On March 13, 2003, FDA issued a proposed rule establishing current Good Manufacturing Practices (cGMPs) for dietary ingredients (DIs) and dietary supplements (DSs), which, under the Federal Food Drug and Cosmetic Act FFDCA as amended by the Dietary Supplement Health and Education Act (DSHEA)—collectively referred to as FFDCA)—are required to be “modeled” after food cGMPs. In certain respects, the requirements set forth in the proposed rule mirror food cGMPs. However, there is also a great divergence with regard to certain other provisions. Indeed, these provisions undoubtedly resemble drug cGMPs. FDA recognizing the volatility of this issue has attempted to rationalize its approach by stating that “dietary supplements have their own set of unique requirements as a result of the characteristics and hazards due to their ‘hybrid’ nature…fall somewhere along the continuum between conventional foods on the one hand and drugs on the other.” Of course, FDA failed to recognize that under the FFDCA dietary supplements are classified as food and not as a hybrid between food and drugs.
According to FDA, the benefits of the proposed rule include (1) fewer illnesses, resulting in decreased health costs, (2) fewer product recalls and (3) more consistent, higher quality products. All of these goals are worthy, however, to achieve these goals, it appears that FDA has placed unnecessary and burdensome requirements on small and medium size dietary supplement manufacturers by placing human drug standards on the manufacturing processes. Accordingly, questions arise as to whether FDA has complied with its statutory obligation under the FFDCA and adequately modeled the dietary supplement cGMPs after the food cGMPs or whether the agency is attempting to regulate dietary supplements as drug products.
Provisions of the Proposed Dietary Supplement cGMPs
Many aspects of the proposed dietary supplement cGMPs raise questions as to the FDA’s authority to issue such expansive and comprehensive regulations. The initial sections such as personnel, physical plant and equipment and utensils remain consistent with the food cGMPs. However, the proposed dietary supplement cGMPs cover two additional sections that are not addressed in the food cGMPs (i.e., there are five sections in the food cGMPs, while the proposed dietary supplement cGMPs include seven). These additional cGMP sections include aspects, which have not been previously addressed with regard to food such as Consumer Complaints and Record-Keeping. In fact, not even the Hazard Analysis and Critical Control Point (“HACCP”) regulations requires compliance with elements identified in the proposed dietary supplement cGMPs.
The deviation from the food cGMPs begins with FDA’s requirement for a quality control (QC) unit. The QC unit first appears in the Equipment and Utensils section and becomes an integral part of the Product and Process Controls, Holding and Distribution and Consumer Complaint sections of the proposed dietary supplement cGMPs. The QC unit is responsible for monitoring products, establishing test methods for the DIs and DSs, ensuring adequate laboratory facilities and reviewing consumer complaints. A QC unit with these functions has not been addressed in the food cGMPs and the origin of these practices most likely stems from drug cGMPs.
Other requirements that resemble drug cGMPs are seen in the Production and Process Control section of the proposed dietary supplement cGMPs. For example, the proposed rule requires that either the finished batch of DIs or DSs be tested in compliance with “scientifically valid analytical methods” or, if such methods are not available, each incoming shipment of component DIs or DSs must be tested individually to ensure identity, purity, quality, strength and composition of the final product. This section also requires the development of manufacturing and batch production records, representative reserve samples of all batches and adequate laboratory facilities to perform the testing to ensure compliance with the specifications. Again, such detailed manufacturing practices are generally associated with the production of human drug products and the food cGMPs do not address such issues.
Finally, the proposed dietary supplement cGMPs include two additional sections, Consumer Complaints and Record-Keeping. FDA has not addressed these issues in the food cGMP regulations and to include such requirements increases its resemblance to human drug cGMPs. FDA is proposing to require that all complaints be reviewed by a qualified person and those complaints associated with a failure to comply with a specification or other requirement must be further reviewed by the QC unit to determine whether an investigation is warranted. As for the record-keeping requirement, written records must be kept for three years “beyond the date of manufacture of the last batch of dietary ingredients or dietary supplements associated with those records.” Until recently, there has not been a recordkeeping requirement for food manufacturers and review or investigation of complaints regarding a food product is at the manufacturer’s discretion. Clearly, if these requirements do not currently exist, it cannot be modeled after the food cGMPs.
