What is it used for?
active ingredients from Tables 1, 2, and 3
Source of probiotics.
active ingredients from Tables 1, 2, and 3 except Lactobacillus crispatus and Lactobacillus gallinarum
Helps support intestinal/gastrointestinal health [Source note 3].
Could promote a favorable gut flora [Source note 4].
| active ingredients | Strains | Uses or Purposes |
|---|---|---|
| Lacticaseibacillus rhamnosus | GG | Helps to manage acute infectious diarrhea |
| Lacticaseibacillus rhamnosus | GG | Helps to manage and/or reduce the risk of antibiotic-associated diarrhea |
| Lactobacillus johnsonii |
| An adjunct to physician-supervised antibiotic therapy in patients with Helicobacter pylori infections |
| All | Helps to reduce the risk of antibiotic-associated diarrhea |
What this guide covers
By submitting a product documentation referencing this reference, the applicant is attesting that the product will comply fully with the recommended conditions of use and specifications section outlined in this reference. These include species identification, strain characterization, quantification in colony forming units (CFU), and a complete assessment of virulence properties (including but not limited to: antibiotic resistance profile, virulence factor production, and toxigenic activity).
Any non-viable form of the active ingredients found in Tables 1,2 and 3 (e.g. heat-killed, thermostabilised) is excluded from this reference and the reference-based application process.
All of the microorganisms found in Appendix I (Table 6) are excluded from this reference and the reference-based application process.
Rules when this reference is combined with other references (source review category II and III): These restrictions do not apply if the probiotics are microencapsulated (i.e., Capsule, enteric-coated pellets and Tablet, enteric-coated granules), and provided that the microencapsulation is impermeable when the product contains prebiotics or resistant to enzymatic degradation when the product contains enzymes:
Dry probiotic preparations can be combined with other references at Class II when the finished product remains a dry formulation, except when the product contains enzymes.
Any preparation type other than dry (e.g., liquid) or any combination of probiotics with enzymes can only be submitted as a source review category II if no probiotic claim is made and the brand name does not refer to probiotics as the efficacy of probiotics may be affected. If a probiotic claim is associated with these products, a source review category III should be submitted with supporting evidence.
Liquid formulations containing only probiotic and prebiotic ingredients can be approved at Class II provided prebiotic claims are not made for the product and the brand name does not refer to prebiotics. If a prebiotic claim or brand name is associated with these products, a source review category III should be submitted with supporting evidence. Prebiotics are commonly found within products containing probiotics because they help maintain probiotic viability; however, prebiotics can also be degraded by the probiotics themselves prior to ingestion (reducing prebiotic efficacy).
Liquid formulations containing probiotics, prebiotics, and other ingredients can only be submitted as a source review category II if no prebiotic or probiotic claims are made and the brand name does not refer to probiotics or prebiotics. If a probiotic or prebiotic claim or brand name is associated with these products, a source review category III should be submitted with supporting evidence. Probiotic viability can be readily impacted within a liquid formulation by other ingredients (reducing probiotic efficacy).
Who does this guide cover?
Children 1 to 11 years, Adolescents 12 to 17 years and Adults 18 years and older [Source note 6].
How is it taken?
Oral
Which forms are covered?
this reference excludes foods or food-like dosage forms as indicated in the Compendium of references Guidance Document.
Acceptable dosage forms by age group:
Children 1-2 years: The acceptable pharmaceutical dosage forms are limited to emulsion/suspension and solution/liquid preparations(Giacoia et al. 2008; EMA/CHMP 2006). Children 3-5 years: The acceptable pharmaceutical dosage forms are limited to chewables, emulsion/suspension, powders and solution/liquid preparations (Giacoia et al. 2008; EMA/CHMP 2006). Children 6-11 years, Adolescents 12-17 years, and Adults 18 years and older: Although delayed release dosage forms are usually not supported by the source authority's references, this reference includes the following dosage forms commonly used for products containing probiotics: Capsule, enteric-coated; Capsule, soft, enteric-coated; Capsule, enteric-coated pellets; Granule enteric-coated; Tablet, enteric-coated; Tablets, enteric-coated granules.
