Policy Summit’s First Day Focuses on Ethical and Regulatory Issues

Ethics Sessions

The ASGCT 2020 Policy Summit began on Wednesday with a focus on ethical and regulatory issues in gene and cell therapy.

The two-and-a-half-day virtual event kicked off with a keynote address from George Q. Daley, M.D., Ph.D. (Harvard Medical School). In a talk about science advocacy, Daley called for scientists to responsibly educate, advocate, and critically analyze the work that they do as new technologies like gene editing and stem cells continue to be studied.

Science serves society, Daley said, but sometimes science moves forward with ethical and societal considerations chasing behind. For technologies with far-reaching implications like genome editing, those considerations should come first. And as several companies are moving forward with potential vaccines for COVID-19, Daley said, we can’t minimize the importance of rigorous scientific review and putting public health over politics.

“These issues are not political, they are humanistic,” Daley added.

Following Daley’s talk, attendees heard from Eric Juengst, Ph.D. (University of North Carolina at Chapel Hill), R. Alta Charo, J.D. (University of Wisconsin Law School), and Sandy Macrae, M.B., Ch.B, Ph.D. (Sangamo Therapeutics), who spoke about responsible development and use of technology. These speakers discussed challenges related to somatic and germline gene editing and the need for better systems to monitor research into these processes. Charo said there was no mechanism for a uniform policy across the globe and there should be ways to create more effective community conversation or raise concerns around gene editing.

“If you want to be able to influence things, you’ve got to know what’s going on,” Charo said.

For patients with genetic diseases who have undergone treatment, Macrae said we also need systems to track them long term instead of trying to fit new technology into old systems. Monitoring patients can be difficult, but scientists in genomic medicine have a long-term responsibility when they’re dealing with potentially life-long treatments.

“Solutions need to start with the patient, they are the people we are responsible for,” Macrae said, adding that urgency is also important because many patients are waiting for treatments.

During the second morning session on nontherapeutic uses of gene editing, Renee Wegrzyn, Ph.D. (Ginkgo Bioworks; formerly Defense Advanced Research Projects Agency), talked about transient gene therapies for prophylactic use. Transient gene therapies are temporary and programmable, Wegrzyn said, and have the potential to both transform our approach to the pandemic and also enable new avenues to access druggable targets. David Relman, M.D. (Stanford University), discussed security implications of gene editing and focused on human microbes. For the first time, Relman said, it’s possible to modify genes and expression patterns amongst previously intractable microbes for which genetic systems were not available. Additionally, it’s now possible to modify indigenous organisms with a group of genes to allow the organisms to take advantage of something they wouldn’t respond to before, like an unusual nutrient. Wegrzyn and Relman both noted that these strategies are meant to enhance health security and would require oversight and leadership from organizations that don’t currently exist but should offer a balanced perspective about risks and benefits.

Regulatory and Manufacturing Sessions

The Policy Summit’s afternoon sessions focused on manufacturing and regulatory issues. During the session on challenges and solutions in large-scale manufacturing, Andrew Byrnes, Ph.D. (FDA), provided insights from a regulator on what sponsors should emphasize and consider in the manufacturing process design, product characterization, vector concentration, and visible particulates. He called the manufacturing process the most important factor in ensuring quality for gene therapies. Byrnes noted that the workload at the Center for Biologics Evaluation and Research (CBER), much more than the pandemic, has had an unfortunate impact on meetings and communications between the FDA and sponsors. The volume of IND submissions has continued to increase, he said, leading the staff to cancel meetings, hold them late, or utilize written responses. Byrnes said they’ve been trying to schedule pre-IND meetings, especially for sponsors who are new or less experienced. Byrnes also confirmed a guidance on CAR T-cell therapy would come out by the end of the year as planned, which would include a small section on comparability. He acknowledged that the existing FDA guidance on comparability is not that useful for gene and cell therapy products.

Chris Murphy (Thermo Fisher Scientific’s Pharma Services Group) provided a CMO perspective on the factors CMOs need to consider to ensure quality manufacturing processes. He indicated that he has had some virtual inspections during the pandemic, in which regulators directly engaged with those in the lab in real time, and they went well. Robert Baffi, Ph.D. (BioMarin), provided a developer perspective on manufacturing, outlining the process of development of BioMarin’s hemophilia A program.

In the final session of the day on CMC and regulatory issues, Herb Runnels, Ph.D. (Pfizer) talked about critical quality attributes for AAV vector products, which he said were still evolving. Katie Miller, Ph.D. (Dark Horse Consulting) discussed considerations and challenges in identifying critical quality attributes for gene-modified cell therapies. Miller advised that casting a wide net during the beginning of development and then narrowing it after feedback is a good approach to take. During her discussion on the FDA perspective on global CMC convergence, Denise Gavin, Ph.D. (FDA) gave an overview of efforts toward global regulatory convergence across countries. She indicated that the gene therapy working group of the International Pharmaceutical Regulators Program (IPRP) has grown from nine countries initially to 21 countries now, many of which have limited regulatory experience with these products. This working group has been especially helpful in discussing the emerging science and best regulatory practices for participants to learn from countries with more advanced frameworks in regulating gene therapies.

Join us Thursday morning for the second day of the Policy Summit, which will focus on more regulatory issues, as well as legislative and access issues, in gene therapy! If you missed anything, all Policy Summit sessions are free for registered attendees to watch on the meeting website for 30 days.

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