Contains Nonbinding Recommendations 
Draft - Not for Implementation 
 
 
Policy Regarding Quantitative Labeling 
of Dietary Supplements Containing Live 
Microbials: Guidance for Industry 
 
 
 
 
Draft Guidance 
 
This guidance is being distributed for comment purposes only. 
 
 
Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure 
that FDA considers your comment on this draft guidance before we begin work on the final 
version of the guidance, submit either electronic or written comments on the draft guidance 
within 60 days of publication in the Federal Register of the notice announcing the availability of 
the draft guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852.  All comments should be identified with the 
docket number which is listed in the notice of availability that publishes in the Federal Register.  
 
For questions regarding this draft document, contact the Food and Drug Administration, Office 
of Dietary Supplement Programs, 5001 Campus Drive (HFS-810), College Park, MD 20740, 
Toll Free (855) 543-3784, or 240-402-2375.  
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition 
 
September 2018  Contains Nonbinding Recommendations 
Draft - Not for Implementation 
Table of Contents 
 
I.   Introduction ............................................................................. 1  
II.   Background .............................................................................. 2 
III.   Discussion ................................................................................. 3 
 
  Policy Regarding Quantitative 
Labeling of Dietary Supplements 
Containing Live Microbials: Guidance 
1
for Industry  
 
 
This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
Administration (FDA or we) on this topic.  It does not establish any rights for any person and is 
not binding on FDA or the public.  You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.  To discuss an alternative approach, 
contact the FDA staff responsible for this guidance as listed on the title page.  
 
 
I.  Introduction 
The purpose of this guidance is to advise firms that manufacture, market, or distribute dietary 
supplements of our intent to exercise enforcement discretion with respect to the declaration of 
live microbial2 quantity in colony forming units (CFUs), in addition to the quantitative amount 
by weight declaration required by regulation, within the Supplement Facts label of dietary 
supplements containing live microbials, provided that certain conditions are met.  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe our current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
                                                           
1 This guidance has been prepared by the Office of Dietary Supplement Programs in the Center for Food Safety and 
Applied Nutrition (CFSAN) at the Food and Drug Administration. 
2 A live microbial is a single-celled prokaryotic or eukaryotic microorganism that is intended to be viable at the 
point of ingestion.  Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Draft Guidance 
for Industry, at 97 (August 2016) (available at 
https://www.fda.gov/downloads/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/UCM51573
3.pdf). When final, this guidance will represent the FDAs current thinking on this topic. Many dietary supplements 
that are described as probiotics contain live microbial ingredients.  Probiotics are not defined as a regulatory 
product category under the Federal Food, Drug, and Cosmetic Act (FD&C Act) or the Public Health Service Act 
(PHSA), and products that may be considered to be probiotics may be foods, drugs, and/or biologics under the 
FD&C Act and/or PHSA, depending on various factors, such as the intended use of the product.  Probiotics have 
been defined in other contexts as live microorganisms which, when consumed in adequate amounts of food, confer a 
health benefit on the host (see Joint Food and Agriculture Organization and World Health Organization Working 
Group Report, Guidelines for the Evaluation of Probiotics in Food (April 30 and May 1, 2002)).  The focus of this 
document is on live microbial dietary ingredients in dietary supplements.  
  Contains Nonbinding Recommendations 
Draft - Not for Implementation 
The use of the word should in FDA guidances means that something is suggested or 
recommended, but not required. 
II.  Background 
Under section 403(q)(5)(F) and (s)(2)(A)(ii) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 343(q)(5)(F) and (s)(2)(A)(ii)), a dietary supplement3 is misbranded if 
the presentation of the nutrition information does not include the quantity of each dietary 
ingredient (or of a proprietary blend of such ingredients) per serving.  Our regulations, at 21 CFR 
101.36, establish the requirements for nutrition labeling of dietary supplements, including that 
dietary ingredients for which a Reference Daily Intake (RDI) or Daily Reference Value (DRV) 
has not been established must be listed inside the Supplement Facts label along with their 
quantitative amount by weight per serving in metric units, as described in 21 CFR 101.36(b)(3).  
Additionally, dietary supplements that contain a proprietary blend of dietary ingredients must, 
among other requirements, list in the Supplement Facts label the proprietary blend name, the 
dietary ingredients contained in the blend, and the quantitative amount of the total weight of the 
proprietary blend per serving, as described in 21 CFR 101.36(c).  Further, under 21 CFR 
101.36(c)(2), certain dietary ingredients contained in the proprietary blend must be declared in 
descending order of predominance by weight.  
 
