Ensuring Quality for Dietary Supplements - Pharmaceutical Technology

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Ensuring Quality for Dietary Supplements
FDA's long-awaited GMPs for supplements appear as food and drug safety concerns override lingering opposition.

Pharmaceutical Technology

Consumer advocates and some members of Congress complained that the new rule does too little to ensure safe and effective supplements. There are no preapproval filing requirements for supplement makers, and the industry and its Congressional backers have long opposed them. DSHEA requires the manufacturer of a new dietary ingredient to notify FDA at least 75 days before it markets a new supplement product, but this requirement applies only to formulations and ingredients developed since 1994 and is fairly vague about what kind of information a company must provide the agency.

Comparing the food versus drug models

Premarket notification, moreover, is far different from prior approval and reflects the main premise of DSHEA: that FDA regulation of dietary supplements follows the model for foods rather than drugs. Supplements are considered safe unless evidence indicates otherwise, and no premarket clinical testing or approval is required. FDA notes, though, that dietary supplements, unlike foods, are packaged into tablets, gelcaps, and capsules, thus requiring process controls to ensure that each tablet contains the ingredient, purity, strength, and composition intended.

Because supplements often contain ingredients found in drugs and make claims about improving or affecting health, many policymakers believe that these products should adhere to some drug standards. At the same time, DSHEA won support from the supplement industry and policymakers who believe that these products are safe, can make a real contribution to public health, and should not be hamstrung by excessive and unnecessary regulation.

The 1994 act does provide FDA with a process for documenting that a supplement is harmful or contaminated and should be removed from the market. But the process is long and complex, and FDA has attempted to use it only with ephedra-containing supplements, with limited success.

The US Pharmacopeia assesses supplements
The food–drug dispute has colored the debate over GMPs for the past decade. Dietary-supplement manufacturers generally agreed that setting GMPs was a reasonable approach for ensuring product safety and quality. CRN, a trade group representing larger supplement makers, has backed product-quality standards as one way to establish a level playing field for the many companies testing their products voluntarily through third-party organizations such as NSF International, http://ConsumerLab.com/, and the US Pharmacopeia (see sidebar, "USP assesses supplements"). Many small companies complained, however, that GMPs would establish ingredient-testing requirements too similar to standards for drugs and much too expensive for many small manufacturers.

Consequently, it took years for FDA to craft GMP regulations acceptable to industry and their allies on Capitol Hill and in several administrations. Following extensive discussions with manufacturers, FDA issued an Advance Notice of Proposed Rulemaking in 1997 that posed several questions for public comment. It took another six years for the agency to publish just the proposed rule.

Cracking down

During this period, evidence emerged about serious health risks associated with supplements containing steroids and stimulants. In January 2000, FDA launched a broad crackdown on supplements making unsubstantiated health claims. The agency seized products that promised to prevent cancer and cure autism. FDA laboratories identified numerous products that lacked key ingredients, had excessive amounts of lead, were contaminated with bacteria, or had ingredients not listed on the label. Then-FDA commissioner Mark McClellan announced further initiatives to improve consumer information on supplements and sent out a wave of Warning Letters. The Federal Trade Commission also filed complaints against supplement firms for allegedly unsubstantiated or false advertising claims.

Support for stronger supplement regulation came in April 2001 from the Health and Human Services Office of the Inspector General. It issued a report recommending the registration of supplement manufacturers with FDA and mandatory adverse-event reporting to strengthen federal oversight of the supplement industry. Soon after, Senate investigators reported thousands of adverse reactions to weight-loss dietary supplements containing ephedra. FDA moved to ban the substance from over-the-counter drugs, but could only begin the convoluted legal process for pulling ephedra supplements off the market.

These problems culminated in 2003 with the death of a major-league baseball player, which prompted more Congressional hearings on supplement regulation and new legislative proposals. Even Senator Orrin Hatch (R-UT), the prime advocate for limited federal oversight of dietary supplements, backed legislation adding supplements with anabolic steroids to the controlled substances list.


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