Not a week goes by without a negative article in the mainstream or trade industry press about the quality and safety of nutraceutical ingredients, particularly herbal dietary supplements. ConsumerLab.com recently issued press releases noting that only 40% of Asian and American ginseng and only 50% of S-adenosyl methionine (SAMe) products passed its finished product testing programs. The Center for Science in the Public Interest (CSPI) lambasted functional foods as ineffective and fraudulent and called for FDA to remove 75 products (mainly beverages) from the market that contain ingredients not Generally Recognized as Safe (GRAS). Why does this continue to happen? How can manufacturers assure that their products are safe and of high quality and will stand up to scrutiny by the media, consumer organizations and product testing programs?
One way to combat this negativity is for manufacturers to concentrate on the quality and safety of nutraceutical ingredients during product development and manufacturing of products. In addition, the nutraceutical trade as a whole needs to develop strong self-regulation. Presently, industry trade associations have a number of self-regulatory programs. Among them are:
• The TruLabel and Good Manufacturing Practices (GMP) certification programs by the National Nutritional Foods Association (NNFA).
• Monographs published by the American Herbal Pharmacopoeia (AHP) that provide comprehensive documentation on specific herbs in commerce.
• The Methods Validation Program developed by the Institute for Nutraceutical Advancement (INA) to verify standardized testing of botanicals.
• The American Herbal Products Association (AHPA)'s quality manual for its members outlining specific methodologies that should be used to assure the quality of botanical products.
"What the industry lacks, however, is an integrated program of self-regulation with 'teeth,'" noted Susan Haeger, president and CEO of Citizens for Health, Boulder, CO. "As an organization that helped get millions of positive comments supporting dietary supplements to Congress for the passage of Dietary Supplement Health and Education Act (DSHEA), it is disappointing to see that in the absence of such an integrated industry effort, consumers will believe these negative media messages and lose confidence in the quality of products on the market."
What are the key issues that manufacturers should pay attention to for the assurance of safe, quality nutraceutical products?
Product Design
Good quality nutraceutical products and ingredients should first focus on finished product design and labeling. If the product is making health or structure/function claims to the consumer, there must be efficacious amounts of the ingredients in the product. The efficacy of a nutraceutical should be evaluated based on a thorough review of the literature and of any proprietary research that may have been conducted by the ingredient supplier. Many manufacturers have been known to put small amounts of a popular ingredient in a product as "label dressing." This practice is misleading to consumers and triggers strong negative reaction from public interest and consumer groups, as well as FDA. For example, FDA issued an eight-page warning letter to a well-known functional beverage manufacturer, noting, among other issues, that the mention of soy on the front panel implied significant levels of soy in the product, which was not the case.
The efficacy of the product must also be evaluated post-manufacturing, meaning that the ingredient must survive the food or supplement process and not create potential impurities during processing. A recent study of creatine products noted that some contained creatinine and dicyandiamide, byproducts that are formed during improper manufacturing or handling of the product. Tryptophan products were removed from the market by FDA, due to severe neurological injuries and death caused by an impurity formed during a new fermentation process used by a supplier. The efficacy of certain products may be affected by thermal processes, such as pasteurization, or may be affected by other ingredients in the food or supplement that may have synergistic or antagonistic effects.
Good taste is a primary consideration in the development of nutraceutical products, as consumers will not trade off taste for efficacy. Many nutraceutical ingredients, particularly botanicals, contain bitter alkaloids. It is possible to use flavoring agents that are complementary to the bitter taste, such as citrus flavors, or to use flavor-masking agents. Many flavor suppliers have participated in the development of new nutraceutical products and have new masking techniques that should be investigated.
Manufacturers should also consider the specific consumer audience targeted. Some nutraceutical ingredients, especially certain botanical ingredients, are not appropriate for pregnant or nursing women and/or children, for example. An all-family product, like a breakfast cereal or certain beverages, should then carry a warning label that would indicate the product was inappropriate for those population groups. AHPA has published a book entitled The Botanical Safety Handbook, which contains valuable information about the safety of over 600 botanicals in commerce. This book should be used as a guide during product development and labeling of a product.
Ingredient Safety
It is incumbent on every food and dietary supplement manufacturer to sell only safe products to the consumer. Nutraceutical ingredients used in foods must be listed as GRAS by FDA or self-determined as GRAS by the manufacturer for use in that particular product. Proper self-determination of GRAS reviews should be conducted by an independent expert scientific panel of three to five scientists, to include at least one toxicologist. This panel then develops a consensus opinion that the ingredient is safe for use in a particular product. CSPI, for example, has alleged that many botanical ingredients, such as St. John's Wort, are not GRAS for use in foods, yet the ingredient is present in snack foods and cereals. Without a formal self-determination of GRAS, companies are marketing products of unknown safety according to FDA.
The ingredients used in dietary supplements must be either dietary ingredients used in supplements prior to October 1994 or new dietary ingredients submitted to FDA prior to marketing the product. Each supplier or marketer of a particular ingredient should submit a new ingredient petition to FDA at least 75 days prior to marketing the new dietary ingredient in a product.
