ADUFA V Negotiations Meeting Minutes
December 2, 2021, 9AM – 3PM
Section 740A(d)(1)(F) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) requires that FDA consult with representatives of the regulated industry to negotiate recommendations for reauthorization of the Animal Drug User Fee Act (ADUFA) program, ADUFA V. For the ADUFA negotiations, regulated industry is represented by the Animal Health Institute (AHI). FDA’s meetings with AHI, which tentatively are planned to run through January 31, 2022, will satisfy the requirement in section 740A(d)(1)(F) of the FD&C Act. The overall purpose of this meeting was for FDA and AHI to present and discuss possible program enhancements for the ADUFA program.
Matt Lucia, Center for Veterinary Medicine (CVM)
Roxanne Schweitzer, CVM
Tim Schell, CVM
Julie Bailey, CVM
Chuck Andres, CVM
Cassie Ravo, CVM
Petra Garosi, CVM
Steve Fleischer, CVM (subject matter expert)
Crystal Groesbeck, CVM (subject matter expert)
Elizabeth Cash, Office of Chief Counsel (OCC)
Lori Talley, OCC
Rachel Cumberbatch, Animal Health Institute
Jan Cunningham, Dechra
Grace Gowda, Boehringer-Ingelheim Animal Health
John Hallberg, Zoetis
Gareth Harris, Merck
Alicia Henk, Ceva
Todd Rhodes, Vetoquinol
Kelly Rosenkrans, Elanco
Alan Taylor, Virbac
Kathy Vannatta, Animal Health Institute
Ron Phillips, Animal Health Institute
Ryan Carroll, Zoetis (subject matter expert)
Beth Norton, Boehringer-Ingelheim Animal Health (subject matter expert)
A.R. Matura, Boehringer-Ingelheim Animal Health (subject matter expert)
The meeting began at 9:00 a.m.
FDA and AHI introduced new participants included for their subject matter expertise for today’s meeting.
FDA presented on the topics of Raw Data, H Submissions, and Chemistry, Manufacturing, and Controls (CMC). FDA provided the reasons raw data are requested and outlined the current business process improvement (BPI) efforts that are aimed at making it easier for industry to understand what information needs to be submitted. BPI efforts include formalizing the pilot for remote access to a company’s Electronic Data Capture (EDC) system and the pilot to clarify required raw data in an H submission, as well as exploring potential certification of contract research organizations (CROs). FDA proposed several options for the submission of raw data moving forward. Options included further use of Bioresearch Monitoring (BIMO) inspections to potentially reduce the amount of raw data needed for a submission, new Guidance for Industry (GFI), and new Question-based Review (QbR) templates.
FDA provided the reasons H submissions are requested and proposed options to increase transparency of what’s expected to be included in H submissions. FDA proposed to create a sentinel submission category for H submissions with CVM reviewing and acting on 90% of qualifying H submission requests within 100 days after the submission date.
FDA discussed the reasons there are multiple review cycles for CMC. FDA expressed that they were encouraged by the finding from AHI’s internal survey showing completion of 80% of CMC technical sections in two review cycles or less, indicating improvement and FDA expressed willingness to continue discussing options for further process enhancement. FDA stated that each product has unique manufacturing information with different levels of complexity. FDA shared their perception that many CMC incompletes result from sponsors not submitting the information needed to support the CMC technical section or not understanding what information is needed for submission. The suggested solutions to mitigate these issues included updating the CMC section of the FDA.gov website with dosage form specific information, an improved e-Submitter CMC template that gives sponsors: 1) enhanced ability to communicate with FDA between sections and submissions, 2) the ability to cross-reference previous information submitted to CVM, and 3) the opportunity to provide real-time feedback on the templates. FDA mentioned the possibility of an eCTD concept with interactive capabilities between Modules 2 and 3.
FDA presented on budget erosion. The presentation was meant to be informative regarding budget challenges that have an impact on programs. Resources for mission-critical CVM programs continue to decline due to increasing payroll full time equivalent (FTE) costs for such things as cost-of-living adjustment (COLA) and Federal Employee Retirement System (FERS) increases. Being the smallest Center in the Agency, CVM continues to have limited means to meet these ever-increasing costs of doing business. Additionally, FDA indicated that because the ADUFA program is a relatively small program, a small change can have a significant impact on CVM’s ability to meet the ADUFA spending trigger, as required by the FD&C Act.
