The Draft Guidance states that NDA and ANDA holders can determine whether a chemical, physical or other change or deterioration has taken place by evaluating the potential impact on the drug product’s identity, strength, purity, stability, efficacy and potential impact on an individual using the product. 

All applicants of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) are required to submit Field Alert Reports (FARs) for distributed drugs that provide incident information, such as labeling mix-ups and quality control issues. See 21 CFR §§ 314.81(b)(1) and 314.98(b). To enable efficient online FAR submissions, the Food and Drug Administration (FDA) has created Form FDA 3331a. Now, to “help increase their consistency and relevancy,” the FDA has published a draft guidance for FAR submissions entitled “Field Alert Report Submission, Questions and Answers” (the Draft Guidance).

The FDA promotes FARs as “an early warning system to help protect patient health” used to assess the risk to public health and the adequacy of response to the risk. The criteria that give rise to mandatory FAR submissions are outlined at 21 CFR § 314.81(b)(1), including information showing (1) “any incident that causes a drug product or its labeling to be mistaken for, or applied to, another article,” or (2) “any bacteriological contamination, or any significant chemical[1], physical, or other change or deterioration in the distributed drug product, or any failure of one or more distributed batches of the drug product to meet the specification established for it in the application.” 

The Draft Guidance states that NDA and ANDA holders can determine whether a chemical, physical or other change or deterioration has taken place by evaluating the potential impact on the drug product’s identity, strength, purity, stability, efficacy and potential impact on an individual using the product. Any information about packaging or components outlined in 21 CFR § 314.81(b)(1) will require a FAR submission. Further, aseptic process simulation (media fill) failures indicate a potential problem related to sterility assurance and will require a FAR submission. Even if NDA and ANDA holders lack complete information, timely submission of a FAR is required with whatever information is available. The Draft Guidance recommends that NDA and ANDA holders supplement the partial information with follow-up FARs and/or final FARs. 

The Draft Guidance describes three types of FAR submissions: an initial FAR is a mandatory submission in compliance with 21 CFR § 314.81(b)(1), which reports given information for the first time within three working days (i.e., Monday through Friday, excluding federal holidays) of receiving the information. The Draft Guidance also defines follow-up FARs as submissions providing additional information, and final FARs as providing “the root cause and describing any corrective actions taken or to be taken.” Follow-up FARs and final FARs are nonmandatory; however, the FDA recommends submitting them so it can assess the risk to public health and the adequacy of the firm’s response. 

Even if the root cause of a problem is identified and corrected within three working days, if the information falls under the criteria described in 21 CFR § 314.81(b)(1), a FAR submission is required. Likewise, even if an NDA/ANDA holder initiates a recall because of the information, when the information meets the criteria under 21 CFR § 314.81(b)(1), a FAR is required. Even the products that are approved under an NDA/ANDA but are distributed exclusively outside the United States are subject to the FAR submission requirements. In addition, an out-of-specification (OOS) result may mandate a FAR submission when the criteria defined in 21 CFR § 314.81(b)(1) are met. However, not every consumer complaint may need a FAR submission, unless it meets the criteria outlined in 21 CFR § 314.81(b)(1); but, evaluation of all complaints is still required within three working days.   

In terms of logistics, NDA or ANDA holders have ultimate responsibility for submitting FARs within three days of obtaining the information, even if another entity performs manufacturing, holding, packaging, labeling or distribution activities. Electronic submission of Form FDA 3331a is sufficient. However, if a product is the subject of multiple NDAs or ANDAs, one Form FDA 3331a is required to be submitted for each NDA or ANDA. 

The Draft Guidance advises that failure to file an FAR is a violation of section 505(k) of the Federal Food, Drug and Cosmetic Act, and the FDA may include the failure as an observation on Form FDA 483 and take a regulatory action. 

Comments and suggestions on this Draft Guidance should be submitted by September 16, 2018.

For More Information

If you have any questions about this Alert or how to formulate any comments on the new Draft Guidance, please contact Frederick R. Ball, Carolyn A. Alenci, any of the attorneys in our Pharmaceutical, Medical Device, Pharmacy and Food Practice Group Industry Group or the attorney in the firm with whom you are regularly in contact.

Notes

Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.