With the mid-size company compliance deadline of June 25 nearly upon us, Nutrition Business Journal had the opportunity to speak with Brad Williams, member of the Dietary Supplements Programs at the Center for Food Safety and Applied Nutrition (CFSAN), which a division of the Food and Drug Administration (FDA), about the first year of Good Manufacturing Practice enforcement in the dietary supplement industry. Williams talks about some of the specific areas of concern for investigators and gives manufacturers advice on how to better prepare a company for an inspection.
NBJ: What was the primary motivation (of the FDA) for requiring a set of Current Good Manufacturing Practices (cGMPs) specific to the dietary supplement industry?
Brad Williams: DSHEA, published in 1994, authorized FDA to develop current Good Manufacturing Practice regulations specific to the dietary supplement industry. As discussed further in the preamble to the final rule, we determined that while food GMPs (21 CFR 110 et seq.) provide requirements for sanitation and that food products are safe, clean, and wholesome, these requirements alone do not address the unique characteristics of dietary supplement products and the need for process controls to ensure that a dietary supplement product contains what the manufacturer intends. Since these products are tablets, capsules, or gelcaps generally, we have provided detailed requirements for process control which differ greatly from what is needed for a food product.
NBJ: As we near the deadline for mid-sized company compliance, can you give a very general assessment of how well the implementation of cGMPs in large companies has gone? Are the cGMPs having the desired effect on the industry based on what you have seen?
BW: We have been generally pleased with the results of the first inspections under the cGMP program for dietary supplement manufacturers. We anticipated this dealing with the larger firms. They usually have resources and experience in regulatory matters and have been meeting the earlier and more rigorous requirements of the private GMP audits conducted by many of the trade associations.
While there are certainly areas needing improvement and reinforcement, we believe at this stage, the regulations are well received and positive. However, as we reach into the smaller, less resource intensive firms, it is possible that more problem areas will be found, and we can adjust our outreach efforts to focus attention on those areas of need.
NBJ: What has the FDA learned over the first year of enforcing cGMPs that will help with enforcement efforts in the coming years?
BW: It is too early in the implementation program to give a comprehensive “lessons learned” answer to this question. Once we have inspected more firms we will have a better idea of where problems are most likely to be found. As noted above, so far the firms we have inspected have been the largest in the industry.
NBJ: What type of feedback have you gotten from the large companies who have undergone a cGMP inspection? How about from the inspectors?
BW: The firms inspected so far have been cooperative and have generally made positive efforts to correct any observed deficiencies. Investigator feedback has also been positive.
NBJ: Is there a particular area of enforcement that the FDA has struggled with?
BW: Most of the rule has been presented to our investigators, compliance officers, and supervisors so that they are adept at interpreting the requirements of this rule.
NBJ: What have been some of the greatest difficulties that the FDA has encountered in trying to create, implement, and enforce cGMPs in the dietary supplement industry?
BW: An example of one minor challenge we faced was that once it was clear the rule was about to be published, we needed to quickly coordinate resources to prepare training for FDA field investigators. CFSAN and the Office of Regulatory Affairs collaborated to develop a professional course for presentation to FDA field personnel. Many individuals were involved in this effort which culminated in smoothly run training sessions and field investigators ready to conduct inspections under this program.
NBJ: What approach did the FDA take in training the inspectors who will be active?
BW: The Center for Food Safety and Applied Nutrition (CFSAN) and Office of Regulatory Affairs (ORA) have developed an investigator training program. ORA University in conjunction with CFSAN has held two train-the-trainer sessions and one session for state regulators. More sessions are planned as the staggered compliance dates approach.
NBJ: Do you think the industry is doing enough to police itself? Should companies be reporting other non-compliant companies?
BW: Some of the industry has always been proactive in policing itself, while others are lacking. If anyone has evidence that a manufacturer is violating existing regulations, they should contact FDA.
NBJ: If traceability and identity are such key issues, why not require suppliers to comply with cGMPs?
BW: The goal of the rule was to place the importance on ensuring the quality of the finished dietary supplement throughout the production and process control system. This approach emphasizes establishing specifications for components and ensuring those specifications are met. It is ultimately the manufacturer of the finished product who will have these systems in place and can determine their accuracy.
NBJ: Was it primarily an issue of jurisdiction, or was it more logistics and cost? Perhaps it’s all of the above?
BW: It was primarily an issue of logistics and cost.
NBJ: How many petitions has the FDA received for exemption from the 100% identity testing? Can you give us a general sense as to how companies are responding to this?
BW: While several parties, including the major trade associations filed comments with the interim final rule, we have not received any petitions to date.
NBJ: Can you talk about how the FDA goes about trying to implement a standard on such a contentious topics as Total Plate Count when dealing with a wide range of feedback?
BW: cGMPs require a manufacturer to set its own standards and analytical methods for components and finished products and FDA expects them to be scientifically valid. We do not require any compendial or “legally binding” standards, but recognize that some of those methods (if from USP, AOAC, or some other such organization) may have been collaboratively evaluated and found acceptable.
FDA has also received many questions about product and ingredient sterility in several venues where we have spoken, and frankly, since there are no “sterile” dietary supplements (injection, opthalmics, optics, etc), we are somewhat at a loss. If these questions are asked from the perspective of determining that working surfaces or equipment are free of microbiological contamination, a manufacturer must set a reasonable limit for cleanliness, however if they are asked from the perspective of the product or component being sterile, we would need the context of the question to discuss it further.
NBJ: UNPA Executive Director Loren Israelsen likened the first year of cGMP inspection to letting an EKG machine run for 90 seconds to establish a baseline reading during a heart exam. Do you agree with that analogy? Has the first year been a learning experience for the FDA? Do you anticipate the level of enforcement will be stepped up as each year passes?
BW: FDA has been monitoring the industry to see how it reacts to the rule and our investigators are well trained in what they need to look for in order for the industry to be in compliance. Of course, FDA is learning a great deal more about the industry while we implement cGMPs; however, a slight modification to Loren’s analogy is that if abnormalities are detected, FDA would take necessary action to achieve corrections.
NBJ: Are there any topics or issues that we did not address as it relates to CGMP compliance? Is there anything that you’d like to communicate to manufacturers in the industry?
BW: We would recommend that manufacturers concentrate on having written procedures, especially for handling unusual or unexpected occurrences while preparing their products. While these procedures are required by the rule, we have seen some confusion about what might be expected. A rule of thumb for all records is if it isn’t written, it wasn’t done.
An additional area that has become an item of concern to us is the mechanism for qualifying suppliers of components by dietary supplement manufacturers. Firms are expected to qualify all suppliers of components used to manufacture dietary supplement prior to using them in dietary supplement products. While components that are dietary ingredients require a minimum of an identity test prior to use, a firm is permitted to rely on Certificates of Analysis supplied by the vendor of qualified components for all other analyses under certain conditions.
While we anticipate that the largest dietary supplement manufacturers have regulatory resources in house to qualify all of their vendors, we would expect that the smaller firms may need to rely on third party contractors to conduct necessary audits, reviews and even testing in some cases, especially in the case of suppliers who are located overseas. As long as a manufacturer has records and documentation that a vendor is properly qualified, FDA should be satisfied during our coverage of their cGMP status.
NBJ explores the issue of GMP compliance and what to expect from an FDA audit in our U.S. Nutrition Industry Overview issue, which will publish in July and be distributed at the 2009 NBJ Summit, July 22-24. To order your copy of the issue, subscribe to NBJ or download a free 32-page sample issue, go to www.nutritionbusinessjournal.com. To register for the NBJ Summit, go to www.nbjsummit.com.
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