FDA Drafts Guidance on Tentatively Approved ANDAs
In a first for the US Food and Drug Administration (FDA) during the shutdown, the agency has posted new draft guidance to assist generic drug applicants in preparing and submitting amendments to tentatively approved abbreviated new drug applications (ANDAs), including requests for final approval.“We are posting this document on the FDA website as Federal Register (FR) publication is not currently available for this document,” the agency said. “This posting is to provide advance notice to the public. When publication in the FR becomes available, this document will be available in the FR as will a notice detailing how to submit comments on this document.”
The 12-page draft guidance provides recommendations on the timing and content of amendments to tentatively approved ANDAs to help companies reach final approval on the earliest date by which the ANDA may lawfully be approved.
In the background section, the draft walks readers through the process of submitting an ANDA, discussing paragraph I, II, III and IV certifications, and explains how and why FDA would tentatively approve an ANDA.
As far as amendments to tentatively approved ANDAs, the draft explains the review goals for amendments other than requests for final approval, and it also notes what will happen to ANDAs submitted and tentatively approved under the President’s Emergency Plan for AIDS Relief (PEPFAR).
“FDA will not delay assessment of amendments to ANDAs submitted and tentatively approved under the President’s Emergency Plan for AIDS Relief (PEPFAR). Under PEPFAR, certain antiretroviral products that have been granted a TA may be distributed for use outside of the United States, even when there is still patent and/or exclusivity protection in the United States. For such products, FDA will set a goal date for assessing amendments to PEPFAR ANDAs consistent with the criteria outlined in the Amendments Guidance,” the draft says.
Requests for Final Approval
As far as requests for final approval, the draft notes that if an ANDA received a tentative approval less than three years before the earliest lawful approval date, FDA recommends that the ANDA applicant submit an amendment with enough time to permit FDA to assess that amendment before the date on which the applicant seeks approval (e.g., the earliest lawful ANDA approval date).
“If an applicant is seeking final approval of an ANDA for which the applicant has provided a paragraph III certification, FDA recommends the applicant submit the request for approval 15 months before the earliest lawful ANDA approval date,” the draft adds.
Requests for final approval that contain substantive changes to an ANDA will be classified as a major or minor amendment based on the content in the request for final approval and will be assigned a review goal date that corresponds with that classification.
And a request for final approval that contains no new data, information or other changes to the ANDA is considered a minor amendment, which FDA generally assesses within three months.
However, regardless of when a tentative approval was granted, if an ANDA applicant submits a request for final approval that contains no new data, information or other changes less than three months from the earliest lawful ANDA approval date but “(1) could have identified the earliest lawful ANDA approval date and (2) failed to submit a timely standard request for final approval, the ANDA applicant risks the application not being approved by that date.”
The guidance runs through various scenarios for ANDA applicants, such as if an ANDA has been in tentative approval status for three or more years before the earliest lawful approval date, FDA says that the lengthy passage of time since the initial tentative approval may necessitate a more extensive assessment of the ANDA before final approval may be granted.
“For example, the applicable product-specific guidance for the ANDA may have been revised; manufacturing standards may have changed; or significant RLD labeling changes may have been approved. Therefore, FDA recommends that the ANDA applicant submit the request for final approval as a major amendment,” which should be submitted 10 months before the earliest lawful approval date.
The draft guidance also discusses post-tentative approval changes that may impact final approval, such as product quality updates, labeling updates and Orange Book or exclusivity updates. In addition, the draft explains how applicant requests for final approval should clearly identify, in a cover letter, all changes to an ANDA that have been made since the tentative approval was granted.
ANDA Submissions – Amendments and Requests for Final Approval to Tentatively Approved ANDAs Guidance for Industry