Leading Regulatory and Public Policy Actions to Advance the Field

I am continuing the theme of using my monthly messages to highlight the contributions of ISSCR committees and the members who dedicate their time and talent to advancing the field and the mission of the Society. This month, I’ve had the privilege to talk with Melissa Carpenter and Tennielle Ludwig, the chair and vice chair of the Manufacturing, Clinical Trials, and Regulatory Committee (MCTR), and to learn more about the work of the Public Policy Committee, led by Sean Morrison. The contributions they are making address critical priorities of the ISSCR and reinforce why membership in the Society is so vital – it supports initiatives that ease pathways for research and clinical advances so they may thrive. I learned so much from these interactions and look forward to sharing that with you this month, along with their voices.

 Q: What are the most important initiatives or projects the MCTR Committee is working on?

MC: The mission of MCTR Committee is to facilitate translation of discovery research to clinical products. During the last 10 years there has been great interest in creating stem cell therapies. One of the biggest gating issues for translation is navigating regulatory requirements. We are working to educate scientists about what regulators are looking for through meetings we have held with FDA, EMA, MHRA, and this month PMDA.

TL: It takes more than just great science to bring something to the clinic. The ISSCR community is fabulous with moving innovative science forward. Translating the science to the clinic requires regulatory knowledge, for example, how to select the proper starting material. And, knowing how to move through production of drug substance/drug product so that the work is regulatory complaint across multiple jurisdictions. We are working to provide information to help speed therapy development and to save money.

Q: Can you share more about the talent and background of members on the committee and how the composition of members contributes to the committee’s work and effectiveness?

MC: Conducting meetings with regulatory authorities is a heavy lift. We form subgroups that develop agendas with key scientific issues and regulatory questions, create presentations and determine who will moderate the discussions with the regulatory agencies. It takes an enormous amount of work, and we tap into committee and society members in different jurisdictions – 15% of our committee members are from Asia, 25% from Europe and the UK, and the balance from North America. Forty-five percent of members have regulatory experience, 10% have clinical trial expertise – which we want to increase – 55% bring CMC experience (Chemistry, Manufacturing, and Controls), and 10% with automation experience. The composition of the committee members and this experience is essential.

TL: Getting ready for the regulatory meetings takes a village. And for our committee, beyond the regulatory priorities, many of our members serve on the working groups for the next phase of the Standards initiative, Best Practices for the Development of PSC-derived Cellular Therapies, and work with the Public Policy Committee. Many of us participate in Congressional Advocacy Day on Capitol Hill in Washington, D.C. It really helps that the ISSCR staff committee liaisons, Tyler Lamb and Denise DeVilla, work with both committees, and this allows for even strong alignment between the two ISSCR committees on several priorities.

Q: Describe how the committee’s work is helping to advance the field or create opportunities for stem cell research to grow and thrive?

MC: There is no clear roadmap for the development of stem cell therapies. By meeting with regulatory agencies about common issues in the development of stem cell therapies and bringing this information back to the Society members, we hope to enable investigators to translate their discovery research to cell therapies for patients. Some of our next activities will include the development of educational webinars for ISSCR members. Our goal is to make the translational process less opaque.

 Q: What drives you to invest in/give so much of your time and talent to the ISSCR and the work of the committee? Describe the value you see in this volunteer work?

TL: I work for WiCell, a non-profit organization with a mission to support stem cell technology to rough to clinical application.  So, my day-to-day job is to support the scientific community and help as we can to enable progress in the field.  This aligns closely with the goals and mission of the ISSCR, so it is a natural extension for me.  I enjoy this kind of support role and frankly it’s my happy place.  Working with researchers and providing what they need in terms of materials, reagents, information, etc. so they can take their research to the next level and ultimately impact the human condition in a positive way.  This is how I feel I can have a positive impact and make a difference, and that is what drives me.

 MC: I can respond by sharing a story. In November of 1998, Jamie Thomson’s seminal paper was published (Embryonic Stem Cell Lines Derived from Human Blastocysts). I joined Geron Corporation in December of that year and immediately went to Thomson’s lab to learn how to grow hESCs – it was intense and complicated. Geron Corporation was the first group to enter clinical trials with a PSC-derived therapy – hESC-oligodendrocyte progenitor cells (GRN-OPC1) for the treatment of Spinal Cord Injury (SCI). I was deeply involved in the early development of this product.  Fast forward to 2019, I was at the ISSCR Annual Meeting in Los Angeles, and I was sitting at a table when a young man in a wheelchair sat next to me. He was accompanied by his mother and the two of them started to chat with me.  It turns out that this young man was a patient in Geron’s SCI trial (when he was 18, he had become quadriplegic). The young man ate his lunch using a fork and knife. When the mother realized who I was, she became very emotional. It was a powerful moment. It reminded me that 20 years earlier I was in the lab working on the fundamental science which enabled the GRN-OPC1 product, and 20 years later this work was having an impact.  It has to be faster than this.  With the technologies that we are developing today, the development of these products needs to be faster and more cost effective.

 We are effective at treating 10-20 patients. But we need to be able to treat 100 patients, 1,000 patients. This takes skill sets in bioengineering, computational biology, AI etc. It takes serious innovation, and these are the skill sets that we need to bring to the table.  These are the next skill sets we are bringing into the MCTR.

I am grateful for all of the work that Melissa and Tenneille are doing, and for all of the members of the MCTR Committee who are contributing in partnership.

