Apotex Inc. (Apotex) was founded in 1974 and is currently the largest Canadian-owned pharmaceutical company. From its two original employees and its 5,000 square foot beginning, the company has grown to employ more than 10,000 people in research, development, manufacturing, and distribution facilities worldwide, which produce more than 300 generic pharmaceuticals in approximately 4,000 dosages and formats. The company's pharmaceuticals are exported to over 115 countries around the globe. Export markets represent an ever-growing portion of the total sales. Apotex has also established a presence through subsidiaries, joint ventures, or licensing agreements in countries including, but not limited to: Australia, Belgium, Czech Republic, Mexico, Netherlands, New Zealand, and Poland.
The Apotex management team wanted the following Modality Solutions’ assistance with Apo-Filgrastim DP (pre-filled syringes) being manufactured, tested, and released at Intas (Ahmedabad, India):

  • Assessing the product quality following simulated study under the worst-case conditions in terms of shaking, vibration, shock, pressure, and temperature excursions that the product would encounter based on the shipping route and method(s) of transport.
  • Demonstrating that the shipping configurations for its final proposed commercial packaging format are capable of maintaining the recommended storage temperature at the anticipated minimum and maximum load for the worst-case anticipated shipping route.

The objective was to prepare the management team for the FDA review meeting. This meeting allows the FDA to review the approach and the protocols, provide other guidance, and approve the path forward.
The focus of the engagement was to:

  • Identify the correct simulation studies to demonstrate DP quality during transit.
  • Review and compare EU shipping studies to US distribution and explain their value to the FDA reviewing team.
  • Propose and author a simulation study protocol.
  • Prepare the management team to discuss approach and gain approval on path forward.

Value to Company
The completion of the following deliverables helped determine measures of success:

  • US supply chain map and process flow diagram.
  • Simulation study distribution profiles and protocol test plan.
  • Technical report integrating EU distribution testing in US approach.
  • Simulation study protocol for review with FDA.
  • Presentation and training for FDA approval.
  • Specific value of this project included:
  • Access to our experience in development of multiple simulation studies to assess product for FDA review and approval.
  • Sophisticated transport simulation testing laboratory in an FDA-approved, GMP-compliant facility in Bloomington, Indiana.

The detailed approach on the assistance that we provided to Apotex included:

  • Mapping US supply chain and creating process flow diagram. The US supply chain map was used to create the process flow diagram. The process flow diagram shows the detailed steps in the US supply chain designed into the transport simulation study.
  • Designing distribution profiles and creating the test plan. The process flow diagram was translated into distribution test profiles for temperature, shock/vibration, and pressure. Once the distribution profiles for each environmental hazard was established, a test plan using ISTA 4A/B method was created for the protocol.
  • Reviewing EU distribution testing reports. A technical report summarizing the applicability of the distribution study for the US supply chain was authorized for review and approval by the Apotex management team.
  • Authoring proposed protocol. The US supply chain map, process flow diagram, distribution profiles, test plan, and summary technical report was used to create the proposed protocol for simulation testing. This protocol was reviewed with the FDA in February 2016 to confirm path forward.
  • Reviewing FDA presentation. The proposed path forward for simulation testing and thermal packaging qualification was presented to the FDA. This presentation was reviewed and edited to clearly identify proposed path forward.

Apotex and Modality Solutions worked together to ensure scheduling, access to key personnel and documentation, on-site administrative support, and off-site technical support was available. Per our joint agreements, we informed each other of any intelligence or findings that would impact the success of the project so that alternatives could be considered. Hence, the proposed path forward for simulation testing and thermal packaging qualification was presented to the FDA.