Making Sense of GMPs

Making Sense of GMPs

Currently, there are no federal good manufacturing practice regulations specific to dietary supplements. In general, the Food and Drug Adminstration (FDA) defines the term good manufacturing practices (GMP) as procedures in manufacturing of foods, drugs and medical devices that are designed to ensure production consistency.

GMPs are about maintaining manufacturing standards--they are not necessarily a guarantee that a product is safe."GMPs are supposed to ensure that only what is supposed to go in a product is actually what goes into it," said attorney Marc Ullman withUllman, Shapiro and Ullman. "They also ensure that the product has been manufactured in a sanitary environment." They operate in accordance with label claims that say the product's ingredients are in a safe, uncontaminated and pure form. As Ullman noted, there is always an inherent risk that there may be side effects associated with a product, whether it's a dietary supplementor a pharmaceutical.

The term "cGMP" is used by the federal government as current good manufacturing practices. By definition, "cGMP" indicates that the current GMP--which is "state of the art"--can change. "GMP" and "cGMP" are often used interchangeably and essentially they have the same meaning.

The History of GMPs for Dietary Supplements

The Dietary Supplement Health and Education Act of 1994 (DSHEA) authorized but did not require the FDA to adopt new federal regulations for GMPs for dietary supplements. Under DSHEA, the FDA can issue GMP regulations for dietary supplements that are modeled after food GMPs. A number of organizations developed a model for the regulations and passed it to FDA in late 1995. The sponsors were the American Herbal Products Association (AHPA), the Council for Responsible Nutrition (CRN), the National Nutritional Foods Association (NNFA) and the Utah Natural Products Alliance (UNPA).

"InDSHEA, Congress ordered FDA to model any specific GMPs for supplements on foodGMPs," Ullman said. "The food GMPs [as opposed to pharmaceutical GMPs] had less rigorous steps to take against impurity--not every batch needs to be tested and record retention isn't as rigorous."

Unfortunately, it's now 2000 and the FDA has not proposed any new regulations for dietary supplement GMPs. This has placed the industry in a regulatory gray zone and has many industry members questioning why the FDA is taking six years to create new GMPs.

DSHEA mandates that FDA's GMPs would require companies to ensure quality control through written record keeping and the faithful monitoring of manufacturing operations. Written records would validate safety, purity and potency of ingredients. FDA would also like companies to track complaints such as illnesses and injuries alleged to have occurred through use of dietary supplements, but this would not track food GMPs, said attorney Anthony Young with Piper Marbury Rudnick & Wolfe.

The Current Status of GMPs for Supplements

"Currently, dietary supplement manufacturers are required to follow food GMPs and many supplement manufacturers have also established additional GMPs," said Phillip Harvey, Ph.D., NNFA's director of science and quality assurance.

Until the FDA or the industry comes through with a set of dietary supplement GMPs that are approved by or applicable to all, companies are setting internal GMPs and using them as a template for quality standards. For instance, Tamara Smith, the department head of marketing at Whitsett, N.C.-based Shionogi Qualicaps, said her company has its own set of self-imposed GMPs. It has a list of suggestions for manufacturers to help determine the quality of a supplier, regardless of the presence of federal GMP regulations.

According to Smith, companies that comply voluntarily with FDA inspections and GMPs manufacture in a validated continuous production environment, which guarantees consistent quality. The best feature in-house labs, scientific and technical staff and testing capabilities. She also noted that they offer their own inspection programs that involve regular sampling and monitoring of product quality and they perform additional tests to monitor process controls at prescribed intervals. The FDA may also do its own inspections.

Other companies such as Traco Labs have initiated in-house GMP programs that ensure quality control from within. "While the temptation may exist to sacrifice quality for the sake of profits, we feel that this attitude is counter-productive to long-term goals," said Harlee Sorkin of Traco Labs. "We have made a number of efforts over the course of years to earn the trust of supplement manufacturers." For example, Traco adopted ISO 9000 standards to govern its GMPs.

