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With unscrupulous manufacturers operating alongside scrupulous ones, an uneven playing field has taken hold of the dietary supplements industry. Thanks to the dietary supplement Current Good Manufacturing Practices (CGMPs), soon to be fully implemented, this gap will start to close-at least as far as manufacturing and sourcing are concerned. The looming threat of food safety legislation is beginning to force a paradigm shift, from an industry that emphasizes price and a laissez-faire approach to quality, to one that holds quality and accountability above all else. But there is still a ways to go.
While the CGMPs are raising the bar on production standards and are helping to ensure quality of both raw materials and finished products, there are still challenges and obstacles that need to be addressed, especially as the rules are phased in and as the passage of food safety legislation is awaited. Faced by FDA and industry alike, if these challenges can be overcome, the CGMPs will serve as a major impetus toward closing the quality gap and achieving the ultimate goal of enhancing consumer confidence in dietary supplements.
Challenges For FDA: Resources and Funding
In recent years, FDA's budget, resources, and manpower have been stretched thin. This has posed problems, particularly in the area of food safety. Congress has pledged to address this through increased fiscal appropriations-an increase of $325 million in FY 2009 over FY 2008 (see www.strengthenfda.org for more information)-as well as additional funding through new food safety legislation, including facility-registration fees. (The Food Safety Enhancement Act calls for a $500 annual registration fee per facility.) At the SupplySide East trade show this past April, an FDA representative acknowledged that currently, the agency has a shortage of inspectors but that aggressive hiring and training of new inspectors is underway.
Given FDA's limited resources, the inability to inspect all manufacturers' facilities (let alone ingredient suppliers) and FDA's history of risk-based enforcement, it should not come as a surprise that FDA may be looking to make examples out of the companies it does inspect. During an industry meeting, an FDA representative noted, "What we need to do is get your attention and get you into compliance." Companies must remember that FDA is watching, and the onus is on the industry to be certain that it is in compliance.
A Work In Progress
The Dietary Supplement CGMPs (21 Code of Federal Regulations, Part 111) are a substantial improvement over the current food CGMPs (21 Code of Federal Regulations, Part 110) to which dietary supplement manufacturers were held until recently.
The inspection process is a critical component of the regulation. It is "where the rubber meets the road," so to speak. Only through inspections of manufacturers' facilities-truly the only means by which FDA can demand accountability-will the full effect of the CGMP regulations be realized. All stakeholders are (or should be) feverishly working toward implementing and applying the standards called for in the regulations. However, the CGMPs are new to everyone, including FDA inspectors, dietary supplement manufacturers, and ingredient suppliers, and as such, implementation is expected to require a learning curve.
Thus far, under the new dietary supplement CGMPs, FDA has conducted approximately 15 inspections that the Council for Responsible Nutrition (CRN; Washington, DC) is aware of. These inspections have been of large manufacturers with more than 500 full-time employees. A handful of the Establishment Inspection Reports can be viewed on FDA's Office of Regulatory Affairs' Freedom of Information Act Electronic Reading Room Web site. Inspections of medium-sized companies, with 20 to 500 full-time employees, were expected to ensue this fall. (Small companies with fewer than 20 full-time employees have until June 2010 to comply with the CGMPs.)
Based on FDA's initial round of inspections, the areas that appear to have generated the most observations include faulty recordkeeping, such as inadequate batch-production records and equipment-cleaning records; and improper analytical methods, such as use of methods not fit for purpose and/or not demonstrated to be scientifically valid. These areas do not appear to be considered major violations by FDA and are easily addressed, especially by the largest firms with many resources and the expertise to be able to more easily implement the CGMPs.
Looking ahead to the inspection of medium- and small-sized firms, FDA and manufacturers do have significant concerns. For one, unlike dietary supplement manufacturers, suppliers of dietary ingredients and other dietary supplement components such as excipients are still subject to the less-stringent food CGMPs, not the stricter dietary supplement CGMPs. This "gap" alone renders proper supplier qualification an absolutely critical aspect of dietary supplement CGMP compliance for manufacturers. Because ingredient suppliers are held to a lesser manufacturing standard, and because the quality of a dietary supplement is only as good as that of its components, inadequate supplier qualification or the absence of supplier qualification can have devastating effects.
Furthermore, many manufacturers, especially smaller firms, may still be operating under the illusion that they can accept at face value the information provided on a supplier's Certificate of Analysis. CGMP regulations state otherwise, however, citing that a manufacturer must confirm the reliability of a supplier's Certificate of Analysis and the results of any tests or examinations. Manufacturers must also maintain documentation on how they qualified a supplier, as well as periodically reevaluate a supplier's Certificate of Analysis.
Challenge For Industry: Know Your Supplier
As the CGMPs are phased in, one of FDA's primary reminders to industry is to "know your supplier," a phrase that the agency and other experts have repeated.
Indeed, since the publication of the dietary supplement CGMP final rule in 2007, FDA officials have repeatedly stressed the importance of ingredient supplier qualification by manufacturers. FDA also emphasized that examination of manufacturers' records of supplier qualification will be a primary focus of CGMP inspections. (This will be one of the topics addressed by FDA's Bill Frankos, PhD, director of the division of dietary supplement programs, at the upcoming Expo East and SupplySide West trade shows in September and November, respectively.)
