Recently, KCAS’s Senior Director of BioPharma Services, Jeff Hester, PhD, was invited by Bioanalysis Zone to discuss key developments in the emerging field of Cell & Gene Therapy products (CGT). Along with other industry opinion leaders Stephanie Pasas Farmer, PhD (Ariadne Software, KS, USA) and Boris Gorovits, PhD (Sana Technology, MA, USA), Jeff addressed why research into CGT has increased over the last decade and helped uncover roadblocks he has experienced in CGT assay development, qualification and validation. The current regulatory landscape is also reviewed, highlighting how bioanalytical laboratories have kept up with the complexity of these products.
Why don’t we begin with an introduction?
“My name is Jeff Hester. I work at KCAS Bioanalytical and Biomarker Services. I’m a Senior Director here in the Biopharma Services department – more specifically in the Cell & Gene Therapy space within our organization.”
Can you explain why research into CGT products has increased over the last decade?
“There are many actors that have played a role in that and they all feed into each other. So I see it more simplistically as a circle of events that continue to feed and lead to increased output in all of this. But specifically, I look at scientific breakthroughs as one. And really, cell and gene therapy is a very complex thing. There are many different products therapies here. You’re talking about cellular products, you’re talking about genetic editing, you’re talking about genetically edited cellular products. So there are many different therapies that we lump into some of gene therapy. But really, the breakthroughs that I think of gene editing technique are CRISPR or previous to that was TALEN – a major gene editing tool – and then the continued identification of vectors, viral vectors and refinement of that process.”
What are the challenges associated with developing CGT products?
“The challenge is making sure they’re safe. I mean, the products need to be safe in order for them to be adopted and – of course – for them to get approved. Ensuring appropriate delivery of the correct replacement genes to the necessary cells without excessive toxicity is really what when we look at gene editing; that’s paramount. Issues with immunogenicity is another. Much like any drug therapy for which there isn’t already an established immunogenicity. And then, of course, after, if you have to follow up with a second or third dose – making sure that they’re not neutralizing antibodies to that product or reducing it.”
What are the major roadblocks with CGT assay development, the qualification and then the validation?
“One of the major challenges we have in Cell & Gene Therapy assay development qualifications and validation space is the diversity of the platforms, the techniques, the technologies and really the expertise required to perform these assays. The complexity requires that for any of these therapies, you can have viral-based vectors, you can have cells that have been transfected by lentiviral vectors, you can have CRISPR gene edited, the cells or viruses, you can have nucleotides or primary mRNA delivered via liposomal formulations… the diversity of the products vary so much that it requires a bio A laboratory has expertise in all of these areas.”
How has the bioanalytical laboratory kept up with the complexity of CGT products?
“Hiring scientists with deep scientific knowledge, really in cellular and molecular techniques, establishment of the workflows required for the diversity of these platforms, techniques, technology and expertise required to form the assays. Having regulatory teams that understand the complexity of the cell and gene therapy space has been critical. And then our ability – without a lot of guidance documents, established guidance documents – to validate assays and validate platforms, that provide quality to our pharmaceutical clients has been something we’ve been keeping up with.”
How do you see the development and management of CGT products evolving over the next 5 years?
“Of course with any therapeutic area that’s still very much in its infancy, new ones will be identified, and the current ones will mature within the next five years. From a regulatory perspective, there will be much more established guidance documentation specifically for the bio A work that we do here at KCAS.”
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