Animal Origin Free Strategies for Gene Therapy Manufacturing and Formulation

High-Performance, Regulatory-Friendly Viral Vector Production for Gene Therapy

After decades of effort, the field of gene therapy has finally reached critical mass. The FDA has now approved two adeno-associated viral vector (AAV) therapies, LUXTURNA (voretigene neparvovec-rzyl) for inherited retinal dystrophy and ZOLGENSMA (onasemnogene abeparvovec-xioi) for pediatric, inherited spinal muscular atrophy. An attenuated, genetically modified herpes simplex virus, IMLYGIC (talimogene laherparepvec), has also been approved for local oncolytic viral therapy of unresectable cutaneous, subcutaneous, and nodal melanoma lesions after postsurgical recurrence. There are now hundreds of gene and cell therapies in the FDA approval pipeline, on pace to reach as many as 10 to 20 related approvals per year by 2025.

Gene therapy relies on viral vectors like AAV or lentiviral vectors, which deliver the desirable genetic sequences into the cells of the target tissue. To produce enough material for clinical use, the viral vectors must be propagated in a host cell such as HEK293. Cultured cells and viral vector products destined for cell and gene therapy or other clinical cGMP applications must meet the highest standards for manufacturing quality, safety, performance, consistency, and efficiency. InVitria has carefully optimized its animal-free, serum-free, defined media formulations for clinically and industrially significant cultured cell lines. InVitria’s product line and media formulations services take the guesswork out of transitioning to regulatory-friendly, serum-reduced, or serum-free cell culture for your RUO or cGMP needs.

InVitria’s Products for Gene Therapy Include:

• Cellastim S recombinant human albumin to replace BSA or purified human albumin in cell culture.
• Exbumin excipient-grade recombinant human albumin for improving stability of viral vector particles in injectable therapeutics.
• Optiferrin recombinant human transferrin for managing iron in serum-free or serum-reduced culture applications.
• Insulin-transferrin supplements provide supplemental rh-insulin, rh-transferrin, and selenium, with or without ethanolamine and rh-albumin for serum-free or serum-reduced culture applications.

OptiPEAK Media Optimization Services

Let InVitria help you discover how much further you can push cell growth, viral vector titer, and viral product stability in serum-reduced or serum-free culture. Starting with our pre-formulated HEK293 Complete media, InVitria offers the experience and know-how to help you take advantage of its full line of animal-free, serum-free, recombinant individual cell-culture components. Our Product Applications team is ready to help you build a serum-reduced or chemically defined medium optimized to your application. Reducing or eliminating fetal bovine serum (FBS) from cell culture:

• Reduces or eliminates the introduction of undesirable viral RNA and DNA, prion proteins, undefined antigenic molecules, as well as human or bovine cytokines and hormones.
• Provides better, more consistent, more scalable cell growth and viral titer in culture, and more dependable manufacturing yield, product validation, and clinical safety of downstream clinical products.
• Reduces foaming and other technical challenges in bioreactors.
• Eliminates concerns about the fluctuating global agricultural supply chain and limitations on availability of bovine serum.