By Devon Powell
In 2007, FDA published the final rule regarding GMP (good manufacturing practice) regulations applicable to dietary supplements (21 CFR 111). The regulations were created with the intention of ensuring manufacturers produce quality finished dietary supplement products.
In the preamble to the final rule, the agency defined “quality" to be: ‘‘that the dietary supplement consistently meets the established specifications for identity, purity, strength and composition, and has been manufactured, packaged, labeled and held under conditions to prevent adulteration under section 402(a)(1), (a)(2) (a)(3), and (a)(4) of the Federal Food, Drug and Cosmetic Act.’’
This assurance of the quality of dietary supplements is satisfied via manufacturers establishing a comprehensive system of process controls, including documentation of each stage of the manufacturing process, that can minimize the likelihood of, or detect, problems and variances in manufacturing as they occur, and before the product is in finished form. The regulations require products to be manufactured, processed, packaged and held under sanitary conditions, and in such a way so they contain what the manufacturer intends, are safe, and have traceability.
The final rule became effective on August 24, 2007, and compliance dates included a three-year rollout period based on the total number of full-time equivalent employees at a business. Now, entering 2015 and coming up on five years since all companies were required to be in compliance, a significant number of FDA warning letters contain the same issues: no master manufacturing records, no established specifications for components, no or limited testing to meet the required specifications for purity, strength and composition, and—the most regular issue with regards to botanicals—no established specifications for identity and/or no identity testing.
Warning Letters: Just the Facts
Since October 2014, every warning letter sent to a dietary supplement company and published on the FDA’s website has essentially the same issue: failure to verify identity/no identity testing.
For example: “Your firm did not conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient prior to its use, as required by 21 CFR 111.75(a)(1)(i), nor has the FDA received a petition from you, and granted the petition, to exempt you from this testing requirement, pursuant to 21 CFR 111.75(a)(1)(ii). Specifically, you have not conducted identity testing to verify the identity of any components that are dietary ingredients, prior to their use in the manufacturing of your [product name] and [product name], nor has FDA received from you and granted a petition exempting you from such testing requirement."
And this one: “You failed to establish specifications for the identity of components as required by 21 CFR 111.70(b)(1). You also failed to establish component specifications necessary to ensure that specifications for the purity, strength, and composition of dietary supplements manufactured using the components are met, as required by 21 CFR 111.70(b)(2)."
The GMP regulations state that every component used as a dietary ingredient in a supplement must be tested for identity before use. Though there is an exemption petition opportunity for what’s been dubbed “100-percent identity testing" (for which I’m not aware of any business applying), it seems many companies simply aren’t investing in the basic processes and procedures in order to document the methods and means by which key compliance efforts (must) occur.
In addition to the 100-percent identity testing requirements, in-process specifications and finished products are to be tested to demonstrate the specifications set by the manufacturer/brand marketer for each product are met – specifications meaning, again, strength, purity and composition. In products with multiple ingredients, especially botanical ingredients, which may make a more complicated product matrix, this can become a more complex process—and in some cases, seemingly not possible via the “scientifically valid methods" available.
One of the warning letters since October 2014 specifically noted the following with regard to finished product testing to demonstrate specifications are met: “Your means of verifying strength and composition of these dietary ingredients are ‘Based on Input’ or ‘Ensured by documented control,’ meaning that your operators have identified that they have added the ingredients to the batch of product. Ensuring that an ingredient is added to the batch of product does not provide adequate assurance that the finished product specifications are met."
The warning letter went on to note the firms response that the next number of batches of the products mentioned in the Warning Letter will be tested—but also noted the firm failed to indicate via what tests—and that the response is therefore not adequate.
Dietary supplements as a category have enjoyed incredible growth since formally coming into existence in 1994 with the passage of the Dietary Supplement Health and Education Act (DSHEA). It’s a fairly easy business to get into with relatively very few barriers to entry in the United States. Though there are certainly a number of firms that are compliant and are producing products of the highest quality, as well as those who are clearly interested in doing so, it’s time the industry as a whole figured out how to take a bigger leap in the right direction.
Solutions: The “Big Step Forward"
Here’s a potential direction the industry could take: require third-party GMP certification for all products sold in the United States.
There are literally hundreds of companies whose facilities are already third-party certified for GMP compliance, and thousands of products already carrying a seal of some sort that indicates they have had their label claims reviewed and tested against, among other things. Certification tends to cost about $15,000 for a facility (required) and then approximately $3,000 or less per product, annually.
So, while true that such a law would add an additional amount per product at the register for consumers, can you imagine the marketing and PR that could be generated from those efforts to counter that increase, and perhaps even increase sales? And further, consider the additional benefits of removing from the marketplace all of the “competitors" that are making illegal drug claims and poor-quality products.
If industry truly wants to step up its game, promulgating new legislation making third-party certification a requirement for all products to be sold in the United States would increase consumer confidence as well as eliminate the “bad players" from the marketplace. Now would be an ideal time to move on such a concept, given the Congressional allies (and detractors) currently in place, it should be fairly easy to find support for that kind of industry-backed, essentially self-policing, on both sides of the aisle.
Devon Powell was formerly the chief operations officer at the American Herbal Products Association and executive director at the International Aloe Science Council. He is currently a consultant to the dietary supplement industry, assisting manufacturers and brand marketers with regulatory initiatives including GMP compliance, QA, QC, auditing, and related elements. He can be reached at [email protected].