Groundhog Day

Most people in North America observe Groundhog Day on February 2. One exception is the natural products industry, which observes Groundhog Day year-round. Since the passage of DSHEA in 1994, the industry has waited patiently for the advent of official good manufacturing practices (GMPs) for dietary supplements. The arrival of the GMPs, like the much-anticipated emergence of the groundhog, could herald either a long “winter” clouded with new regulatory burdens, or an early “summer” that levels the corporate playing field.

While Groundhog Day is a good metaphor for the state of the industry, it probably overstates the influence of the GMPs. By now, most responsible companies are already following the proposed GMPs. And while the presence of official GMPs could help finally dispel the notion that the supplement marketplace is unregulated, budget shortfalls at FDA will make it difficult for the agency to fully enforce the rules when they do appear. In addition, the prolonged absence of a permanent commissioner could further dilute FDA’s focus and ability to supervise long-term programs such as the GMPs.

OUT OF THE HOLE

Will the GMPs exit their burrow at the Office of Management and Budget and enter the Federal Register this year? An early sign that momentum may be building for the GMPs appeared several months ago when nine members of Congress wrote to U.S. Department of Health and Human Services (HHS) secretary Mike Leavitt to urge prompt publication of the GMPs. The nine representatives, who included Mary Bono (R–CA), Pete Sessions (R–TX), and Chris Cannon (R–UT), called the GMPs “an essential element of an effective regulatory program.”

According to Steven Mister, president and CEO of the Council for Responsible Nutrition (CRN; Washington, DC), getting the GMPs published was a primary goal of the council’s annual lobby day in March. “One of the priorities was to urge Congress to urge FDA to do what was needed to get the final GMP rule out,” explains Mister. “We have been encouraged in recent years by the active efforts FDA has been making in more fully implementing DSHEA through regulatory enforcement actions, but we can’t strongly enough express how important it is for industry to have a final GMP rule to level the playing field and improve consumer confidence.”

In the April 4, 2006, edition of the Federal Register, HHS predicted that FDA would publish the GMPs by December. Even if the GMPs appear this year, however, their effects on the industry may turn out to be relatively modest. As mentioned earlier, many companies have already taken the initiative to follow the proposed GMPs, and some have even sought out certification for their facilities. There also are several indications that FDA may have difficulty enforcing the GMPs once they are published.

In a series of speeches this year, CFSAN director Robert Brackett, PhD, warned that FDA’s resources are limited and its priorities are shifting. Brackett noted in May that CFSAN’s operating funds are now only $30 million, compared with $47 million three years ago. FDA has also lost personnel. The double threat of declining resources and dwindling personnel may force FDA to focus on other projects instead of the GMPs.

“This is obviously a valid concern, because without proper enforcement, the GMPs will be virtually meaningless,” Mister says. “And consumers deserve to know that in our industry, not just some companies, but all companies, are mandated by law to follow procedures that will help ensure that products are well manufactured.”

“Quite clearly, FDA’s declining resources and inspection staff will make enforcement of any dietary supplement GMP difficult,” agrees Loren Israelsen, president of the LDI Group Inc. (Salt Lake City) and executive director of the Utah Natural Products Alliance (Salt Lake City). “Also, unlike the food and drug sectors, dietary supplement manufacturing has, to some degree, its own unique characteristics that will require additional expertise and training to assure competent inspection and enforcement practices. As an industry, we would be foolish to either expect or rely on FDA to assure FDA compliance. It is first and foremost industry’s job to do so. This has been discussed for some years, and we need to put on a full-court press to develop internal practices that are seen as competent and reliable.”

While the stakes are high, Mister is upbeat about FDA’s ability to enforce the GMPs. “We have been very supportive of the need for Congress to appropriately allocate funding to FDA,” Mister says, noting that the Senate Appropriations Committee approved resources for CFSAN in the area of dietary supplements and adverse-event reporting that was triple what had originally been suggested. “It will be up to FDA to create a case that supports the level of funding and resources necessary to implement GMPs, and if we can be helpful in that process, we will. But at the end of the day, in today’s world, we’re all learning to do our jobs with fewer resources. Enforcing GMPs is part of FDA’s job, and we expect they will find a way to get it done.”

A TWO-FRONT SOLUTION

If the GMPs are the groundhog, then adverse-event reports (AERs) are the shadow. In the wake of the ephedra controversy, the issue of adverse-event reporting has taken on added importance. AERs may, in fact, eclipse GMPs in significance. Even though most industry trade associations have long supported a mandatory AER system, a major state-of-the-science conference hosted by NIH in May helped place the issue at the top of the public agenda. At the conference, the expert panel decried the lack of an AER system and called on Congress to “expand FDA’s authority and resources to require manufacturers to disclose adverse events, to ensure quality production, and to facilitate consumer reporting of adverse events.”

On June 21, Senators Orrin Hatch (R–UT) and Dick Durbin (D–IL) introduced a bill intended to do just that: The Dietary Supplement and Nonprescription Drug Consumer Protection Act (S. 3546). The bill attempts to put natural products and nonprescription pharmaceuticals on the same footing by requiring manufacturers of supplements and OTC drugs to submit AERs to FDA in a timely manner. According to Linda Suydam, president of the Consumer Healthcare Products Association (Washington, DC), the legislation “will ensure that FDA has the tools it needs to fulfill its public health mission to more aggressively monitor the medicines and nutritional supplements it regulates.” Although some organizations oppose the bill, it appears to have widespread support. In July, a coalition of nine consumer advocacy groups and industry trade associations sent a joint letter to all 100 members of the Senate in support of S. 3546, which sailed through its first committee hearing in June.

ROOM AT THE TOP

A third unresolved matter is the fate of the FDA commissioner. As the industry has seen, programs like the GMPs and AERs can take years to perfect. The absence of a permanent commissioner to oversee their implementation could make things even worse.

Some experts believe that the absence of a permanent commissioner should not affect FDA’s ability to enforce the law. “Despite the number of transitions at FDA in recent years, we’ve been fortunate that commissioners like Doctors McClellan and Crawford took seriously the authority granted to the agency under DSHEA and looked to make the law work,” Mister says. “We are hopeful that if Acting Commissioner von Eschenbach is confirmed, he will take as strong an interest in assuring that FDA is using the full powers DSHEA provides to the agency.”

According to Mister, CRN would like to see the Senate confirm a commissioner who “appreciates the positive role that supplements can play in the healthcare system and is not afraid to cite companies that jeopardize the ability of other companies to appropriately manufacture and sell safe, high-quality, and effective products to consumers.”

On the other hand, a vacancy in the commissioner’s chair could turn out to be an issue for all FDA-regulated industries, suggests Israelsen. “Perhaps it’s a poor analogy, but we all recall the problems faced by substitute teachers in the seventh grade,” Israelsen says. “So long as there is not a confirmed and permanent FDA commissioner, uncertainty and ambiguity will persist as to FDA’s enforcement philosophy and political support, when it comes to developing difficult policy and enforcing major regulations.”

A MORE CONFIDENT 2007

While mandatory GMPs and AERs may not satisfy all critics, their combined appearance in 2007 should help boost consumer confidence and improve the state of the industry. With those contentious issues out of the way, manufacturers will have more energy to devote to other important tasks, including the development of clinical trials, validated methods, and innovative products.

By Groundhog Day in 2007, if HHS’s predictions are true, the industry could have the GMPs it has been asking for. Then again, groundhogs, and other fortune-telling creatures, have been wrong before.