NNFA's GMP Program--Pros and Cons

Rather than waiting for federal GMPs, NNFA rolled out a GMP program in January, 1999. When its GMPs were put in place, NNFA required all of its members to comply; that policy is no longer enforced. According to the NNFA, the policy changed because its bylaws require that a new condition of membership cannot be created without the full vote of the NNFA membership, which had not been done. It has also added a disclaimer this year, which is used in conjunction with the NNFA GMP seal, that reads, "This seal certifies that the manufacturer of this product uses quality systems and procedures that comply with NNFA's Dietary Supplement GMP standards. The quality of individual ingredients, however, has not been certified."

According to Tracy Taylor, public affairs and communications coordinator at the NNFA, the legend keeps consumers from making incorrect inferences about products with the seal. "Products that display the GMP seal are not of the same quality," she said. "Raw materials must be tested for identity, but many have higher grades of ingredients."

In order to qualify for the seal, manufacturers must be audited for their compliance to NNFA's GMP guidelines. All of a manufacturer's facilities, including production, packaging, testing and/or distribution, may be audited by independent, third-party auditors who have been trained on the association's protocol. NNFA's Advisory Committee may assess the quality of the audits. The company is then rated by NNFA on a scale of A to C [A is "excellent compliance, minimal deficiencies; B is good compliance, few minor/major deficiencies; C is fair/poor compliance, many major deficiencies]; it is then determined whether follow-up inspections are necessary.

"There are no exact numbers as to how many major and minor deficiencies a company might have and still receive an 'A' compliance rating," said Harvey. "Some deficiencies requiring corrective action could be addressed during the actual audit. However, a critical deficiency [e.g., not using potable water or lack of raw material identity testing] would automatically result in a 'C' rating, which then requires a re-audit as part of the corrective action. It is important to note that the auditor will confirm the existence of all mandatory policies, procedures and records and will review a representative sampling of the procedures for adequacy and adherence. A member supplier that lacks even a few of the mandatory elements will not receive an 'A' compliance rating." It is only after receiving an 'A' rating that a member company can apply for the NNFA GMP seal, which it can apply to its packaging.

But what if a company gets a 'C' rating and refuses to comply? "Theoretically, if a company chooses not to institute corrective action and not to bring their compliance rating up to an 'A' level, the audit would then be closed and the company is not eligible to become NNFA GMP Certified," Harvey said.

Currently there are 13 companies GMP-certified by the NNFA, out of approximately 1,000 supplier members [a number that includes manufacturers, raw material suppliers, distributors, brokers, etc.] According to the NNFA, there are 60 more companies in the certification 'pipeline.' "Of note," Harvey said, "is that approximately 10 companies have joined NNFA this past year specifically to participate in the GMP program. The enrollment figures speak volumes about the popularity of this program among member suppliers."

Though its program is currently the only GMP program in the industry, its reception has been mixed. "Some companies have more resources than others, so they're forced to comply because of investments [such as trademarks]," said Ken Hassen, vice president of sales and marketing at Biosint USA. "For others with limited resources, [getting the GMP certification] may not be a priority."

Hassen added that getting the certification may be overwhelming for manufacturers, but it's better to apply for the [NNFA] audits and meet them head-on, because the need for this sort of evaluation will not go away. "If we don't police ourselves," said Hassen, "it will be incumbent on others [FTC, FDA] to do it for us." According to Hassen, there has to be some sort of industry-wide standard that can allow consumers to be make informed decisions when choosing products.

"We're one of the companies that really wanted it [the label]," said Jodi Drexler with Country Life. "We needed it for a long time [in the industry]. A company has to be certified--and it's a grueling process. It's more than having clean floors and machines. It's making sure that what you say is in the product is actually in it." According to Drexler, the NNFA's GMP logo inspires consumer confidence. "The logo is important because consumers can buy products anywhere--that's why [NNFA's] GMPs are important. How does a consumer know a vitamin is good?"

However, some companies that have become certified are not as effusive. Though NNFA is the first organization in the industry to offer GMP certification, "its certification process is only a one-time shot," said Dean Morris of Murdock MadausSchwabe, parent company of Nature's Way. "There's little follow-up [by the NNFA] and it's not effective for label claim validation." And regarding the logo, said Morris, "It's a start, but itneeds progress."

