The U.S. Food and Drug Administration, FDA, recently finalized its guidance on expectations for submitting Field Alert Reports (FARs) for potentially defective drugs. The final document supersedes a draft guidance that was issued in July 2018.
The FDA requires submitting FARs within 3 working days of receiving information that the drug product or its labeling may be mistaken for another product. Additionally, FARs must be submitted when applicants receive any information on microbial contamination, or any significant chemical, physical, or other change or deterioration in the distributed drug product; or any failure of a distributed batch to meet the specification. This requirement applies to any product approved under a new drug application or as a generic drug, including drug-device combination products.
Manufacturers still have to submit a FAR even if a root cause of a problem related to a distributed drug product is identified and corrected within 3 working days.
Questions and Answers
What is a FAR and what triggers its submission?
According to the agency, FARs are part of an early warning system to protect patient health. Submission of FARs should take place by using Form FDA 3331a. In that form, the term problem refers to the incident or possible / actual quality issue that is the subject of the FAR. Not every consumer complaint warrants submission of a FAR. Such complaints should be evaluated within 3 working days to determine if the information provided in the complaint meets the FAR criteria. If a recall is initiated after an initial FAR is submitted, FDA encourages submitting a follow-up or final FAR at the time of the recall notification. Moreover, a recall notification is not a substitute for a required FAR submission.
The applicants of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) have to submit the FAR. If there is a contractual agreement with another person or entity to perform manufacturing, holding, packaging, labeling, or distribution activities or services, the applicant is still responsible for submitting the FARs within 3 working days. Agreements with contracted entities should establish a procedure to ensure that FARs are submitted as required.
When should I submit a FAR?
The FDA considers working days to be any day from Monday through Friday, excluding U.S. Federal holidays. For example, if information meeting the criteria requiring a FAR is identified on Friday (Day 0), then Day 1 begins on the first working day after the information is identified (Monday), and the FAR has to be submitted on Wednesday (Day 3). This time frame applies regardless of where the information is identified (e.g. the day a contract lab learns of a sterility failure is Day 0). An FDA finding (e.g. during an inspection) regarding a failure to submit a FAR, as required, may result in a regulatory action, whether or not the finding was cited on Form FDA 483.
How do I submit a FAR?
The FDA recommends using Form FDA 3331a to submit FARs electronically. Submitting electronically will expedite FDA’s review process and fulfill the obligations to submit the FAR to the relevant district office. However, the agency accepts also other types of submissions.
Where do I submit a FAR?
By using the automated features of Form FDA 3331a, the FAR will be submitted simultaneously to the CDER (Center for Drug Evaluation and Research) and to the FDA district office selected. The CDER will forward FARs to the CBER (Center for Biologics Evaluation and Research), as appropriate. Form FDA 3331a provides contact information (e.g., email and postal addresses) for all district offices.
Should I submit a follow-up or final FAR?
Follow-up FARs are not required but recommended in case there are significant findings during the investigation of the problem identified in the initial FAR (e.g., additional lots impacted, different locations identified) or when information submitted in a previous FAR is incorrect. The agency recommends submitting final FARs promptly to inform FDA when the root cause is identified, corrective action is taken, or the investigation is closed. The FDA will use the information in these reports to assess the problem, risk to public health, and status and adequacy of corrective actions. The information also triggers the need for inspections or other surveillance activities.