WASHINGTONFDA is finding through inspections that dietary supplement manufacturers often are failing to set specifications for products, properly test ingredients and verify finished batches match the specs and facts listed on labels.
Dietary supplement manufacturers continue to violate basic regulations that first took effect in 2008 for the largest companies, an FDA official and several other sources close to the industry told Natural Products INSIDER.
Noncompliance with cGMPs (current good manufacturing practices) is infuriating to FDA and frustrating to supplement advocates in Washington whose bread and butter consists of promoting the fast-growing industry.
"I'm really disappointed in the industry," said Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), whose trade association represents dietary supplement manufacturers and ingredient suppliers. "These regulations were issued in 2007. We have had over six years to get ready for these."
According to a Sept. 25 presentation from an FDA official during a U.S. Pharmacopeia Convention workshop in Rockville, Md., the most common violation of the cGMPs is failure to confirm the identity of dietary ingredients. Dan Fabricant, Ph.D., director of FDA's division of dietary supplement programs, presented the data.
Companies that make supplements are supposed to test their incoming ingredients to verify the components listed by an ingredient supplier on a certificate of analysis (CoA) are accurate and match what the manufacturer ordered, said Shelly Maifarth, principal of the FDA Compliance Group, a Broomfield, CO-based firm that helps companies adhere to FDA requirements.
"That is a problem if that's our top violation," Fabricant said in a phone interview. "It's very basic. You don't know what you are putting in a product is basically what you are telling consumers. That's a big problem."
Maifarth terms a requirement that manufacturers establish product specifications, such as documenting milligrams in vitamin C, as a "basic, basic kindergarten step." To the consternation of FDA, many firms are failing to make this elementary move. The agency cited failure to establish specs for the identity, purity, strength and composition of supplements as the second most common violation.
"This is the proverbial crawling before you run. You've got to be able to do this. This is something people don't get credit for," Fabricant said. "This is something you should be doing regardless. These are basics to ensure consumers get products that meet minimal quality standards."
The cGMPs for dietary supplements21 C.F.R. Part 111took effect for the largest companies in 2008, and the smallest firms had to comply with them by June 2010.
More than three years later, many manufacturers are still failing to verify that their finished batches conform to product specifications. This requirement is the third most commonly cited violation by FDA inspectors.
"Too frequently, firms are not confirming the identity, strength and composition of their finished supplements," said Pieter Cohen, M.D., an assistant professor at Harvard Medical School, who has studied supplement safety. "This leaves consumers wondering, 'what's actually in my botanical supplement''?
Mister likened the cGMPs to a person seeking to make grandma's cookies.
"They are much like a more elaborate way of making sure when you make your grandmother's cookies from her cookie recipe, you are going to end up with something that tastes like your grandmother's cookies," he said.
Failing to test incoming ingredients is akin to reaching into a canister for flour to make cookies without looking inside.
"For all you know, you picked up the sugar or baking soda," Mister said. "The level of trust our consumers have in our products is much higher than a chocolate chip cookie. So we owe it to our consumers to have a specification for what that product looks like and to do a batch record test to make sure we have followed the recipe."
Marc Ullman, a New York-based supplement lawyer, expressed dismay that companies continue to be cited "for fundamental failures."
"On one hand, I am surprised. They are the most basic requirements of the GMPs for supplements," he said. "On the other hand, based on my experience, I am not surprised."
Mister asserted most of CRN's members are following cGMPs. And while he stated firms with a poor cGMP record typically are under-the-radar companies that aren't recognizable to most consumers and don't exhibit at large trade shows like VIRGO's upcoming SupplySide West, Ullman expressed a different opinion.
"The excuse that these citations just go to weird or fringe Internet marketers doesn't fly," Ullman said. "It's not true."
FDA has been bringing down the hammer on one out of three dietary supplement firms for failing to comply with cGMPs. Through the first several months of fiscal year 2013, of the 350 cGMP inspections FDA originally designated and concluded as falling under Part 111, the agency's 19 district offices collectively classified 33 percent, or 117 businesses, as OAI (official action indicated).
FDA defines the latter action as occurring "when significant objectionable conditions or practices were found and regulatory action is warranted to address the establishment's lack of compliance with statute(s) or regulation(s)," according to an FDA document. Firms that receive an OAI are subject to a number of FDA actions ranging from an untitled letter to more serious enforcement such as a warning letter and injunction, Fabricant explained.
In total, 151 of the 505 firms inspected for cGMPs, or 30 percent, were classified as OAI, according to Fabricant's presentation. The data is somewhat confusing because FDA didn't originally designate 155 businesses, or 31 percent, of the 505 firms, as being subject to a Part 111 inspection. But some of the firms scheduled for a conventional food cGMP inspection may have been reviewed for compliance with Part 111, Fabricant explained.
