ADUFA V Negotiations Meeting Minutes
November 9, 2021, 10AM – 2PM
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 discuss challenges, opportunities, and potential enhancements to 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
Elizabeth Cash, Office of Chief Counsel (OCC)
Lori Talley, OCC
Matt Lockeed, Office of Legislation
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
The meeting began at 10:00 a.m.
FDA provided responses to follow-up questions from the October 26, 2021, negotiation session. Follow-up questions related to activity time reporting (ATR) codes, hours spent by CVM supporting activities of the United States Pharmacopeia (USP), Veterinary Innovation Program (VIP) sponsors who have received fee waivers, and allowable user fee activities in the event of a lapse in government funding. In response to an AHI question regarding user fees and ATR practices, FDA clarified that employees are funded by both budget authority and user fees.
Challenges and Opportunities
Based on lesson learned activities conducted after concluding the ADUFA IV negotiations, CVM and AHI formed business process improvement (BPI) subgroups to openly discuss challenges each group faces and brainstorm ideas that both sides could implement to make progress towards addressing those challenges. FDA proposed several of the recommendations from this effort to be included in the ADUFA V negotiations.
FDA proposed the following program enhancements:
- Clarifications regarding data requirements to support study review and regulatory decision making (i.e., raw data).
- Bioresearch Monitoring (BIMO) program enhancements.
- Mutual Recognition Agreement (MRA) and Veterinary International Conference on Harmonization (VICH) enhancements.
- A proposal to support the integrity of the approval process.
- Chemistry, manufacturing, and controls (CMC) enhancements, including eSubmitter enhancements, to improve communication and time to approval dosage form specific template letters, updates to the CMC website, and prioritization of the communication activities discussed.
- Other ideas to enhance premarket review, such as clarifying the use of H submissions, clarifying what can be included in an investigational new animal drug (INAD) A-0000 (the initial submission to open an INAD file), workshops on the review process, and defining “early information.”
FDA also proposed legislative corrections related to expanded conditional approval (XCA).
AHI asked clarifying questions about the MRA and XCA-related proposals.
AHI observed that H submissions, raw data, and CMC were the areas of overlap in the FDA and AHI presentations. AHI and CVM agreed to begin the discussion with the areas of commonality before exploring the additional topics.
AHI responded to CVM’s post approval proposals by expressing their overall support for post market activities but based on the original Congressional intent for ADUFA, such topics are out of scope of negotiations and their priority is to focus on ADUFA’s original intent of expediting the animal drug development process and the review of new and supplemental animal drug applications and investigational animal drug submissions.
AHI presented a summary of priority topics for consideration as part of ADUFA V that were identified by industry to address ADUFA’s original intent of expediting the animal drug development process and the review of new and supplemental animal drug applications and investigational animal drug submissions and meet industry’s stated goals of protecting animal and public health. AHI’s presentation focused on performance and enhancements for the program. AHI’s proposals were organized into three focus areas: Performance, Enhancements, and Sustainability.
- Comprehensive Metrics: AHI proposed more comprehensive metrics for ADUFA V. Industry expressed concerns that current metrics did not measure overall time in agency review and do not meet the goal of expediting the animal drug development process. Multiple cycles of review are a concern for AHI, especially for CMC submissions. AHI would like to work with FDA to implement a strategy to reduce the number of multiple review cycles and to develop additional metrics to provide greater transparency to the review process. AHI pointed to the PDUFA Performance Report as an example of comprehensive metrics.
- Meetings: AHI proposed increasing efficient and effective interactions with the Agency by shortening the time to schedule a meeting, particularly virtual meetings, and to expedite the receipt of the memorandum of conference from FDA.
- H Submissions: AHI explained industry’s concern that members are experiencing an increased number of H submission requests with no definitive conclusion to the detriment of timely protocol concurrence. There is a perception that H submissions are used too often and can be abused to manipulate the ADUFA time clock. Therefore, AHI would like to create a performance goal around H submissions for predictability of review, as well as defining best practices for requesting and submitting H submissions.
- Responding When Complete: Industry’s view is that FDA is waiting until the due date to respond to submissions instead of responding when the review is complete.
- Shortened Reviews: AHI would like to see greater use of the shortened review process, which was put in place under ADUFA IV.
