Since December 2007, manufacturers or brand owners—referred to as own label distributors (OLDs)—of dietary supplement products are required to report serious adverse events (SAEs) regarding their products. The law requiring this reporting is the Dietary Supplement and Nonprescription Drug Consumer Protection Act, which amends the Federal Food, Drug and Cosmetic Act. The law also requires the identity and contact information of the manufacturer and/or OLD to be on all dietary supplement product labels. In addition, “responsible persons” must submit “serious adverse event reports” (SAERs) received for finished dietary supplements, along with a copy of the product’s label to FDA. The law preempts any state or local requirements for reporting adverse events not identical to federal requirements.
FDA has established a comprehensive program for serious adverse event reporting of dietary supplements that covers the following:
- A requirement that manufacturers or OLDs report all SAEs they receive to FDA. These usually come from consumers or consumers’ relatives, friends or retail outlets;
- An FDA notification to companies when FDA receives a SAE involving one of their products; and
- FDA encouraging all health care professionals to report SAEs to the agency for tracking purposes.
FDA’s “Guidance for Industry: Questions & Answers Regarding Adverse Event Reporting and Recordkeeping for Dietary Supplements as required by the Dietary Supplement & Nonprescription Drug Consumer Protection Act,” issued in October 2007, is a helpful guide for compliance with SAER requirements. As discussed in the guidance, nothing prevents voluntary submission of adverse event reports (AERs) that do not rise to the level of being “serious.” In any case, records of all adverse events, whether serious or not, must be kept for six years for FDA review. An FDA inspector will almost always ask to review AER and SAER files during a facility inspection.
Major dietary supplement trade associations strongly support this law, since it has helped increase consumer confidence in the safety of dietary supplement products by providing FDA with the means to monitor potential health risks associated with their use.
Serious Adverse Event Reports
A “serious adverse event” is an event that a) results in death, a life-threatening experience, hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth defect; or b) requires medical or surgical intervention to prevent one of the above outcomes. All SAEs must be submitted to FDA within 15 business days from the date the adverse event information is received. New information concerning the adverse event received within one year of the initial report must also be submitted to the agency. Although not specifically mentioned in the definition of a SAE, emergency room treatment is also often reported to FDA.
The submission of a SAER is not construed as an admission that the dietary supplement product involved caused or even contributed to the adverse event.
The MedWatch form, Form 3500A, must be used to report a SAE to FDA, and these must be submitted electronically. MedWatch forms can be easily accessed on FDA’s website. The form must identify the injured person by name, age, sex and full address whenever this information is available. Thereafter, this information will be represented by initials to protect the privacy of the “patient.” The MedWatch form must also include:
- An identifiable initial reporter of the event (the person who contacted the manufacturer or OLD);
- The identity and contact information for the responsible party submitting the SAER to FDA;
- Name of the specific product, not just brand name, suspected of causing the adverse event;
- Description of the SAE, including outcome; and
- Any additional information gathered from the manufacturer or OLD that may assist with the determination of the event’s cause.
Amendments can be made to the MedWatch form, as necessary, and if or when more relevant information is received or obtained.
All dietary supplement product labels must include a full domestic address or domestic phone number through which the responsible person, or company, can receive and monitor reports of adverse events from consumers. This includes products imported from foreign manufacturers and OLDs. Products that do not include contact information on their label will be deemed to be “misbranded” and subject to regulatory enforcement action by FDA.
Adverse events and SAEs received by the manufacturer or OLD are a category of complaints and must be handled in accordance to regulatory requirements for complaints dictated in Subpart O—Product Complaints of 21 CFR 111, Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements. The regulation states all complaints must be reviewed by a qualified person to determine if the complaint involves failure of the dietary supplement product to meet specifications, any part of 21 CFR 111, or that may result in illness or injury. An investigation must be performed when the latter is the case and this investigation must extend to all relevant batches and records. Quality control (QC) personnel must then review complaints to ensure needed investigations were conducted, findings were scientifically valid and appropriate follow-up actions were taken. There must be a written procedure to instruct on this entire process and records that include the following must be kept per Subpart P—Recordkeeping of 21 CFR 111:
- Name and description of the dietary supplement;
- Batch, lot or control number, if available;
- The date the complaint was received;
- Name, address, telephone number of the complainant, if available;
- Nature of complaint;
- Reply to complainant; and
- Findings and follow-up actions
The use of a detailed manufacturer and OLD controlled form with specific complainant “interview” questions and locations on the form to document all necessary information is highly recommended. Adherence with these complaint procedural requirements with documentation will also ensure information needed to submit a MedWatch 3500A form is available when necessary. A separate procedure, or a section of the complaint procedure, should also describe how to distinguish between reportable and non-reportable adverse events. It is best to err on the side of caution and submit all adverse events that could be serious to FDA. In some cases, it may also be beneficial to consult with a medical professional. The complaint procedure, or adverse event section, should also instruct personnel on how to complete and submit a MedWatch form, and define the tight timeframe in which to do so (15 business days).
EAS Consulting Group’s (easconsultinggroup.com) Independent Consultant, Norma Skolnik, has over 35 years of regulatory experience working with the pharmaceutical, OTC drug and dietary supplement industries. She served as Director of Regulatory Affairs for the Americas for Cadbury Adams until her retirement and as a consultant advises foreign and domestic OTC drug and Consumer Healthcare companies on FDA regulatory issues.