Another 143 firms that were scheduled for a Part 111 inspectionor 41 percent of such businesses expressly designated as falling under the supplement cGMPs were classified as VAI (voluntary action indicated) in fiscal year 2013 (FY13). FDA makes the above classification when it finds "objectionable conditions or practices" that don't rise to the level "of regulatory significance."
"I am going to look at it right now as a tale of two cities. A lot of the industry doesn't really seem to be getting on board with the basics, whether it's OAI or VIA," said Fabricant, who pulled the data in early September and noted it probably excluded two months of the government's fiscal year.
In FY12, as INSIDER previously reported, FDA inspectors cited 70 percent of firms for violating cGMPs on a document known as a form 483. Some firms received as few as two observations while one company was cited for 58 violations. From FY10 through FY12, firms that received a form 483 were cited for an average of seven observations, government data shows.
Ullman said he believes warning letters aren't a big enough hammer to compel compliance with the regulations. For instance, he recommended FDA criminally prosecute dietary supplement firms that are noncompliant with cGMPs and make prohibited claims of treating diseases like cancer. Ullman also noted FDA can make a statement without involving the judiciary.
FDA officials "don't need to go to court to slap an administrative detention on somebody and shut a facility down for 20 days," he said.
In the first legal action for noncompliance with cGMPs, FDA, through Justice Department lawyers, filed for a permanent injunction in late 2011 against a dietary supplement manufacturer in Pennsylvania. FDA has taken a select number of similar actions in recent years.
Most recently, in a Sept. 25 lawsuit, FDA moved for a permanent injunction against a dietary supplement firm in Oregon. FDA alleges that James G. Cole Inc. violated cGMPs and made unlawful claims through labels, product brochures and websites that its supplements can treat such diseases as autism, Alzheimer's and cancer. The Hood River-based firm plans to mount a defense.
"I don't think we have been real shy about using the authority," Fabricant said.
Mister said he is in favor of FDA pursuing stronger enforcement actions beyond warning letters, such as civil and criminal prosecutions that are authorized under the Federal, Food, Drug and Cosmetic Act.
"FDA needs to be a lot more aggressive in the enforcement stage because if they do that, it will send a message to the other companies. A warning letter is not enough to send a message in some cases," he said.
Dean Cirotta, president and COO of EAS Consulting Group, which specializes in FDA regulatory matters, cited a "general lack of understanding of what it takes" to fully comply with cGMPs.
"We're still seeing too many companies receiving significant 483s and significant warning letters," he said. "I still think there's a long way to go."
FDA has threatened to pull the trigger on another weapon that could close the gap in compliance. The FDA Food Safety Modernization Act (FSMA) grants the agency power to assess fees for re-inspections. In warning letters, FDA has cited its authority to assess these fees.
Effective Oct. 1, the hourly domestic fee is $237 and $302 for work outside the United States, according to a government notice in the Federal Register.
The agency can bill for its time traveling, inspecting a facility and conducting other work such as analyzing samples and writing a report, said Cara Welch, Ph.D., senior vice president of scientific and regulatory affairs with the Natural Products Association (NPA), a 77-year-old organization representing the natural products industry.
The fees could add up to tens of thousands of dollars for a company, according to Cirotta. "A one-week re-inspection could cost a company in my estimation $25,000 to $30,000 easily," he said.
Fabricant said he couldn't comment on whether FDA has assessed fees for re-inspections.
Welch said she wasn't aware of the agency invoking its authorityyet. She expressed optimism that the fees, once FDA begins assessing them, will motivate companies to avoid an enforcement action like a warning letter. "Hitting folks in the pocketbook is very effective," she said. "When the invoices start going out;, hopefully that's a wake-up call."
Meantime, consumers of dietary supplements need to be "more savvy" about their purchasing decisions, said Mister. "They need to purchase products from companies they trust," he said.
Mister also recommended consumers consult with a healthcare professional before beginning a new regimen of supplements.
"In addition, consumers should avoid companies they've never heard of before, that have only a P.O. box as a mailing address or make claims that sound too good to be true," he said.
Cohen, the assistant professor at Harvard Medical School, recommended consumers only purchase single-ingredient supplements that NSF International or the U.S. Pharmacopeial Convention (USP) have certified.
"From the perspective of ensuring quality, the term 'third-party certification' has become meaningless. If a supplement has been certified by a third party, it doesn't tell the consumer anything useful," Cohen told INSIDER. "The question is who has done the certifying. If it has the official USP or NSF International stamp on the label, then one can assume that what is on the label is in the bottle. If it doesn't have one of these two stamps, then you have no assurance of what is actually in the bottle."