FDA Guidance Breakdown: Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act

On 5 February 2024, FDA issued draft guidance intended to assist applicants and manufacturers in providing FDA with timely, informative notifications of changes in the production of certain finished drugs and biologics and certain APIs, which in turn may assist the agency in its efforts to prevent or mitigate shortages. The draft guidance also explains how FDA will communicate information about shortages to the public.

Introduction and Background

The guidance addresses notification requirements under Section 506C of the FD&C Act and FDA regulations. It emphasises the importance of timely notification to prevent and mitigate drug shortages. It also outlines the legal bases designed to address drug shortages, including amendments to FDASIA and the CARES Act.

Main Content

Who must notify FDA?

The guidance requires manufacturers of approved NDAs, ANDAs, or BLAs for certain finished products (including finished products that do not require approval but meet specific criteria) to submit a notification.

What products are subject to notification?

The guidance specifies the reporting requirements for prescription medications and biological products critical for life support or treating serious conditions. It includes products vital for sustaining life or necessary for continuing key bodily functions, those aimed at preventing or treating debilitating diseases with significant health impacts, and items essential for public health in an emergency as declared by the Secretary under the Public Health Service Act. Radiopharmaceuticals and other FDA-specified exclusions are not covered by these criteria.

When to notify?

The guidance introduces a six-month notification requirement for the FDA to address potential supply disruptions effectively. It acknowledges situations where meeting this timeframe might be impractical and sets forth the expectation for notifying the FDA as promptly as feasible under such circumstances.

What information should include?

Notifications should include comprehensive details about the product, the reasons for stopping or interrupting its production, and any issues affecting the availability of active or inactive components.

How to notify FDA?

Manufacturers of covered finished products regulated by CDER: submit initial notifications via email to drugshortages@fda.hhs.gov or through the CDER Direct NextGen Portal.

Manufacturers of covered finished products regulated by CBER: submit initial notifications via email to cbershortage@fda.hhs.gov.

All additional updates should be submitted by email to the applicable Center (CDER or CBER), not through the NextGen Portal.

Failure to notify

If the applicant fails to notify the FDA as required, the FDA will send the applicant a noncompliance letter, which the applicant must return to the FDA within 30 days of the date of issuance, explaining the reasons for the noncompliance and information about the suspension or discontinuance.