FDA Releases Draft Guidance on Field Alert Reports

by Jennifer A. Davidson

Today FDA published a draft guidance entitled Field Alert Report Submission: Questions and Answers (“Draft Guidance”).  Field Alert Reports, or FARs, are a type of post-marketing report intended to rapidly notify the FDA of potential quality defects or labeling discrepancies with distributed drug products that may pose a safety risk.  FDA regulations at 21 C.F.R. §§ 314.81  and at 21 C.F.R. §§ 314.98 require sponsors of NDAs and ANDAs to submit a FAR to FDA within three working days of receipt of any of the following four types of information that may suggest a quality defect in a distributed drug product:

  • Situations in which the drug product may be mistaken for another product, such as when the wrong labeling is applied to it;
  • Bacterial contamination;
  • Any significant chemical, physical, or other change or deterioration in the distributed drug product;
  • Any failure of a distributed batch of the drug product to meet the specifications established in its application.

FDA’s newly released Draft Guidance provides additional clarity on the circumstances under which a FAR should be submitted.

  • To determine whether a chemical, physical, or other change or deterioration in the distributed drug product is “significant,” and therefore subject to FAR requirements, a sponsor should evaluate the potential impact on the drug product’s identity, strength, purity, stability, and efficacy, as well as the possible impact on a patient. This analysis should be product-specific, taking into account intended use, route of administration, dosage, duration of treatment, and patient population.  The Draft Guidance advises sponsors to document both their investigations and their rationale for determining whether an incident resulted in a significant chemical, physical, or other change or deterioration.
  • “Bacterial contamination” is intended to include any type of microbial contamination, such as bacteria, yeast, fungus, or virus.
  • FAR reporting requirements extend beyond situations in which there is a confirmed quality defect of the type described in 21 C.F.R. 314.81. One example in the Draft Guidance states that information about a stopper used for a vial that could result in contamination of a distributed batch must be submitted in a FAR.  Similarly, following a media fill validation failure, a FAR must be submitted for any distributed drug product within the scope of the media fill failure investigation within three working days of initial receipt of information about the failure.  This approach is consistent with the preamble to the final regulation, in which the Agency stated that, “[b]ecause these reports can lead to preventing potential safety hazards from products already in distribution, the agency emphasizes that the reports are required for both confirmed and unconfirmed problems.”  50 Fed. Reg. 7452, 7477 (Feb 22, 1985).
  • An out-of-specification (“OOS”) result necessitates a FAR only if the batch has been distributed, and only if the result is considered valid at the time a FAR must be submitted, e., within three working days of the OOS. If the OOS is scientifically invalidated within three working days, e.g., by confirmation of an analytical laboratory error, no FAR is required.  If the OOS result is still under investigation and has not been invalidated within the three-day period, a FAR is required to be submitted and, if later invalidated, updated with that information.
  • A FAR must be submitted even if the sponsor believes the root cause of the quality defect has been identified and corrected. Under these circumstances, the FAR should include detailed information about the root cause identified and any ongoing or completed corrective action.
  • A recall does not obviate the requirement to submit a FAR. If a recall is initiated due to information that meets the FAR criteria, a FAR must be submitted.

With respect to timely submission of FARs, sponsors must have procedures in place to ensure information is quickly gathered and evaluated.  For example, the Draft Guidance provides that the three-working-day clock begins to tick as soon as relevant information is identified, even if the information is first identified at a contract laboratory.  Similarly, consumer complaints must be evaluated rapidly, so that a FAR may be submitted within three working days of receipt of the complaint, if the information meets the FAR criteria.

Addressing the scope of FAR obligations, the Draft Guidance provides that all drug products marketed under an NDA or ANDA are subject to FAR requirements, including those distributed only outside of the United States.  This approach is consistent with a statement in the Agency’s 2016 Compliance Program Guidance Manual 7356.021 in which the Agency indicated that FAR requirements apply to products distributed in foreign markets.

The Draft Guidance also addresses logistical questions on FAR submission, proper completion of Form 3331a, and submission of follow-up and final FARs.

Compliance with FAR reporting requirements is assessed during FDA inspections.  As explained in CPGM 7356.021, in order to prepare for an inspection, the district office reviews the establishment’s FAR history. Inspectors will assess not only a firm’s timely submission of required FARs, but also the adequacy of SOPs associated with FAR reporting, the thoroughness of investigations of the quality defects underlying FARs, and the adequacy of associated corrective and preventative actions implemented to address these quality defects.

Comments on the draft guidance may be submitted through www.regulations.gov to Docket No. FDA-2018-D-2326.