How you approach the new dietary-supplements GMPs can ultimately affect the measure of success you have in designing a programme that will satisfy FDA requirements.
The publication of 21 CFR Part 111 in 2007 has evoked a spectrum of responses from members in the industry that range anywhere from abject fear and moderate ambivalence to complete denial. Realistically, however, all must accept the fact that the GMPs are here to stay and, from now on, will necessitate significant changes in the way that products are manufactured, advertised and sold to dietary-supplements consumers.
Bringing products to market that are safe and effective is the primary goal of the dietary-supplements industry. It needs to be recognized that this goal is also shared by the people at the FDA and, as such, should be considered when designing any compliance system.
Consider the case of an herbal manufacturer we recently met who receives some of his ingredients as whole herbs. He was aware that Paragraph 111.75 (h) (2) of the regulations allows for "gross organoleptic analysis" for identity testing, if this is appropriate. Although he was currently using this method, he was fearful that the FDA would not consider his results scientifically valid. Consequently, he was in the process of acquiring an expensive piece of HPLC equipment that he hoped would produce more acceptable results. Knowing that his current testing procedure would most likely be acceptable to the FDA, we encouraged him to contact it to gain clarification and direction, stressing that regulators always welcome this type of dialogue with industry members. However, he replied, apprehensively, that he could not possibly do that, because he did not want to bring attention to his company within the agency.
In a subsequent conversation with Brad Williams, assistant to the director, dietary supplements, CFSAN, at the FDA (while keeping the company's identity confidential), we learned that, in this case, organoleptic testing was appropriate and acceptable. Williams also stated that he would be very happy to speak to the company's representative in an effort to address any questions or concerns regarding this issue or any other part of the regulations. Unfortunately, the manufacturer would not reconsider his earlier decision, thus setting a specification that was overly restrictive and further binding himself to using a very precise, and difficult to manage, analytical technique that was probably unnecessary.
Taking the time to build a relationship with the FDA as you develop your compliance programme is well worth the effort, when faced with the eventuality of a regulatory inspection. If, during inspections, the FDA investigator finds conditions which, in the investigator's opinion, violate GMPs, he will provide these in writing on an FDA Form 483 (commonly called 'a 483'). These findings are typically responded to in writing, stating what the company will do to remediate the observations. However, if the response is determined inadequate or the observations are considered serious violations, the FDA may issue a warning letter, to which the company must respond within 15 working days of receipt.
These are difficult times and are seldom conducive to establishing your first contact with local FDA personnel, because the circumstances tend to be more confrontational. For this purpose, it is decidedly better to initiate discussions with the agency as soon as possible. Keep in mind that the FDA will still inspect your facility, and expect you to be following GMPs, but it is much easier to converse with people whom you already know.
As you begin to institute the new GMPs into your existing processes, take a proactive approach in your interactions with regulators. From this point forward, you should think of the FDA as one of your most important customers, and treat them as such.
Michael J Plover is president of Quality Systems Design (North Wales, Pennsylvania), a consulting firm specialising in assisting companies to develop robust and maintainable processes. He also is the author of Your Sourcebook for Dietary Supplement Compliance, which breaks down the regulations and offers insights for developing maintainable and affordable GMP compliance systems. www.QualitySD.com