AHI asked clarifying questions:
- AHI asked about tools to provide information to industry including best practices, position papers, public meetings, and modifications to the eSubmitter template. FDA expressed openness to looking for ways to improve the process of providing public information. FDA explained that GFIs are not written in conjunction with industry but do involve an opportunity for public input on a draft.
- FDA further clarified steps taken to identify and remedy conflicts between existing GFIs and eSubmitter templates. FDA added that templates provide consistency for the reviewers and make it easier for them to find elements within submissions.
- The parties discussed questions on the use of BIMO inspections and ideas for certification of CROs to alleviate the need to submit raw data for every study by providing alternate methods to access the information. Both proposals are early concept and additional discussion is needed before any action is considered.
- AHI asked several questions about FDA’s discussion on budget erosion. As part of the discussion, AHI and FDA agreed the ADUFA triggers were beneficial and recognized that budget authority for the ADUFA program has increased overall since the start of ADUFA in FY 2004.
AHI proposed to improve CVM’s performance by adding comprehensive metrics, including the following additions to the traditional sentinel submission reporting: more detailed reporting for NADAs and NADA supplements, meetings, H submissions, raw data, inspections under mutual recognition, and FTEs. AHI also proposed program enhancement in the areas of raw data, clock stops, CMC cycles, CMC phased submissions, residue method trials, ADAA combinations, import tolerances, and labeling.
FDA asked clarifying questions about AHI’s proposals.
General Discussion on Raw Data, H Submission and CMC
- Raw Data: FDA and AHI discussed the idea of a public document to outline raw data expectations. FDA will create a proposal on how BIMO inspections and/or certification programs could serve in the place of submitting raw data for a study. The current data pilot will continue. AHI does not recommend QbR for prioritization.
- H submissions: FDA and AHI discussed the idea of a public document to clarify requirements for H submissions.
- CMC: FDA referred to the ideas presented earlier in the meeting for helping sponsors understand what needs to be submitted regarding CMC. FDA will assess if parallel CMC P submissions are possible for drug substances versus animal drug products. AHI does not recommend QbR for prioritization because it adds to the burden of sponsors and increases risk of human error without offering a tangible benefit to review times.
- Comprehensive Metrics: FDA sought to understand how data from the proposed metrics would benefit both FDA and sponsors. AHI had requested a metric measuring total time to NADA approval, total time in CVM, and total time with sponsor. FDA raised a question about “overlapping” reviews. FDA also noted that “context” for incompletes needed to be included to provide a reason for incomplete letters. FDA stated that they would review and provide feedback on AHI’s proposed metrics.
Integrity of the Review Process
FDA asked for AHI’s thoughts regarding whether to include FDA’s earlier proposals for supporting the integrity of the approval process and harmonization activities. FDA noted the limitations of these programs without user fee support. AHI stated that their focus is on premarket activities. FDA stated that without discussing the lifecycle of products, including post-approval activities, FDA must address as much risk as possible in the pre-approval stage. FDA noted approximately 60% of the products approved in the last five years needed substantial labeling changes after approval and the difficulty in getting sponsors to change labeling. FDA encouraged broader product lifecycle discussions to manage risks and to remain comparable to regulatory agencies outside the U.S. AHI noted that none of the post-approval topics proposed by FDA were related to the opportunity to reduce burden on premarket reviews. FDA responded that the post-approval proposals presented were directed at specific industry requests and were thought to have the highest appeal to industry. FDA further stated that other proposals were not presented due to industry having stated a lack of interest in including post-approval activities in the authorization. AHI reiterated its view that ADUFA’s original and continued intent was and is expediting the animal drug development process and the review of new and supplemental animal drug applications and investigational animal drug submissions. AHI expressed support for post-approval activities and stated the importance of budget authority to fund such efforts. FDA encouraged future discussions on how post-approval activities can impact the pre-approval process.
FDA and AHI team members agreed to discuss informally CMC topics with conversation focusing on multi-cycle reviews including CMC parallel reviews.
FDA and AHI will exchange meeting materials on December 13, 2021, for the December 16, 2021, negotiation session. The materials will include initial financial proposals and FDA’s program enhancement proposals resulting from this session.
The meeting adjourned at 3:00 pm.