Quantities
Method of preparation: Live
active ingredients from Tables 1 and 3
1.0 x 10⁷ total Colony Forming Units (CFU) or more, per day [Source note 7].
The minimum daily dose is the total CFU count per day provided from all live microorganisms present in the product formulation; it is not to be interpreted as a minimum quantity for individual microorganisms.
| active ingredients | Strains | Uses or Purposes | Doses (CFU/day) / Minimum | Doses (CFU/day) / Maximum |
|---|---|---|---|---|
| Lacticaseibacillus rhamnosus | GG | Management of acute infectious diarrhea | 6.0 x 10⁹ | 1.2 x 10¹⁰ |
| Lacticaseibacillus rhamnosus | GG | Management/risk reduction of antibiotic-associated diarrhea | 1.0 x 10¹⁰ | 2.0 x 10¹⁰ |
| Lacticaseibacillus rhamnosus | All | All other uses¹ | 1.0 x 10⁷ | N/A |
| Lactobacillus johnsonii |
| H. pylori infections | 1.25 x 10⁸ | 3.6 x 10⁹ |
| Lactobacillus johnsonii | All | All other uses¹ | 1.0 x 10⁷ | N/A |
| All | Risk reduction of antibiotic- associated diarrhea | 1.0 x 10¹⁰ | 3.0 x 10¹⁰ |
| All | All other uses¹ | 1.0 x 10⁷ | N/A |
¹For 'All other uses', the total recommended daily CFU count must meet the minimum of 10⁷ either as a single ingredient or in combination.
All individual strain quantities of live microorganisms must be indicated on the product documentation form, label and finished product specifications in Colony Forming Units (CFU) per dosage unit.
Multiple microorganisms cultured together with only one combined microorganism count (i.e., blends) are not included in this reference.
Gravimetric or volumetric amounts (e.g. g, mL) are not acceptable.
How is it used?
All active ingredients found in Tables 1 and 2 except Saccharomyces cerevisiae and S. boulardii
Take at least 2-3 hours before or after antibiotics [Source note 9].
All active ingredients found in Table 3
Take at least 2-3 hours before or after taking antifungal medications [Source note 10].
How long is it used?
The reference does not require an additional label statement in this section. This does not establish an absence of risk.
Warnings and precautions
Ask a healthcare professional before use if you have fever, vomiting, bloody diarrhea or severe abdominal pain [Source note 11].
Stop use and ask a healthcare professional if symptoms of digestive upset (e.g. diarrhea) occur, worsen and/or persist beyond 3 days [Source note 12].
When should it be avoided?
Do not use if you have an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment) [Source note 13].
Possible side effects
The reference does not require an additional label statement in this section. This does not establish an absence of risk.
Storage
Must be established in accordance with the requirements described in the applicable product regulations.
Liquid products
Store in refrigerator in a tightly closed, light-resistant container.
This requirement does not apply to shelf-stable liquid dosage form preparations (i.e. oil suspensions and emulsions indicated in the Compendium of references Guidance Document).
Non-liquid products (optional)
Store in refrigerator in a tightly closed container [Source note 14].
Appendix I
| Proper and Common Name(s) | References |
|---|---|
| Bacillus clausii | Nielsen et al. 1995 |
| Bacillus coagulans | Skerman et al. 1980 |
| Bacillus indicus | Suresh et al. 2004 |
| Bacillus subtilis | Skerman et al. 1980 |
| Bacillus subtilis subsp. inaquosorum | Rooney et al. 2009 |
| Clostridium butyricum | Skerman et al. 1980 |
| Enterococcus faecalis | Schleifer et al. 1984 |
| Enterococcus faecium | Schleifer et al. 1984 |
| Escherichia coli | Skerman et al. 1980 |
| Streptococcus salivarius | Skerman et al. 1980 |
| Streptococcus salivarius subsp. thermophilus | Farrow and Collins 1984 |
Preparation details
Ingredient identity, preparation requirements, and other details that define the scope of this guide.