Others echo those concerns. "In a sense, the GMP that NNFA is promoting is simply a process for documenting the production process with no regard for the quality of the ingredients so long as they meet the company's written specification," said Stephen Ashmead, head of research and development at Clearfield, Utah-based Albion Labs. "I am concerned that there is no enforcement policy associated with the audit, and that certification is good for three years. Also, it is not known how FDA's guidelines will differ from NNFA's."

Another question is what does the presence of the GMP seal on a product mean to consumers? Some note that a lack of consumer education about the seal may confuse consumers about what it actually represents. "While the program is sound in theory, the implementation has left quite a bit to be desired," Sorkin said. "The NNFA GMP program indicates that products bearing its logo are safe, and that implies a certain level of quality. In fact, GMPs provide no assurance of the quality or safety of a product; they simply set guidelines for production which help to ensure consistency. So if a product is of low quality, GMPs only ensure that it will be low quality every time."

According to Jarrow Rogovin, president of Jarrow Industries Inc., the NNFA's program blurs the distinction between "quality" and "raw material." The solution, he said, is to eliminate the logo. "As far as the NNFA having a GMP program goes, even the FDA hasn't convinced itself that it needs GMPs [for dietary supplements]," Rogovin said. It takes a great deal of time and money to meet the NNFA's standards, he added, and he belives that having NNFA's GMP seal on a product insinuates that the product is "co-branded." In addition, he said, some companies have standards that are higher than the NNFA's, so having NNFA's logo on all products makes them all look the same. "A logo from an organization that represents small, independent health food stores will be seen on the shelves of mainstream drugstores and supermarkets, because you can't control distribution," he remarked. "What message does this send to the membership?"

The Future of GMPs for Supplements

According to the FDA, there are a number of reasons why GMPs have not yet been put in place. In a Federal Register notice issued Oct. 6, 1999 [vol. 64, No. 193], the FDA noted its concerns about the lack of cGMP for dietary supplements. The FDA's numerous concerns--ranging from ways to enhance the quality of information collected to minimizing the burden of information collection on individual companies--all point to a need for more clarification about procedures within the guidance. [The issues raised by the FDA were open for comment.]

The FDA is currently working on creating regulations for GMPs and, according to an FDA spokesperson, "It's a priority to have a proposed rule on GMPs for dietary supplements within this fiscal year [2000-2001].

Some in the industry said they have been meeting with the FDA in "small business discussions" called by the FDA. Those discussions have been a forum for the industry to make its needs known to the FDA before it publishes its guidance. AHPA is one of the organizations that has attended every one of the meetings.

"I hope the FDA is astute enough [under DSHEA] to avoid creating drug GMPs for dietary supplements," said Michael McGuffin, president of AHPA. "My hope is that they'll present a GMP that's crafted in the spirit of the industry." McGuffin noted that AHPA hopes to see FDA use the 1995 industry draft GMPs as its guideline. Also, once there are federal GMPs, McGuffin anticipates additional market pressure on dietary supplement companies to ensure quality of materials. AHPA is currently working on a manual for identification of botanicals in order to establish a procedure for identification. McGuffin also assisted in drafting specific guidance for botanical identification that was adopted by the FDA's Food Advisory Committee.

Presently, the food GMPs apply to the manufacture of dietary supplements, Young said. "The dietary supplement industry should look to the cGMPs for food as guidance for areas that need to be addressed in any reasonable GMP program," he said. FDA's inspectors use the food GMPs as a matrix for compliance when they visit a company, which FDA has the authority to do for any reason.

"Companies should be able to benefit from a common-sense approach to quality manufacturing," said attorney Tony Martinez with Martinez and Associates. "However, the new dietary supplement GMPs will be different from food GMPs and companies will have to allocate and invest in new resources to make compliance efficient."

In the meantime, Ullman said, companies can implement their own GMP and other QC programs. "They are essential as a formalized set of procedures designed to ensure that a product is what it represents itself to be," he said. "That should include testing of incoming raw material--manufacturers should not rely on assays handed to them"

At the end of the day, "a GMP is the baseline," McGuffin said. "It's the least a company is allowed to do. Quality control is a part of that. The basic steps involve isolating raw materials." However, he noted, "there is still no right way to ensure internal quality control."