The evaluation of the specifications for acceptance of an ingredient is only as good as the analytical method that is followed; that is, if the method provides inconsistent results, less of the ingredient will meet the overall specifications, ultimately increasing both production timelines and financial loss. The methods used to verify that ingredient specifications have been met must also be shown to be valid for the specific ingredient matrix: analyses for phytosterols in a fruit extract may not be appropriate for determining the level of phytosterols in a microalgal concentrate, for instance. Therefore, FDA also requests that methods used in determining specifications must be validated for the specific use. Validation in this context means that the analytical methodology is accurate, specific, and reproducible for the specific matrix being tested. A number of different methods have been published by various organizations, including the United States Pharmacopeia (USP) and AOAC International; methods used in the analysis of food specifications do not need to be published, but do need documentation that they have been validated for the particular parameter and the matrix (e.g., oil-based or water-based ingredients).
The importance of a manufacturer’s degree of rigor for specification conformance was highlighted in a recent FDA warning letter to a dietary supplement manufacturer.5 While the letter lists numerous violations for a variety of subjects, one that is applicable in the present context is the lack of label specifications for the supplements the firm packaged, labeled, and held. FDA made clear in the letter that the firm had an obligation to ensure that products conformed to established specifications. Further, the firm failed to examine supplier information on shipments, which led to a separate violation, as one of the packaged products was voluntarily recalled due to an undeclared drug ingredient-another example of the importance of verification of the identity and purity of the ingredient.
Verification and Validation
Verifying that the ingredients being used in the production of your food or supplement product is only one small, but integral, aspect of the increased level of transparency being required by consumers and FDA. The core concept of the FSMA final rule is to utilize science-based preventative controls throughout the food supply, a main component of which is extensive use of ingredient and final product tracking and analysis, along with documentation of the company-established control mechanisms to limit food contamination (i.e., preventative control rules). Under FSMA, product testing must be scientifically valid and must identify the test(s) conducted, including the analytical method(s) used.6 In addition, both food and dietary ingredient suppliers will be required to have a written plan that: (1) evaluates hazards that are reasonably likely to occur in their ingredients, such as pathogens, allergens, and contaminants; (2) outlines the steps that will be put in place to minimize or prevent hazards from occurring; (3) specifies how these controls for hazard mitigation will be maintained; (4) maintains routine monitoring records and; (5) details what corrective actions will be taken when necessary.
FDA uses the terms verification and validation within the FSMA final rule employing specific definitions that are not commonly used in daily vernacular. Under the FSMA definition, verification is intended to ensure that controls taken during risk-reduction activities are effective. Verification is described, in part, as “validating with scientific evidence that a preventive control is capable of effectively controlling an identified hazard.”7 Product testing can be considered a verification activity. Validation is a subset of verification and focuses on giving scientific basis to a preventive controls plan to ensure that the plan is effective in controlling food hazards. FDA requires that all preventive controls listed in a food safety plan are validated.
It is important to recognize the subtle differences when addressing different food regulations (e.g., FSMA risk-control activities versus product specifications for food ingredients under FSMA). Analyzing batches of an ingredient to determine if they meet the correct specifications, which define both the identity and safety aspects of a food or dietary ingredient, is an integral part of the FSMA process to continuously verify that there is no potential safety hazard with the ingredients being incorporated in a final product.
Toxicologist Alex LeBeau, PhD, and director of toxicology Ray A. Matulka, PhD, represent the Burdock Group, the leading food safety and regulatory consulting firm headquartered in Orlando, FL.
1. U.S. FDA Food Safety Modernization Act Fact Sheet; www.fda.gov/Food/GuidanceRegulation/FSMA/ucm383763.htm. Accessed September 24, 2015.
2. 21 CFR §111.70. Current good manufacturing practice in manufacturing, packaging, labeling, or holding operations for dietary supplements. What specifications must you establish?
3. www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm124917.htm; Guidance for Industry: Recommendations for Submission of Chemical and Technological Data for Direct Food Additive Petitions; site last visited September 24, 2015.
4. www.usp.org/food-ingredients/food-chemicals-codex. Accessed September 25, 2015.
5. www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm462745.htm. Accessed September 25, 2015.
6. Federal Register, vol. 80, no. 180; Docket No. FDA-2011-N-0920. Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food.
7. www.fda.gov/Food/GuidanceRegulation/FSMA/ucm334115.htm. FSMA Final Rule for Preventive Controls for Human Food: Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food; site last visited September 25, 2015.