Three Questions with CEO Andrew Knudten

  1. What excites you about the gene and cell therapy industry right now?
    We are fortunate to be part of an extremely exciting time for gene and cell therapy product development. Advances in technology, the sheer number of programs in development as well as recent product approvals all point toward continued progression. One thing I’m particularly excited about is that regulators are supportive of the rapid growth we are seeing in the gene and cell therapy space. The U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research has made it clear that they aim to address key challenges to the development of gene and cell therapies, especially for rare disorders, and they want to work with sponsors to advance medicines for patients. This is great news, but I think we as an industry play a key role in that effort. Frankly, we need to make the jobs of regulators easier, especially in the area of manufacturing and analytical testing.
  2. That’s not something you hear very often. What exactly do you mean when you say the industry should make the jobs of regulators easier?
    Industry and regulators are sometimes framed in opposition, but we are on the same side. We all want to see safe and effective treatments reach the patients and families who need them. As an industry, our approach to manufacturing, analytical method development, and QC testing has not fully enabled the development of therapeutics regulators want to see and patients are desperately seeking. We need to evolve as an industry and begin delivering the quality of product that patients deserve and regulators expect. In the past, it may have been that technology was still catching up, but now we have access to the technology we need. It’s not just technology, though. We need to have people with the breadth of experience and expertise needed to harness the technology. Simply put, more time and energy needs to be invested in CMC product development so that CMC is not a major topic during regulatory interactions. How great would it be for regulatory interactions to focus exclusively on preclinical data review and clinical trial design instead of CMC-related topics? Choosing a CDMO with experience can help achieve this goal for complex gene and cell therapy medicines.
  3. What are some of the common CMC challenges that come up in regulatory discussions? Are they solvable?
    One issue that has been widely scrutinized is product purity or rather a product’s impurity profile. Immature manufacturing processes may produce drug product that has unacceptable levels of process and product-related impurities. Regulators assess a product’s impurity profile as part of their quality and safety assessments. Another challenge biopharmaceutical companies may come up against is bridging between an early manufacturing process and a commercially-viable manufacturing process. Ideally, sponsors should develop a commercially-viable manufacturing process at the onset of a program. Financial and strategic considerations, though, do not always allow for this. Some sponsors may also find themselves in a situation where they’ve inherited a product that has promising clinical data but was supplied with an immature manufacturing process. This might seem provocative, but sponsors should not be afraid of comparability or bridging studies! Recently, regulators have reinforced that they are very open to modifying a gene or cell therapy manufacturing process if the sponsor can confirm the dose, demonstrate process control and its impact on critical quality attributes, and prove analytically the product produced via a new manufacturing process is more pure than the previous iteration. An experienced CDMO like Advanced Medicine Partners can help a sponsor develop a prospective comparability plan that will be looked on favorably by the regulators. We do this through employing advanced analytics to clearly quantify attributes of product made through each manufacturing process. This allows us to ensure product quality is better through the new manufacturing process and that we are delivering an accurate and precise dose. Sponsors should not be satisfied with a sub-optimal manufacturing process. Patients deserve better.

If you’re curious to know how the Advanced Medicine Partners team can work with you to ensure a robust and proactive CMC approach, reach out to us at