December 6, 2019
“Le mieux est l'ennemi du bien. [The perfect is the enemy of the good.]” — Voltaire
GMPs (good manufacturing practices) as found in the dietary supplement regulations are considered the minimum standards for regulatory compliance. These are titled “good” even though the expectation from FDA can often be closer to the “perfect” standard. It can be difficult for brands to meet the perfect standard, since the definition of compliance with these regulations is ever-evolving.
As GMP inspections continue, and deficiencies are recorded, the statistical probability is that the relative same number of GMP violations would occur year over year. On one hand, we find companies that have, for some reason, either not fully implemented GMPs in their operation or likely have no clue as to the GMP requirements for their business model (own-label distributor versus contract manufacturer). In addition, FDA has increased the depth of its inspections along with its expectations. GMPs for dietary supplements have been finalized for a dozen years now. That is likely enough time for everyone to understand and have at least implemented the fundamentals, yet warning letters are still issued to companies for rudimentary and basic issues. Therefore, FDA is looking more closely at different aspects of compliance beyond the basics. This is a logical progression when mixed with the “flexibility” afforded in the regulations. This flexibility additionally affords individual FDA inspectors with differing interpretations that results in the stock language at the end of warning letters that reads, “The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist in connection with your products.”
Looking at the change in depth and approach helps anticipated how brands can comply with the deepening expectations. Two areas to examine are identity testing and laboratory performance, which drive the creation of data. These topics are interrelated and a clear sign of the new depth and areas of interest that FDA has in its sights.
Identification is required for all components and finished dietary supplement products. These activities fall into two broad categories: dietary ingredients and other components. The initial findings of GMP inspections commonly noted a lack of identification testing. Regulation mandates that each lot of each dietary ingredient be identified with a scientifically valid method before use. FDA has begun to examine the identification methods, not simply whether identification was performed. The use of scanning spectroscopy (such as Near InfraRed [NIR] and Fourier-transform infrared spectroscopy [FTIR]) is popular in the industry for identification of a variety of components because of the low cost and rapid process compared to other methods. FDA has taken note of the over-use and common inadequacy of this analytical technique. FDA didn’t find the analytical method “scientifically valid,” owing in part to the lack of use of appropriate reference standards. The agency is looking at supporting documentation and traceability, such as reference standards and voucher specimens needed to be qualified.
Consider the scientific validity of using a voucher specimen to affirm the identity of a botanical. FTIR and NIR instruments generate scans that are compared to reference scans. The validity of the reference scan, or the voucher specimen, is the key. Consider a reference scan of materials received as an already blended dietary ingredient. Comparing the first batch received against the current batch without complete affirmation of the reference is common practice. When called for and applicable, a legitimate voucher specimen can be a scientifically valid tool, but the validity of the specimen must be affirmed, and the adequate documentation must be on hand. FDA is evaluating the details behind identity affirmation as part of compliance with GMPs.
FDA has also reviewed the laboratories. A lab’s operations and facilitates are just as important as any other entity within the supply chain. FDA has begun to find challenges with contract laboratories performing work on behalf of this industry. A lab can have International Organization for Standardization (ISO) accreditation, but not be fully GMP compliant. A GMP compliant lab does not need to have ISO methods or accreditations. Laboratories are being generally evaluated now; however, as time passes, the importance of laboratory operations will become more evident as GMP inspections place greater emphasis in this area. This is a thorny issue for contracted laboratories because these must be properly qualified. Should there be a challenge with a chosen contracted laboratory, a brand will need to ensure transparency of its data and documentation.
These regulations are for good manufacturing practices, not perfect manufacturing practices, and they use the minimum standard for performance expectations. These standards are being enforced to an ever-deepening degree of detail, and the industry needs to prepare for greater scrutiny.
As chief operating officer, Jim Lassiter oversees all consulting operations at REJIMUS, formerly Ingredient Identity. He has more than four decades of experience in quality control (QC), and government and regulatory affairs throughout the pharmaceutical, dietary supplement and natural product industries with organizations such as Nutrilite, Robinson Pharma, Irwin Naturals, Chromadex, the American Herbal Products Association (AHPA) and the Council for Responsible Nutrition (CRN). A respected author and speaker, Lassiter has served on numerous industry and trade boards.
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