Guidance Breakdown: Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA
Guidance Breakdown: Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA
We break down the FDA's latest draft guidance on PSG meetings and how they impact your ANDA submissions.
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The FDA's new guidance on "Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA" outlines the processes and protocols for holding meetings between the FDA and generic drug sponsors to discuss product-specific guidance (PSG).
These meetings are part of the FDA's efforts under the Generic Drug User Fee Amendments (GDUFA) to streamline the development of generic drugs and ensure that sponsors understand how new or pending PSGs could impact their drug development programs.
This guidance primarily impacts generic drug manufacturers, ANDA applications, CROs, and regulatory professionals.
We break it down below.
Introduction and background
The guidance provides recommendations on conducting PSG meetings, including pre-submission and post-submission teleconferences and meetings. These meetings help ensure that generic drug sponsors are aligned with the FDA's expectations and can efficiently develop their drug products in accordance with the latest guidelines.
PSGs provide recommendations for developing generic drugs and describe the FDA’s current thinking on the evidence needed to demonstrate that an ANDA is therapeutically equivalent to a reference-listed drug (RLD). The guidance emphasizes the importance of consulting these PSGs when considering bioequivalence (BE) studies or other related studies.
Meeting types
The guidance outlines three types of meetings:
1. PSG Teleconferences
These offer a platform for ANDA applicants to obtain FDA's feedback on the potential impact of a new or revised PSG on their ongoing drug development programs. This is particularly critical when an applicant has already started or completed a bioequivalence BE study before the publication of the PSG.
During these teleconferences, the FDA will review the recommendations in the PSG, provide feedback on their potential impact on the applicant's development program, and suggest further communication methods like controlled correspondence or additional meetings if needed. There are two types of PSG teleconferences:
Pre-Submission PSG Teleconferences: These teleconferences are held before the ANDA submission when a new or revised PSG introduces or revises recommendations related to an in vivo BE study. If an applicant has commenced an in vivo BE study prior to the PSG's publication, they can request this teleconference to discuss how the new recommendations may affect their study.
Post-Submission PSG Teleconferences: These take place after an ANDA has been submitted. They are requested when a new or revised PSG introduces changes that could affect an ongoing or completed in vivo BE study. Additionally, if a new PSG recommends an in vivo BE study that the applicant has not conducted, or if a revised PSG introduces an in vivo BE study requirement where none existed before, a post-submission PSG teleconference can be requested to assess the impact on the submitted ANDA.
2. Pre-Submission PSG Meetings
Pre-submission PSG meetings provide a forum for prospective ANDA applicants to discuss the scientific rationale for pursuing an alternative approach to the recommendations outlined in a PSG. These meetings are crucial when an applicant believes their approach, which differs from the PSG, is scientifically justified and compliant with regulatory requirements.
Timing-wise, these meetings are requested after a pre-submission PSG teleconference but before the actual submission of the ANDA. The purpose is to ensure that applicants receive FDA feedback on their alternative approach before finalizing their ANDA submission.
These discussions focus solely on the applicant's proposed alternative BE approach and whether it adequately demonstrates bioequivalence in accordance with the relevant statutes and regulations. The FDA will not address questions unrelated to the alternative approach during these meetings.
3. Post-Submission PSG Meetings
Similar to pre-submission meetings, post-submission PSG meetings allow ANDA applicants to discuss their scientific rationale for an alternative approach after the ANDA has been submitted. These meetings help address issues that may arise from a new or revised PSG after an ANDA submission and during its assessment by the FDA.
These meetings are typically requested after a post-submission PSG teleconference. However, the FDA advises applicants to consider the timing of the request carefully, especially in relation to the ANDA’s assessment cycle. For instance, it may be beneficial to wait until after receiving a Discipline Review Letter (DRL) or Complete Response Letter (CRL) before requesting a post-submission PSG meeting.
Discussions during these meetings are focused on the alternative BE approach proposed by the applicant, particularly in response to new PSG recommendations that affect the ongoing ANDA review. Similar to pre-submission meetings, only questions directly related to the alternative approach will be addressed.
GDUFA III performance goals
The FDA's commitment under GDUFA III includes specific performance goals for scheduling and conducting PSG meetings. These goals ensure timely interactions between the FDA and ANDA applicants:
PSG Teleconferences: If a PSG teleconference request is granted, the FDA commits to holding the teleconference within 30 days of the request.
Pre-Submission PSG Meetings: The FDA must grant or deny the meeting request within 14 days of receiving it. If granted, the meeting is scheduled within 120 days of the request.
Post-Submission PSG Meetings: Similar to pre-submission meetings, the FDA must respond to the request within 14 days. If the request is granted, the meeting is scheduled within 90 days of the request.
These timelines ensure that applicants receive timely feedback, allowing them to make informed decisions about their development programs and ANDA submissions.
Meeting requests
Submitting a meeting request requires careful attention to detail, as the FDA has outlined specific requirements for each type of meeting.
Firstly, all meeting requests must be submitted electronically. Pre-submission PSG teleconferences and meetings are submitted through the CDER NextGen Portal, while post-submission PSG teleconferences and meetings are submitted through the Electronic Submissions Gateway (ESG).
Secondly, firms need to make sure they include all the required information:
ANDA Number or Preassigned ANDA Number: The request must include the ANDA number if applicable or the preassigned ANDA number for pre-submission requests.
Meeting Type: The specific type of meeting being requested must be clearly stated.
PSG Publication Date: The month and year of the PSG's publication must be provided.
Summary of BE Study Differences: A detailed summary of how the applicant’s BE study deviates from the PSG recommendations is required.
Signature Page of BE Study Protocol: If the request involves a BE study, the signature page of the relevant in vivo BE study protocol, signed by the study sponsor and/or contract research organization, must be included.
RLD Details: Information on the RLD, including its application number, established name, dosage form, route of administration, strength(s), and proposed indications, is required.
Contact Information: The name, title, affiliation, secure email address, and phone number of the person responsible for coordinating the meeting must be provided.
Meeting Package: A comprehensive meeting package must be submitted alongside the request. This package should include background information, the proposed agenda, and a list of attendees from the applicant’s organization.
Evaluating meeting requests
The FDA evaluates meeting requests based on their completeness and the questions' relevance.
The key factors considered during this evaluation include:
Completeness of the Request: A meeting request must include all required documentation and information as specified by the FDA. Incomplete requests are likely to be denied.
Relevance of Questions: The questions posed in the request must be relevant to the type of meeting being requested. For example, questions for a pre-submission PSG meeting must focus on alternative approaches to the PSG recommendations. If the FDA determines that the questions could be better addressed through controlled correspondence or another meeting type, the request may be denied.
Denial Reasons: Common reasons for denial include incomplete submissions, requests that overlap with other ongoing communications, or situations where the FDA believes the issues are more appropriately addressed through alternative means.
Rescheduling and canceling meetings
The FDA guidance outlines clear protocols for rescheduling or canceling meetings. Rescheduling a meeting is generally discouraged unless absolutely necessary. If a meeting must be rescheduled, the FDA aims to do so as soon as possible without requiring a new meeting request. Reasons for rescheduling might include the unavailability of essential attendees or the need for additional information from the applicant.