Last week, at The Bioprocessing Summit in Boston’s Seaport district, we heard from industry leaders on their CMC and analytical strategies for developing gene therapy products. This was a timely discussion given the recent news on late stage products being investigated (Novartis’ Zolgensma®) or delayed (Bluebird Bio’s Zynteglo®) due to CMC issues.  The general consensus was to use an orthogonal, phase-appropriate approach geared toward better understanding the critical quality attributes (CQA) and critical process parameters (CPP) of these complex products.  Unlike more established therapeutics like vaccines and monoclonal antibodies, a greater investment must be made in CMC for gene therapies to ensure the appropriate analytical tools are in place for consistent and scalable manufacturing. This upstream investment is intended to balance out long term development costs due to the expedited path for licensure that accompanies many gene therapies.

One of the key parameters used to define CQA and evaluate the impact of manufacturing processes is the potency assay. Measuring potency of a vector-based gene therapy product requires a matrix-based approach to evaluate the following steps: 1) infectivity of the vector into the target cell, 2) transcription of the gene of interest, 3) translation to the protein of interest, and 4) functional activity of the expressed protein. Early stage potency assays may focus on infectivity and expression only, using standard analytical methods such as qPCR, RT-qPCR, ELISA, and Western Blot. However, by Phase III, a quantifiable assay must be in place to measure functional potency, which may require more specialized equipment such as LC-MS/MS or high content imaging (HCI).  All methods, whether standard or specialized, must be suitable for qualification, validation, and testing in a cGMP environment.

ACF Bioservices has a long history of developing functional potency assays across diverse product types with custom and complex MOA. Our experts will support your phase-appropriate strategy by bridging the gap between R&D and cGMP and providing commercially viable potency assays.

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Additional Resources:

Potency Assay Guide: Request a download of our new eBook, “Understanding Potency Assay Development for Cell & Gene Therapy Products”
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Case Study: Potency Assay for AAV Vector Encoding RPE65 – View Spark Therapeutics poster which includes Absorption Systems’ data
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