FDA Communications and Meetings Chapter 4 FDA Communications and Meetings

Introduction Good communications between FDA and the industries it regulates are key to successful product development and promoting an understanding of the regulation process and regulatory compliance. Understanding the various types of communications and meetings, their purposes, formats and timelines is critical to the success of regulatory professionals and the organizations they represent and is vital if they are to achieve their desired objectives in the most efficient and effective way.

Types of FDA Communications Four basic types of regulatory interactions apply to drugs, biologics and devices: regulatory communications product application meetings administrative meetings and communications public administrative proceedings Significant guidances issued by FDA address the above interactions. They describe for sponsors when and how to request and execute the various administrative communications and meetings. Following the published guidances has numerous benefits, such as: Design testing and development plans that will expedite reviews and approvals Saving sponsors time and money Providing a more collaborative approach Significantly reducing the possibilities of development surprises

Regulatory Communications 21 CFR 10 (Administrative Practices and Procedures) – governs practices and procedures for preparing and communicating FDA regulations, guidances and recommendations. Regulations: with limited exceptions, regulations are published in the Federal Register available for public comment and are generally subject to a 60 day comment period Guidance Documents: describe FDA’s current thinking on a topic should be viewed only as a recommendation unless specific regulatory or statutory requirements are cited differ from a regulation because they are non-binding (not legally enforceable) on FDA or the public Recommendations: FDA’s advice on specific regulatory policy Disseminated in the Federal Register or via emails to a specific audience Provide specific advice that does not involve direct regulatory action under law

Regulatory Communications (Continued) Three (3) Types of Regulatory Communications – Citizen Petitions, Suitability Petitions and Advisory Opinion 1. Citizen Petitions: A formal written request to FDA asking to take or refrain from taking an administrative action FDA must respond within 180 days of receipt Petition should contain: action requested, statement of grounds, environmental impact, economic impact and a certification by the submitter 2. Suitability Petitions: Specific type of citizen’s petition used to file an abbreviated application for new human or animal drug whose active ingredients, route of administration, dosage form or strength differ from that of the approved drug FDA will approve or deny a suitability petition within 90 days of submission date 3. Advisory Opinion: FDA’s formal position on a matter FDA statements of policy, such as the preamble to a final rule or the Compliance Policy Guides Manual, constitute advisory opinions

Product Application Meetings Three (3) main types of product application meetings for pharmaceuticals and biologics: Type A, Type B and Type C (Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants) communications and meetings are requested at critical product development points to establish or confirm that a company’s product development plan will lead to an FDA marketing approval. application meetings requested by sponsor and are private, two-way communications (either by phone or in person) between FDA and the sponsor meetings follow a systematic approach and well-established FDA procedures FDA Guidance advises notifying appropriate review division CDER or CBER prior to submitting an official request for all types of meetings official meeting requests should be submitted to the appropriate review division in writing and should include a complete listing of questions the sponsor wishes to address or resolve clearly explain the rationale for the request and the issues to be discussed FDA reserves the right to grant or deny Type A, B or C meeting requests If denied FDA will include an explanation for the denial; notification from FDA for Type A meetings usually occur within 14 days and within 21 days for Types B and C

Product Application Meetings (continued) 1. Type A Meeting: immediately necessary to resolve issues with a product submission- one delaying FDA’s view generally reserved for dispute resolution, discussion of clinical holds or Special Protocol Assessments a Type A meeting should be held within 30 days of FDA’s receipt of a written request meeting package should be submitted to FDA at least four weeks before the meeting 2. Type B Meeting: Pivotal development meetings that occur prior to progression to the next development stage Should be discussed with appropriate review division before submission of formal request Will be scheduled within 60 days of receipt of written request Sponsor should submit a meeting package at least four weeks before the formal meeting

