Jun 1, 2018
Best Practices Voluntary Guidelines for Probiotics
This document was initially developed1 by members of CHPA Dietary Supplements Committee (DSC) Probiotics Labeling Group (Labeling Group) to provide voluntary guidelines for use by manufacturers of dietary supplement products containing probiotic ingredients. They are not intended to replace, interpret, or circumvent any applicable local, state, or federal regulations, statutes, or guidance. Manufacturers are responsible for ensuring all product labeling is in compliance with applicable law.
The guidelines take into account current U.S. laws and regulatory requirements and will be updated as best practices, and FDA regulations regarding probiotics, evolve.
I. Labeling Recommendations
- The quantitative amount(s) of probiotics in a product should be expressed in Colony Forming Units (CFUs).2
- The labeled quantity of probiotics should reflect the quantity of live microorganisms at the end of the stated shelf life, not at the time of manufacture, in accordance with 21 CFR 101.9(g)(3) and (g)(4).
- The label should identify the genus, species, and strain for each microorganism in the product.
- Quantities should be declared as follows –
- For a product containing only one strain: Declare the quantity of the strain in CFUs.
- For a product containing multiple strains: Declare the total count of the blend in CFUs.
- Proprietary blends are permitted by law for dietary supplements.3 When determining the order of listing on a product label for individual ingredients within a proprietary blend, CHPA member companies should use appropriate and scientifically-valid measures to establish predominance.4 If a claim pertaining to individual strains or a blend of strains contained in the product is made, the manufacturer should maintain evidence that the amount(s) provided in the product is consistent with the scientific evidence in support of the claim.
II. Stability Testing Recommendations
- Stability testing should be conducted under the same temperature conditions as the recommended storage conditions on the finished product label. The storage temperature should be well defined in the stability testing protocol. When defining storage temperatures, firms may consider the following storage conditions from the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Stability Testing of New Drug Substances and Products Q1A(R2) or the United States Pharmacopoeia (USP) General Chapter <659> Packaging and Storage Requirements.
ICH Guideline for Stability Testing Q1A(R2) Storage Conditions for Long Term Stability Studies Storage Storage Condition Products intended for storage in a freezer -20ºC ± 5°C Products intended for storage in a refrigerator 5°C ± 3°C General case5 25°C ± 2°C/60% Relative Humidity (RH) ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH USP General Chapter <659> Storage Conditions Definitions Storage Storage Condition Refrigerated 2ºC to 8°C Cold Not exceeding 8°C Cool 8°C to 15°C Controlled room temperature 20°C to 25°C
- Stability testing should be conducted under real-time conditions to support the stated shelf life of the product. Use of accelerated or other testing in a program to support product stability should be scientifically justified and documented.
- The product (formulation and process) and packaging (primary container closure system) used in stability testing should be supported by scientifically sound evidence. Similar to the recommendation in the ICH guideline, stability testing should be conducted under conditions that are representative of the finished product in the final packaging proposed for marketing.
- Products should contain 100% of the quantity of probiotics declared on the product label at end of shelf life.
- All stability test methods, including proprietary test methods, should be scientifically sound, repeatable, and reproducible. The specific test method used should be documented.
III. Storage Recommendations
Probiotic organisms are generally sensitive to changes in temperature and humidity. The degree that an individual product is impacted by temperature and humidity is dependent on the probiotic strains in the product, formulation matrix and dosage form, and product packaging.
Manufacturers should provide storage and handling instructions to customers, taking into account individual formulations and packaging. Instructions should be based upon data and experience with each product and should take into account all of the environments in which the product will be reasonably expected to be held throughout its lifecycle (e.g., warehouse, shipping, retail and consumer shelves).
CHPA recommends that member companies comply with these guidelines for products manufactured for sale as soon as possible, but no later than twelve months from the effective date of the revised guideline (February 20, 2020).
1 Original version of this document adapted from the International Probiotics Association (http://internationalprobiotics.org/home/) “Voluntary Quality Guidelines for Supplement Products.” The 2019 update is based on the “Best Practices Guidelines for Probiotics” document developed jointly by the Council for Responsible Nutrition and the International Probiotics Association (effective date: January 9, 2017).
2 CFU is the scientifically accepted unit of measure for probiotics and provides meaningful information to consumers about the quantity of viable microorganisms present in the product throughout shelf life. However, 21 CFR 101.36(b)(3)(ii)(A) requires that the quantity of probiotic dietary ingredients be declared in metric units. In a September 2018 Draft Guidance (“Policy Regarding Quantitative Labeling of Dietary Supplements Containing Live Microbials: Guidance for Industry”), FDA announced their intention to exercise enforcement discretion with respect to the declaration of live microbial quantity in CFUs. However, the Draft Guidance also specifies that the labeling for a probiotic product must also list the quantitative amount by weight and live microbial dietary ingredients in a proprietary blend must be listed in order of predominance by weight. As this is an evolving topic and FDA has yet to update the draft probiotic guidance in response to public comments received, CHPA members should continue to label probiotics in CFUs while acknowledging the labeling requirements according to 101.36(b)(3)(ii)(A).
3 21 CFR 101.36(c)
4 FDA regulations (21 CFR 101.36(c)(2)) state that for those dietary ingredients for which no RDI or DRV has been established (i.e., “other dietary ingredients”), these ingredients “…shall be declared in descending order of predominance by weight, …”. The Voluntary Guideline released jointly by the Council for Responsible Nutrition and the International Probiotics Association (‘Best Practices Guidelines for Probiotics’, January 2017) stipulates that “Individual dietary ingredients within a proprietary blend should be listed in descending order by CFUs” although the document does cite FDA regulations requiring declaration of ‘other dietary ingredients’ in descending order of predominance by weight (21 CFR 101.36(b)(3)(ii)(A) and 21 CFR 101.36(c)(2)).
5 Applies if the product is not specifically covered by other conditions listed in the guideline.