As we continue Cell & Gene’s 2020 Outlook series, in which many of our Editorial Advisory Board members have provided their data-driven insights for the coming year, here you’ll hear from Michael Blackton, Vice President QA CMC at Adaptimmune on what’s new for 2020 in cell and gene therapy and Jiwen Zhang, VP, Regulatory Affairs at Passage Bio on cell and gene in 2020 through the regulatory lens.
Michael Blackton, Vice President QA CMC at Adaptimmune on what’s new for 2020 in cell and gene therapy.
As we move into 2020 and beyond, there will be a continued evolution of cell and gene therapy landscape, particularly as it relates to regulator guidance and supply chain. As more companies move toward later stage clinical trials, we are seeing a tangible evolution of regulatory guidance in the U.S. and rest of world toward a more facilitating clarity. In addition, with later stage trials, it is important to acknowledge how patient supply impacts the industry. Considering this, and given the rise in investment in cell and gene therapy, we will continue to see a need for contract testing and manufacturing in order to feed the clinical trial engine. In short, 2020, in my mind, is the year of facilitating innovation from the industry, regulators, and suppliers.
In 2019, the FDA harmonized terminology for cell and gene therapy products with the adoption of the EU term Advanced Therapy Medicinal Products (ATMP). This relatively minor terminology change is significant because it removes some ambiguity in interpretation of international guidance. As we started the New Year, we saw the FDA double down on their effort to support ATMP with the release of no less than five new guidance documents. Internationally, we will see PIC/S finalize Annex 2A relating to ATMP manufacture for human use. What does all this mean? Because the regulators see significant advancement in this area with the potential to revolutionize how we treat disease, they want us to be successful innovators, and they will continue their innovation so we as an industry can bring more medicine to the patient. Make no mistake; the regulators see a horizon where these products will transcend the mere treatment of a disease into the real possibility of curing the previously incurable!
Supply chain matters. If we can get a cell therapy product to patients faster, then we cure disease faster. We will continue to see innovations that facilitate rapid lot release, patient scheduling and lot track and trace. New software technologies will continue to advance the engagement between clinical sites and drug manufacturers, and electronic batch records will see a renaissance in this area. In 2020, we will see a world where vein-to-vein time, or the time from patient apheresis collection to patient infusion, becomes one of the most critical elements of supply. Quality systems, manufacturing processes, data management, and clinical engagement will all innovate around the singular focus of getting important medicine to the patient safely and quickly — especially as trials move toward completion. The question for the industry is whether outside service providers will be able to keep up.
Considering contract manufacturing and testing suppliers, we will unfortunately continue to see bottlenecks in this area. Despite that, I can see 2020 being a year where more clean room space becomes available for cell and gene therapy, and a focus on higher yields and quality for vector supply as a drug product (gene therapy) and starting material (cell therapy). The market is hot right now for contract manufacturing, and as a result we will continue to see more investment and efficiencies in this area. In the area of contract testing laboratories, I see the same thing. More companies will acknowledge that the days of batch release times of months or weeks are over because the industry is demanding days and hours. Hopefully, 2020 will be a year where we see lead times for testing reduced, but those companies with enough resources will likely develop more robust in-house manufacturing and testing capabilities.
In conclusion, 2020 will be a year of continued innovation and major advancements in the clinic, and I am looking forward to the exciting times we have ahead for us.
Jiwen Zhang, VP, Regulatory Affairs at Passage Bio on cell and gene in 2020 through the regulatory lens.
In the cell and gene space, CMC challenges have been well described and deliberated. Progresses have been made, but challenges remain in manufacturing, analytical testing, supply chain, and in almost all critical areas. CMC development and acceleration demands continued discussions and shared knowledge and experiences. After two years of success, CASSS will be conducting the third annual symposium of cell and gene therapy products in June a conference dedicated to only CMC topics. The three-day conference will bring together CMC experts from the industry, regulatory agencies, academia, and clinical operations in medical centers. FDA debuted CMC related guidance at the 2018 CGTP conference. We shall see if anything new this year from the FDA or other agencies.
As more countries develop regulatory framework for cell and gene products, regulatory convergence continues to be the focus for stake holders. For example, the challenge associated with meeting the GMO requirements to obtain CTA approval in EU countries has resulted in much lower increase in number of clinical trials in EU compared to North America, Asia, as published by the Alliance for Regenerative Medicine. Stake holder initiatives by APEC RHSC, ARM, ISCT, ASGCT should proactively advocate the need and importance of suitable regulatory framework for cell and gene products, and regulatory convergence, which will be even more crucial to support clinical trials for rare and ultra-rare diseases globally.
Speaking of rare diseases, recently, an EMA colleague voiced the need for a stake holder meeting focused on AAV gene therapy for monogenic neural diseases, which often are rare or ultra-rare conditions. Though different AAV gene therapy products are designed to target different indications, as a technology platform, there are common scientific and technological challenges that can benefit from collaborations among stake holders to better characterize AAV products regarding their route of administration, durability of treatment effects, and potential toxicities. An appropriate forum to foster a pre-competitive discussion and collaboration will bring tremendous value to the field.
In conclusion, I want to share a very recent experience. In the latest ISCT Regulatory Committee meeting while brain storming 2020 webinar ideas, the committee members got into a very lively discussion about how to facilitate cross talks between product developers in academia and industry: what are the expectations, standards, infrastructure, and capabilities on each side that will ultimately drive cell and gene product development and commercialization. The shared passion, knowledge, and expertise among committee members from both the industry and academia are truly valuable for everyone there at the meeting. So again, I want to encourage colleagues to connect with peers and participate in initiatives. FDA just issued the much-anticipated draft guidance document, “Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations.” Industry associations and professional societies will be organizing working groups to collect comments. Join these groups. Give your thoughts and insights. Together, we can bring the transformative cell and gene therapies to patients in need.