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Overcoming Analytical Challenges for Gene Therapies featured in Pharma’s Almanac

Gene therapy developers face numerous analytical challenges, from discerning what product qualities are critical attributes to the need for fit-for-purpose analytical methods for viral vectors that offer a combination of speed, sensitivity, and resolution. Leveraging a contract research organization (CRO) partner with specialized expertise and awareness of evolving technological and regulatory development that functions as part of their customers’ internal analytical teams can lead to accelerated timelines and a higher probability of program success.

Short List of High-Level Challenges for Viral Vector–Based Therapies
Gene therapy based on viral vector delivery is still in its infancy, and like all other emerging technologies faces several high-level analytical challenges. One of the biggest is gaining the necessary depth of understanding of these novel materials. What is the best approach for analytically identifying viral vectors, and how does that approach scale so that it continues to provide valuable information? Making the right choices is central to the development of these products.

The in vivo outcomes of gene therapy drug products are becoming increasingly important in establishing the longevity and persistence of these treatments from the payer perspective. Gaining a platform understanding through detailed molecular characterization and interfacing that knowledge with clinical outcomes (safety and efficacy) is, therefore, essential, but can be difficult to achieve.

More specifically, what features of the molecules dictate both positive and negative aspects of the infectivity, productive transcription, and persistence of the therapeutic product in the body must be understood. Liquid chromatography (LC) and mass spectrometry (MS) are increasingly important because applying different methods to establish in vivo outcomes is critical.

Particular to viral vectors is the issue of full versus partial versus empty capsids. Production platforms that maximize full at the expense of partial and empty capsids are needed, as are methods for efficiently and effectively separating the desired full capsids from the undesirables.

Fortunately, because the application of analytics is really dictated by the product itself, there is a great deal of flexibility from a regulatory perspective. The key is to go back to the fundamentals of controlling quality for the purpose of known safety and efficacy, and safety is, ultimately, the priority for these products.

ProtaGene Author
Jennifer Chadwick, Ph.D.
Vice President of Analytical Development

Original Publication
Pharma's Almanac 
March 20, 2022

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