FDA issues guidances on facility readiness and early DMF assessments under GDUFA III

Regulatory NewsRegulatory News | 04 October 2022 |  By 

The US Food and Drug Administration’s (FDA) on 3 October released two draft guidances that implement new enhancements under the new Generic Drug User Fee Act (GDUFA III) program. One guidance covers FDA’s criteria for assigning a review goal date based on facility’s readiness for inspection, and the other addresses the early assessment of drug master files (DMFs) prior to the submission of generic drug applications.
These program enhancements were specified in the GDUFA III commitment letter released in November 2021. (RELATED: GDUFA III commitment letter details coming changes to FDA’s generic review program, Regulatory Focus 2 November 2021)
The guidances were also published on FDA’s newly launched GDUFA III web page; the webpage is designed to share information related to GDUFA III enhancements.
Facility readiness
In the guidance on facility readiness, FDA addresses how it intends to assign a goal date based on a generic drug manufacturing facility’s readiness for inspection, as certified on Form FDA 356h.
Per the commitment letter, a firm can denote on an FDA Form 356 whether if it ready or not ready for an inspection. If a firm is not ready for an inspection, it will be assigned a 15-month review goal date.
The guidance states that “an applicant can amend its original [abbreviated new drug application] ANDA to reset the 15-month goal date to a standard or priority assessment goal, as applicable, once all facilities become ready for inspection. However, the commitment letter also explains that for an application that continues to include a facility not ready for inspection 30 days before the 15-month goal date expiration, FDA will reset the goal date for an additional 15 months.”
FDA considers a facility ready for inspection if it complies with current good manufacturing practice (CGMP) requirements; the facility operations, methods, and product formulation are the same as those described in the application and the data at the facility are complete and accurate and are consistent with data in the applications; and the facility is ready for commercial manufacturing.
“FDA has experienced cases where facilities were not aware they were listed on Form FDA 356h,” said the guidance. “This often results in a greater likelihood that a facility will be unprepared for an inspection.”
The guidance does not cover facilities involved in bioequivalence studies, amendments submitted after a complete response or tentative approval letter, or amendments to a supplement.
Early assessment of Drug Master Files
The second guidance describes instances when an early assessment of a Type II active pharmaceutical ingredient (API) DMF can be submitted prior to an ANDA or prior approval supplement (PAS) that reference the DMF.
The GDUFA III commitment letter specifies that to eligible for early assessment, a DMF holder should submit at least one of the following: a Letter of Authorization (LOA) with one pre-assigned ANDA number; a reference to the corresponding reference listed drug (RLD) listed in in FDA’s Orange Book; or documentation attesting that the DMF holder has paid a GDUFA DMF fee.
In addition, FDA said that one of five criteria must be met to qualify:
  • “All patents and exclusivities on the product will expire within 12 months of the planned submission date;
  • The submission is for a drug product for which there are not more than three approved drug products listed in the Orange Book, for which there are no blocking patents or unexpired exclusivities listed for the RLD…;
  • The submission is for a drug product that could help mitigate or resolve a drug shortage and prevent future shortages, including submissions related to products that are listed on FDA’s Drug Shortage List at the time of the submission of the DMF assessment request;
  • The submission is for a drug product that either could help address a public health emergency declared by the Secretary of the U.S. Department of Health and Human Services under section 319 of the Public Health Service Act (PHS Act); or anticipated under the same criteria as apply to such a declaration; or
  • The submission is for a drug product for which (a) there is only one approved drug product listed in the Prescription Drug Product List (i.e., the “Active Section”) of the Orange Book and that product is approved under an ANDA (i.e., the RLD is in the “Discontinued Section” and there is not more than one ANDA in the “Active Section”); (b) the approved ANDA for the drug product listed in the “Active Section” was not approved pursuant to a suitability petition under section 505(j)(2)(C) of the FD&C Act; (c) there are no blocking patents or exclusivities for the RLD; and (d) the submission does not qualify for prioritization under any other factor listed in MAPP 5240.3: Prioritization of the Review of Original ANDAs, Amendments, and Supplements.”
FDA draft guidance on facility readiness
FDA draft guidance on DMFs


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