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By Susan Crane, EAS Senior Advisor for OTC Drugs and Labeling

As part of its mission to protect the public health, the FDA monitors the safety of drug products marketed in the United States. This is accomplished through laws enacted by Congress as well as regulations established by the agency that require the pharmaceutical industry to document and, as applicable, report adverse events experienced by both patients and consumers when using their products.

For OTC drugs that are not marketed under an NDA or ANDA, documenting of adverse events at one time had only been required as part of the record-keeping requirements of the Good Manufacturing Practices regulations related to complaint files. No action was taken by the FDA or legislatively until the matter came to the attention of Congress in 1997 following numerous media reports of consumers experiencing health problems after using ephedra-containing products. Upon investigation, it was found that many of the firms marketing these products did not have, or denied having, any such reports on file.

This led to the passage of the Dietary Supplement and Nonprescription Drug Consumer Protection Act in 2006 which made the reporting of serious adverse events mandatory. The law mandates that manufacturers, packers and distributors of OTC drug products (as well as dietary supplements) submit reports to the FDA of any serious adverse event received. Serious adverse events are defined as those that:

  • Result in death, a life-threatening experience, inpatient hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth defect; or
  • Require, based on a reasonable medical judgment, a medical or surgical intervention to prevent an outcome described above.

The FDA subsequently issued two guidance documents to assist firms in complying with the law, the first dealing with reporting requirements and the second addressing labeling.

To facilitate the reporting of these events by consumers, the law requires that OTC drug labeling includes a domestic telephone number or complete domestic address through which a “responsible person” may receive the report. While this often presents an obstacle for foreign firms that wish to sell products to the US market, it’s critical in providing consumers with a mechanism for easily reporting such events.

In addition, it’s essential that the designated person receiving the reports has the necessary training and/or experience to evaluate them and can follow-up with pertinent questions. While larger firms often employ healthcare professionals, this may not be feasible for smaller companies. In these cases, a standardized questionnaire should be developed to ensure that all relevant information is obtained to determine if an event is “serious” and therefore reportable. Alternatively, there are firms that offer pharmacovigilance services to the industry.

For adverse events that do not meet the definition of “serious”, there is no requirement to submit a report to the FDA however, the details of any such report should still become part of the company’s complaint files for the subject product and be maintained in accordance with the GMP regulation.

As of June 2015, all serious adverse event reports received on OTC drug products must be submitted to the agency through FDA’s Adverse Events Reporting System (FAERS) in electronic format using either a Database to Database Transmission or through the FDA’s Safety Reporting Portal. Additional information is available both on the FAERS website and Guidance Document finalized in April of this year.

When completing the electronic ICSRs, firms should follow good pharmacovigilance practices and include the four basic data elements: information about (1) the patient, (2) the suspected product, (3) the adverse event details and (4) the reporter (if different from patient). The format and content of such reports are completed using the Medical Dictionary for Regulatory Activities (MedDRA), a medical terminology standard developed by the International Council for Harmonization for coding the medical terminology used in the report.

The law requires that serious adverse event reports are submitted to the agency within 15 business days of receipt of the four data elements. The submission should include a copy of the product label, preferably the version associated with the product used by the consumer/patient. In addition, if any new medical information is subsequently received that relates to the initial event, this should also be submitted within 15 days.

It has also become clear through FDA warning letters that company and/or product websites are considered an extension of labeling, so firms should monitor posts and comments received through these and other social media platforms. This presents a challenge in that such posts may lack sufficient detail to adequately complete Individual Case Safety Reports (ICSRs) required as part of the submissions – and there may be privacy concerns. However, companies should make good faith efforts to follow-up with the consumer if possible.

With the widespread use of OTC drugs, the reporting of these serious adverse events is a crucial step in monitoring their safety. Manufacturers, packers and distributors should develop procedures and programs to ensure that this regulatory obligation is managed competently and efficiently to assist the FDA in its mission to protect public health.

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