Dietary supplement GMPs

Richard Prince

Large corporations that have various divisions that manufacture a wide range of products falling under the FDA regulatory umbrella face an interesting business and compliance challenge. Do these firms implement a common Good Manufacturing Practices (GMP) standard across the board or instead implement industry-specific GMP systems for each of the respective business units, e.g., foods, dietary supplements, devices, and drugs/biologics? In February 1997, FDA published in the Federal Register, a proposed GMP regulation governing the dietary supplements industry. This industry encompasses, for example, products such as herbs, minerals and vitamins.

The proposed dietary supplement GMP regulation has four central objectives: to prevent product adulteration and misbranding; to ensure that dietary supplements possess the necessary identity; to help ensure that the product contains the desired quantity of ingredients as declared on the label; and to ensure that all quality specifications are met. Overall, they are broadly modeled on the food GMPs. The dietary supplement industry (heretofore “the industry”) further intends to avoid the stringent validation and documentation requirements that constitute such a significant portion, for example, of the drug GMPs.

The industry recognizes the importance of microbiological quality attributes of product batches. Thus, manufacturers must demonstrate that potentially harmful microbes such as Escherichia coli and Salmonella sp. do not adulterate product batches. There should be “rational” sampling regimens and each test sample must be representative of the product batch. Batches may be reworked. The industry places a heavy emphasis on the importance of proper sanitization and cleaning practices. The plant should ensure that it has training documentation detailing the education and qualifications of its workforce.

Physical plant

The industry recognizes the importance of maintaining the physical plant and grounds. Proposed requirements discuss the need for litter and waste removal, lawn maintenance, drainage and pest control measures. There should also be effective plumbing, sewage treatment and disposal, and adequate space to facilitate maintenance, cleaning and sanitary conditions within the plant.

Manufacturing operations

The firm must install the necessary “product safety controls” and implement good operating practices. The plant should use potable water or higher quality water that is maintained at suitable temperatures for cleaning and processing applications. Equipment and utensils should be of proper design, construction, readily cleanable and maintainable. Processing equipment must be corrosion-resistant, smoothly bonded and clean. There should also be device-controlled cold rooms enabling accurate temperature readings. Cold rooms should be suitably alarmed. Manufacturing instruments and controls must be accurate, maintained and effective for their intended purposes. The cleaning and sanitation program should, for example, be composed of procedures that discuss cleaning frequencies, process interruptions, cleaning of product contact vs. non-product contact surfaces, disposal of single service articles, use of safe and adequate sanitizers, proper storage of cleaned and sanitized equipment, equipment breakdown, and cleaning logs or their equivalent.

Laboratory operations/Quality assurance

Laboratory operations are charged with the responsibility and attendant authority to determine whether or not product batches conform to appropriate standards of quality, purity and composition. Laboratory operations are responsible for approving and rejecting all procedures, specifications, controls, tests and examinations (and any deviations thereto), labeling and suitability of packaging materials, raw materials and finished products. The test department`s responsibilities are to be driven by approved procedures. Product shelf life or expiration dating should be supported with appropriate data and rationale; however, the industry does not call for mandatory expiration dating of marketed dietary supplements. Product shelf life shall be confirmed/ extended on the basis of real-time product studies under labeled storage conditions.

For the business conglomerate, the decision to implement the most stringent set of prevailing GMPs across all business units results in a harmonized approach, but one which will likely increase the cost of manufacture within some business units. Alternatively, the conglomerate`s assorted business units can adopt tailored approaches to implement the full scope of a respective industry`s GMPs. Regardless, the key to achieving sustainable compliance and a continuous supply of regulated products to the marketplace is through the use of integrated quality systems.

Richard Prince, Ph.D., is president of Richard Prince Associates Inc. (Short Hills, NJ), a compliance and technical based consultancy,and an officer of Microgen, a provider of quality disinfectant-cleaner products. He can be reached at (973) 564-8565, fax at (973) 564-8731 or by e-mail: [email protected].