Ingredients and preparations
Note Refer to Appendix I, Table 6 for active ingredients that are excluded from this reference.
| Proper name(s) | Common name(s) | Source Information¹ / Part(s) | Source Information¹ / Strain(s)² |
|---|---|---|---|
| Bifidobacterium adolescentis | Bifidobacterium adolescentis | Whole cell | Strain designation |
| Bifidobacterium animalis subsp. animalis | Bifidobacterium animalis subsp. animalis | Whole cell | Strain designation |
| Bifidobacterium animalis subsp. lactis | Bifidobacterium animalis subsp. lactis | Whole cell | Strain designation |
| Bifidobacterium bifidum | Bifidobacterium bifidum | Whole cell | Strain designation |
| Bifidobacterium breve | Bifidobacterium breve | Whole cell | Strain designation |
| Bifidobacterium longum subsp. infantis | Bifidobacterium longum subsp. infantis | Whole cell | Strain designation |
| Bifidobacterium longum subsp. longum³ | Bifidobacterium longum subsp. longum | Whole cell | Strain designation |
| Bifidobacterium longum subsp. suis | Bifidobacterium longum subsp. suis | Whole cell | Strain designation |
| Companilactobacillus farciminis (Formerly Lactobacillus farciminis) | Companilactobacillus farciminis (Formerly Lactobacillus farciminis) | Whole cell | Strain designation |
| Fructilactobacillus sanfranciscensis (Formerly Lactobacillus sanfranciscensis) | Fructilactobacillus sanfranciscensis (Formerly Lactobacillus sanfranciscensis) | Whole cell | Strain designation |
| Lacticaseibacillus casei (Formerly Lactobacillus casei) | Lacticaseibacillus casei (Formerly Lactobacillus casei) | Whole cell | Strain designation |
| Lacticaseibacillus paracasei (Formerly Lactobacillus paracasei) | Lacticaseibacillus paracasei (Formerly Lactobacillus paracasei) | Whole cell | Strain designation |
| Lacticaseibacillus rhamnosus (Formerly Lactobacillus rhamnosus) | Lacticaseibacillus rhamnosus (Formerly Lactobacillus rhamnosus) | Whole cell | Strain designation |
| Lactiplantibacillus paraplantarum (Formerly Lactobacillus paraplantarum) | Lactiplantibacillus paraplantarum (Formerly Lactobacillus paraplantarum) | Whole cell | Strain designation |
| Lactiplantibacillus plantarum (Formerly Lactobacillus plantarum) | Lactiplantibacillus plantarum (Formerly Lactobacillus plantarum) | Whole cell | Strain designation |
| Lactobacillus acidophilus | Lactobacillus acidophilus | Whole cell | Strain designation |
| Lactobacillus amylolyticus | Lactobacillus amylolyticus | Whole cell | Strain designation |
| Lactobacillus amylovorus | Lactobacillus amylovorus | Whole cell | Strain designation |
| Lactobacillus crispatus⁴ | Lactobacillus crispatus | Whole cell | Strain designation |
| Lactobacillus delbrueckii | Lactobacillus delbrueckii | Whole cell | Strain designation |
| Lactobacillus delbrueckii subsp. bulgaricus | Lactobacillus delbrueckii subsp. bulgaricus | Whole cell | Strain designation |
| Lactobacillus delbrueckii subsp. delbrueckii | Lactobacillus delbrueckii subsp. delbrueckii | Whole cell | Strain designation |
| Lactobacillus gallinarum⁴ | Lactobacillus gallinarum | Whole cell | Strain designation |
| Lactobacillus gasseri | Lactobacillus gasseri | Whole cell | Strain designation |
| Lactobacillus helveticus | Lactobacillus helveticus | Whole cell | Strain designation |
| Lactobacillus jensenii | Lactobacillus jensenii | Whole cell | Strain designation |
| Lactobacillus johnsonii | Lactobacillus johnsonii | Whole cell | Strain designation |
| Lactobacillus kefiranofaciens | Lactobacillus kefiranofaciens | Whole cell | Strain designation |
| Lactococcus lactis | Lactococcus lactis | Whole cell | Strain designation |
| Latilactobacillus curvatus (Formerly Lactobacillus curvatus) | Latilactobacillus curvatus (Formerly Lactobacillus curvatus) | Whole cell | Strain designation |
