FDA published a how-to guide to push dietary supplement firms toward tighter compliance with the requirement to submit serious adverse event reports to the agency.

Daniel Fabricant, director of FDA’s Division of Dietary Supplement Programs, said “there have been a few things that suggest that we may not be getting” all the reports that should be sent to the agency.

The annual number of AERs from the supplement industry grew from 668 in 2008 – the first year firms were required to submit the reports to FDA – to 716 in 2009 and 1,039 in 2010, an agency spokesman said.

Voluntary MedWatch reports from consumers, health care providers and other parties totaled 430 in 2008, 580 in 2009 and 297 in 2010.

Fabricant said that with more than 1,400 firms considered responsible for submitting reports, the number likely should be higher.

“I think that certainly is interesting,” he said.

Defining “Serious”

Supplement industry regulatory experts, however, say the disparity between FDA’s expectation and the number firms submitting may stem from different interpretations of the AER law, the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006.

They say some adverse events could meet FDA’s threshold for serious, but firms might decide those cases do not meet the law’s reporting criteria.

“It’s something the industry really worked with the FDA on how to set up and so I feel like the industry has embraced it,” said Cara Welch, VP of scientific and regulatory affairs at the Natural Products Association.

Welch said that the number of AERs industry submitted in 2010 “doesn’t raise any red flags with me.”

The “at-a-glance” guide lists serious adverse events as those that result in:

death;
a life-threatening experience;
inpatient hospitalization;
a persistent or significant disability or incapacity;
a congenital anomaly or birth defect;
or one that requires, based on reasonable medical judgment, a medical or surgical intervention to prevent one of the other outcomes.

Duffy MacKay, VP of scientific and regulatory affairs at the Council for Responsible Nutrition, said some adverse events that consumers or other parties report might not fit squarely in the act’s definition of serious.

For instance, following a report of a consumer experiencing an autoimmune allergic reaction after using a supplement, a manufacturer could decide, “Well, this person wasn’t hospitalized, and they didn’t die, therefore we’re just going to keep this one” and not deem it serous, MacKay said.

The firm “may be thinking they’re following the rules,” he said.

Welch noted manufacturers decide whether an AER is serious.

Supplement industry regulatory experts say some adverse events could meet FDA’s threshold for serious, but firms might decide those cases do not meet the criteria for reporting to the agency.

“It’s up to the discretion of certain employees in the facilities and that’s always up for debate.” Welch said.

“You always hope that they are well-prepared and really know about the AER law.”

Welch added the how-to guide should help firms, particularly with information about what FDA considers serious adverse events.

The two-page guide, available on FDA’s website, also details who must report, how and when to submit a report and for how long a firm must keep the information in its files.

Not An Admission Of Cause

The guide reminds firms that FDA does not consider a submitted report an admission that a product caused or contributed to an adverse event.

“We just want to make sure folks are aware that that is what’s in the law and there are ways to comply with the law,” Fabricant said. “It should be as simple as filling out the MedWatch form and sending it to us in the 15-day timeframe.”

He added that the AER law is “a very important pillar of the regulatory structure of dietary supplements.”

Other supplement regulatory pillars – like the new dietary ingredient notification draft guidance and good manufacturing practices inspections – “have been getting a lot of attention these days [and] we wanted to make sure this one got its proper due,” he said.

FDA sent the guide to industry trade groups to pass along to their members. “I imagine at some point in the near future we’ll get together with them and look at ways we can do further outreach,” Fabricant said.

AERs Build Valuable Database

MacKay said the guide will help and should be the subject of webinars and training sessions at industry conferences.

Accurate reports are “really valuable to everyone” because they not only bring actual problems to light, but also prevent identifying risks where there are none, he added.

“For both reasons, it’s important to have standardized, valuable data there,” McKay said, pointing out that “adverse event reporting collectively is our only post-market surveillance mechanism.”

The AER law mandates submission of serious AERs for supplements and monograph OTCs within 15 days of a firm receiving a report (Also see "Adverse Event Collection Expected To Be In Force By Christmas 2007" - Pink Sheet, 18 December, 2006.).

While the law set a compliance date of January 2007, FDA extended the deadline a year for supplement and OTC drug firms to start submitting reports of serious adverse events (Also see "Final Guidance For Reporting Adverse Events Gets Serious On Definitions" - Pink Sheet, 20 July, 2009.).

The agency separately extended to January 2010 the deadline for firms to add to product labels manufacturers' complete address or domestic telephone number and an introductory statement that the information is for making adverse event reports (Also see "Final AER Guidance Requires Full Address, Recommends Prefatory Language" - Pink Sheet, 7 September, 2009.).

By Carolyn B. Phenicie

FDA Says Supplement Adverse Event Under-Reporting Should Feed Growth

More from Archive

More from Pink Sheet