OIG Releases Final Report on Supplement AERs

WASHINGTON--After a month and a half of "draft report" scuttlebutt, the final version of recommendations for handling adverse event reports (AERs) for dietary supplements has been released. In Adverse Event Reporting [AER] for Dietary Supplements: An Inadequate Safety Valve, the Office of the Inspector General (OIG) gave its overview and recommendations about how the industry and Food and Drug Administration (FDA) deal with AERs. Murmurings about this report began when a "draft" report was given to FDA, industry organizations and public interest groups in early March in order to add their comments and suggestions to the final version.

OIG's Office of Evaluation and Inspections assembled the report to "protect the integrity of the Department of Health and Human Services programs as well as the health and welfare of beneficiaries served by them." In collecting information for this report, OIG analyzed data from FDA's database; FDA laws, regulations, policies and procedures; several AERs; and relevant literature. It also interviewed FDA officials, industry representatives and scientific experts. However, OIG did not evaluate the internal operating procedures of the current AER system, a fact that many in the industry say negate the findings of this report.

"You can't find out if FDA can do its job with its existing authority until it is investigated why they aren't able to do the job," said Tony Young, counsel for the American Herbal Products Association (AHPA), one of the organizations to comment on the report before it was made final. "OIG didn't look at the system to ascertain why it wasn't working, they simply assumed it wasn't working and offered [through these recommendations] a bunch of improvements."

FDA, according to the OIG's findings, has limited medical, product, manufacturer, consumer and trend information relating to dietary supplements. This lack of "vital information to adequately assess signals of possible public health concerns generated by the [AER] system," might have led to FDA rarely taking safety actions to protect consumers, according to OIG. For example, between 1994 and 2000, OIG documented 32 safety actions whereas there were more than 100 million people taking supplements in that time period. And in 1999, Poison Control Centers received 13,000 reports related to dietary supplements compared to FDA's 460.

In response to these findings, OIG recommended "a blueprint for action" for both FDA and dietary supplement manufacturers. Some of the actions for FDA included comparing AER information with Poison Control Centers, informing healthcare providers how to distinguish AERs from dietary supplements and expediting the development and implementation of Good Manufacturing Practices (GMPs). The actions OIG suggested for manufacturers included reporting serious adverse events to FDA and registering the company and its products with FDA.

The dietary supplement industry had mixed reactions to the report. In early March, OIG circulated draft reports of this paper to public interest groups, industry organizations and FDA for their perspective on OIG's findings. The public interest groups criticized OIG for not asking for more regulatory action; the industry organizations faulted OIG for not evaluating AER's internal operating procedures and for comparing dietary supplements with drugs; and FDA reported that the findings were a fair assessment of the challenges the agency faces due to lack of funds and manpower. Here is a brief summary of some of the points that were hit in the letters:

Public Citizen Health Research Group Response

This organization highlighted the discrepancy in reported adverse events by Poison Control Centers and FDA. "This must be viewed, however, as just a symptom of the larger issue: the crippling effect that [DSHEA] has had," stated Sidney Wolfe, M.D., director. According to Wolfe, without additional legal authority, FDA is positioned to wait until there are enough deaths or injuries before a recall can begin, such has he sees the case has been with ephedra. He went on to state that better regulations need to go in effect in order to combat current-day concerns, including the potential for BSE-contamination in various supplements.

Center for Science in the Public Interest (CSPI) Response

In a letter dated April 11, CSPI concurred with OIG's view on FDA's AER system and reiterated the report's main points. Not only does FDA need sufficient funding to establish a mandatory registration and listing system for manufacturers and dietary supplements, according to CSPI, but it needs specific statutory authority. The letter's authors--Bruce Silverglade, director of legal affairs and Ilene Ringel Heller, senior staff attorney--also note that "it is ... in the interest of both industry and consumers to support a systematic, comprehensive review of dietary supplement safety and efficacy," excluding GRAS vitamins and minerals.

American Herbal Products Association (AHPA) Response

AHPA questioned, among other things, OIG's comparison of adverse event reporting between Poison Control Centers and FDA in its April 6 letter, citing that the Centers have a different definition of adverse events. The organization did concur that FDA performs little outreach to consumers with respect to reports AERs; however, this is true with FDA's other sectors, including drugs, cosmetics and foods. Concerning FDA not having access to information about the dietary supplement industry, AHPA stated that there are various private-sales tracking companies that gather this information, which could be utilized by FDA. Tony Young, counsel for AHPA and the letter's author, noted that OIG should not request more from manufacturers (i.e. registering dietary supplements) but rather request that FDA keep a more updated AER site for consumers and companies.

Council for Responsible Nutrition (CRN) Response

"We are extremely troubled by the view repeatedly expressed in the OIG report that the appropriate comparison [of dietary supplements] is to prescription drug reporting systems," stated Annette Dickinson, vice president of scientific and regulatory affairs for CRN in a letter dated April 6. CRN believed this and other factors led to the overall negative view this report took on dietary supplements. "The popularity of dietary supplements and the belief that they are generally safe are viewed as risk factors, rather than as evidence that the vast majority of products are indeed both beneficial and benign."

Consumer Healthcare Products Association (CHPA) Response

In its April 4 letter, CHPA agreed with FDA that it is seriously under-funded and that the agency has "asked Congress for two years in a row for $2.5 million for operational development of its AER reporting system." However, the association believed that mandatory adverse event reporting, registrations and labeling requirements (which include toll free numbers to report adverse events to FDA) is unnecessary as an effective safety valve. "It is not the failing in the current AER system for dietary supplements that has led to the relatively low number of FDA actions but rather the generally excellent safety profiles of many dietary supplements" among other factors, according to CHPA. The letter's author, R. William Soller, Ph.D., senior vice president and director of science and technology, explained that public awareness campaigns would effectively bridge the gaps that are inherent in AER surveillance systems.

FDA Response

In its response to the draft report, FDA wrote in its April 6 letter that the agency asked for but didn't receive additional funds for its AER system in fiscal years 2000 and 2001. However, FDA will submit to Congress this spring a report on the cost for implementing its Dietary Supplement Strategic Plan that covers a better AER system, a plan it published last January. FDA is "hopeful" that Congress will give more funding based on this report.

FDA stated that it has already begun addressing OIG's recommendations, including designing a better computer system to track AERs. It also reiterated that it has drafted proposed GMPs that are currently being reviewed by the new administration. The agency also suggested changes to the final report, such as changing the title of the report to FDA Needs Better Tools to Provide Adequate Safety Valve. This, in the agency's opinion, would connote the proactive, and not inactive, role FDA has in the dietary supplement industry.

By press time, the Centers for Disease Control and CSPI had not returned phone calls for comment. To read the 110-page report, visit www.hhs.gov/oig/oei/reports/a519.pdf.