It is recognized that gene therapy manufacturing processes result in low yields, particularly in early product development stages. Gene therapy products, however, are largely subject to many of the same regulatory requirements and expectations as other large molecule biopharmaceuticals, which are produced at much greater scales.
In terms of stability studies, this situation means that if gene therapy manufacturers adhere to common paradigms, the outcome would often be little, if any, remaining product for patients or studies to support investigational new drug applications.
This need to conserve volumes of gene therapy products is why we have published Minimizing the impact of stability testing on gene therapy batch yield.
In the paper, we outline strategies for reducing the volumes required for stability studies with the goal of conserving product for patients, while remaining compliant and delivering data on critical quality attributes across the shelf life of gene therapy products.
We also make recommendations covering both drug substance and drug product, focusing on strategies for routine stability studies. To give our work some focus, we identified and clearly defined a mock viral vector product so we could make specific recommendations for the conservation of material.
Gael Debauve, Head of Gene Therapy CMC Analytics at UCB, said, “By presenting a concrete case study and discussing the available mitigation strategies, this paper aims to provide clear guidance on how to minimize the impact of stability studies on batch yield and maximize the amount of material available for the patients.”
While its scope focuses on viral vector gene therapies, the concepts discussed may apply to other modalities within cell and gene therapies, such as ex vivo genetically modified human cells.
If you are in QC, QA, regulations, or CMC leadership, this paper will help you avoid getting lost in generic considerations that may not be relevant to your product and guide you to apply them specifically to gene therapies.
“There is a strength in having something documented to take back to your organization and validate ideas that you have had, as well as share new approaches,” said Laura Sands, Head of Regulatory Affairs at Lonza. “The paper helps the reader to think outside of the norm as there is verification that others are also doing so.”
Gene therapies do not fit the standard approaches taken for traditional biologics and there is a need to think differently. Any material we can preserve and deliver to clinical studies is always in the best interest of everyone involved, especially patients. This paper gives you the strategies to do this.
This paper is a companion to the Minimizing the impact of container closure integrity testing on gene therapy batch yield and Minimizing the impact of bioburden and sterility testing on gene therapy batch yield.