CRN recently commented to FDA on www.regulations.gov about the importance of proper ingredient supplier qualification as a means of preventing economically motivated adulteration. It is important for ingredient suppliers to also be held to the highest regulatory standards, simply because manufacturers cannot test raw materials for every possible adulterant known-and certainly cannot test for unknown adulterants. With some exceptions-for instance, melamine-economic adulterants are benign and can easily go unnoticed.
Imposing Higher Standards
Many of the measures that Congress has proposed over the past several years are due in part to outdated food CGMPs, which ingredient suppliers abide by. In fact, many of the provisions in proposed food safety legislation are already addressed by the stricter dietary supplement CGMPs. However, one area that is not currently addressed by either the food or dietary supplement CGMPs is the requirement for traceability.
The most recent version of food safety legislation recently passed by the House of Representatives seeks to impose strict requirements for traceability. The intent is to facilitate tracking the sources of food-born and other types of contamination. The Senate's version of the same bill, likely to be addressed this fall, contains similar provisions.
The CGMP regulation provides few details about ingredient supplier qualification, and there is no guidance pending that CRN is aware of. Currently, the standard industry practice of qualifying ingredient suppliers largely consists of manufacturers requiring ingredient suppliers to fill out various forms or questionnaires in order to gather the necessary information. However, with individual manufacturers requiring different forms or questionnaires of their ingredient suppliers, this approach is inefficient, ineffective, and also allows for a large margin of error.
To help fill the gap in the lack of guidance for supplier qualification, dietary supplement trade associations, including CRN, have developed the Standardized Information on Dietary Ingredients (SIDI). (For more information, visit www.crnusa.info/sidi.) SIDI is a tool to assist with information exchange between ingredient suppliers and dietary supplement manufacturers. Along with CRN, it was developed by the American Herbal Products Association, the Consumer Products Healthcare Association, and the Natural Products Association. Together, these four organizations form the Joint SIDI Working Group.
SIDI isn't a questionnaire for ingredient suppliers, nor is it a template for a questionnaire. Rather, it is a guideline that outlines the type of information necessary to help qualify ingredient suppliers, such as an ingredient's origin, manufacturing process, potential contaminants, and quality-control measures. Through a voluntary, standardized system, SIDI provides manufacturers with standards on the relevant information they need to obtain in order to qualify a dietary raw-ingredient supplier. SIDI also boasts a comprehensive glossary, which includes links to authoritative regulatory bodies, and key terms, which manufacturers can use to access more information.
SIDI has already helped a number of manufacturers with the supplier-qualification process. In some cases, it has reduced the time required for obtaining ingredient information from weeks to hours. SIDI's benefits have been realized by ingredient suppliers, too, by streamlining the information-gathering process. Additionally, since companies must make records readily available to FDA during an inspection, the use of SIDI protocol allows firms to retrieve or download forms more readily.
Important aspects of ingredient-supplier qualification were discussed at the Ingredient Supplier Qualification Workshop, organized by the Joint SIDI Working Group and held this past June in Washington, DC. At the event, FDA clarified its expectations for supplier qualification.
According to the agency, it expects manufacturers to have a sound basis for supplier qualification. This includes-but may not be limited to-verification (and periodic reverification) of the reliability of suppliers' Certificate of Analysis, supplier audits (by the manufacturer or by a third party), and strictly maintained documentation on how each supplier was qualified. FDA has specifically stated that vendor questionnaires alone are inadequate means of supplier qualification.
Though SIDI is still a free and voluntary program, it has been adopted by a number of large manufacturers and ingredient suppliers as a self-regulatory step. SIDI has also been presented to FDA. Though the agency is not willing to officially endorse or require SIDI at this time, it has come out in support of the initiative: "Use of a standardized reporting format such as SIDI will provide customers valuable information that can be used for qualifying a supplier," said FDA's Frankos at the Ingredient Supplier Qualification Workshop.
As useful as the information provided by SIDI is, it is only one aspect of ingredient supplier qualification-and it is no more a replacement for an on-site audit of an ingredient supplier than a vendor questionnaire is. Given this reality, the members of the Joint SIDI Working Group are considering the development of other useful guidelines to assist with supplier qualification. Potential items of interest include a guideline to standardize ingredient Certificate of Analysis, a guideline for how manufacturers should verify suppliers' Certificate of Analysis, a guideline for CGMPs specific to dietary ingredients, and others.
Whether food safety legislation will require audit information on all players throughout the distribution chain, including ingredient suppliers, remains to be seen. However, if it does, it will continue to pose perhaps the greatest challenge to the dietary supplement industry, because manufacturers cannot audit every supplier they work with, and suppliers cannot function with auditors constantly in their facilities. This is an evolving process, and widespread industry input is welcome.
For nearly fifteen years, the industry pushed hard and encouraged FDA to promulgate dietary supplement–specific CGMPs, recognizing that these standards have the potential to make industry stronger and to give consumers more confidence in the quality of these products. Working together through implementation and enforcement of the CGMPs, industry and FDA can help to level the playing field.
Andrew Shao, PhD, is the vice president of scientific and regulatory affairs for the Council for Responsible Nutrition (Washington, DC).