GMP Update: Total Compliance

Requiring supplement manufacturers to have proper controls in place to ensure dietary supplements are processed and handled in a consistent manner and meet high-quality standards is not too much to ask. This is the definition of good manufacturing practices (GMPs) for dietary supplements, which, thankfully, FDA put forth in its long-awaited release of these requirements. While called for by DHSEA in 1994, the GMPs took a while to come to fruition under FDA’s creation, and a three-stage staggered compliance schedule meant all companies subject to the rule were not necessarily required to comply until June 2010. Now that this last deadline, which was for the smallest companies per number of employees, has passed, the big questions remaining include: Are manufacturers ready to prove compliance? And, is FDA going to inspect and enforce the GMP regulation to help improve the quality of the industry and force out rogue companies not interested in long-term commitments to quality and integrity?

Since these aren’t easily answered questions, it can be helpful to look at all the work, resources and effort put into the race to prepare for the compliance deadline. From the announcement of the GMPs in  June 2007, the industry has bound together to organize seminars and workshops; consultants with FDA GMP experience in other areas offered advice and a third-party partnership toward compliance; and industry media continued to find ways to inform and educate manufacturers and others facing some level of GMP scrutiny.

The GMP regulation (21 CFR Part 111) actually covers more than just manufacturing; it also mandates minimum requirements for packaging, holding and labeling supplements. Its provisions cover the physical plant design (safety, functionality, etc.), cleaning methods and frequency, testing of incoming and outgoing products, quality control (QC) and manufacturing procedures, complaint handling and how it is all recorded and documented. In fact, recordkeeping is a large part of GMPs.

As the 483 reports from FDA’s early inspections of companies in the initial stage of compliance (i.e. large companies) showed, documentation was a point of deficiency and worry for companies trying to reach compliance. Standard operating procedures (SOPs), master batch records and corrective action plans were among the documentation giving companies GMP challenges. The related problem was companies having such records, but not following them consistently.

The issue of testing is also a troublesome point, as Daniel Fabricant, vice president of scientific and regulatory affairs at the Natural Products Association (NPA), noted tests must be specific and selected. He also highlighted the ongoing importance of test methods, as early FDA reports indicated selecting the right method was important not just for a specific incoming ingredient or outgoing formula, but also for ensuring bottles or packages are properly sealed.

Joy Josephs, founder of Joys Quality Systems, reported the main trouble spots are raw material and finish product testing. “Most companies are having interpretation problems with reduced testing by sub-set testing based upon statistical sampling plans of batches,” she said, noting others are unclear on vendor qualification for raw materials. “Most are running identity test only without the pre-requisite of vendor verification of Certificates of Analyses. Also qualified laboratory personnel are hard to come by.”

The reports from the field add to the education for the rest of the industry yet to face an FDA GMP inspection. As Casey Coy, NSF International, noted one of the key areas that give dietary supplement companies difficulty is in the interpretation of the regulation, along with defining the criteria needed for their specific operations to be considered compliant. The path to compliance is paved with knowledge, and this has not been a road built overnight.

The journey to bring industry manufacturers on board with GMPs began before FDA coughed up its final rule on supplement GMPs. NPA established its own GMP standards for dietary supplements in 1999 and has updated them over the year. In a move to stay relevant, NPA recently updated its GMP certification program to at least cover the requirement of 24 CFR 11, while leaving in place prior NPA GMP standards that were higher than FDA’s GMPs. Fabricant noted some areas where NPA’s GMPs were higher included requirements for expiration dating, stability testing and dedicated QC personnel.

In the NPA’s program, companies strive for an “A” rating, which allows the use of the NPA’s GMP certification mark. Achieving this top rating requires completion of several steps: NPA member companies registered for the GMP certification program must have key QC people attend a GMP training seminar conducted by NPA. Based on this seminar and the NPA self-assessment questionnaire, the companies must conduct an internal self-assessment of its current operation’s compliance with NPA GMP standards. A gap analysis will identify areas of non-compliance, and a corrective/preventive action plan should be devised to address deficiencies—NPA offers resource materials to its GMP program participants to help them achieve compliance. Hiring an industry consultant is another option.