GDUFA III commitment letter details coming changes to FDA's generic review program

Regulatory NewsRegulatory News
| 02 November 2021 | By Michael Mezher 

With the negotiations for the third iteration of the Generic Drug User Fee Amendments (GDUFA III) program completed, the US Food and Drug Administration (FDA) has released the commitment letter laying out its performance goals and the program enhancements that will shape the program over the next five years.
 
The commitment letter follows a year-long process of meetings and negotiation sessions to gather input from the public, industry and other stakeholders on the agency's generic drug review program and is nearly twice the length of the GDUFA II commitment letter released more than five years prior. (RELATED: FDA kicks off GDUFA III reauthorization process, Regulatory Focus 21 July 2020)
 
"New enhancements to the program are designed to maximize the efficiency and utility of each assessment cycle, with the intent to reduce the number of assessment cycles for abbreviated new drug applications (ANDAs) and facilitate timely access to quality, affordable, safe and effective generic medicines," FDA writes in the letter. The agency also notes that some of the enhancements specifically pertain to complex generic products.
 
Several issues throughout the negotiation sessions with industry proved to be sticking points between the agency and industry, though the two sides have worked through some of those in order to get to the commitments laid out in the letter. In total, FDA and industry met three dozen times in 2020 and 2021 and FDA held eight separate meetings with stakeholders on the upcoming program. (RELATED: Capacity adjustments, DMFs under discussion for GDUFA III, Regulatory Focus 12 May 2021; Regulatory science pilot floated in BsUFA III negotiations, Regulatory Focus 15 July 2021).
 
While the GDUFA III program contains numerous changes from GDUFA II, the agency's commitments surrounding goal dates for standard and priority original ANDAs, prior approval supplements (PASs) and amendments to such submissions are largely unchanged.
 
One notable change from GDUFA II is that FDA will now extend the review goal to 15 months for standard or priority original ANDAs where the site or facility listed in the submission is not ready for inspection. "FDA will conduct a filing review of such an ANDA but will not commence the substantive assessment of the application until an amendment … is submitted, or the goal date is reset," FDA writes.
 
The agency notes that it will move the goal date forward if the applicant submits an amendment with Form FDA 356h certifying that all facilities are ready for inspection to eight months from the date of the submission for a priority original ANDA or 10 months for a standard ANDA. If the amendment is not submitted prior to 30 days before the goal date, FDA says it will tack on another 15 months to the goal date and commits to reviewing and acting on 90% of such ANDAs within 30 months of the date of the original submission.
 
How certain types of correspondence are handled will shift compared to GDUFA II. Correspondence from applicants following a complete response letter (CRL), tentative approval, or ANDA approval will be considered controlled correspondence under GDUFA III. "During an ANDA assessment cycle, a Controlled Correspondence may only be submitted if an applicant seeks further feedback from FDA after a product-specific guidance (PSG) Teleconference … or to seek a Covered Product Authorization. During an ANDA assessment cycle, all other correspondence will be general correspondence," FDA explains.
 
GDUFA III tweaks the agency's approach to determining whether to receive an ANDA, with the goal of making such a determination within 60 days of submission. FDA commits to communicating minor technical deficiencies to applicants within 10 days of receipt, and if such deficiencies are resolved within 10 days, they will not be used as the basis for a refuse-to-receive decision.
 
The new agreement also sets new goals for FDA's response to suitability petitions, including to "work diligently to enhance [its] processes for reviewing and responding to petitions submitted … and to review and respond to pending suitability petitions in FY2023. From FY2024-2027, FDA will conduct completeness assessments for suitability petitions submitted during that time and strive to respond within six months. FDA's goal on responding to suitability petitions within the goal timeframe scales from 50% in FY2024 to 90% by FY2027, with a cap on the total number of petitions the agency will be held to responding to in each year.
 
The letter explains that responses to major deficiencies, or "minor deficiencies that include data and information that require comparable FDA assessment resources to those required for major deficiencies … will be considered Major Amendments," and will extend the goal date by the number of months needed to assess a comparable standard or priority major amendment.
 
It also outlines several scenarios for "imminent actions" in which FDA would continue its review of an ANDA past its goal date if it could be approved within 60 days of the goal date. One potential scenario in which an imminent action could play out is when extending the review would allow FDA to issue a full approval instead of a tentative one. In such circumstances, the commitment letter says the goal date would b considered to have been met if the application is approved or tentatively approved within 60 days of its initial goal date.
 
To help spur the development of more complex generics, FDA has committed to including product specific guidances (PSGs) for complex products in its goal for PSG development. Under GDUFA II, FDA was not held to a specific goal for issuing PSGs complex products. In GDUFA III, FDA commits to issuing PSGs for 50% of new complex products within two years after approval and 75% by three years after approval beginning in FY2023.
 
Another major change under GDUFA III is the establishment of the ANDA Assessment Meeting Program, which aims to provide "targeted, robust advice to ANDA applicants as thy work to meet the standards for ANDA approval. The program will offer both mid-cycle review meetings and enhanced mid-cycle review meetings to give applicants the opportunity to ask the agency about deficiencies identified in discipline review letters (DRLs). Applicants will also have the ability to request a post-CRL scientific meeting to "provide an applicant scientific advice on possible approaches to address deficiencies identified in a CRL related to establishing equivalence."
 
FDA

 

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