As the evidence mounted about risky supplements, FDA unveiled its GMP proposed rule in March 2003. Despite public concerns
about supplement quality, several manufacturers maintained that DSHEA did not require FDA to issue GMPs at all, and that industry
self-regulation was perfectly adequate to ensure product quality and safety.
To address such contentions, FDA asked the Institute of Medicine (IOM) to assess supplement risks and propose appropriate
regulatory action. The resulting report, which was issued in April 2004, urged Congress to strengthen quality controls on
supplements, ensure the accuracy of product labels, and take stronger enforcement action against misleading claims. The report
stopped short of recommending premarket approval for supplements, but called for mandatory adverse-event reporting and supported
more research into the clinical effectiveness of these products. While consumer groups praised the study, manufacturers objected
that FDA already had sufficient authority to remove harmful products from the market and that new legislation was not needed.
Another IOM report in early 2005 addressed the need for more research into the efficacy and safety of "complementary and alternative
medicines," which include dietary supplements. The report found that manufacturers have little incentive to finance such studies
and that the National Institutes of Health and other researchers would have to provide support. The report noted that a general
lack of quality control for supplement manufacture made it difficult for researchers to obtain consistent samples needed for
clinical trials, and that manufacturing-process standards were critical for such research to go forward.
Meanwhile, FDA's draft rule on GMPs generated some 400 comments from industry, healthcare professionals, consumer groups,
and government officials and agencies. There were questions about the lack of validated tests for ingredient purity and composition
and concerns about added record keeping requirements. Although it took months for agency staffers to review and process all
the comments, by 2005, FDA was promising that a final rule would be issued "soon." But complaints from small companies that
new testing requirements would force them out of business delayed approval by the Office of Management and Budget, which gives
the final sign-off on major new federal regulations.
Addressing oversight difficulties
The GMPs escaped from regulatory limbo this year, partly because Democratic leaders in Congress cast a sharp eye on dietary-supplement
oversight. In addition, the discovery of toxic substances in pet foods, toothpaste, and other imported Chinese products raised
concerns that similar risks may apply to the growing volume of raw materials from Asia used in the production of pharmaceuticals
and dietary supplements. It was hard to argue against standards for ensuring the quality of related products.
This latest scandal involving poorly regulated ingredients from China is not without precedent. Patients in Haiti and other
countries have been poisoned on several occasions by cough syrup and other liquid medicines containing toxic diethylene glycol
(DEG) instead of pure glycerin. In June, Chinese regulatory authorities announced a five-year plan for increasing inspections
and surveillance of food and drug ingredients and closed down some manufacturers, but this appeared to be part of an effort
to avoid more curbs on US imports of Chinese food products, additives, and other ingredients.
Continued evidence of DEG in health products, however, prompted FDA to issue a guidance in May 2007, recommending that manufacturers
perform appropriate tests to ensure that any glycerin used in preparing liquid drugs is not contaminated. The document refers
to limit and identity tests listed in the USP glycerin monograph and a thin-layer chromatography test method. FDA also advises
manufacturers to identify reliable suppliers for glycerin and other ingredients associated with contamination problems.
Persistent evidence of contaminated imports reflect FDA's difficulties in monitoring and identifying noncompliant food and
drug ingredients from overseas. In announcing the new GMP rule, FDA officials said they would adopt a risk-based approach
to ensuring manufacturer compliance with quality standards. That translates into relatively few direct inspections of manufacturers,
particularly those overseas, unless evidence of contamination or rule violations surfaces. FDA's reliance on supplement manufacturers
and packagers to ensure ingredient quality is a symptom of the limits on agency enforcement and oversight capabilities. While
FDA conducts more than 1000 drug GMP inspections in the US every year, it visits only a few hundred foreign manufacturers,
despite the growing portion of drug ingredients and generic drugs now coming from India, China, and other countries.
Whether FDA's GMP rule will ensure high-quality and safe dietary supplements will be examined further by Congress. The House
Energy and Commerce Committee recently asked the Government Accountability Office to examine dietary-supplement concerns,
including overly vague health claims in product labels, FDA's ability to detect safety problems, and the status of adverse-event