Product Application Meetings (continued) Type B meetings generally occur in the following order: Pre-Investigational New Drug (IND) meetings (21 CFR 312.82) Certain End-of-Phase 1 meetings (21 CFR 312.82) End of Phase 2 meetings/Pre-Phase 3 meetings (21 CFR 312.47) Pre-NDA/Biologic License Application (BLA) meetings (21 CFR 312.47) Sponsors should only request one of each of these Type B meetings (pre-NDA meeting is intended to discuss formatting of the submission) 3. Type C Meeting: discussion of any other product development meeting not included in Type A or B meeting will be scheduled within 75 days of receipt of a written request process for requesting a meeting is the same as for Types A and B. meeting packages should be submitted to FDA at least four weeks before the formal meeting

Product Application Meetings (continued) Meeting Requests by Sponsors or Applicants Should Include: product name application number, if applicable and assigned chemical name and structure proposed indication(s) or context of product development type of meeting requested (Type A, B or C) brief statement of the meeting purpose and objectives (The statement should include a brief background of the issues underlying the agenda. It should provide enough information to facilitate understanding of the issues.) proposed agenda list of proposed questions grouped by discipline (For each question, there should be a brief explanation of the context and purpose of the question.) list of individuals (including titles) who will attend the meeting representing the sponsor’s organization list of FDA staff, by title or discipline, requested by the sponsor to participate in the meeting suggested dates and times for the meeting meeting format (face-to-face, teleconference or videoconference)

Product Application Meetings (continued) Meeting packages generally should include the following information: product name and application number (if applicable) chemical name and structure proposed indication dosage form, route of administration and dosing regimen an updated list of sponsor or applicant attendees, affiliations and titles background section that includes: a brief history of the development program and the events leading up to the meeting the status of the product development (e.g., the target indication for use brief statement summarizing the purpose of the meeting Proposed agenda list of final questions for discussion grouped by discipline with brief summary of each question to explain the need or context of the questions data to support discussion organized by discipline and question

Product Application Meetings (continued) Communications During and After FDA Meetings: Assign individuals to take careful notes during the meeting Make a summary of the minutes of the meeting available to all participants for review and comment then publish internally FDA will prepare official meeting minutes, summarizing meeting outcomes, agreements, unresolved issues and action items Generally within 30 days of the formal meeting FDA will issue the official minutes to the sponsor In rare case where FDA exceeds the 30 day limit, the sponsor may consider submitting to FDA its formal meeting minutes

Table 4-1. Description of FDA Product Application Meetings and Timing   Type A Meeting Type B Meeting Type C Meeting Meeting description Dispute resolution Clinical holds Special Protocol Assessment (SPA) Pre-IND EOP1 EOP2 Pre-NDA/Pre-BLA Any other meeting not identified as Type A or B meeting Confirmation of scheduling following sponsor request 14 days from time of request 21 days from time of request Timing window for meeting to occur 30 days from time of request 60 days from time of request 75 days from time of request Briefing information and relevant questions for discussion due to FDA 14 days prior to meeting 28 days prior to meeting

Medical Device Application Meetings There are five (5) basic types of meetings available to sponsors of medical device applications submitted to CDRH: Agreement Determination Pre-Investigational Device Exemption (Pre-IDE) Pre-PMA PMA day 100 Agreement Meetings: CDRH reach concurrence on key parameters of the investigational plan Sponsor intending to perform a clinical study of any class of device has the opportunity to present its investigational plan to FDA and obtain agreement on the plan before applying for an IDE Agreements reached in the meeting are binding on FDA and can only be changed with written agreement of the sponsor or when there is a substantial scientific issue essential to determining the device’s safety or effectiveness

Medical Device Application Meetings (continued) Determination Meetings: limited to PMAs or PDP (product development protocol) applications determine the type of valid scientific evidence required to demonstrate that a device is safe and effective for its intended use discussions will include types of clinical studies and other types of evidence to support effectiveness, and the least burdensome way of evaluating effectiveness Pre-IDE Meetings: established, formal medical device collaboration meetings purpose is to expedite the regulatory review process and minimize product development delays provide sponsor an opportunity to present product development plan to FDA and obtain official acceptance pre-IDE meeting does not need to occur prior to filing an IDE and is also available for medical devices that do not require an IDE may address items such as but not limited to: analytical protocols, clinical protocols, proposed study designs, statistical plan, preclinical (animal) safety testing to support initiation of a clinical trial, guidance on significant versus non-significant device determinations, feasibility study protocols, guidance on appropriate regulatory approval pathways