FDA responded with some initial thoughts on AHI’s proposals related to performance.
AHI then presented its proposed program enhancements.
- Raw Data: AHI would like to work with CVM to identify which raw data are to be submitted to support an animal drug approval, ensuring the raw data are commensurate with the criticality of the study.
- Clock Stops: With the goal of increasing single cycle reviews and modeled on the European Union (EU) drug application review methodology, AHI proposed the implementation of defined “clock stop” options during the individual review cycles for full new animal drug applications (NADAs), and for all individual major technical section submissions reviewed within an INAD file.
- CMC Cycles: AHI proposed creating new metrics to monitor the CMC program and addressing the fact that pre-approval inspections (PAIs) can cause incompletes in CMC technical section submissions.
- Phased CMC: AHI proposed multiple changes to the current two-phased CMC review process. Two major proposals included allowing parallel or overlapping phased CMC submissions and allowing independent CMC amendments and reactivations per phase.
- Residue Method Trials: AHI proposed saving time on residue method trials by aligning with international practices of submitting acceptable (desk review of the method) validated method(s) for residues.
- ADAA Combinations: AHI proposed concurrent review of the original NADA and application for the Animal Drug Availability Act (ADAA) combination product.
- Import Tolerances: AHI proposed a risk-based approach and improved predictability of import tolerance reviews by setting specific timelines and publishing a guidance.
- Labeling: AHI proposed utilizing the BPI process to establish a consistent labeling guideline. To increase predictability and decrease risk of delays, AHI recommended that any substantive labeling comments from FDA are provided to the sponsor prior to the completion of the label technical section.
FDA responded with initial thoughts on some of AHI’s proposed program enhancements, including a suggestion that, based on resource constraints, the clock stop proposal be focused on the traditional NADA process.
FDA noted that AHI’s presentation included many proposals. FDA requested that AHI prioritize the top three to five items so that both groups could explore those further for possible inclusion in the ADUFA V package.
AHI explained the proposals were developed through a transparent, inclusive process with members to identify, develop, and refine proposals. AHI emphasized the importance of the ADUFA program to member’s customers (Pet Owners and Producers) of ongoing improvement to the ADUFA program. To fairly consider each of the AHI proposals, AHI proposed a series of interim sessions to discuss the proposals. AHI maintains that each of the proposals presented warrants full consideration and adequate time to negotiate.
The parties agreed to discuss program enhancements prior to discussing financial proposals.
AHI and CVM discussed the original goal of the ADUFA program and also what expediting the development process and predictability of review times means to each other. Additional discussions were anticipated to gain alignment.
CVM stated that BPI activities are expected to continue after the conclusion of the ADUFA V negotiations. CVM believes some of the proposals made to date require more time for both sides to discuss and provide recommendations and that such proposals are better suited for the BPI process.
AHI and its members are focused on how to return the program focus back to its original intent of expediting the animal drug development process and the review of new and supplemental animal drug applications and investigational animal drug submissions. AHI gave examples of how the program is both increasing development costs to its members and increasing time to approval. Industry expressed concern that approval times are falling behind other international agencies. Industry cited examples and again referenced internal data from the EU showing some drugs achieving approvals in the US up to 2 years behind these established agencies. AHI believes that this purported delay in approval hurts US competitiveness and discourages companies from seeking first approvals in the US.
CVM and AHI agreed to discuss the proposals in more detail at the next meeting, which is scheduled for December 2, 2021. The two parties reached an agreement to lengthen the meeting time.
For the next meeting, FDA offered to develop a presentation regarding CMC program enhancements, H submissions, and raw data, including any metrics associated with these three topics. FDA’s presentation will include recommendations taken from the BPI subgroups and will consider AHI’s presentation from today. FDA will also present the costs of the program as it currently exists. AHI will develop a presentation on potential new metrics for the overall ADUFA program. FDA will send the agenda for the next meeting and the materials it develops relating to CMC program enhancements, H submissions, raw data, and metrics associated with these topics, to AHI by Thursday, November 18, 2021. FDA and AHI will use the December 2, 2021, meeting to discuss FDA’s proposal.
FDA will provide its interpretation of what is within scope for the ADUFA negotiations per Congressional report language regarding user fee negotiations.
The meeting adjourned at 2:10 PM.