By Cynthia Kradjel, Integrated Technical Solutions, Inc.
This June (2008), the estimated $25 billion US dietary supplement industry passed a major milestone: the first FDA deadline requiring companies with more than 500 employees to be compliant with dietary supplement cGMPs. Mid-sized companies, with less than 500 employees, have until June 2009, while small companies of less than 20 employees have until June 2010 to implement the requirements of this regulation, which is notably distinct from pharmaceutical GMPs and food GMPs.
The dietary supplement industry appeared on the radar screen when the Dietary Supplement Health and Education Act (DSHEA) passed into law in 1994. DSHEA amends the Federal Food, Drug, and Cosmetic Act of 1938 (FDCA) to alter the way dietary supplements are regulated and labeled.
DSHEA defines “dietary supplement” by law in Section 3 of the Act to mean “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary supplement used by man to supplement the diet by increasing the total dietary intake, such as enzymes or tissues from organs or glands; or (F) a concentrate, metabolite, constituent, extract or combination of any ingredient described in clause (A), (B), (C), (D), or (E).”
According to DSHEA, a dietary supplement is a product that is labeled as a dietary supplement and is not represented for use as a conventional food or as the sole item of a meal or the diet. The definition describes the variety of forms — capsule, powder, softgel, gelcap, tablet, liquid, or other form — by which these products can be ingested.
In addition to laying the foundation for a regulatory framework for dietary supplements and their ingredients, DSHEA, under Section 9, provides FDA with the authority to promulgate good manufacturing practice (GMP) regulations for supplements. In 2003, almost ten years after DSHEA was passed, the guidelines for the dietary supplement GMPs were published for review and comment. Four years of discussion and controversy led to the final regulation being published in June 2007. The outcome establishes standards that require that dietary supplements are manufactured consistently as to their identity, purity, strength, and composition. It seeks to ensure that they are not adulterated with contaminants or impurities and are labeled accurately to reflect the active ingredients and other ingredients in the product.
Prior to the dietary supplement GMPs, many suppliers had rigorous programs to self-police their manufacturing, but others did not, simply relying on the certificate of analysis (COA) to verify quality of the incoming raw materials. The recent example in the pet food industry of melamine adulteration in wheat gluten highlighted just how dangerous it is to solely rely on the COA parameters for overall quality assessment. Melamine was added to give false positive results for protein value in the Total Kjeldhal Nitrogen method.
Without guidelines, a wide range of manufacturing standards were applied, leading to extremes in overall quality. Consumers purchased products that had positive impact, others appeared to have no effect and a small number had negative impact. Third party testing labs publicized findings that, while some products were true to label claim, some had less active than label claim and in extreme cases some products contained no active at all. Unethical producers cut corners on processed ingredients that were not what they were purported to be. Articles appeared in the media (such as “Get What you Pay For”, Food Processing, September 2000) about false positive HPLC testing results of chondroitin sulfate and FTNIR spectral pattern recognition being used to flag the adulterated material. Manufacturers who built quality into their processes had to justify higher prices compared to manufacturers who cut corners. The industry itself worked to self-regulate for its own survival. Stories of herbal products on the market being discovered that actually contained undisclosed synthetic adulterants or prescription drugs were frightening. Proactive companies worried that one problematic material receipt could destroy their business.
Developing regulations that would effectively improve consumer quality, result in consistent products, and be implementable posed many challenges in this industry. The major problem for many manufacturers was to make a step-change from operating a company in an industry that had no required testing to one that now required a comprehensive quality control program. Although some products may be mixtures of few components, many have anywhere between twenty to thirty ingredients. Product proliferation is also rampant with formulations being designated for seniors, one for males, one for females, etc., resulting in a large number of SKU’s and thousands of different raw materials in the warehouse. This is especially true for contract manufacturers.
Then, there is the aspect of controlling the quality of natural products. Natural Vitamin C, for example, contains not only the nutrient identified as the vitamin, but also enzymes, coenzymes, antioxidants, and trace element activators. Phytomedicines are botanicals or herbal products derived from plants or parts of a plant valued for their therapeutic properties. Testing of phytomedicines and their raw materials is an extremely complex analytical problem. Different parts of the plant will have different composition such as root, leaf, flower or stem. The entire plant may be used in a formulation or a specific part of the plant. Botanicals may be in powdered or liquid form with or without a carrier. And, when raw botanicals are concentrated to form extracts, each individual process yields a different product, depending upon the process conditions. In order to reach a consistent level of actives, the extract is tested after production and “standardized” to the target value with native extract or with the corresponding synthetic material.