In a final rule published in the Federal Register of May 27, 2016, titled Food Labeling: 
Revision of the Nutrition and Supplement Facts Label (81 FR 33742) (Nutrition and 
Supplement Facts Label Final Rule), we amended the labeling regulations for conventional foods 
and dietary supplements to provide updated nutrition information on the label.  In the Nutrition 
and Supplement Facts Label Final Rule, in response to a comment, we addressed the issue of 
whether we should permit the use of additional units of measure for dietary ingredients to allow 
for use of more appropriate units of measure when metric weight is not the most accurate way to 
express the quantity of the dietary ingredient.4  The comment gave as examples the use of CFUs 
in the labels of dietary supplements containing live microbials and enzyme assay units for 
enzymes.  Another comment requested that we amend our regulations to state that these 
amounts shall be expressed in metric or other appropriate units of measure.5  We declined to 
change our regulations in response to these comments, explaining as follows:   
We decline to permit the use of additional units of measure for dietary ingredients. The 
comment provided the examples of CFUs for probiotics and enzyme assay units for 
enzymes; however, the broader change suggested in the comment, by including other 
appropriate units of measure, would allow for the use of units of measure for dietary 
ingredients other than just probiotics and enzyme assay units. 
 
We recognize that manufacturers are using a number of different units of measure for 
probiotics, enzymes, and other dietary ingredients.  We need to fully evaluate each unit of 
                                                           
3 Section 201(ff) of the FD&C Act (21 U.S.C. 321(ff)) defines the term dietary supplement. 
4 81 FR 33742 at 33933. 
5 Id. 
 
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measure for dietary ingredients to determine if it is appropriate for use on the Supplement 
Facts label, and if there are any implications to allowing for the use of such units of 
measure on the label.  Because of the complexity of these labeling concerns, we plan to 
issue information related to this subject at a later date.  We have, therefore, finalized 
 101.36(b)(2)(ii)(A) without change.6 
Subsequently, FDA received a citizen petition asking us to amend our regulations at 21 CFR 
101.36 to require the quantitative amount of probiotic ingredients in a dietary supplement to be 
presented in terms of colony forming units (CFUs) instead of by weight.7  In developing this 
guidance we have considered, among other things, the evidence submitted to the docket 
concerning the petition. 
III.  Discussion 
Many dietary supplements, often marketed as probiotics, include claims that the live microbial 
ingredient, formulated in adequate amounts, will confer a health benefit on consumers.  The 
weight of microbial dietary ingredient in a product represents the products total cellular mass, 
consisting of both live and dead microorganisms, and therefore does not necessarily correlate 
with the number of viable microorganisms in that product.  Additionally, the labeled weight of 
the microbial ingredient may not accurately reflect the number of live microorganisms 
throughout the range of times a product is expected to be consumed because live microorganisms 
are susceptible to cell death throughout the shelf life of a product.8  
A colony forming unit, or CFU, is a measurement of viable microbial cells that are capable of 
replicating on agar plates and forming colonies which are then counted.9  Under existing law, 
dietary supplements are permitted to bear information about the quantitative amount of live 
microbial dietary ingredients in CFUs in areas of the dietary supplement label outside of the 
Supplement Facts label, as long as this information is not false or misleading.10  However, within 
the Supplement Facts label itself, these ingredients can be quantified only by weight.11 
CFU is currently the mostly widely recognized measure of live microbials used by FDA and 
foreign governmental organizations.  In guidance relating to clinical trials for live biotherapeutic 
products, FDA has stated that potency of live microbial products is generally measured in 
CFUs.12  FDA has evaluated and responded to a number of Generally Recognized as Safe 
                                                           
