Alcami

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Testing the physical integrity of sublingual tablets in the pharmaceutical supply chain.

Alcami is a top contract drug development, manufacturing and analytical services company providing solutions to pharmaceutical, biotech and healthcare clients. It has developed more than 450 drug products supporting clinical trials over the past 30 years. Their industry-leading accuracy, timeliness and customer service is considered the gold standard among peers. Their experienced teams work with customers to integrate their laboratory operations seamlessly with their in-house processes. Alcami operates two cGMP contract manufacturing facilities – one in Charleston, South Carolina for parenteral products and the other in Wilmington, North Carolina for oral solid dose products.  All facilities are US and EU compliant and process a variety of pharmaceutical products, including controlled substances (Schedule II-V) and potent compounds.  Alcami manufactures and packages clinical supplies ranging from Phase I to Phase III, with scale-up and validation support to address commercial launch and supply. 

Objectives
The Alcami facility in Wilmington, North Carolina, specializes in manufacturing oral solid dose forms to support Phase I to Phase III clinical production through commercial launch and supply.  The facility features flexible suites and low/high shear granulation and spray/fluid bed drying capabilities to support a variety of oral solid dose products and is equipped to support an array of delivery methods, including immediate and extended-release tablets and capsules. The development team recognized the need to conduct physical integrity studies with representative bulk packaging on two types of sublingual tablets (one is round, and one is triangle) that possess transport challenges due to their inherent fragility. The studies focused on tablet quality when exposed to shock and vibration consistent with over-the-road transport while other environment hazards (e.g. temperature, humidity) are held constant. The goal was to design a suitability for use design of experiment to provide a comparison between the two tablet designs (round and triangle) during simulated shipping and handling conditions. The focus of the engagement was to:
  • Define and execute a comprehensive transport study to ensure physical integrity for two types of fragile sublingual tablet designs packed in representative bulk packaging.
  • Inspect post-transport quality of two types of tablets to testing protocols after simulated transport conditions.
  • Compare results and recommend best tablet shape based on testing results.
  • Recommend improvements to representative bulk packaging.
  • Reduce compliance risk by improving and updating current documentation in the quality management system.
Value to Alcami
TheAlcami management team selected Modality Solutions to address their objectives because of their experience in resolving these issues for the lifesciences industry and their fixed-fee approach. The team recognized four key value propositions for this engagement:
  • Access to experience in conducting transport studies in multiple jurisdictions (FDA, EMEA, etc.).
  • Learning opportunity across the organization to better understand current best practices in designing and conducting transport studies.
  • Proper documentation for compliance audits from regulators and customers.
  • Mitigation of potential product quality risks when shipping sublingual tablets.
Measures of Success
The deliverables were clearly detailed prior to engagement by intensely defining and diagnosing the situation, concerns, and challenges beforehand. By defining the objectives up front, agreeing on a fixed-fee approach, and tying deliverables to milestone payments, both teams could focus on collaborating to design and execute the required simulation studies. The objectives were:
  • Two (2) tablet shapes tested and compared against multiple concurrent environment hazards in the Advantage Transport Simulation Laboratory (TM) designed by Modality Solutions.
  • Recommendations on bulk packaging design improvements to ensure product quality was maintained during transport in the pharmaceutical supply chain.
  • Approved protocols and reports in the Alcami quality management system for the simulation transport study of bulk packaging options.
Methodology
As with the deliverables, the approach to meeting the objectives and providing the deliverables were agreed upon by both teams prior to engagement. This agreement on not only the deliverables, but also the methodology, ensured a cooperative partnership throughout the process. The steps were:
  1. Define simulated transport study to test physical integrity of tablets. A comprehensive transport study to test the physical integrity of tablets was designed.  Two (2) tablet options selected by Alcami were tested. The ISTA 4AB Procedure was used to design the simulation study. ASTM and other public test methodologies were used in the simulation procedure. ASTM D4169-09 Standard Practice for Performance Testing of Shipping Containers and Systems were consulted as required to design the simulation study in the test protocol in lieu of ISTA 4AB Procedure.
  2. Perform pre-execution inspection. A pre-inspection tablet sorting of a statistically relevant sample size were selected. Pre-execution inspection was conducted to Alcami standards using an ASNI standard and other appropriate public standards as defined and agreed to in the protocol. Both tablet types (round and triangle) were inspected to their specific inspection protocol. The pre-execution sampling for both tablet types were inspected on two (2) elements: visual inspection and weight.
  3. Execute simulated transport study. The design study protocols were executed in the Advantage Transport Simulation Laboratory (TM) to determine tablet capabilities to resist shock and vibration hazards in representative bulk packaging while other hazards (e.g. temperature, humidity) were held constant. The transport study was conducted with proper cGDP documentation in a simulation laboratory in an FDA-approved facility to ensure regulatory compliance. The simulated transport study was executed as a single continuous test at a specific temperature (profile or constant) as defined in the protocol. 
  4. Perform post-execution sampling and testing. A post-simulation statistical sampling of a statistically relevant sample size was selected. Post-execution testing was conducted to Alcami standards using an ASNI standard and other appropriate public standards as defined and agreed to in the protocol.  Both tablet types (round and triangle) were inspected to their specific inspection protocol.The post-execution testing was conducted on two (2) inspection elements: visual inspection and weight loss.
  5. Document results in quality management system. All study findings, response plan, and recommended bulk packaging required were documented in theAlcami quality management system. The successful technology transfer package for the protocols, results, and findings were provided for the review and approval by Alcami quality assurance professionals, external regulatory agencies, and customers.
Results
The resulting design and findings from the executed protocols confirmed the suitable for intended use of the bulk packaging design for the current and proposed transport lanes. This review confirmed that both the visual appearance and weight loss of bulk tablets were within the acceptable range as defined in the acceptance criteria of the protocol.