Part 1: Impact of FDA Proposed CGMP Standards for Dietary Supplements
By Richard H. Meer
In 1994 the DSHEA Act establishes a new category of dietary supplements, which allows products "may bear statements about a substance's effect on the structure or function of the body." Benefits are derived from these ingredients through its nutritive value, and labels may not make statements that claim to "treat, cure, mitigate, prevent, or diagnose disease." The Act instructed the FDA to prepare its own set of CGMP rules that are to be modeled after the food industry standards.
On March 7, 2003, the FDA changed the ground rules by publishing its long awaited its "Proposed Rule for Current Good Manufacturing Practices (CGMP's) in Manufacturing, Packing, or Holding Dietary Ingredients or Dietary Supplements" including both functional foods, and nutraceuticals. The proposed rulings are so comprehensive that they will eventually affect everyone in the food industry as well since there is an extensive crossover of products.
According to the FDA announcement, the CGMP's are "intended to ensure that dietary supplements and their ingredients are not adulterated with contaminants or impurities, and are labeled to accurately reflect the active ingredients and other ingredients in the product". Clearly, there have been some troubling issues associated with dietary supplements in the last few years like over or under assay of active components, adulteration and product contamination. The most dramatic example of dietary supplement misuse surrounds the death of Steve Bechler, a Baltimore Orioles pitcher, who took an excessive dose of the weight reducing herb ephedra. The FDA will also require manufacturers to maintain very specific records relating to CGMP standards that were not previously mandated.
The DSHEA legislation provided for the FDA to establish CGMP regulations but they were to be modeled after the food industry CGMP regulations. The supplement industry believes that FDA went too far as many of the proposed standards in many more closely resemble pharmaceutical CGMP's. The FDA is aware of the industry's complaints but the agency has a list of product recalls that were not labeled properly, were the wrong ingredient, or caused a health risk by including unregulated pharmacologically active ingredients. Clearly the industry will have to respond to the proposed regulations, but that will not be an easy task. This presentation, and those that follow, will identify specific requirements proposed for industry members, and to assist them in responding to the most egregious or unfair regulations that will affect their daily business.
The announcement provides for a 90-day comment period before FDA reviews these rules again. They will probably begin enforcing the rules within one year for larger firms following their second review. So realistically, the maximum timetable before enforcement begins is two years from today. One conciliation the FDA granted for small businesses up to $10 million in sales is a three-year phase in period after the final ruling. Previously the trade association, National Nutritional Foods Association (NNFA) was trying to encourage voluntary compliance of food GMP guidelines, with only about 60 firms passing through the rigorous compliance procedures. Now, the FDA will now regulate the entire dietary supplement industry of over a thousand firms through its new CGMP standards. Through its new CGMP regulations, the FDA expects to build consumer confidence in all dietary supplements they purchase by insuring the identity, purity, quality, strength, and composition that the label proclaims.
Under DSHEA, manufacturers have the essential responsibility to substantiate the safety and efficacy of the dietary ingredients they use in manufacturing a product. Dietary supplements have been recalled because of microbiological, pesticide and heavy metal contamination that the FDA hopes to prevent through a uniform standard of manufacturing requirements. What is important to appreciate is the FDA is requesting comments from the public on nine specific issues that were not completely addressed in the regulatory document.
The first question asks, "Is there a need to develop specific defect action levels (DALs) for dietary supplements?" This issue is addressed toward botanicals that may contain pharmacologically active components. It furthermore may include insect fragments or "mammalian excreta" as was developed for the spice industry 30 years ago. This is the easiest of the nine questions under review.
Secondly, "We [FDA] request comments on appropriate testing requirements to provide positive identification of dietary ingredients particularly plant materials used in supplements." In this case, the FDA is trying to avoid a public health concern by having analytical methodology developed by the manufacturer and then approved by independent laboratories by collaboration.
The "FDA requests comments on standards that should be met in certifying that a dietary ingredient or supplement is not contaminated with filth; that it is free from harmful contaminants, pesticide residues or other impurities; that it is microbiologically safe; and that it meets quality and identity standards." The FDA does not agree that the products are free from filth or microorganisms based on the supplier's certificate alone. Accordingly, the supplier's certificate does not guarantee purity, quality, strength, or composition of the component. This will be a challenge for foreign ingredient firms to have their products incorporated without domestic laboratory collaboration.
