CRN-IPA Best Practices Guidelines for Probiotics final

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INTRODUCTION

The Council for Responsible Nutrition (CRN)1 and the International Probiotics
Association (IPA)2 support and encourage responsible production and marketing of
dietary supplements and functional foods that contain probiotics. Therefore, CRN
and IPA have developed scientifically-based voluntary guidelines that address
labeling, stability testing, and storage recommendations for probiotic-containing
dietary supplements and functional foods. These guidelines are intended to facilitate
transparency and consistency.

1 The Council for Responsible Nutrition (CRN) is the leading trade association representing dietary
supplement and functional food manufacturers and ingredient suppliers. CRN represents more than
150 companies that manufacture dietary ingredients and/or dietary supplements, or supply services to
those suppliers and manufacturers.

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2 The International Probiotics Association (IPA) is an international organization bringing together
through its membership the probiotic sectors stakeholders, from academics, scientists, health care
professionals, consumers, industry, and regulators. IPA’s mission is to be the unique platform where
all these stakeholders interact and collaborate to increase probiotic awareness among all users and
help enable the probiotic industry’s sustainable growth.

 

Labeling guidelines were developed to provide information about the identity and
quantity of the probiotics in a product that will help consumers make informed
choices. Stability testing guidelines were established to ensure that the stated shelf
life of a given probiotic product is scientifically supported. Storage
recommendations were provided to facilitate the communication of storage and
handling instructions to customers.

 

The guidelines take into account the current United States (U.S.) laws and
regulatory requirements. While the guidelines do not specifically address regulatory
requirements outside of the U.S., the scientific principles underlying the guidelines
may apply to international regulatory paradigms. The guidelines reflect the most
up-to-date science and industry thinking, and will be updated as best practices
evolve.

 

The precise definition of probiotics is the subject of ongoing discussions. For the
purposes of the guidelines, probiotics are defined in accordance with the Food and
Agriculture Organization of the United Nations (FAO) and World Health Organization
(WHO) definition: “live microorganisms which when administered in adequate
amounts confer a health benefit on the host.”3

3 Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in
Food including Powder Milk with Live Lactic Acid Bacteria. (2001). Health and nutritional properties of
probiotics in food including powder milk with live lactic acid bacteria. Available at:
ftp://ftp.fao.org/docrep/fao/009/a0512e/a0512e00.pdf.

4 CFU is the scientifically accepted unit of measure for probiotics. Labeling quantity in CFUs 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.

5 When technically feasible, also declare the quantity of each genus or species in the blend.

6 21 CFR 101.36(c)(2) requires that dietary ingredients in a proprietary blend be declared in
descending order of predominance by weight.
GUIDELINES

In addition to compliance with applicable labeling laws and regulations, CRN and
IPA recommend that their members adhere to the following guidelines:

 

I. Labeling Recommendations
A. The quantitative amount(s) of probiotics in a product should be
expressed in Colony Forming Units (CFUs).4

 

B. 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.
C. The label should identify the genus, species, and strain for each
microorganism in the product.

 

D. Quantities should be declared as specified below.
i. Product containing only one strain: Declare the quantity of the
strain in CFUs.
ii. Product containing multiple strains: Declare the total count of
the blend in CFUs.5

 

E. Proprietary blends are permitted by the law for dietary supplements.
Individual dietary ingredients within a proprietary blend should be
listed in descending order by CFUs.4,6 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
A. 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(R)27 or
the United States Pharmacopoeia (USP) General Chapter <659>
Packaging and Storage Requirements8.
7ICH. (2003). Harmonised Tripartite Guideline. Stability testing of new drug substances and products
Q1A (R2) (Section 2.2.7). Available at:
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_
R2__Guideline.pdf.

8 United States Pharmacopeial Convention. (2016). General Chapter <659> Packaging and Storage
Requirements. United States Pharmacopeia and The National Formulary (USP 39-NF 34) (pp. 479-
486). Rockville, MD.

 

ICH guideline for Stability Testing Q1A(R2) storage conditions for
long term stability studies

Storage

Storage condition

Products intended for storage in a
freezer

– 20°C ± 5°C

Products intended for storage in a
refrigerator

5°C ± 3°C

General case*

25°C ± 2°C/60% Relative Humidity
(RH) ± 5% RH

or 30°C ± 2°C/65% RH ± 5% RH

* The general case applies if the product is not specifically covered by other
conditions listed in the guideline.

USP General Chapter <659> storage condition definitions

Storage

Storage condition

Refrigerated

2°C to 8°C

Cold

Not exceeding 8°C

Cool

8°C to 15°C

Controlled room temperature

20°C to 25°C

 

B. 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 release should be scientifically
justified and documented.
C. The product and packaging conditions used in stability testing should
be supported by scientifically sound evidence. Similar to the
recommendation in the ICH guideline9, stability testing should be
conducted under conditions that are representative of the finished
product in the final packaging proposed for marketing.
D. Products should contain 100% of the quantity of probiotics declared on
the product label at end of shelf life, except for any variability that is
attributable to methods.
E. All stability testing methods, including proprietary testing methods,
should be scientifically sound, repeatable, and reproducible. The
specific testing method used should be documented.
III. Storage Recommendations
9ICH. (2003). Harmonised Tripartite Guideline. Stability testing of new drug substances and products
Q1A (R2) (Section 2.2.4). Available at:
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_
R2__Guideline.pdf.

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).

 

IMPLEMENTATION

Within twelve months of the effective date, CRN and IPA recommend that
companies comply with these guidelines for products manufactured for sale.

 

 

Effective Date: January 9, 2017