The Design of Clinical Trials in Pharmaceutical Development

The Design of Clinical Trials in Pharmaceutical Development

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.

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/