| Lentilactobacillus buchneri (Formerly Lactobacillus buchneri) | Lentilactobacillus buchneri (Formerly Lactobacillus buchneri) | Whole cell | Strain designation |
| Lentilactobacillus hilgardii (Formerly Lactobacillus hilgardii) | Lentilactobacillus hilgardii (Formerly Lactobacillus hilgardii) | Whole cell | Strain designation |
| Lentilactobacillus kefiri (Formerly Lactobacillus kefiri) | Lentilactobacillus kefiri (Formerly Lactobacillus kefiri) | Whole cell | Strain designation |
| Leuconostoc citreum | Leuconostoc citreum | Whole cell | Strain designation |
| Leuconostoc lactis | Leuconostoc lactis | Whole cell | Strain designation |
| Leuconostoc mesenteroides | Leuconostoc mesenteroides | Whole cell | Strain designation |
| Leuconostoc pseudomesenteroides | Leuconostoc pseudomesenteroides | Whole cell | Strain designation |
| Levilactobacillus brevis (Formerly Lactobacillus brevis) | Levilactobacillus brevis (Formerly Lactobacillus brevis) | Whole cell | Strain designation |
| Ligilactobacillus salivarius (Formerly Lactobacillus salivarius) | Ligilactobacillus salivarius (Formerly Lactobacillus salivarius) | Whole cell | Strain designation |
| Limosilactobacillus fermentum (Formerly Lactobacillus fermentum) | Limosilactobacillus fermentum (Formerly Lactobacillus fermentum) | Whole cell | Strain designation |
| Limosilactobacillus mucosae (Formerly Lactobacillus mucosae) | Limosilactobacillus mucosae (Formerly Lactobacillus mucosae) | Whole cell | Strain designation |
| Limosilactobacillus panis (Formerly Lactobacillus panis) | Limosilactobacillus panis (Formerly Lactobacillus panis) | Whole cell | Strain designation |
| Limosilactobacillus pontis (Formerly Lactobacillus pontis) | Limosilactobacillus pontis (Formerly Lactobacillus pontis) | Whole cell | Strain designation |
| Limosilactobacillus reuteri (Formerly Lactobacillus reuteri) | Limosilactobacillus reuteri (Formerly Lactobacillus reuteri) | Whole cell | Strain designation |
| Loigolactobacillus coryniformis (Formerly Lactobacillus coryniformis) | Loigolactobacillus coryniformis (Formerly Lactobacillus coryniformis) | Whole cell | Strain designation |
| Oenococcus oeni | Oenococcus oeni | Whole cell | Strain designation |
| Pediococcus acidilactici | Pediococcus acidilactici | Whole cell | Strain designation |
| Pediococcus pentosaceus | Pediococcus pentosaceus | Whole cell | Strain designation |
| Propionibacterium acidipropionici | Propionibacterium acidipropionici | Whole cell | Strain designation |
| Propionibacterium freudenreichii | Propionibacterium freudenreichii | Whole cell | Strain designation |
| Propionibacterium freudenreichii subsp. shermanii | Propionibacterium freudenreichii subsp. shermanii | Whole cell | Strain designation |
¹The source material should be the same as the proper name. ²The product documentation and label must identify the strain designation as the source material for each microorganism (e.g. Lactobacillus acidophilus ABC123 where "ABC123" is the strain designation). ³Bifidobacterium longum is an acceptable synonym for Bifidobacterium longum subsp. longum and the two terms can be used interchangeably on the label. ⁴For "source of probiotics" claim only. References: Zheng et al. 2020; JCICSB 2008; Mattarelli et al. 2008; Masco et al. 2004; Roos et al. 2000; Validation List No. 68 1998; Curk et al. 1996; Wiese et al. 1996; Dicks et al. 1995; Vogel et al. 1994; Fujisawa et al. 1992; Howey et al. 1990; Collins et al. 1989; Farrow et al. 1989; Fujisawa et al. 1988; Validation List no. 20, 1985; Validation List no. 16, 1984b; Validation List no. 11, 1983; Validation List No. 8, 1982; Nakamura 1981; Johnson et al. 1980; Skerman et al. 1980; Validation List No. 4 1980; Beijerinck 1901.
