StemCell Therapy

After kicking off the Prescription Drug User Fee Act (PDUFA) reauthorization process in July, the US Food and Drug Administration (FDA) has released the first set of meeting summaries in its ongoing negotiations with industry that will shape its prescription drug review program from FY2023-2027.The meeting summaries, while brief, provide insights into what FDA and industry hope to get out of the multi-billion-dollar agreement, with representatives from government and industry alike agreeing that the exploding field of advanced biologic therapies must be a priority. In some other areas, though, the wish lists diverged. (RELATED: PDUFA VII: FDA, industry preview their reauthorization wish lists, Regulatory Focus 23 July 2020).Steering committeeThe PDUFA reauthorization steering committee met three times in September to hash out the ground rules for the negotiations and review the major topics and proposals both sides will work through via designated working groups.FDA and industry both noted the impact of the COVID-19 pandemic on the agency and the reauthorization process at the first meeting on 15 September.Despite historic workload and operating challenges in the time period, the steps taken in PDUFA VI to protect the program from financial uncertainty have proven critical and important to maintaining FDAs operations, FDA said.During the meeting, FDA pitched six areas it wants to focus on for PDUFA VII: digital health and informatics, postmarket, CBER-specific enhancements, pre-market, regulatory decision tools and finance.Industry, on the other hand, expressed interest in build[ing] upon past user fee agreements and to ensure FDA and industry can mutually keep pace with scientific development. Topics presented by industry include: strengthening scientific dialogue, enhancing patient-centric drug review, supporting the next wave of advanced biologic therapies, modernizing regulatory evidence generation, advancing digital and IT technologies, enhancing innovation in quality and manufacturing, and optimizing FDA infrastructure, staffing, and resources.Industry also said it was keen on adopting some of the lessons from the COVID-19 pandemic and translating them into improved processes going forward.During the next steering committee meeting on 22 September, FDA and industry reviewed the overall timeline for reauthorization and the two sides sought clarification on each others proposed topics. The following week the committee met again and reviewed the timeline for communicating with Congress, agreed to topic assignments and looked at some of the overlap between the agencys COVID-19 response and PDUFA interests.CBER subgroupIncreased support for FDAs Center for Biologics Evaluation and Research (CBER) is set to be a focus for both FDA and industry in the negotiations.FDA told industry at the first CBER breakout meeting that it would like to see enhanced resources for its cell and gene therapy program, which has been overwhelmed by an influx of applications and meeting requests in recent years.FDA noted that its new regenerative medicine advanced therapy (RMAT) designation program has seen exponential growth and is now outpacing breakthrough therapy designations in the Office of Tissues and Advanced Therapies (OTAT), despite not receiving any dedicated resources for the fledgling program.With more resources, FDA told industry that it could spend more time on cell and gene therapy submissions, provide more opportunities for engagement and develop policy and guidance for sponsors. FDA also said it will seek dedicated resources for the RMAT program under PDUFA VII.Industry suggested three CBER-related commitments it would like to work into the reauthorization agreement, including workshops and guidance on the use of sponsor-specific prior knowledge in gene therapy submissions, evidentiary standards for RMAT designation and gene therapy manufacturing issues.Industry would like a public workshop to focus on key learnings from the RMAT program resulting in an update to the RMAT guidance, including potential uses of Real World Evidence (RWE) for regulatory decision making, FDA writes, noting that meaningful guidance on the matter may be difficult to develop due to the limited number of approved cell and gene therapy products and the fact that there have not been any products approved to date with RMAT designation.For gene therapy manufacturing, industry specifically said it would like to explore whether submitting portions of a chemistry, manufacturing and controls (CMC) module could facilitate biologics license approval (BLA) review. FDA said it has concerns that a partial submission could actually slow approval down if development is ongoing but agreed to carry the discussion forward.Regulatory decision toolsOn 29 September, the regulatory decision tools subgroup met for the first time, with FDA and industry reviewing potential areas of enhancement and agreeing to a schedule for the next several meetings.FDA raised four topics it would like to tackle in PDUFA VII, including model-informed drug development (MIDD), complex innovative trial designs (CID), patient-focused drug development (PFDD), and advancing translational models and tools for drug development (ATMT).For MIDD, FDA said its goal is to build on the lessons learned during PDUFA VI and to ensure the programs sustainability. Doing so would require public engagement and the development of comprehensive end-to-end guidance, which FDA said would necessitate increased staffing.Digital health and informaticsFDA and industry began discussions aimed at enhancing the use of digital health and informatics technologies under PDUFA VII on 30 September.FDA pitched three topics for discussion at the meeting, including a proposal for an integrated cloud-based technology environment, a framework for leveraging digital health technology-generated data in submissions, and CBER IT modernization.PremarketFDA and industry addressed several premarket issues in the first meeting of the premarket subgroup, including user related risk analysis (URRA) and human factor (HF) protocol review and developing efficacy endpoints for rare diseases.FDA proposed increasing the user fee timeline for reviewing HF protocols and said the current goals will be unsustainable in the future due to increasing volume and complexity of HF submissions. The two sides discussed the creation of a new user fee goal and timeline for review of URRA.FinanceAt the first of two finance subgroup meetings, FDA presented a host of goals for PDUFA VII: To enhance the operational capabilities, efficacy, and agility of the PDUFA program. FDA proposed continuing to advance resource capacity planning, updating the inflation adjustment to accurately account for program costs, enhancing flexibility in the operating reserve, eliminating a problematic limitation on allowable expenditures, streamlining annual reporting requirements, and implementing technical fixes.Industry representatives, however, stressed that their goal is to build on the enhancements made in PDUFA VI and to improve on user fee resource management, hiring and retention of review staff and performance reporting.During the second finance meeting, FDA and industry looked at a proposal to clarify the maximum and minimum amount of operating reserves to be maintained each year and a proposal to further implement the resource capacity planning (RCP) capability instituted in PDUFA VI.Stakeholder meetingFDA also released a meeting summary from the first round of stakeholder discussions. More than 60 stakeholder organizations, including patient groups, consumer representatives, public health advocates and medical associations, registered to attend the meeting, though a third of those registered did not attend.Some of the themes frequently cited by stakeholders included enhancing the incorporation of patient voice in drug development and regulatory decision making, modernizing FDAs infrastructure, ensuring FDA has adequate resources to recruit and retain qualified staff including in the areas of cell and gene therapy, increasing the strength and reach of patient and rare disease programs including improving diversity in clinical trials and patient engagement, enhancing FDAs use of regulatory science (e.g. COAs, MIDD, RWE), and improving the integration of and guidance for the use of real-world evidence (RWE), FDA reported. Stakeholders also raised decentralized trials and lessons learned during the COVID-19 pandemic as topics for future discussions.FDA tasked stakeholders with identifying their top issues for further discussion and said it would survey them to rank the topics on the agreed to shortlist.FDA

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PDUFA VII: FDA and industry set priorities in first round of negotiations - Regulatory Focus

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