NEJM Article Calls for DSHEA Overhaul, Industry for Serious Enforcement

Are safety and quality control oversight challenges due to faulty regulation or weak enforcement? In response to an Online First article in the New England Journal of Medicine (NEJM) that criticized the safety and regulation of dietary supplements, the Council for Responsible Nutrition (CRN) said the issues with safety and quality control oversight are more to do with an underfunded FDA than to problems with the Dietary Supplement Health and Education Act (DSHEA).

In the article, Pieter Cohen, M.D., a physician with the Cambridge Health Alliance and Harvard Medical School, argued the current system for monitoring dietary supplement safety is inadequate due to weak FDA oversight and lack of premarket requirements. He said public health officials have been better at recognizing developing adverse event trends than the current FDA method of managing adverse event reports (AERs) via the MedWatch system. "MedWatch reports have rarely provided sufficient and adequately timely data to permit detection of clusters of serious adverse effects from supplements," he reasoned.

He cited the recent recall of OxyElite Pro brand dietary supplements following numerous reports of liver damage in Hawaii as evidence of the faulty AER system, noting it was public health officials that caught on to the signals, not FDA. He also referenced the issue with DMAA (1,3-dimethylamylamine) in sports nutrition. "It took the FDA an additional 16 months after the military ban to gather sufficient safety data from MedWatch to alert consumers about DMAA's risks," he reported. MedWatch, Cohen wrote, offers no medical advice to physicians, who instead turn to poison control centers, which offer free medical advice.

At the center of both the Hawaii and military cases cited by Cohen was USPLabs, which manufactured OxyElite Pro (recalled) and Jackd3D (reformulated to remove DMAA). This may be indicative of the industry argument that problems are with bad apples, not the whole bunch.

Steve Mister, president and CEO of CRN, assured the safety concerns identified by Dr. Cohen are troubling not only for consumers, but also for those reputable companies that follow the law and seek long-term relationships with their customers. "However, the problems noted by Dr. Cohen are not an issue of the law itself, but rather the result of a chronically underfunded government agency that has yet to use the full extent of its enforcement authority and seems to lack the political willpower to prosecute even the most blatant offenders," he said. "Time and time again, FDA has issued warning letters for egregious behavior by a few outlier firms, yet not taken further action when the products—many of which are clearly not legal dietary supplements—remain on the market."

This Cohen article comes at a time when FDA has reported an uptick in mandatory supplement-related AERs, which rose from 2,844 reports in 2012 to 3,289 reports in 2013. Industry and safety experts attribute this to better compliance in submitting serious AERs. FDA has increased its enforcement activity in this area and has included AER compliance checks in its inspections of supplement companies for good manufacturing practices (GMPs). Cohen gave credit to the increased compliance with AERs but said he expects to see even greater increases in such reporting in the next few years. 

In addition to the increased monitoring from FDA, the agency recently announced a submission method alternative to MedWatch paper form 3500A. Companies can now submit AERs electronically via a safety portal on the Health Department website.

FDA said it must show a product is adulterated before taking enforcement action, and the agency has contended it acted swiftly against OxyElite Pro.

Mister pointed out the AER surveillance system for supplements is the same as that used for over-the-counter (OTC) medicines.

Cohen called for regulatory changes, including increased premarket requirements, such as a proposed bill from Senators Dick Durbin (D-IL) and Richard Blumenthal (D-CT) to mandate supplement companies register their products with FDA before they reach the marketplace. This would provide the agency with safety information, such as AERs, he said. However, he noted the bill is a first step but would not address FDA's inability to detect and remove supplements that pose health risks. "Sweeping changes would be needed to create an effective surveillance system capable of rapidly detecting supplement-related adverse events in the United States," Cohen offered. "I believe that accurate information on every supplement sold in this country should be incorporated into databases maintained by both the FDA and poison centers."

As part of this sweep, he suggested a dedicated special response team, composed of scientific and government experts, could quickly investigate troublesome AERs. He noted a pilot project showed such a response effort can quickly identify potentially dangerous products, but the project was tabled due to lack of funding.  

Again, Cohen warned even such "sweeping changes" would not adequately protect consumers. Instead, he called for a major regulatory change. "If consumers and physicians are to have confidence that all supplements are safe, the law regulating supplements must be reformed," he proclaimed, referring to DSHEA.

Mister argued no amount of new regulation would help if the agency charged with enforcing any new laws is not equipped for the task. "There should be stronger consequences for those not following the law, rather than adding bureaucracy for those who are," he said.

Mister acknowledged Cohen may be an expert in medicine, but not in dietary supplement regulation. "While he has some legitimate observations, he misses the mark in some of his solutions." Mister chalked this up, in part, to the common trait of many DSHEA critics: a lack of knowledge of the nuances of the regulation and the dietary supplement marketplace. In this void, such critics lean on pharmaceutical standards such as premarket approval, he said.

"This ignores the fact that pre-market approval is not viable for the supplement industry nor is it a guarantee of safety," Mister explained. "Even with pre-market approval for pharmaceuticals, counterfeit drugs appear in the market and phony online pharmacies sell dangerous medicines, and at the same time, some FDA-approved pharmaceuticals have reached the market, only to be recalled years later for safety concerns."

Mister advised a less bureaucratic approach to the recent dietary supplement quality and safety issues, namely increased funding for FDA's enforcement activities. "Serious enforcement of the existing law is the best way to provide consumers with meaningful assurance of the safety of these products," he said.