Advancing Gene Therapy by Solving Challenges in Scale-Up & Manufacturing

Sponsored by Avantor

October 14, 2020

Today’s biologic drugs give the promise of breakthrough treatment options for the world’s most challenging diseases and chronic conditions. In the case of gene therapies, the impact of these treatments will only expand as they are administered to larger patient groups and studies expand to address diseases that are broader reaching. Dr. Ger Brophy, Executive Vice President of Biopharma Production at Avantor, offers insights on how the biopharma industry can evolve gene therapy manufacturing processes to meet these growing needs.

Dr. Ger Brophy, Executive Vice President, Biopharma Production, Avantor

Today’s biologic drugs give the promise of breakthrough treatment options for the world’s most challenging diseases and chronic conditions. In the case of gene therapies, the impact of these treatments will only expand as they are administered to larger patient groups and studies expand to address diseases that are broader reaching.

As the biopharmaceutical industry sharpens its focus on gene therapy, opportunities for advancements in manufacturing processes remain. Dr. Ger Brophy, Executive Vice President of Biopharma Production at Avantor, offers insights on how the biopharma industry can meet these growing needs.

What successes did the industry see in cell and gene therapy technology 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; 1,273 trials and counting were reported as “on hold” as of the end of May, impacting well over 200,000 individuals, and that number has only grown. 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.

Focusing on gene therapy, what are the most promising targets and 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. Scalability and manufacturability are the two closely related challenges the industry faces, especially if gene therapies are to fulfill their clinical potential.

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

There are many process challenges but across the board, we need to implement improvements in raw material inputs and innovations in manufacturing technology in order to deploy gene therapies economically and at scale.

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 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.

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. Download the full article to continue reading.

About the author

Avantor Dr Brophy

Dr. Ger Brophy is Executive Vice President, Biopharma Production at Avantor. In his current role, he is responsible for developing and implementing Avantor’s Biopharma Production offering to support current and future customer needs. Prior to joining Avantor, Dr. Brophy held a variety of research and development, strategy, advanced systems, and business development positions with GE Healthcare Life Sciences, GE Healthcare Medical Diagnostics and Amersham for nearly 30 years. Dr. Brophy earned a Bachelor of Science in biotechnology, as well as a doctorate in molecular biology from Dublin City University in Ireland.