Medical Device Application Meetings (continued) 4. Pre-PMA Meetings: intended to help guide the development of PMA submissions include such topics as result of pre-clinical testing not included in the IDE submission, reliability testing, and CMC issues and clinical results may also discuss formatting PMA Day-100 Meetings: Scheduled to occur 100 days after a PMA is accepted for filing Discuss the application’s review status and obtain any additional information needed to complete the PMA review FDA will inform applicant in writing of any identified deficiencies and what additional information is required to correct those deficiencies or complete the review

Administrative Meetings and Communications Administrative Meetings or communications: Are ad hoc, private two-way communications (phone, mail or in person) between FDA and outside parties on matters within FDA’s jurisdiction Used to discuss scientific issues that warrant discussion with the FDA

Public Administrative Proceedings Public’s demand for greater transparency of FDA policy and procedures Four (4) types of Public Administrative Proceedings (meetings) 1. formal evidentiary hearings 2. public board of inquiry 3. hearing before the commissioner 4. Advisory Committee meetings Public Administrative meetings generally occur as needed, except Advisory Committee meetings which usually occur prior to the PDUFA action date occur as specified by regulations, ordered by commissioner or requested by sponsors and approved by commissioner

Public Administrative Proceedings (continued) 1. Evidentiary Hearing: administrative equivalent of a civil court hearing with comparable preparation and procedural controls occur when specifically provided by law, when mandated by congress, or when ordered by FDA commissioner to discuss public health concerns for a product or review proposed guidances such as Risk Evaluation and Mitigation Strategies (REMS) reference 21 CFR 10.50 Board of Inquiry: called when specifically authorized by regulation, at the discretion of the FDA commissioner or as an alternate to a formal evidentiary public hearing a hearing to review medical, scientific and technical issues Proceedings are conducted as scientific inquiry and therefore are not comparable to a legal trial Public Hearing: occurs when the commissioner determines that it is in the public interest to permit persons to present information and views at a public hearing on matters pending before the agency (21 CFR 16) Intended to solicit general views and information from interest parties on a particular topic

Public Administrative Proceedings (continued) Advisory Committee Meetings: Held by FDA to obtain recommendations and advice from subject matter experts on the safety and efficacy of foods, drugs, biologics and medical devices Composed of independent experts and public representatives Provide medical expertise on product approvals, labeling conditions, scientific issues and research projects The Food and Drug Administration Amendment Act of 2007 (FDAAA) explicitly mandates that FDA must either convene an Advisory Committee panel for all new molecular entities or provide a written explanation as to why one is not required 50 advisory committees organized by the different centers in FDA, each committee is subject to a 2 year renewal Two types of committees: technical advisory committees - focus on product-related regulatory decisions; policy advisory committees – focus on general policy issues Format of a typical advisory committee meeting: FDA provides the committee with a packet of questions to guide the discussion; open to the public; 45-90 minute presentation by the drug, biologic or device sponsor; presentation by FDA; public comment period; Q & A session, deliberation session and a vote

Advisory Committee Meetings (continued) any individual or company presenting at an Advisory Committee must understand that if any of the information declared as proprietary has been shared in a public forum, such as a scientific meeting, filed under patent, published, given to a customer, provided to financial analysts and stockholders or otherwise distributed upon request, it is not exempt from disclosure. Advisory Committee votes or recommendations are not binding on FDA but they are given significant consideration In 2008, FDA issued the following final guidance documents on Advisory Panels: Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committee Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members’ Financial Interest Information and Waivers Guidance for FDA Advisory Committee Members and FDA Staff: Voting Procedures for Advisory Committee Meetings Guidance for Industry: Advisory Committee Meetings—Preparation and Public Availability of Information Given to Advisory Committee Member