Advancing gene therapy by solving challenges in scale-up & manufacturing

As the biopharmaceutical industry sharpens its focus on gene therapy, opportunities for advancements and challenges in manufacturing processes still remain. Dr. Ger Brophy, executive vice president of biopharma production at Avantor, offers insights on how the biopharma industry can evolve its processes through lessons learned from manufacturing monoclonal antibodies (mAbs) or vaccines, improving supplier collaboration, and other factors.

We’ve heard a lot over the past year about cell and gene therapy–two of the most exciting medical innovations with the potential to cure some pediatric cancers and other life-threatening or previously incurable diseases. What successes did the industry see over the past year, and what challenges are still ahead?

Genuine progress is being made in the long-standing battle to effectively treat and control disease, as evident with some of the first regulatory approvals for new therapies of their kind and the M&A activity within the pharmaceutical industry we witnessed in 2019.

The COVID-19 pandemic has temporarily disrupted the pace of research and approvals of new gene therapies related to cancer and other conditions. We’re seeing delays to clinical trials across the board; not only for gene therapies but all molecules, and from small to large biotech firms. However, we are currently setting a new, historic pace at which new therapies are being taken from research to full-scale manufacturing. This may set a precedent for the future to help with fast-tracking cell and gene therapies, as well.

What are the most promising targets within gene therapy, and what are some of the challenges in commercializing them?

While the approvals for treatments for rare diseases are certainly early wins, the impact of gene therapies will significantly expand as approved treatments are administered to larger patient groups and studies expand to address diseases that are broader reaching—for example, with treatments for multiple myeloma, leukemia and other forms of cancer.

What are some of the major gene therapy production components that impact optimization potential?

There are two major routes: First, we have to anticipate innovation and optimization coming through from advances in academia. Second, we expect step changes in process improvements from contract development and manufacturing organizations (CDMOs) and other producers. This can be done with closely monitoring, and where relevant even partnering with, these organizations early on, as well as through involvement in consortiums and professional organizations like Rx360 or DCAT.

In raw materials, specifically, we are seeing more requests for cGMP grades of materials which have never needed to be made at scale or to cGMP specifications before. Even if these are available at the correct analytical grade, there is considerable raw material expense associated with components such as plasmid DNA.

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Dr. Brophy shares additional insight about how producing viral vectors can be made more efficient, the lessons that can be learned from manufacturing mAbs and applied to gene therapies, navigating regulatory approvals as a therapy progresses from early to commercial stages, and more.

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