Undoubtedly, quality is becoming a necessity in today’s marketplace pertaining to the manufacture of dietary supplements. This is true especially for companies that not only want to stay competitive but also highly value consumer satisfaction. Furthermore, while there are instruments in the marketplace that companies can use to demonstrate levels of quality, they may not be utilized to their full potential. This gap often leads to a consumer making uninformed purchasing decisions. For these reasons, it is essential to examine the aspects of quality that the dietary supplement industry can control and how it can identify and convey quality, not only to the end consumer but at all points of the value chain.
Typically, manufacturers of both ingredients and finished supplement products can ensure their quality by adhering to strict testing procedures, thorough testing for ingredient purity and contaminants, comprehensive monitoring schedules, analytical chemistry-based laboratory analyses and ensuring compliance with good manufacturing practices (GMPs). Manufacturers that adhere to all of these criteria will be far more likely to produce a consistent, quality product. However, the manufacturer that takes these extra steps has also chosen to undertake a significant investment in its product—a cost that a non-quality manufacturer avoids. So the questions is, if the consumer cannot determine a difference between the two products when purchasing them at a store, how will the quality supplement manufacturer make a return on investment? One way is to subscribe to a powerful consumer signal that demonstrates that a product is manufactured against high quality standards by means of third-party product certification. This mark indicates to consumers that a manufacturer and its products have undergone significant testing, that they are GMP compliant and that they are monitored on an ongoing basis. As a result of these benefits, manufacturers can easily justify the cost through the demonstration of high quality to their customers and therefore realize increased sales.
Verification of Ingredients and Testing for Contamination
Many manufacturers seek out independent laboratories for a confidential assessment of product formulations and labels by expert scientists and toxicologists. These laboratories are able to establish the appropriate testing for ascertaining the quality of a product or of each raw material in a product. Further, products should be tested to verify that they meet the standards of quality, including identity and quantity of the ingredients declared on the label of a product. It must also be determined that a particular product does not contain undeclared ingredients or unacceptable levels of contaminants.
A variety of chemical analyses can be used to determine a products’ composition. These include chromatographic fingerprinting and thin-layer chromatography (TLC), in addition to other analytical techniques. Laboratories are able to verify manufacturers’ quantitative claims on products with quantitative analytical techniques such as high-pressure liquid chromatography (HPLC), gas chromatography (GC), liquid chromatography/mass spectroscopy (LC/MS) and polymerase chain reaction (PCR) methods. The procedures used for these processes are recognized by public health and regulatory officials and defined by organizations such as the Association of Official Analytical Chemists (AOAC), the Institute for Nutraceutical Advancement (INA), the United States Pharmacopeia (USP) and the American Herbal Pharmacopoeia (AHP).
In the absence of analytical methods or when dealing with a product matrix that poses a unique analytical problem, a laboratory will work to develop applicable and reliable techniques for characterizing a product. For example, in the case of herbs and botanicals, many times there are hundreds or even thousands of chemical substances, the relative amounts of which are naturally variable depending on the growing conditions and processing of the plant. Furthermore, even today it is rare that all of the “active” components of any medicinal herb are known. This situation contrasts sharply with that of most pharmaceutical drugs, which consist only of a single “active” molecular substance present in a standardized quantity in each dosage unit of the drug. The complexity of herbal supplements poses significant challenges and requires the use of sophisticated analytical techniques to verify the botanical identity as well as the quality of the final product.
Independent laboratories are able to evaluate raw botanical materials qualitatively by both gross and microscopic morphologic examination, chromatographic fingerprinting, DNA typing or other appropriate methods. Additionally, both raw herbal and other materials and finished products are compared to reference materials and standards, and, as appropriate, to the specifications set forth in health and regulatory monographs.
Such analyses not only help to ensure the validity of a manufacturer’s claims for the content of an herbal product, but also reveal plant materials that may be adulterating the product. Many case reports of herbal toxicity have in fact been traced to such adulterants rather than to the medicinal herb itself in an herbal product. An example of this was the contamination some years ago of the herb plantain with digitalis1.
Herbal products may even be adulterated with prescription drugs, as recently reported for the Chinese herbal formula PC-SPES2. PC-SPES contains eight Chinese herbs. It is for these reasons that screening for adulterants is critical to assuring the safety of dietary supplements.
