New FDA Guidelines on Gene Therapy IND Process A Significant Step Forward

Thu, Feb 06, 2020 | By Phil Wilson, Sr. Vice President, Global Logistics and Supply Chain

Recently the FDA’s Center for Biologics Evaluation and Research issued its guidance to the regenerative medicine industry on best practices for submitting an IND application to the FDA for gene therapies. The document provides valuable guidance on key aspects of the IND process and the potential pitfalls for errors or key omissions, but it has left key logistics aspects vague as the regenerative therapy industry works in parallel to develop best practices.

LongTallquoteTemperature controlled shipping is not new for the pharmaceutical industry; developers have been shipping valuable temperature-sensitive products around the globe for years without any major issue or concerns. For the most part, the industry has an attitude that this process is figured out. The new guidance document from the FDA simply says that the industry should “describe any related shipping processes and procedures. Although icould be tempting for some to rest on their laurels and say they have it under control, nothing could be further from the truth with cell and gene therapies.  A tremendous number of pharmaceutical products require a cold chain solution to ensure the drug or vaccines we use every day arrive in a safe, secure and viable manner, but none are as sensitive, fragile, and valuable as cell and gene therapies. Many cold chain logistics professionals may spend their entire career in the industry and never need to ship anything below -80°C (with dry ice), but most cell and gene therapies must be stored and shipped below -150°Ca temperature band that brings unique and critical requirements. 

In the cryogenic preservation process, human cells become thermodynamically stable below -137°C. This is a key milestone in the preservation process and a threshold in creating stability in the cells for storage and transportation. From this point, further preservation to a cryogenic state is relatively easy. Ensuring the product stays there during the transportation process from the manufacturing facility to the point of care is critical.  

Generally, there are two options for shipping material in a cryogenic state: LN2 in a liquid phase and LN2 in a dry vapor form. In the liquid phase, regulations require the goods to be shipped as dangerous goods under UN 1977, limiting the transportation methods and routing. Shipping via dry vapor, however, maintains cryogenic temperatures in a nonliquid form and as such, is not considered dangerous goods and can be shipped as general cargo, which creates many more logistics options. The key for either LN2 option is to monitor and maintain the temperature throughout the shipping cycle. To help minimize the risk during transportation one should ensure the shipping system being used can endure the rigors of the transportation process. This should include a vetted and qualified shipping system for the cryogenic vessel; outer purpose-built enclosures to reduce shock, tilt events and maintain security; and active monitoring equipment to ensure the condition of the shipment is maintained through the entire end-to-end shipping cycle. With active monitoring, if an adverse event does happen in transit, it can be proactively managed to maintain the stability and integrity of the product being moved.   

In January 2017, the FDA awarded a one-year contract to Nexight Group and the Standards Coordinating Body (SCB) to engage with experts to recommend processes and outline a strategic plan for developing standards in regenerative medicine and advanced therapies. This work has helped to lay the foundation for standards development in regenerative medicine research and product development.  

Currently the SCB is attempting to create standards to mitigate risks in the regenerative medicine supply chain by bringing together industry experts from a range of stakeholder organizations across the regenerative medicine communityThe scope of the SCB covers all aspects of manufacturing, testing, and the supply chain – including the transportation requirements of cells for therapeutic use, which is specifically covered under ISO/TC 276 Working Group 4. 

The SCB has coordinated the drafting of a combined standard  incorporating perspectives from cell therapy suppliers and users  to define minimum requirements for regenerative medicine information technology infrastructure and transportation, shipment tracking and monitoring protocols, chain-of-custody requirements, and centralized logistics management systems. This new ISO standard is due to be finalized in June 2020. Chain of Compliance

Cryoport’s Chain of Compliance™ process was put into place in 2019 in anticipation of the creation of the ISO standards and regulatory bodies around the world adopting more stringent regulations for 
regenerative therapies.  Chain of Compliance provides a comprehensive record during transit of the custody of each patients' therapy, the condition of the therapy, the identity of the patient attached to each therapy in a shipment, as well as full traceability of the equipment that is used in the process.  By contributing to the SCB and by leading the way in creating a system to mitigate as much risk as possible, Cryoport has established the best solutions for maximizing success for all of the patients being treated. 

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