"We [FDA] ask for comments on whether a CGMP rule should require manufacturers to establish procedures to document, on a continuing or daily basis that followed preestablished procedures for making dietary supplements." Currently this rule is not required of food manufacturers. For dietary supplements, it will include day-to-day records documenting procedures were followed to ensure products are safely manufactured. The new regulations include documented employee training, self-audit programs, batch records, and a variety of quality control documents. Do you want to prepare 250 batch records annually for a nutraceutical product that you manufacture daily?
"We [FDA] invite comments on whether dietary supplement CGMP regulations should require that firms have competent medical authorities to evaluate reports of injuries or illnesses and determine what follow up action is necessary to protect the public health." The industry has requested that FDA's Med Watch program handle these issues but the FDA does not have the manpower resources and will want to have each manufacturer follow his own products.
"We [FDA] invite comments on whether a CGMP regulation for dietary supplements establishes procedures to identify, evaluate, and respond to potential safety concerns with dietary supplements, and if so, what elements need to be included in such an evaluation and their relative importance¡" The FDA is seeking comments on what standards are to be established and what records are to be kept. DSHEA already establishes a procedure that a manufacturer submit a "new dietary ingredient" notification to FDA 75 days before introducing or delivering it into interstate commerce. This could easily delay new product introductions one year or even more.
"We [FDA] invite comments on whether specific controls are necessary on computer controlled or assisted operations and how best to ensure that the software programs and equipment used to direct and monitor the manufacturing process are properly designed, tested, validated and monitored." Calibration, inspection and checks are needed to ensure proper performance especially in the finished product packaging stage that is more likely to be automated.
"We [FDA] ask for comments on whether certain or all the requirements for manufacturing and handling dietary ingredients or dietary supplements can be effectively addressed by regulation based on principals of Hazard Analysis and Critical Control Point (HACCP), rather than the system outlined in the industry submission." FDA believes that HACCP maybe more flexible and useful for microbiological control, and perhaps less burdensome for the manufacturer overall. However the FDA believes, as a regulatory framework, HACCP is less applicable for dietary supplement control.
"Lastly, the FDA inquires: "We invite comments on whether broad CGMP regulations will be adequate, or whether it will be necessary to address the operations of particular segments of the dietary industry." One industry member proposes the FDA focus on manufacturing operations that deal with specific segment of the nutraceutical industry like botanicals; however, the FDA supports one overall set of CGMP regulations. Clearly, the FDA previously segmented the food industry when they issued specific HACCP regulations initially for the seafood industry with its own unique set of processing issues. Why should the dietary supplement industry be treated any differently?
This series of nine comprehensive questions touches only the surface of detail included in the complete 540-page report. The FDA has created a new regulatory category that resembles many of the pharmaceutical industry regulations, or at least some OTC requirements. The full document, can be located in text form on the Internet at http://www.fda.gov/OHRMS/DOCKETS/98fr/03-5401.html
To respond to the proposed CGMP rules, it must be done within 90 days of March 7, 2003 or by June 5, 2003. Address written comments to Dockets Management Branch (HFA-305), Department of Health and Human Services, Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. As members of the dietary supplement industry become acquainted with the regulations it will be in their best interests to send their educated comments to the FDA within the comment period.
If you have any further questions, please address them to Richard H. Meer, Principal Consultant, Engineering & Management Consultants (EMC), 742 Butternut Drive, Franklin Lakes, NJ 07417, Tel & Fax: 201-847-0748, e-Mail: [email protected].
Engineering & Management Consultants (EMC)
Richard H. Meer, Principal Consultant
742 Butternut Drive, Franklin Lakes, NJ 07481-2243
Tel: 201-847-0748 Fax: 201-847-0748 e-mail: [email protected]
EMC provides hands on consulting services in process and product development for botanical, nutraceutical and functional food industries. Services include production control, industrial marketing, and corporate management assistance for mid-sized firms. In addition, EMC is a specialist Good Manufacturing Practices with over 25 years of experience.