6 Id. 
7 Citizen Petition from International Probiotics Association (IPA Citizen Petition), November 18, 2016, Docket 
FDA-2016-P-3968 (available at https://www.regulations.gov/searchResults?rpp=25&po=0&s=FDA-2016-P-
3968&fp=true&ns=true). 
8 M. E. Sanders, et al., Safety assessment of probiotics for human use, 1 Gut Microbes (2010). 
9 Goldman, E. (Ed.), Green, L. (Ed.). (2015). Practical Handbook of Microbiology, Third Edition. Boca Raton: CRC 
Press. 
10 21 CFR 101.13(i)(3). 
11 See 21 CFR 101.36(b)(3).   
12 Early Clinical Trials with Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information: 
Guidance for Industry (June 2016), at page 12, available at https://www.fda.gov/ucm/groups/fdagov-
public/@fdagov-bio-gen/documents/document/ucm292704.pdf. 
 
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(GRAS) notices, related to uses of live microorganisms in food, where the concentration (or use 
level) of live microbials was expressed in CFUs.13,14  FDA also has reviewed and responded to 
premarket notifications for new dietary ingredients (NDIs) where the subject NDI is a live 
microbial ingredient, and the proposed conditions of use for such notifications is typically 
expressed in CFUs for the serving size.15  A number of other countries have similarly recognized 
CFUs as the appropriate unit of measurement for live microbial ingredients,16 and the use of 
CFU as a quantitative measure of live microbial activity is prevalent in the scientific and other 
literature.17    
Because the Supplement Facts label is required for all dietary supplements in a standardized 
format, allowing firms to declare live microbial quantity in terms of CFUs would permit 
consumers to more readily identify the amount of viable microorganisms for each product and 
more easily compare products, without searching through various parts of the product label.  
Declaring quantity in terms of CFUs also would promote confidence that a particular dietary 
supplement product contains the labeled amount of live microbial ingredient, providing the 
specified number of viable microorganisms throughout the shelf life of the product.18  FDA data 
suggest that consumers consult supplement labels to, among other things, find out amounts of 
specific ingredients in a supplement product and compare supplement products.19  
While we currently believe that CFUs provide a useful description of the quantity of live 
microbial dietary ingredients, we are aware that researchers are currently evaluating other 
methods and units of measure for live microbial dietary ingredients and that such alternative 
methods have the potential to more accurately and more efficiently quantify the number of viable 
                                                           
13 Antonia Mattia, Robert Merker; Regulation of Probiotic Substances as Ingredients in Foods: Premarket Approval 
or Generally Recognized as Safe Notification, Clinical Infectious Diseases, Volume 46, Issue Supplement_2, 1 
February 2008, Pages S115S118, https://doi.org/10.1086/523329. 
14 FDA GRAS Notice Inventory, available at http://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices. (See, 
e.g., GRN 268, 445, 455, 502, 531, 685). 
15 See, e.g., NDIN 924, available at https://www.regulations.gov/document?D=FDA-2016-S-0023-0068; NDIN 900, 
available at https://www.regulations.gov/document?D=FDA-2016-S-0023-0014; NDIN 608, available at 
https://www.regulations.gov/document?D=FDA-2009-S-0608-0141. 
16 See, e.g., Guidance Document  The Use of Probiotic Microorganisms in Food at  16(d) (April 2009), available 
at https://www.canada.ca/en/health-canada/services/food-nutrition/legislation-guidelines/guidance-
documents/guidance-document-use-probiotic-microorganisms-food-2009.html; Ministerio della Salute, Linee Guida 
su Probiotici e Prebiotici  1.3 (March 2018),  available at 
http://www.salute.gov.it/imgs/C_17_pubblicazioni_1016_allegato.pdf. 
17 E.g., Tina Didari, et al., A systematic review of the safety of probiotics, 13 Expert Opinion on Drug Safety (2014); 
F. Guarner, et al., World Gastroenterology Organisation Global Guidelines: probiotics and prebiotics October 
2011, 46 J Clin Gastroenterol (2012); and M. E. Sanders, et al., Safety assessment of probiotics for human use, 1 Gut 
Microbes (2010). 
18 For further information on our requirements for the minimum quantity of dietary ingredients throughout the shelf 
life of a dietary supplement, see 21 CFR 101.9(g)(3) and (g)(4), and 101.36(f)(1).   
19 Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration,2014 Health and Diet Survey: 
Topline Frequency Report (2016), available at 
https://www.fda.gov/downloads/Food/FoodScienceResearch/ConsumerBehaviorResearch/UCM497251.pdf.  
 