Impact on the Industry
Although it may be common practice in industry to institute many of the measures that are identified in the proposed dietary supplement cGMPs, to require compliance through the promulgation of cGMP regulations exceeds the statutory authority granted to FDA under the FFDCA. As previously mentioned, many of the requirements go far beyond the provisions of the food cGMPs, and more closely resemble human drug cGMPs. The impact of the proposed dietary supplement cGMPs will be the greatest on the small and medium size manufacturers, without any assurances that the benefits identified by the agency will be achieved.
The results of an industry survey on current industry practices was included in the proposed dietary supplement cGMP regulations and indicate that in some instances manufacturers are already utilizing some sort of good manufacturing practice. For example, 65% indicated that they follow some type of model for good manufacturing practices, generally those established for foods; however, 31% follow drug cGMPs established by FDA. With respect to QC, 85% indicated they have a person or unit responsible for QC activities. The majority also performs some test on incoming components and DIs, as well as on in-process materials or finished products. However, only 19% report consumer complaints to FDA. In light of these facts, it appears that FDA may be over-regulating an industry that may already be in compliance with the statutory criteria established by the FFDCA.
FDA has also determined that the proposed rule would “have a significant economic impact on a substantial number of small entities.” The adjusted total annual costs of testing the final products under this proposed rule amount to $11,230 for very small establishments (those with fewer than twenty employees), $19,907 for small establishments (those having 20-499 employees) and $7,626 for large establishments (500 or more employees). The annual total costs per establishment are estimated to be $38,000 for very small entities (median revenue less than $1 million), $61,000 for small entities (median revenue $5-10 million) and $47,000 for large entities (median revenue $20-50 million). FDA specifically notes that low revenue firms (those with annual sales revenues of less than $500,000) will be impacted the greatest by this proposed rule and may force some to close their businesses. The agency believes that if the requirements are phased in over a three-year period the impact may be mitigated. However, the agency is only guessing and the reality might be significantly different. Indeed, it is likely that Congress understood the potential impact of applying drug-like cGMPs on the supplement industry when it made clear that any cGMPs promulgated for DSs must be modeled after food cGMPs and not drug cGMPs. Although it appears that FDA has made some minor concessions by using a phase-in approach, industry would be better served by a reevaluation of the proposed dietary supplement cGMPs by FDA.
The obvious divergence of the proposed dietary supplement cGMPs from the food cGMPs indicate that FDA has exceeded it statutory authority and promulgated rules that more closely resemble drug cGMPs. Also, in light of the significant economic impact due to compliance and the fact that FDA’s survey showed that many manufacturers have already implemented some type of cGMPs, the benefits from implementation of the proposed dietary supplement cGMPs is unclear. At this point, it appears that the proposed cGMPs will only benefit large manufacturers by raising the standards for small manufacturers. In essence, rather than facilitating the safety of DIs and DSs, FDA has created a barrier to entry. It is questionable that such comprehensive and detailed requirements are even necessary. Indeed, FDA has failed to demonstrate that DSs pose such a significant risk to public health to justify controls that are similar to drugs.
FDA’s deft attempt to rationalize its approach by indicating that Congress only intended that the agency should use “the food cGMPs as a ‘preliminary pattern’ for the dietary supplement cGMPs” fails to be credible. There is no indication in DSHEA or its legislative history that Congress intended that dietary supplement cGMPs be so restrictive. By proposing such comprehensive and detailed cGMPs, FDA will inevitably face legal challenge. In the meantime, some very fine small manufacturers will be threatened with bankruptcy if the rules are finalized. This will lead to the inevitable loss of jobs in small communities that desperately need them. Clearly, Congress did not intend such consequences when it enacted DSHEA in 1994.