In late July 2021, the United States Food and Drug Administration (FDA) finalized guidance on expectations for field alert reports (FARs) for potentially defective drugs on new drug applications (NDAs) and abbreviated new drug applications (ANDAs). Currently, the FDA requires that NDA and ANDA applicants submit FARs within 3 working days or receiving information that its drug product (or its labeling) may be mistaken for another product and when applicants receive any information on bacterial contamination; any significant chemical, physical or other change/deterioration in the distributed drug product; or any failure of a distributed batch to meet the specification established for it in the application.
To help determine whether a chemical, physical, or other change or deterioration in the distributed product is significant, manufacturers should evaluate the potential impact the change has on the identity, strength, purity, and stability of the product as well as consider the potential impact on efficacy. In making that determination, the manufacturer should consider the products intended use, route of administration, dosage, length of treatment, and patient population.
The guidance clarifies that FAR reporting requirements only apply to products that have been distributed and therefore, it a batch failed specifications but has not yet been distributed, manufacturers do not need to submit a FAR.
Additionally, the guidance confirms that FAR reporting applies not only to finished drugs but also to packaging components (active and inactive ingredients, processing aids, etc.), such as stopper vials, if the manufacturer receives information that the vials “could result in contamination of a distributed batch.”
FDA also clarifies that if the manufacturer resolves the root cause within 3 working days of its identification, the manufacturer must still submit a FAR. Failure to submit a FAR within the three-day time frame results in a violation of both § 314.81(b)(1) and section 505(k) of the Federal Food, Drug, and Cosmetic Act. If you miss the three day timeline, you must still submit the required FAR after the fact.
The FDA also recommended (but does not require) that applicants file voluntary follow-up and final FARs. Such filings would help the FDA “assess the problem, risk to public health, and status and adequacy of your corrective action, or your determination that there was no actual defect as initially suspected.”
Draft Revisions
The final guidance only includes a handful of revisions from the 2018 draft guidance, including clarification that the FAR requirements apply to positron emission tomography drugs, designated medical gases, and combination products that contain a drug constituent under an approved NDA or ANDA. Another point of clarification found in the final guidance is that if products under an approved NDA or ANDA are produced domestically but do not have any US-labeling and are only marketed abroad pursuant to a foreign label, they are not subject to FARs reporting.