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cells in a product at a future time.20, 21  Therefore, at this time, we intend to continue monitoring 
the development of new technologies and their potential impact on the use of other units of 
measure on the Supplement Facts label before deciding whether to engage in rulemaking to 
revise the Supplement Facts regulations.  However, we are mindful that dietary supplement 
manufacturers are already in the process of preparing new labels to comply with the Nutrition 
and Supplement Facts Label Final Rule; the compliance date for that rule is January 1, 2020, for 
manufacturers with $10 million or more in annual food (including dietary supplement) sales, and 
January 1, 2021, for manufacturers with less than $10 million in annual food sales.22  In the 
interim, until we decide whether to engage in rulemaking to amend 21 CFR 101.36, we intend to 
exercise enforcement discretion for those firms that choose to declare the quantitative amount of 
live microbial ingredients in the Supplement Facts label by CFUs in addition to weight, provided 
the following conditions are met: 
  The quantity is first listed in terms of weight; 
  The declaration of quantity in CFUs is expressed in a manner that is clearly separate and 
readily distinguishable from the weight, e.g., as a parenthetical or in a subset line; 
  The declaration of quantity in CFUs is formatted in clear terms that can easily be 
understood by a common reader, e.g., 10 billion or 300* (where the unit that * is 
intended to represent, such as million or billion, is a typical measurement of CFUs and is 
clearly indicated elsewhere in the Supplement Facts label);   
  The declaration of quantity in CFUs is accurate and not misleading, and does not render 
misleading other aspects of the Supplement Facts label, or other aspects of the product 
label; 
  The declaration of quantity in CFUs measures only live microbial ingredients and does 
not include inactive, dead, or nonviable organisms;  
  Live microbial dietary ingredients in a proprietary blend are listed in descending order of 
predominance by weight; and 
  The product label otherwise complies with all applicable laws and regulations. 
For the reasons articulated in this document, we have determined that consumers would benefit 
from permitting the label of dietary supplement products to accurately represent the quantity of 
live microbial dietary ingredients in the Supplement Facts label in terms of CFUs.  Our intended 
exercise of enforcement discretion is limited to the labeling of dietary supplements containing 
live microbial ingredients and to the declaration of quantity of such live microbial ingredients on 
the Supplement Facts label in terms of CFUs.  Our exercise of enforcement discretion does not 
                                                           
20 See, e.g., Hansen SJZ, Morovic W, DeMeules M, Stahl B, Sindelar CW. Absolute Enumeration of Probiotic 
Strains Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bl-04 via Chip-Based Digital 
PCR. Frontiers in Microbiology. 2018:9:704. doi:10.3389/fmicb.2018.00704. 
21 See, e.g., Davis C. Enumeration of probiotic strains: Review of culture-dependent and alternative techniques to 
quantify viable bacteria. Journal of Microbiological Methods. 2014:103:9. doi:10.1016/j.mimet.2014.04.012. 
22 83 FR 19619 (May 4, 2018). 
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apply to other foods that contain live or viable microbial ingredients, to dietary supplements that 
do not contain live microbial dietary ingredients, or to any other FDA-regulated commodities.  
 
6