The potential impact of the Food Safety Modernization Act (FSMA) on dietary supplements has been called one of the most important since the Dietary Supplement Health and Education Act of 1994 (DSHEA). Since 2008, dietary supplement manufacturers have been required to meet the GMPs (good manufacturing practices) for dietary supplements in 21 CFR 111, loosely patterned on pharmaceutical GMPs. However, under this rule, supplement ingredient manufacturers were lumped under food GMPs as per 21 CFR 110. This led to a large gap in the quality control and documentation requirements between supplements and their ingredients.
FSMA, enacted November 2015, leaves room for speculation as to how supplement brands are expected to comply, and to what extent the new rules will be enforced. However, there are some steps that can be taken immediately to evaluate preparedness for the new rules.
One place to start is to evaluate or audit the current state of documentation. There are various types of supporting documentation that can be reviewed, through internal paper audits, in-person audits and third-party audits. Supplier standard operating procedure (SOP), statements, certifications, specifications, manufacturing flow charts and independent test reports are documentation that should be part of an initial audit.
Hazard analysis critical control point (HACCP) and supplier qualification are key parts of the new rule intended to add critical layers onto required product safety checks, where previously there existed a gap. While product specifications and testing cover the bulk of product safety issues, knowing where ingredients came from, how they were made and documenting adequate checks on their safety is part of the modernization effort. Plus, solid traceability and an understanding of whether there are inputs that impact genetically modified organism (GMO) status, for example, is increasingly demanded by consumers—not just regulators.
HACCP is the most commonly used control system for types of contamination impacting the safety of foods. It’s historically a key part of food GMP, but not dietary supplements or pharmaceuticals. Key parts of HACCP are beneficial to add as an overlap on a supplement GMP system. Because while supplement GMPs prescribe the general requirement that “effective measures shall be taken" to prevent contamination, they do not recommend the means (such as HACCP) by which this requirement can be satisfied.
A HACCP plan is a detailed document that lists each hazard to product safety and prescribes ways to control them. For example, a typical hazard listed for manufacturing processes that use water is pathogenic microbes; sterilization with heat and limits on moisture in the final product are common critical control points.
If a particular control is prescribed, its effectiveness should be validated with the scientific method. For example, spray drying on its own may not be enough to fully eliminate the hazard of pathogenic bacteria for many products, because of the short amount of time the material is exposed to high temperature. Therefore, the use of spray drying as the sole critical control for pathogens should be tested before being implemented.
Supplier qualification is also a key requirement under the new law. It is now a critical requirement to audit and inspect foreign suppliers, not just test incoming ingredients against their specification. The reasons for a good supplier qualification program make sense, because many possible contaminants are not listed on detailed product specification. Caustic cleaning agents; rarer pathogens like Enterobacteriaceae, Legionella and Listeria; foreign matter; heavy metals; and other types of contamination that are safety risks can be introduced to the product during manufacturing, but are often not listed on the specification.
After the initial evaluation, a gap analysis is ideally performed. What are the major gaps that could raise red flags to an FDA inspector, particularly with respect to product safety? Main areas of focus for an audit include facility suitability and sanitation, personnel, documentation systems and product inputs. Every part of the manufacturing and quality process should be controlled by supporting documentation in the form of SOPs and specifications, and testing/validation against those procedures and specifications. For example, something as simple as water, even if not added to the product and used only for cleaning, should have a specification, and be accompanied by periodic testing that shows the water meets the specification. Otherwise, how does a facility control whether the water is not contaminating the product? A good gap analysis can look something like a checklist that includes an “instruction" such as an SOP or specification, and an accompanying “record," such as a certificate of analysis (CoA), test report or form that demonstrates that the “instruction" was met.
Based on the findings from the initial audit and gap analysis, a more formal supplier qualification program can be developed. Various ways to qualify suppliers exist, each with its own level of rigor. While a paper audit and reliance on a supplier’s third-party audit certificates create a picture of adherence to GMPs, an in-person audit by a qualified independent auditor can be worth a thousand pictures.
For foreign supplier qualification, video-based audits are emerging as a solution that can be more thorough than a paper audit and more cost-effective than an in-person audit. In any case, a minimum requirement for supplier qualification should be described in an SOP devoted to that topic and supported by records that show the SOP was adequately performed.
Setting up a supplier qualification program is often a short-term project requiring specific expertise of ingredient manufacturing and the various food safety risks that can be present. Look for supplier qualification programs to cover all the pertinent bases, including CFR 111, food GMPs, HACCP, as well as identity testing and analytical testing validity.
Successful quality programs aim for a mark beyond the minimum requirements, so look for auditors who offer recommendations supporting continuous improvement efforts beyond minimum compliance requirements.
Blake Ebersole has led a number of botanical quality initiatives and formed collaborations with dozens of universities and research centers. As president of NaturPro Scientific (npscientific.com), Ebersole established quality compliance and product development services for supplements and ingredients such as ID Verified™. Follow him on Twitter at @NaturalBlake.