On July 5, 2018, FDA issued nonbinding guidance on ANDA Submissions — Amendments to Abbreviated New Drug Applications Under GDUFA. The guidance describes to applicants how the review goals from the Generic Drug User Fee Amendments Reauthorization of 2017 (GDUFA II) apply to amendments to (1) ANDAs or (2) prior approval supplements (PASs) submitted to the FDA under the FDCA. Specifically, the guidance provides clarity on the GDUFA II’s amendment classifications and categories, including how those amendment submissions may affect an application’s review goal dates.

The guidance first provides background, explaining that the GDUFA II was enacted and accompanied with a GDUFA II Commitment Letter, where the FDA agreed to certain review goals and procedures for amendments received on or after GDUFA II’s effective date of October 1, 2017. The guidance explains that, while the FDA had previously classified amendments into a complex Tier system based on numerous factors, GDUFA II eliminates the Tier system and simplifies the amendment review goals by categorizing amendments as either standard or priority, further classifying the amendments as either major or minor, and issuing an estimated goal date based on certain factors, including whether the amendment requires a preapproval inspection.

The guidance first provides a general explanation of major and minor amendments. Regarding major amendments, the guidance provides an example of actions that would result in major amendments such as “developing new analytical procedures and providing full validation data.” The guidance further refers readers to the FDA’s list of examples of major amendments in Appendix A. Regarding minor amendments, the guidance explains that those amendments are ones that are not classified as major or ones that could be resolved through an information request or discipline review letter. The guidance adds that unsolicited amendments are amendments with information not requested by the FDA and will be classified as major or minor based on its content.

The guidance next discusses the GDUFA II review goals relating to (1) ANDAs and (2) PASs. The guidance identifies a number of factors affecting the review goals including whether the ANDA or PAS is classified as standard review or priority review, major or minor, or requiring a preapproval inspection. The guidance summarizes the FDA’s review goals for ANDAs and PASs based on these factors as seen below:

  1. Amendments to ANDAs

Submission Type

Review Goal

Standard major amendment to an ANDA

90% reviewed within 8 months of the submission date if preapproval inspection is not required

90% reviewed within 10 months of the submission date if preapproval inspection is required

Priority major amendment to an ANDA

90% reviewed within 6 months of the submission date if preapproval inspection is not required

90% reviewed within 8 months of the submission date if:

(1) A preapproval inspection is required;

(2) The applicant submits a complete and accurate PFC no later than 60 days prior to the amendment submission date; and

(3) The PFC remains unchanged at the time of the amendment submission

90% reviewed within 10 months of the submission date if:

(1) A preapproval inspection is required and

(2) The applicant fails to submit a complete and accurate PFC no later than 60 days prior to the amendment submission date or

(3) Information in a complete and accurate submitted PFC changes

Standard or priority minor amendment to an ANDA

90% reviewed within 3 months of the submission date

Unsolicited Amendments

If submitted during the review cycle, will review by the later of either (1) the goal date for the original submission or solicited amendment being amended or (2) the goal date assigned under the review goals for standard and priority review ANDAs.

If submitted between review cycles, will review by the later of (1) the goal date for the subsequent solicited amendments or (2) the goal date assigned under the review goals for standard or priority ANDAs

  1. Amendments to PASs

Submission Type

Review Goal

Standard major amendment to a PAS

90% reviewed within 6 months of the submission date if preapproval inspection is not required

90% reviewed within 10 months of the submission date if preapproval inspection is required

Priority major amendment to a PAS

90% reviewed within 4 months of the submission date if preapproval inspection is not required

90% reviewed within 8 months of the submission date if:

(1) A preapproval inspection is required;

(2) The applicant submits a complete and accurate PFC no later than 60 days prior to the amendment submission date; and

(3) The PFC remains unchanged at the time of amendment submission

90% reviewed within 10 months of the submission date if:

(1) A preapproval inspection is required and

(2) The applicant fails to submit a complete and accurate PFC no later than 60 days prior to the date of the amendment submission or

(3) Information in a complete and accurate submitted PFC changes

Standard or priority minor amendment to a PAS

90% reviewed within 3 months of the submission date

Unsolicited Amendments

Same as ANDA amendments

The guidance further discusses review goals for amendments to ANDAs and PASs submitted prior to and during GDUFA I, amendments to previously submitted amendments, amendments submitted to tentatively approved applications, and amendments submitted in response to changes in the Drug Master Files. Lastly, the guidance discusses the format of amendment submissions, including recommending applicants to include certain information with the amendment submission, and logistics for applicant requests for reconsideration of major amendment classification status.

Readers are encouraged to read the guidance, also available on FDA’s website.