Scott Burger, MD
This is part one of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.
I. IMPACT OF STABILITY
Raw material and finished product stability, or shelf-life, is a crucial factor in development and commercialization of biologic-based products.
You want extended cell stability. It impacts nearly all aspects of operations, from manufacturing and logistics to patient scheduling and ease of use (Table 1). Stability considerations drive a variety of critical decisions, from location and number of manufacturing sites to transportation methods.
Without cryopreservation, cell therapy products prepared with conventional biopreservation media have quite limited stability, often as little as three days (see Regen Med and FDA-CBER Product Approval Information).
This necessitates releasing the product without final 14-day sterility testing results, overnight shipping, and administration shortly after arrival at the clinical site. Short shelf-life presents other problems as well, not the least that it is quite unforgiving of unexpected events, such as a patient whose treatment should be delayed due to illness on the planned treatment day, or severe weather delaying product transport.
Raw material stability also must be considered, particularly as living, metabolically active cells comprise the critical raw material used in cell therapy manufacturing. This often means stability of 1-3 days in conventional culture media, entailing overnight raw material transport, and with major consequences for manufacturing operations, capacity, and site location.
Cell-based products can be challenging to develop even under the best of circumstances. Lack of stability adds obstacles to commercialization, increasing operational complexity, cost, and risk of failure. (See biopreservation economics.) For most cell-based products, increasing product stability is perhaps the single most effective way to reduce overall operating cost and risk.
Optimizing storage conditions can improve stability significantly. Both cryopreservation and non-frozen (hypothermic shipping media) storage may be used.
See:
Biopreservation Stability (Part 2): Enhancing Stability – Cryopreservation
Biopreservation Stability (Part 3): Enhancing Stability – Hypothermic Storage
Biopreservation Stability (Part 4): New Reagents, New Methods – Effective Process Modification