| Proper name(s) | Common name(s) | Source information¹ / Part(s) | Source information¹ / Strain(s)² |
|---|---|---|---|
| Lacticaseibacillus rhamnosus | Lacticaseibacillus rhamnosus | Whole cell | GG |
| Lactobacillus johnsonii | Lactobacillus johnsonii | Whole cell | La1 |
| Lactobacillus johnsonii | Lactobacillus johnsonii | Whole cell | Lj1 |
| Lactobacillus johnsonii | Lactobacillus johnsonii | Whole cell | NCC 533 |
| Saccharomyces boulardii³ | Saccharomyces boulardii | Whole cell | Strain designation |
| Saccharomyces cerevisiae |
| Whole cell | Strain designation |
¹The source material should be the same as the proper name. ²The product documentation and label must identify the strain designation as the source material for each microorganism (e.g. Lactobacillus acidophilus ABC123 where "ABC123" is the strain designation). ³Saccharomyces boulardii Seguela, Bastide & Massot 1984 (Saccharomycetaceae) is not a valid proper name for a genetically distinct subtype within the species of Saccharomyces cerevisae [Source note 1]. This name is still used in the scientific literature however and pending a more thorough review, will continue to be accepted as a proper name in probiotic products to prevent confusion with non-probiotic subtypes of S. cerevisae [Source note 2]. References: ITIS 2025; NCBI 2020; DSMZ 2020; McFarland 2010; Hawrelak et al. 2005; Malgoire et al. 2005; Pridmore et al. 2004; FAO/WHO 2001; Reid 1999; Sanders 1999; McCullough et al. 1998; Fujisawa et al. 1992; Collins et al. 1989; Skerman et al. 1989; Hansen 1968; Meyen ex E.C. Hansen 1883.
| Proper name(s) | Common name(s) | Source information¹ / Part(s) | Source information¹ / Strain(s)² |
|---|---|---|---|
| Debaryomyces hansenii | Debaryomyces hansenii | Whole cell | Strain designation |
| Kluyveromyces lactis | Kluyveromyces lactis | Whole cell | Strain designation |
| Kluyveromyces marxianus | Candida pseudotropicalis | Whole cell | Strain designation |
| Saccharomyces bayanus | Saccharomyces bayanus | Whole cell | Strain designation |
| Saccharomyces boulardii | Saccharomyces boulardii | Whole cell | Strain designation |
| Saccharomyces cerevisiae |
| Whole cell | Strain designation |
| Saccharomyces pastorianus | Saccharomyces pastorianus | Whole cell | Strain designation |
| Schizosaccharomyces pombe | Schizosaccharomyces pombe | Whole cell | Strain designation |
| Xanthophyllomyces dendrorhous | Xanthophyllomyces dendrorhous | Whole cell | Strain designation |
¹The source material should be the same as the proper name. ²The product documentation and label must identify the strain designation as the source material for each microorganism (e.g. Lactobacillus acidophilus ABC123 where "ABC123" is the strain designation). References: Golubev 1995; van der Walt 1971; Lodder 1952; Saccardo 1895; Lindner 1893; Meyen ex E.C. Hansen 1883; Reess 1870.