Ingredient Quality
High quality consumer products are based on the use of high quality ingredients. Many responsible ingredient suppliers and manufacturers are doing the right things when procuring raw materials for nutraceutical products. "Our nutraceutical analytical business was built supporting companies that care about the quality and safety of their raw materials and finished products," noted Loretta Zapp, president, The Industrial Laboratories, Denver, CO, a contract analytical laboratory and home of the Institute for Nutraceutical Advancement (INA). "The analytical testing of nutraceutical ingredients, particularly botanical ingredients, is not always straightforward. Industrial Laboratories and INA are important sources of information to aid manufacturers in producing high quality products."
It cannot be emphasized enough that manufacturers should have quality ingredient specifications and only purchase ingredients analyzed against those specifications. Manufacturers need to have clear procedures to assure the following criteria regarding specification of their ingredients and finished products:
• Positive identification of the active material
• Measurement of the potency of the active material
• Measurement of the purity of the active material, with absence of adulterants
• Measurement of consistency from lot to lot
The consequences of not addressing some of these issues results in highly publicized instances of adulteration and recall, as was the case with the botanical plantain, adulterated with digitalis. FDA identified the industry-wide adulteration, due to sale of the contaminated plantain, by a highly respected industry supplier. If strict identity confirmation procedures were in place by the industry, this product would not have entered the marketplace.
Manufacturers should also have a strong vendor certification and audit program in place. Many processors merely accept the vendor certificate of analysis as their assurance of quality. As noted in the adulteration case above, a better approach is "trust, but verify." New vendors should be subjected to a strict audit and verification of their certificates of analysis as a standard operating procedure. Only when the identity and analytical evaluation of the material has been verified for several lots should the certificate of analysis be trusted. Existing vendors should be audited periodically as well, but on a much less frequent basis compared to new vendors.
Raw materials, especially those with high economic value, require routine authenticity testing. It is well known in the industry, for example, that much of the chondroitin sulfate sold in the marketplace is not chondroitin at all, but other less expensive chemicals, or it may be mixed with other chemicals. It is no wonder that ConsumerLab.com found that 50% of the glucosamine/chondroitin products sold for joint support contained little or no chondroitin, citing the price difference between glucosamine and chondroitin as one of the reasons why. If there is an economic incentive to substitute a cheaper ingredient or adulterate with a less expensive material, it is likely that at least some raw material manufacturers will do so. Large food manufacturers routinely perform authenticity testing on their high-value raw materials, including juices and flavors, for just this reason. The cost of authentication is considered to be a cost of doing good business and is often shared by the supplier of the ingredient. The nutraceutical industry should develop a similar approach to high value raw materials.
Focus on Quality Manufacturing
Finally, the nutraceutical industry should focus on high quality manufacturing processes and procedures. This includes following the appropriate food or dietary supplement GMP's. FDA has published industry-written proposed GMP's for dietary supplements and botanical ingredients. These should be strictly followed. NNFA has developed a self-audit checklist as part of its GMP certification program that is a very valuable resource for those in the trade.
GMP's cover a number of areas for manufacturing quality products:
• Management and training of personnel and their commitment to good hygiene
• Management of the overall physical plant and grounds to prevent contamination and adulteration of the product
• Appropriate sanitation of the building and facilities
• Sanitary use of equipment and utensils
• Management of quality control and laboratory operations
• Appropriate production and process controls
• Management of warehousing, distribution and post-distribution procedures.
Too often, manufacturers overlook one or more of these issues, which results in unnecessary problems in the marketplace. Good nutraceutical manufacturers should have programs in place to quarantine all raw materials until identified, analyzed and compared to specifications. Each raw material should be assigned a unique lot number for traceability throughout each batch manufactured. The batch lot numbers should be carried throughout the process to the finished package and shipping records. This allows quick and efficient location of all affected finished products and raw materials, in the case of a recall.
Each manufacturer should have a quality assurance manual that includes Standard Operating Procedures (SOP's) for each process and procedure carried out during manufacturing. The person responsible for each process should write and approve the SOP. These documents need to be accurate and kept up to date with changes. Too often, SOP's do not reflect what a manufacturer is actually doing day to day and outdated SOP's are not common to be found in quality manuals.
Other key issues for product quality and safety are good records of customer and/or consumer complaints and returns. Often, problems in the marketplace can be identified and corrected quickly and efficiently through analyzing this information. Too often, manufacturers treat each return or complaint as an isolated incident and do not analyze the data as a whole to pinpoint an ongoing problem.
Consumer expectations of quality and safety are high. If manufacturers and marketers of nutraceutical products and ingredients focus on good product design and use safe, quality ingredients and diligent good manufacturing practices, the consumer will get only the highest quality, safe and effective nutraceutical products. If this were the case, then consumer groups and testing organizations would only attest to this high quality, strengthening the confidence of consumers in nutraceutical products.
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