Serious Adverse Event Reporting for Dietary Supplements

Since December 2007, companies that sell dietary supplements in the United States have had a legal duty to report serious adverse events to FDA. The requirement comes from the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006, which added section 761 to the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 379aa-1).

The rule has a short deadline, 15 business days, and it applies to the company named on the label, whether or not that company makes the product. This guide explains who must report, what counts as a serious adverse event, what to send, how to meet the deadline and what records to keep.

Who must report: the "responsible person"

Section 761 places the duty on the responsible person: the manufacturer, packer or distributor whose name appears on the label of a dietary supplement marketed in the United States.

That means:

• An own-label brand that uses a contract manufacturer is the responsible person, because its name is on the label.

• A contract manufacturer whose name is not on the label is not the responsible person, but it should forward any report it receives to the brand owner.

• A retailer whose name is on the label as the distributor may, by agreement, authorize the manufacturer or packer to submit reports, provided the retailer forwards every adverse event report it receives to that manufacturer or packer.

The label must also carry a domestic address or domestic phone number through which the responsible person can receive adverse event reports (FD&C Act section 403(y)). A product without one is misbranded.

What is a serious adverse event?

An adverse event is any health-related event associated with the use of a dietary supplement that is adverse. It does not have to be proven that the product caused it.

A serious adverse event is one that:

• results in death;

• results in a life-threatening experience;

• results in inpatient hospitalization;

• results in a persistent or significant disability or incapacity;

• results in a congenital anomaly or birth defect; or

• requires, based on reasonable medical judgment, a medical or surgical intervention to prevent one of the outcomes above.

An event that does not meet any of these is not reportable, but it must still be recorded.

Two points cause confusion. First, causality is not a test. If a consumer reports being hospitalized after taking your product, the event is reportable even if you believe your product had nothing to do with it. The law states that a report is not an admission that the product caused the event. Second, the event must be associated with use of the product in the United States.

When a report becomes reportable

FDA's guidance (September 2013) describes four pieces of information that make up a reportable serious adverse event report:

1. an identifiable injured person;

2. an identifiable initial reporter;

3. the identity and contact information of the responsible person; and

4. a suspect dietary supplement,

together with a serious adverse event or outcome. Identifiable does not require a name; enough detail to show that a real, specific person is involved is enough. If any of these is missing, you should make reasonable efforts to obtain it, and record those efforts.

The 15-business-day deadline

The responsible person must submit a serious adverse event report to FDA no later than 15 business days after the report is received. The clock starts when anyone in your company, or acting for you, first receives the information. That includes customer service, sales, social media staff and, in practice, any contractor who receives reports on your behalf.

If you receive new medical information about a submitted report within one year of the initial report, you must submit it within 15 business days of receiving it.

Fifteen business days is about three weeks, and a lot can happen in that time: the report needs to reach quality or regulatory affairs, someone must decide whether it is serious, the missing information has to be chased, and the submission must be prepared. Companies that miss the deadline usually lose the first week because the report sat in a customer service inbox.

What to send and how

Each report must be accompanied by a copy of the product label. Reports are submitted on Form FDA 3500A (the MedWatch mandatory reporting form), either electronically through the FDA Safety Reporting Portal (www.safetyreporting.hhs.gov) or on paper. Electronic submission is quicker and gives you a confirmation.

Include all the information you have: the injured person's age and sex, the event and its outcome, the product name and lot number, the dose and dates of use, other products or medicines taken, relevant medical history and test results, and your contact details.

Records you must keep

The responsible person must keep records related to each adverse event report it receives, serious or not, for 6 years. Records include the initial report, all follow-up, your assessment, the submission to FDA and any correspondence. FDA may inspect and copy these records.

These records connect to your other quality records. Under 21 CFR Part 111, a product complaint that involves a possible failure of the product to meet a specification must be reviewed by a qualified person and investigated where needed (111.553 to 111.570). An adverse event report is often also a product complaint, so it should trigger a review of the batch record, the reserve sample and other complaints about the same lot.

Building a process that meets the deadline

A working serious adverse event process has seven parts:

1. Every channel feeds one intake point. Phone, email, the website, retailer contacts, social media and your contract manufacturer all route to one intake form, completed the same day.

2. Day 0 is recorded. The date of first receipt starts the clock, and the due date is calculated immediately.

3. Seriousness is assessed within days. A trained person applies the definition above and records the decision and the reason.

4. Missing information is chased in writing. Each attempt is logged.

5. A submission checklist is used. It confirms the form is complete, the label is attached and the report went in on time.

6. Follow-up is tracked for a year. New medical information goes in within 15 business days.

7. Trends are reviewed. Adverse events and complaints are trended by product and lot, and signals go to CAPA and management review.

If a contract manufacturer, distributor or retailer may receive reports, your written agreement with it should require it to forward any adverse event information within one business day.

Common problems

• No domestic address or phone number on the label.

• Reports received through social media or a retailer never reached the person responsible for reporting.

• A serious event was not reported because the company believed its product could not have caused it.

• The report was submitted without a copy of the label.

• Non-serious adverse events were not recorded or were discarded after a year.

• New medical information was received but not submitted.

How A.P. Lyon can help

Both of our dietary supplement products include SOP 8-101-DS Serious Adverse Event Reporting, with an Adverse Event Intake and Assessment form, an Adverse Event Log and a Serious Adverse Event Report Submission Checklist, all linked to complaint handling and trending.

• Supplement Brand Owner Compliance Pack: 39 documents for own-label brands that use a contract manufacturer.

• Dietary Supplement cGMP Quality System: the complete 112-document 21 CFR Part 111 system.

References

• Federal Food, Drug, and Cosmetic Act section 761, Serious adverse event reporting for dietary supplements (21 U.S.C. 379aa-1), and section 403(y)

• Dietary Supplement and Nonprescription Drug Consumer Protection Act, Pub. L. 109-462 (2006)

• FDA, Guidance for Industry: Questions and Answers Regarding Adverse Event Reporting and Recordkeeping for Dietary Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act (September 2013)

• FDA, Guidance for Industry: Questions and Answers Regarding the Labeling of Dietary Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act (revised September 2009)

• Form FDA 3500A, MedWatch Mandatory Reporting Form; FDA Safety Reporting Portal, www.safetyreporting.hhs.gov

• 21 CFR 111.553 to 111.570, Product complaints

Related guides: Brand Owner Duties When a Contract Manufacturer Makes Your Supplements; Identity Testing Under 21 CFR 111.75; Dietary supplement GMP procedures.

Official sources: 21 U.S.C. 379aa-1, FD&C Act section 761 (Cornell LII); 21 CFR Part 111 (eCFR).