GMPs Have Arrived!

FDA’s final rule on cGMPs could be the best thing to happen to dietarysupplements since the passing of DSHEA if companies approach these new regulations in a practical, balanced manner.

By
Marian Zboraj
Associate Editor

After anxiously waiting 12 years, the dietary supplement industry has finally received FDA’s final rule establishing current good manufacturing practices (cGMP) for dietary supplements. The rule, released on Friday, June 22nd, essentially ensures that dietary supplements are produced in a quality manner, do not contain contaminants or impurities and are accurately labeled.

The overall consensus is that the final rule is strong and fair, and more reasonable than the proposed version. Rather than keeping the dietary supplement industry on a tight leash with painstakingly precise guidelines, FDA instead provided a basic template for maintaining consistent quality products.

“The true benefit to the industry is that the GMP final rule, along with mandatory serious adverse event reporting, will finally dispel the notion among some that the industry is ‘unregulated,’” said Andrew Shao, PhD, vice president of regulatory and scientific affairs, Council for Responsible Nutrition (CRN), Washington, D.C. “This term can no longer be used to describe dietary supplements.”

There were several key aspects to the final cGMPs, among them the exclusion of dietary ingredient manufacturers from the regulation. During the proposed rule, David Seckman, executive director and CEO, Natural Products Association, Washington, D.C., certainly thought that the burden for product quality shouldn’t be placed solely on the manufacturers, stressing that ingredient suppliers ought to be included as they too are a part of the industry.

Loren Israelsen, executive director, United Natural Products Alliance (UNPA), Salt Lake City, UT, shared the same view, but after reviewing the rule he understood FDA’s reasoning for omitting ingredient suppliers. “Essentially FDA’s theory is that manufacturers will now require ingredient suppliers to provide adequate information to assure identity compliance,” he said. “The FDA does require at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient. So though the GMPs do provide the industry with obligations to follow, the FDA acknowledged the industry’s expertise and felt the manufacturer was in a better position to determine how to achieve compliance.”

“This renders manufacturers’ due diligence regarding the proper qualification of raw materials and ingredient suppliers that much more critical; proper sourcing of ingredients becomes a critical component of the quality of the end product,” said Dr. Shao.

“But as always, if you create that flexibility, inherently you create opportunity for companies to try to figure out how to weasel around the rules,” commented Mr. Israelsen. “Therefore it is the industry that is responsible for supervising this rule.”

Although the final rule is flexible in the use of scientific methods to verify identity, purity strength and composition of dietary supplements, Certificates of Analysis (CoA’s) still need to be harmonized in order to serve as an adequate basis for the acceptance of raw material identity. Mr. Israelsen notes, however, that suppliers who have demonstrated consistent competence and reliability over the years will be provided with a preferred pathway so that their CoA can be the basis for acceptance of the material for the manufacturer.

As a companion document, FDA is also issuing an interim final rule that outlines the petition process for manufacturers to request an exemption to the cGMP requirement for 100% identity testing of specific dietary ingredients. Under the interim final rule the manufacturer may be exempted from the testing requirement if it can provide sufficient documentation that the reduced frequency of testing requested would still ensure the identity of the dietary ingredient. (Comments to regarding the interim final rule may be sent to the Division of Dockets Management Branch at www.fda.gov/dockets/ecomments until September 24, 2007.)

Although the rule offers more flexibility in finished product testing, it does put more focus on process control. According to Mr. Israelsen, recordkeeping is a big element. As he explained, the rule requires more documentation, including the establishment and use of written procedures or records for certain operations, as well as documentation related to equipment, physical plant sanitation, certain manufacturing operations, quality control, laboratory testing, packaging and labeling and product complaints. “The FDA also asserts full authority to request and inspect those records, which is motivation for companies to be rigorous in developing and maintaining their documents,” he commented.

Another key element to the final rule is there will be no requirement for providing an expiration date on dietary supplements, but companies that use such dating will need to have supporting data. “We (Natural Products Association) thought that expiration dates should be included in the mandatory regulations,” said Mr. Seckman. “Nonetheless, we believe that the vast majority of the industry will continue using expiration dates on products.”

Other significant factors covered in the final cGMP include:
• Making GMP compliance relevant to all dietary supplements sold or offered for sale in the U.S., so even foreign firms will be required to meet the new standards
• Establishing minimum requirements for personnel, physical plant and grounds, and equipment and utensils
• Requiring identification and quarantine of returned dietary supplements until quality control personnel conducts a material review and makes a disposition decision
• Requiring a qualified person to investigate any ‘‘product complaint’’ that involves a possible failure of a dietary supplement to meet any cGMP requirement.

The final rule takes effect on August 24, 2007. Companies with more than 500 employees have until June 2008 to comply, companies with less than 500 employees have until June 2009 to comply, and companies with fewer than 20 employees have until June 2010 to comply with the regulations.

One concern that has arisen from this “rule in” period is how the industry will communicate to the outside world that during the next 36 months there will be some companies required by law to comply with these regulations while others are not. As a result, some may call into question the safety of supplements produced by smaller companies granted a longer “rule in” period.

Another issue is the potential trend of companies advertising or promoting that they are “GMP certified,” or something along those lines, when in fact they are not. “The FDA has indicated if a company does make these false statements, the agency has the authority to act under both FDA law and FTC law against the offender,” said Mr. Israelsen. However, Mr. Israelsen is not looking for FDA to be the “nanny” on those issues. Instead, he would like to see the industry develop trade standards, practices and internal guidelines in order to manage its own affairs.

“We knew what needed to be done prior to the release of the final rule,” said Mr. Israelsen. “The GMPs will simply become the catalyst to crystallize our will as an industry to weed out the companies that are producing substandard products.”

Adjusting to the regulation will be no problem for some companies as pointed out by Dr. Shao. “Although the requirement prior to the final rule was for companies to abide by the food-based GMPs, most of the responsible companies in the industry have been manufacturing their dietary supplement products to much higher standards, standards that are close to or even exceed those called for in the final rule,” he said.

The bottom line, according to Mr. Seckman, is that the newly released cGMPs will help increase consumer confidence in the quality and purity of dietary supplements across the board. “Consumers want to be assured that what’s on the label is in the bottle, nothing more, nothing less, and this regulation aims to make sure that is the case,” he said.

Instead of waiting for the one, two or three year deadline, Mr. Israelsen advises the industry to move quickly in complying with the regulations, even if there are disagreements with some elements. “The whole supply chain needs to work together to educate itself and to evaluate and modify their standards of practice. We then can quickly demonstrate to our stakeholders—our consumers—as well as observers in Congress, the national media and international markets, that we are committed to providing high quality products that deliver on their promises. Frankly, this could be the best thing in terms of growth that the dietary supplement industry has seen since the passing of DSHEA in 1994.”