MCTR Committee: Chair, Melissa K. Carpenter, Vice Chair, Tenneille E. Ludwig, Ricardo Baptista, Ivana Barbaric, Jacqueline Barry, Alessandro Bertero, Kapil Bharti, Andrew Gaffney, Derek J. Hei, Zoe Hewitt, Deborah Hursh, Uma Lakshmipathy, Jane S. Lebkowski, Marinna Madrid, Jennifer Moody, Charles Murry, Yoji Sato, Jihwan Song, Yoshie Tsurumaki, Debra Webster, and ISSCR Staff Liaisons Tyler Lamb and and Denise DeVilla.

In addition to the ISSCR’s work on regulatory topics, which has escalated with clinical advances in the field, the Society has a long history of engaging with policymakers to inform and advocate for evidence-based policies that support a robust research environment. Sean Morrison, who also is a former ISSCR president, has been leading these efforts as chair of the ISSCR’s Public Policy Committee, in collaboration with committee members and ISSCR team members Tyler Lamb and Denise DeVilla.

Q: What are the most important initiatives or projects the Public Policy Committee is working on?

SJM and TL: The central goal of the Public Policy Committee (PPC) is to work internationally with regulatory agencies and policy makers to promote regulation that enables good stem cell research and clinical translation while blocking bad science and the marketing of unproven therapies. Sometimes this has meant advocating for reduced regulation, such as in the context of embryonic and fetal tissue research. In other cases, it means advocating for increased regulation, such as in the context of unproven cell therapies.

A key focus this year has been on curbing the marketing of unproven cell therapies and the proliferation of stem cell clinics that prey on desperate patients. In June of 2023, the committee worked with a law firm to file an amicus curiae brief in a case before the Ninth Circuit Court of Appeals: U.S. vs. California Stem Cell Treatment Center, Inc. The case was a critical moment in the fight to regulate unproven cell therapy clinics because the lower court ruled against FDA’s ability to regulate these clinics. In ISSCR’s amicus brief in support of FDA, we provided scientific support for FDA’s position and information on stem cell therapies and the state of clinical use. In September 2024, the Ninth Circuit reversed the lower court’s ruling, finding that the products offered by this unproven cell therapy clinic could be regulated as drugs under the Federal Food, Drug, and Cosmetic Act. This win affirmed FDA’s authority to protect public health by regulating the ability to sell unproven cell therapies. The PPC will continue to monitor policy developments internationally, including in the US, Japan, and Europe, that impact the ability to market unproven cell therapies to patients.

The committee also initiated the formation of the Embryo Models Working Group, led by Amander Clark and Janet Rossant, and contributed to the ongoing external review process of a white paper developed by the working group. The white paper summarizes the current state of the science of stem cell-based embryo models, defines the different types of embryo models currently in use, and proposes recommendations for updating ISSCR Guidelines to accommodate the rapid advances in this area. The working group expects to complete this project in early 2025.

The PPC engages in horizon scanning to identify emerging topics and to ensure ISSCR is providing guidance to the field, stakeholders, and policymakers. In vitro gametogenesis and neural organoids are two subjects the committee is examining to determine how future developments may impact the field of stem cell biology and the clinical translation of future advances in these areas.

Lastly, the second cohort of Lawrence Goldstein fellows is nearing the end of their term. The current fellows, Brian Aguado, Justin Brumbaugh, and Tamra Lysaght, have spent nearly three years engaged in annual advocacy days in the U.S. Congress, preparation of materials for meetings with policymakers, authoring a review article for Stem Cell Reports about the importance of fetal tissue for research, appearing on The Stem Cell Report podcast, and assisting in the development of the Equity, Diversity, and Inclusion session at the 2024 ISSCR annual meeting in Hamburg, Germany. The fellows have been extremely active and have made valuable contributions to the PPC.

Q: Can you share more about the talent and background of members on the committee and how the composition of members contributes to the committee’s work and effectiveness?

SJM and TL: The PPC has a geographically diverse group of stem cell researchers, including several international leaders in the area of stem cell policy. Most committee members have decades of experience working on stem cell policy.

This year we sought out new committee members to meet anticipated policy needs for the next few years. Magdelena Zernicka-Goetz, Yaojin Peng, and Sarah E. Millar joined the committee in July to contribute expertise on stem cell-based embryo models, unproven therapies, fetal tissue research, and legal regulation. The committee prioritizes policy experience, and veterans of stem cell research advocacy such as Alta Charo, Larry Goldstein, Doug Sipp, Robin Lovell-Badge, Alan Trounson, and George Daley provide guidance to address complex policy matters. Because the policy staff is small – just two full time team members – the success of ISSCR policy work is reliant on the expertise and engagement of committee members.

As I reflect on the conversations I have had and the knowledge I have gained about our regulatory and public policy activities, I think that last point is crucial to all of the ISSCR’s strategic initiatives. The expertise of committee members and their willingness to serve the ISSCR is what leads to progress and successful outcomes and the deep expertise of our members makes the ISSCR uniquely capable to advocate on behalf of the field of stem cell biology.

Public Policy Committee: Chair, Sean J. Morrison, Eric Anthony, R. Alta Charo, George Q. Daley, Lawrence S.B. Goldstein, Kazuto Kato, Robin Lovell-Badge, Zubin Master, Sarah E. Millar, Megan Munsie, Malin Parmar, Yaojin Peng, Douglas Sipp, Jeremy Sugarman, Giuseppe Testa, Alan O. Trounson, Fiona Watt, Magdalena Zernicka-Goetz, Ex Officio Members: Brian Aguado, Justin Brumbaugh, and Tamra Lysaght, ISSCR Team Members Tyler Lamb and Denise DeVilla.

 Valentina

 Acknowledgements: I am grateful to Kym Kilbourne for interviewing together our committee members and for her leadership and partnership in co-creating this piece.

 

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New Podcast Episode. Guidelines for Managing and Using the Digital Phenotypes of Pluripotent Stem Cell Lines