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With the June 25, 2009, implementation of the Current Good Manufacturing Practices (CGMPs) for the dietary supplement industry, FDA has begun conducting unannounced inspections at plants nationwide. Dietary supplement manufacturing facilities with more than 20 employees are currently affected by the regulations. (Firms with fewer than 20 employees must be in compliance with the regulations by June 25, 2010.)
Companies can expect the CGMP inspections to be anything but casual. Far from garden-variety reviews, FDA representatives may log a couple of weeks at facilities. Under the sweeping regulations, government inspectors may review all written in-plant policies and procedures, equipment maintenance logs, calibration records, and even training procedures. FDA personnel are permitted to inspect facilities, labels, labeling procedures, raw materials and in-process materials, and finished goods. Moreover, they are allowed to take raw and in-process samples for analysis.
Over the past two years, many dietary supplement companies have invested tremendous amounts of resources fortifying their safety and quality management systems while waiting for the CGMPs to go into effect. With the long-awaited deadline here, the dietary supplement industry is entering new, and in some respects, untested waters.
Burden of Proof
Under 21 CFR Part 11 of the CGMPs, manufacturers of dietary supplements must "identify and use an appropriate scientifically valid method for each established specification for which testing or examination is required to determine whether the specification is met." Additionally, dietary supplement manufacturers must document product specifications and operate with a master manufacturing record (MMR) for production of each product. They must ensure that each batch of in-process and finished product meets product specifications, and ensure labeling is in agreement with the MMR.
Not surprisingly, the principal focus of the CGMPs has largely rested on the product testing requirement in the regulations. Colorful anecdotes decrying, "You can't test quality into a product," have abounded throughout segments of the dietary supplement industry for some time. While there is much underlying truth in these statements, such anecdotes have long been used as an excuse to circumvent analytical testing. A key component of building quality into a product entails verifying the reliability of incoming supplies.
Companies that have cultivated long and positive relationships with vendors may feel their production record, along with few-if any-customer complaints is sufficient enough to validate their compliance with recognized safety requirements. Not so. In a heightened regulatory environment, it is business smart to "trust but verify."
Companies that have done little analytical testing up to now may be in for a bit of a surprise when they begin the process of verifying a vendor's certificate of analysis (COA). They may receive a crash course on method selection, laboratory selection, standard reference materials, variation of analytical methods, and much more. All of these factors directly tie into verifying a supplier's COA.
If the stars align, companies may get the information they want on the first try. More than likely, however, manufacturers will need to open lines of communication with laboratories to get a better handle on testing techniques, processes, and protocols. Even with well-established and characterized materials, there are many subtle variations that can complicate testing. Ginseng is a good example. A simple Internet search revealed that one ginseng supplier offers over 30 different products-all with different extract ratios, ginsenoside content claims, and different testing methods for determining the ginsenoside content claim.
To test one of these products, the reference standards and test methods must be differentiated in order to compare the laboratory results with those obtained by the supplier. As such, it is absolutely critical for dietary supplement manufacturers to work closely with both suppliers and laboratories.
With more than 75,000 different dietary supplement products on the market in the United States, there is an industrywide need for rigorous identification of source material, where the "active principle(s)" may not be readily known. There is also batch-to-batch variation of active principle(s), and lack of availability of "biomarker" or "chemical marker" reference compounds for many ingredients.
Presently, AOAC International, United States Pharmacopeia, and other reputable organizations are developing methods to fill this need. Likewise, the National Institute of Standards and Technology is developing reference compounds for comparison, and many private laboratories have undertaken similar efforts. For in-house or single laboratory validations, AOAC has published a detailed document, Guidelines for Single Laboratory Validation of Chemical Methods for Dietary Supplements and Botanicals, which can be accessed online at www.aoac.org.
Weighing the Pros and Cons
Many dietary supplement suppliers may be weighing the pros and cons of setting up their own laboratories or outsourcing their analytical work to contract laboratories. This decision requires careful strategic and financial analysis.
From adhering to safety regulations, such as the Occupational Safety and Health Administration, to staying abreast of new methodologies and technologies, managing an on-site laboratory is rife with many challenges. Generally, outsourcing offers companies a number of advantages including:
Lastly, in the event of a customer or supplier dispute, testing performed by an outside vendor is generally viewed as being more credible than testing conducted by internal labs. In the event of a regulatory action, independent testing is a virtual necessity.
Some companies may choose to operate internal labs and delegate testing to outside laboratories periodically or as needed. This affords them access to highly trained laboratorians without having to add them to the their payroll.
Only the Beginning
The CGMPs are just the beginning of a continuously evolving system for ensuring the safety and quality of dietary supplements in the United States. The faster a company implements the regulations and initiates an analytical testing program, the faster it will be able to implement a rigorous and reliable safety and quality system. Testing is not the golden ticket of CGMPs, but it is an integral part of the process.
Matt Arveseth is laboratory director of Silliker Inc. (Orem, UT). John Williams Jr. is a Silliker senior communications specialist. Both can be reached at firstname.lastname@example.org.