Other ingredients
Must be chosen from the current source ingredient database and must meet the limitations outlined in the database.
Cryoprotectants: All ingredients that are intentionally added during the manufacturing process of a live microorganism to preserve its stability/viability need to be disclosed as Other ingredients.
Preparation and quality requirements
The active ingredients must comply with the requirements outlined in the source ingredient database and the following requirements are expected to be met by each live microorganism attesting to this reference:
The species Latin binomial identification must be up to date and validated.
Survivability of the microorganisms in the human gut must be demonstrated. In-vitro gastric acid and bile resistance testing is considered acceptable.
The microorganism must be identified by phenotype and genotype:
Phenotyping must be assessed based on characteristics routinely used to distinguish the species from others. This includes a series of testing for sufficient confirmation of observable traits of the species.
Genotyping must be assessed as follows:
Absence of virulence of each live microorganism must be established through the following:
Comparison of antibiotic/antifungal resistance profile to typical species resistance - as published by an internationally recognized panel; AND
Explanation of the genetic basis of each atypical antibiotic/antifungal resistance to the species OR demonstration of the absence of all known genetic mechanisms of resistance; AND
Demonstration of lack of horizontal antibiotic/antifungal resistance transfer ability; AND
Demonstration of susceptibility to therapeutic concentrations of at least two commercially available antimicrobial/antifungal agents; AND
Demonstration of the absence of genetic elements responsible for the production of virulence factors characteristic to the genus; AND
Demonstration of lack of toxigenic activity (i.e. production of toxins) known to the genus.
Regarding risk information:
If any bacterial/fungal strain in the product has come into contact with a priority allergen or derivative (e.g. soy, gluten, milk, fish via the culture media) (list available at: [Source note 15] sc.gc.ca/fn-an/securit/allerg/fa-aa/index-eng.php) that is not listed as a medicinal or non- active ingredient, one of the following risk statements must be included on the product label:
If any bacterial/fungal strain in the product possesses unexplained atypical resistance to any antibiotic/antifungal agent [Source note 16], the name(s) of the antibiotic(s)/ antifungal(s) agent(s) must be indicated as a contraindication on the product documentation form and label as follows:
The finished product specifications must be established in accordance with the requirements described in the source authority source’s product quality guidance. In the case of live microorganisms, this includes the following:
Stability/viability measures put into place must ensure that a minimum of 80% of the quantity declared on the product label is present at the end of shelf life.
In the case where the live microorganism can interfere with microbial impurity testing, a detailed rationale on how the final product complies is required. Such rationale should include measures for live microorganism distinguishing at the finished product stage, along with a detailed explanation on how quality assurance measures are put into place to ensure microbial purity.
Information on the manufacturing process, including but not limited to the above, must be maintained by the applicant or the manufacturer and provided to source authority upon request.
Guide change history
Updates to this SupplementSafety.org guide.
Minor updates
Updated guide wording, organization, and source presentation. Added our editorial change history.
Initial release
Initial SupplementSafety.org guide prepared from source reference material.
Validation: Not yet completed. Editorial updates do not constitute clinical validation.
Sources
Source information
This guide organizes source material about uses, preparations, amounts, and precautions. Read the conditions alongside each statement; the information may apply only to particular preparations or populations.
The source document includes supporting references. We have not independently summarized or assessed every cited study for this guide.
- Source document version
- April 24, 2026
- Source captured
- Aug 15, 2026
- Editorial work
- Editorial preparation. Independent clinical review has not been recorded for this guide.
Full citations are available through the link above. Verification is required to open them; reading this guide does not require verification.
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