These days manufacturers are also looking to keep sports nutrition supplements free of steroids, ephedrine alkaloids and other substances banned by sports regulatory authorities. As a result of these issues, programs such as the Athletic Banned Substance Screening Program offered by NSF International have the capability to assure the absence of these specific ingredients.
The issue of contaminants must also be taken very seriously. Because many dietary supplements are grown in the soil or derived from the earth by mining, as in the case of various minerals, they are naturally exposed to pesticides and heavy metals, and in some cases microbes. The quality manufacturer must be able to determine first if potential contaminants are present and if so, that their levels are so low as to pose no threat to a consumer’s health. Laboratories are able to test for such contaminants at the component or product level. Specifically, they aim to perform analyses for heavy metals including lead, arsenic, mercury, cadmium and hexavalent chromium. Typically, GC/MS is used to test for pesticide residues, taking into account known geographic areas of risk and the thoroughness of the manufacturer’s documentation and control measures. The HPLC method addressed previously is often used to screen for aflatoxin, while microbiologic assays are used to detect the presence of yeast, mold, aerobic bacteria, Salmonella, Escherichia coli and Staphylococcus aureus.
Companies interested in going beyond these testing measures can utilize independent bodies to conduct formulation reviews, which are conducted by expert toxicologists, in order to assure that their products are free of known toxic substances or plants. Additionally, appropriate tests can be applied to confirm label claims on dietary supplements, such as “sugar-free,” “contains no caffeine,” “free of residual solvents” or “contains no wheat.”
Compliance with Good Manufacturing Practices (GMPs)
By now most manufacturers should be aware of FDA’s impending final rule for dietary supplement GMPs. While the proposed FDA rule will likely be highly modified in the coming months, it provided the industry with a glimpse of the level of testing and monitoring that FDA may deem necessary for the supplement industry. Currently, conscientious dietary supplement manufacturers comply with food GMPs or GMPs outlined by the National Nutritional Foods Association (NNFA), Newport Beach, CA, or NSF International, which are also referenced in NSF/ANSI Standard 173. The NNFA and NSF GMPs are based on the 1997 FDA Advance Notice of Proposed Rulemaking (ANPR). While this disparity will disappear when the FDA final rule is announced, dietary supplement manufacturers can get a head start on GMP compliance by looking to an independent body such as NNFA or NSF International to ensure their facility meets the current criteria. The joint committee responsible for maintaining NSF/ANSI 173 plans to adopt FDA GMPs into the standard once they become a final rule, which may be as soon as next year.
To verify that manufacturers comply with GMPs, both NSF and NNFA conduct on-site plant audits of the systems that a supplement manufacturer uses to ensure the correct identity of its raw materials and finished products, and to prevent adulteration. Initial audits involve inspections of manufacturing facilities by trained field auditors to verify that quality control procedures, staff training, cleanliness, equipment maintenance, record keeping and procedures for receipt and registration of raw materials meet outlined specifications.
Manufacturers that meet these audit requirements and the other components of either the NNFA or NSF programs are granted certification or registration, respectively, and may place the NNFA or NSF mark on the product label.
Simply conducting a one time test or inspection of a facility will not ensure that a product continues to meet high quality criteria on an ongoing basis. Ongoing monitoring is a crucial component of good quality assurance program. Using third-party product certification will also help manufacturers gain the additional sales needed to recoup the additional costs of testing, monitoring and certification.
If a large portion of the industry chooses to purse these methods to ensure product quality, the government may see this “self-regulation” as a reason not to step in and create legislation. With the FDA final rule imminent, the threat of further regulation is not only possible but also likely unless the industry takes the initiative to weed out non-quality companies through strong consumer signaling.
|1.||Slifman NR, Obermeyer WR, Aloi BK, Musser SM, Correll WA Jr, Cichowicz SM, Betz JM, Love LA. “Contamination of botanical dietary supplements by Digitalis lanata.” N Engl J Med. 1998 Sep 17;339(12):806-11.|
|2.||http://www.fda.gov/medwatch/safety/2002/safety02.htm#spes (FDA website, Feb. 8, 2002).|
About the author:
Kathleen Pompliano, M.S., R.D. is the manager of new business development for NSF International, Ann Arbor, MI. NSF International is a public health and safety organization involved in the development of national standards and third party certification programs. She can be reached at 800-NSF-MARK; E-mail: [email protected].