“The biggest challenge is uncertainty. There is always some uncertainty with cutting-edge science.” When we spoke with Peter Marks back in 2021, he was looking forward to an exciting future with cell and gene therapies. Back among the news headlines, the much-admired CBER director discussed the qualities required for regulators, the challenges of leadership, and the not-too-distant future of CGTs.
How did you get involved with the FDA?
My first industry role was with Genzyme and involved interacting with the Center for Biologics. The Center had both an applied scientific research component and a regulatory component working with a nifty set of products. It was so interesting to me that, in 2011, I applied for a job there. At the time, gene and cell therapies were becoming very exciting – and, as a hematologist-oncologist, blood products were, of course, of interest to me.
What skills are important for a regulator?
Looking at people who have been mentors in this space, like Janet Woodcock, it’s clear that you need to understand science and medicine really well to do a good job as a regulator. This includes the science at a fundamental level, as well as the manufacturing of products and the technologies involved. Without that knowledge, you can’t make necessary decisions about cutting-edge products. You also have to know how to manage people. The Center for Biologics has around 1,300 full-time equivalents. They are mostly knowledge workers… and managing knowledge workers can be challenging. You need to know when to zoom in to get into the weeds of the data and when to zoom out and let others deal with the data while you make the high-level decisions. That, to me, is an important balance to have.
What is the biggest challenge you face?
The biggest challenge is uncertainty. There is always some uncertainty with cutting-edge science. For example, on one hand, a gene therapy may help to cure a disease or treat it long-term. On the other hand, there may be side effects associated with it. Not knowing exactly what will happen ahead of time is what makes the job challenging. Sometimes, it takes a long time to know whether a decision was a good idea or a bad one. The challenge is to negotiate the uncertainty in as skilful a manner as possible.
How far are we from being able to manufacture gene therapies at scale?
We’re not that far away, but there are challenges. With mAbs, people came together to help develop technologies that could produce and purify large protein quantities. With gene therapies, there is still a lot of proprietary work that can limit information-sharing. One of my goals is to help the field share information and grow. I think we can make better cell lines and purification methods and develop continuous methodologies for producing these gene therapies. But that will require a type of collaboration and cooperation that we haven’t yet fully achieved.
What advances in gene therapy do you think could be transformative?
In vivo genome editing has tremendous potential because it can help overcome some of the problems we have with current gene therapy vectors, including longevity of expression. You need expression of an editing construct for a period of time – ideally in the dividing cells – but after your correction occurs, you’re done. Too much persistence is undesirable because it can lead to off-target effects. Genome editing could treat many diseases, but there is a whole regulatory paradigm that we have yet to fully create for genome editing. It’s very exciting – and it’s advances like this that keep me coming to work every day.
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