlled-environment logistics, is pleased to announce it has transformed Modality-Solutions.com into an engaging, content-rich, all-device compatible website.
 
With Modality Solutions, three firms – regulatory filing support, cold chain operations, and an integrated expertise staffing firm — are combined as your single source for cold chain expertise for the life sciences industry. The new website educates users on the varied ways to work with an established one-stop cold chain provider to best fit their needs. Visitors are encouraged to download case studies, sign up to receive blog posts, and schedule a free one-hour, no obligation consult.
 

Modality Solutions’ new website is specifically designed to:

  • Beautifully display content on all devices—mobile, tablet, laptop and desktop.
  • Vastly improve user experience through well-organized service offerings coupled with case studies to reinforce Modality’s areas of specialization.
  • Make sure all service offerings have a cold chain focus and features regulatory filing support, operations, and staff augmentation information.
  • Showcase the depth of the company’s experience with clients such as Bristol-Myers Squibb, Lilly, Janssen, Shire, TEVA, Abbott Vascular and more.
  • Be highly scalable and easy to add fresh, relevant content through an intuitive content management system for our industry.
  • Provide powerful analytics so that Modality Solutions can measure what is most important to its users and constantly tailor and improve its offerings and blog content.

 
“Our new website is all about sharing relevant cold chain logistics, operations, and regulatory information with life science decisionmakers worldwide,” said Modality Solutions President, Gary Hutchinson. “We are uniquely positioned to provide an outstanding web experience where visitors get a chance to better understand our unique approach to cold chain challenges delivered through actual case studies. We want to share our expertise with other professionals in our industry. Web developer, Shovel Creative, listened to what we wanted to achieve and helped us deliver it to our highly regulated target market of public health, life science, and food industry professionals. Tara and her team really came through for us!”
 
“Gary and the Modality Solutions team are deep subject matter experts in what they do. During our comprehensive intake process, we were blown away by both their knowledge in cold chain as well as how every team member is involved in every project,” said Shovel Creative CEO Tara Kester. “You always get a C-level executive assigned to your account, which is rare today. It’s easy to make clients like Modality Solutions shine.”

 

About Modality Solutions, LLC
Founded in 2011 Modality Solutions integrates cold chain operations systems ensuring regulatory compliance, product quality, and patient safety by combining best practices of process validation, systems qualification, and risk assessment. Modality delivers proper documentation for qualification, validation and training aligned with the necessary procedural controls, visual controls, and monitoring. Key areas of service are: ensure regulatory compliance; deliver cold chain thermal packaging design / qualification and controlled-environment logistics solutions; conduct transport simulation testing; provide staffing augmentation; decrease development cycle times for a faster route-to-market; develop transport validation strategies to support global regulatory applications; and clinical trial operations. For more information, visit modality-solutions.com.