Today, FDA revised the final guidance for industry entitled, “ANDA Submissions – ANDA under GDUFA.”
This guidance describes how the assessment goals under the most recent reauthorization of the GDUFA III apply to amendments to either ANDA or PAS submitted to FDA.
This guidance also details amendment classifications and explains how amendment submissions may affect an application’s assessment goal dates.
FDA considers each submission to an application under assessment to be an amendment. These submissions will be classified based on the content submitted and issued a goal date consistent with that classification, in addition to other considerations in the GDUFA III Commitment Letter.
The types of amendments and assessment goals described in this guidance only apply to submissions that have been received for substantive assessment.
This guidance replaces the July 2018 guidance for industry of the same name.
The revisions address comments received to the 2022 public docket requesting input on appendix A of the guidance, which includes a non-exhaustive list of examples of deficiencies that FDA may consider major. FDA considered all comments carefully, and made changes to the guidance language, including clarifying many of the examples listed in appendix A and making other minor edits to reflect GDUFA III commitments.
CATEGORIES OF GDUFA AMENDMENTS
This guidance provides a detailed description of major and minor amendments:
Major Amendments
Examples of actions that, if requested or taken in response to deficiencies, would result in major amendments include:
- Manufacturing a new batch of drug product for any reason (e.g., a composition change or reformulation, a change in the source of a drug substance, a change in the manufacturing site, the need for a new bioequivalence (BE) study, a new in vitro study for a specific product, a change in a major manufacturing process, a new strength of the product, unacceptable impurities or impurity levels, unacceptable excipients found during assessment, failed stability data, or a change in the container-closure system (other than solid oral dosage forms)).
- Performing a new BE study whether or not related to the manufacture of a new batch or different formulation of the drug product.
- Developing new analytical procedures and providing full validation data.
Minor Amendments
Generally, minor amendments are those not classified as major or are a response to a deficiency that could be adequately resolved through an IR or certain DRLs. Minor amendments often consist of responses to deficiencies that are more easily addressed than those in a major amendment and typically require less extensive assessment by FDA. Examples of minor amendments include responses to:
- Minor deficiencies in the drug substance
- Incomplete dissolution data
- Labeling deficiencies that have not been adequately addressed in response to an IR
Unsolicited Amendments
An unsolicited amendment is an amendment with information not requested by FDA except for those unsolicited amendments considered routine or administrative in nature that do not require scientific review (e.g., requests for final ANDA approval, patent amendments, and general correspondence).
The unsolicited amendment will be classified as either major or minor based on the content of the amendment. For example, if an unsolicited amendment contains information that addresses any of the major deficiencies identified in this guidance, the unsolicited amendment will be classified as major.
Following information is important from DMFs perspective:
Amendments Submitted in Response to Changes in the DMF
A) Changes made to a DMF referenced in an ANDA that may impact the safety, efficacy, quality, or substitutability of the drug product (e.g., new facilities added by the DMF holder that need to be addressed by the applicant in an amendment to the ANDA) may be considered unsolicited amendments to the ANDA and therefore may extend existing assessment goals or may result in a CRL being issued to the ANDA.
B) Reference to an unreviewed secondary DMF or inclusion of a technical dossier from a third-party containing significant additional manufacturing information, which is introduced after the initial review of the primary DMF.
C) Reference to a DMF that is inadequate with respect to certain microbiological quality issues such as failure to provide sterilization validation information.
Refer to original guidance for more information: ANDA Submissions | Amendments to Abbreviated New Drug Applications Under GDUFA
