Cell and Gene Therapies take industry by storm

by Marian McKee, PhD, Vice President, BioSafety; Berangere Tissot, PhD, Director, Biochem Method Establishment & Biologics Characterization

DNA around a man There is no doubt that emerging new cell and gene therapies have taken the industry by storm. As a CRO, we have a unique perspective on this trend. Where we once saw small biotech popping up in various phases of development in this field, we now see big-pharma stepping in with all their influence. The M&A of these biotechs as well as the creation of new cell therapy divisions in big-pharma have led to a plethora of clinical phase programs. Each of these companies has faced a relatively uncertain analytical and regulatory obstacle.

Viral vectors used for gene and cell therapy as well as the raw materials used to manufacture these advanced therapies are all subject to testing either for quality control or characterization to insure product quality and performance. Manufacturing process consistency is mainly controlled by (1) raw material and reagent qualification programs, (2) in-process monitoring, (3) in-process control testing, (4) lot release tests, (5) traceability by using a chain-of-identity system, and (6) validation of the manufacturing process.

The regulatory agencies have all addressed these therapies at one level or another. In January 2020, the FDA published Guidance for Industry on the CMC for Human Gene Therapy IND. In this document, the FDA made clear that it “generally considers human gene therapy products to include all products that mediate their effects by transcription or translation of transferred genetic material or by specifically altering host (human) genetic sequences. Some examples of gene therapy products include nucleic acids (e.g., plasmids, in vitro transcribed ribonucleic acid (RNA)), genetically modified microorganisms (e.g., viruses, bacteria, fungi), engineered site-specific nucleases used for human genome editing (Ref. 2), and ex vivo genetically modified human cells.” This includes the viral vectors and the resulting CAR-T therapies. The agency also provided guidance for specific disorders, rare diseases, and testing for vector-specific safety concerns. Additional guidance is available in the USP including chapters <1046> Cell-Based Advanced Therapies and Tissue-Based Products which has been revised effective May 2020. Together with <1047> Gene Therapy Products and <1043> Ancillary Materials for Cell, Gene, and Tissue-Engineered Products, the USP includes guidance and compendial methods to address raw material and the cell therapy product testing.

Gene Therapy Testing Within the Advanced Therapy space, Eurofins has a history of offering cGMP-compliant CMC testing to ensure the identity, potency, purity, and safety of starting materials, intermediate products, vectors, and final drug products as well as support for manufacturing process development and validation. This includes testing of raw materials, cell and viral bank services, plasmid vector testing, lot release testing, and bulk and finished product testing. Within the Biopharma Biologics Testing group we have recently added analytical ultracentrifugation to support regulatory expectations around empty/full capsid analysis. Eurofins has also invested in technology to allow rapid sterility testing requirements for autologous cell therapies and digital droplet PCR for more precise quantitation of viral particles. Investments in Eurofins BioPharma Product Testing facilities expand CGT capabilities, and include laboratories being updated to accommodate biosafety level-2 (BSL2) work, to maximize space utilization, and to optimize workflows.

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