Hi, I'm Michael Folkendt, Associate Director for Regulatory Affairs in the Office of Pharmaceutical Quality. This presentation will cover one of the generic drug review enhancements added as part of the Generic Drug User Fee Amendments of 2017, or GDUFA II - The Discipline Review and Information Request letters.
An important enhancement of GDUFA II is in the ANDA review process. ANDA stands for abbreviated new drug application and it refers to the application for a generic drug. New in GDUFA II is the introduction of two specific types of letters to improve communications during a review-cycle. They are Discipline Review Letters, or DRL, and Information Request Letters, or IR letters. It also should be noted that there will no longer be communications labeled as ECD, or easily correctable deficiencies.
The Discipline Review letter, or DRL, is used to convey preliminary thoughts on possible deficiencies found by a discipline reviewer, and/or a review team at the conclusion of the discipline review. It is important to note that these are preliminary findings by the primary reviewers and may or may not represent management review at the time the DRL is issued. The DRLs are expected to be issued at about the mid-point of the review cycle and each discipline is responsible for issuing their respective DRL.
For the purposes of implementing this review enhancement, the three disciplines are labeling, bioequivalence and quality. At "about the mid-point" of the review cycle is defined as the mid-point of the GDUFA review clock plus one month. The conclusion of the discipline review has occurred when, at a minimum, the primary reviewer of a discipline has read their section of the ANDA and developed preliminary thoughts on possible deficiencies.
If the discipline completes the review of additional information received in response to a DRL, another DRL may be issued until it is no longer feasible, within the current review cycle.
The information request, IR, letter is the second type of communication the applicant may receive during the review of an ANDA. The GDUFA II Commitment Letter states that an IR letter is used to request further information or clarification that is needed or would be helpful to allow completion of the discipline review. As such, it may also include a requested response time period in order to facilitate the completion of the discipline's review.
If a response is not received in a timely manner, the request may become a possible deficiency in a subsequent DRL or Complete Response letter. Note that the first IR letter may be issued as soon as the ANDA is "Received."
What is the impact? For the CDER reviewers and project managers, the review of original ANDAs must begin much earlier in the review cycle in order to complete the preliminary review prior to the mid-point of the review.
For ANDA applicants, this review enhancement provides improved predictability and transparency of the ANDA review process. Applicants can expect to receive feedback at about the mid-point of the review clock, if not earlier.
This allows the applicant and FDA an opportunity to try to resolve issues in the same review cycle and improves review efficiency by reducing the number of review cycles. This will also bring generic drug products to the market faster which will benefit the American public.
Industry plays a role in the success of GDUFA II. It starts with preparing and submitting high quality, complete applications. Once the application is submitted and received, promptly responding to IR and DRL can have a large impact on the efficiency of the review process and may lead to quicker approvals. Requested response dates may be provided in the letter to assist the applicant. When you respond to the IRs and DRLs, it is strongly recommended that you only submit the requested information and not include or submit any unsolicited information. Applicants can also benefit from previous DRLs and IRs to improve the quality of future ANDA applications.
Everyone plays a role in the successful implementation of this program - industry, reviewers, and discipline project managers.
The review process and issuance of IRs and DRLs are monitored by discipline project managers using internal dashboards as part of the CDER Informatics Platform.
You can find additional information on this topic listed on this slide.
The CDER guidance document and a MAPP will be published early in the implementation of GDUFA II.
Your OGD Regulatory Project Manager is your best source of information about review enhancements and goals related to a specific application.
The Discipline Project Manager is the best source of information about specific Information Requests and Discipline Review Letters.
Thank you for your interest.