Chemistry Manufacturing and Controls (CMC) for gene therapies is one of the biggest obstacles when moving towards regulatory approval and presents a significant risk to the success of new gene therapy drug candidates today.

A key aspect to the CMC documentation of such complex biological products is the application of the Quality by Design (QbD) principle: A rationale of quality being achieved by process design rather than relying on final quality testing alone.

The work presented here provides a framework to illustrate the concept and initial thoughts on the use of the QbD concept for gene therapy, specifically Adeno-Associated Virus (AAV) manufacture. For the four most prominent AAV upstream manufacturing platforms, process and product related impurities as well as adventitious agents are identified.

A preliminary hazard analysis of the impurities allows the identification of the critical quality attributes in AAV manufacture for each step, from media filtration in upstream processing (USP) to final sterile filtration of the AAV drug substance.

With combined knowledge taken from literature, industry and in-house experience, critical material attributes and critical process parameters are assessed. This work shows that a wide process understanding is already created within the industry despite AAV manufacture being a new field. This knowledge may provide a template for future development of AAV-based biotherapeutics.

We invite you to read Pall Corporation’s latest white paper, Quality by Design (QbD) for Adeno-Associated Virus (AAV). Download today!