Probiotics

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

Date

January 27, 2023

Proper name(s), Common name(s), Source information, Strain(s)

Note
Refer to Appendix I, Table 6 for medicinal ingredients that are excluded from this monograph.

Table 1. Proper name(s), Common name(s), Source information, Strain(s) - BACTERIA
Proper name(s) Common name(s) Source Information1
Part(s) 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

Bifidobacterium longum

Whole cell

Strain designation

Bifidobacterium longum subsp. infantis

Bifidobacterium longum subsp. infantis

Whole cell

Strain designation

Bifidobacterium longum subsp. longum

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 crispatus3

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 gallinarum3

Lactobacillus gallinarum

Whole cell

Strain designation

Lactobacillus gasseri

Lactobacillus gasseri

Whole cell

Strain designation

Lactobacillus helveticus

Lactobacillus helveticus

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 PLA 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).

3For "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.

Table 2. Proper name(s), Common name(s), Source information, Strain(s) - BACTERIA and FUNGI
Proper name(s) Common name(s) Source information1
Part(s) 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

  • Baker's Yeast
  • Brewer's Yeast
  • Brewer's yeast fungus

Whole cell

Strain designation

1The source material should be the same as the proper name.

2The PLA 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 (Posteraro et al. 2005). 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 (McFarland 2010; NCBI 2009; Bisby et al. 2006; Malgoire et al. 2005; de Llanos et al. 2004; van der Aa Kühle et al. 2003; McCullogh et al. 1998; Skerman et al. 1989).

References: Euzéby 2012, McFarland 2010, NCBI 2009, Bisby et al. 2006, Hawrelak et al. 2005, Malgoire et al. 2005, Pridmore et al. 2004, Gilliland 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.

Table 3. Proper name(s), Common name(s), Source information, Strain(s) - FUNGI
Proper name(s) Common name(s) Source information1
Part(s) 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

  • Baker's Yeast
  • Brewer's Yeast
  • Brewers yeast fungus

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 PLA 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.

Route of Administration

Oral

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs 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; EMEA/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; EMEA/CHMP 2006).
Children 6-11 years, Adolescents 12-17 years, and Adults 18 years and older:Acceptable dosage forms for oral use are indicated in the dosage form drop-down list of the web-based Product Licence Application form for Compendial applications.

Use(s) or Purpose(s)

Medicinal ingredients from Tables 1, 2, and 3

Source of probiotics.

Medicinal ingredients from Tables 1, 2, and 3 except Lactobacillus crispatus and Lactobacillus gallinarum

Table 4. Medicinal ingredients from Table 2 with specific use(s) or purpose(s)

Medicinal Ingredients Strains Uses or Purposes

Lacticaseibacillus rhamnosus

GG

Helps to manage acute infectious diarrhoea

Helps to manage and/or reduce the risk of antibiotic-associated diarrhoea

Lactobacillus johnsonii

  • La1
  • Lj1
  • NCC 533

An adjunct to physician-supervised antibiotic therapy in patients with Helicobacter pylori infections

  • Saccharomyces boulardii
  • Saccharomyces cerevisiae

All

Helps to reduce the risk of antibiotic-associated diarrhoea

References: Canani et al. 2007, Bergonzelli et al. 2006, Kotowska et al. 2005, Can et al. 2006, Cruchet et al. 2003, Pantoflickova et al. 2003, Cremonini et al. 2002, Armuzzi et al. 2001, Felley et al. 2001, Guandalini et al. 2000, Vanderhoof et al. 1999, Guarino et al. 1997, McFarland et al. 1995, Surawicz et al. 1989.

Dose(s)

Subpopulation(s)

Children 1 to 11 years, Adolescents 12 to 17 years and Adults 18 years and older (Gill and Prasad 2008; Lenoir-Wijnkoop et al. 2007; Hawrelak 2006; Picard et al. 2005; Reid et al. 2003).

Quantity(ies)

Method of preparation: Live

Medicinal ingredients from Tables 1 and 3

1.0 x 107 total Colony Forming Units (CFU) or more, per day (Gill and Prasad 2008; Lenoir-Wijnkoop et al. 2007; Hawrelak 2006; Picard et al. 2005; Reid et al. 2003).

Note
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.

Table 5. Medicinal ingredients from Table 2

Medicinal Ingredients Strains Uses or Purposes Doses (CFU/day)
Minimum Maximum

Lacticaseibacillus rhamnosus

GG

Management of acute infectious diarrhoea

6.0 x 109

1.2 x 1010

Management/risk reduction of antibiotic-associated diarrhoea

1.0 x 1010

2.0 x 1010

All

All other uses1

1.0 x 107

N/A

Lactobacillus johnsonii

  • La1
  • Lj1
  • NCC 533

H. pylori infections

1.25 x 108

3.6 x 109

All

All other uses1

1.0 x 107

N/A

  • Saccharomyces boulardii
  • Saccharomyces cerevisiae

All

Risk reduction of antibiotic- associated diarrhoea

1.0 x 1010

3.0 x 1010

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.

References: Gill and Prasad 2008, Canani et al. 2007, Lenoir-Wijnkoop et al. 2007, Bergonzelli et al. 2006, Hawrelak 2006, Can et al. 2006, Picard et al. 2005, Pantoflickova et al. 2003, Reid et al. 2003, Cremonini et al. 2002, Armuzzi et al. 2001, Felley et al. 2001, Vanderhoof 1999, Guarino et al. 1997, McFarland et al. 1995.

Notes

Direction(s) for use

All medicinal ingredients found in Tables 1 and 2 except Saccharomyces cerevisiae and S. boulardii

Take at least 2-3 hours before or after antibiotics (NIH 2011; APhA 2006; Biradar et al. 2005).

All medicinal ingredients found in Table 3

Take at least 2-3 hours before or after taking antifungal medications (NIH 2011; APhA 2006; Biradar et al. 2005).

Duration(s) of Use

No statement required.

Risk Information

Caution(s) and warning(s)

Contraindication(s)

Do not use this product if you have an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment) (APhA 2006; Cukovic-Cavka et al. 2006; Ledoux et al. 2006; Riquelme et al. 2003; Lherm et al. 2002).

Known adverse reaction(s)

No statement required.

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

Note
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 non-medicinal ingredients.

Storage conditions

Liquid products

Store in refrigerator in a tightly closed, light-resistant container.

Note
This requirement does not apply to shelf-stable liquid dosage form preparations (i.e. oil suspensions and emulsions indicated in the Compendium of Monographs Guidance Document).

Non-liquid products (optional)

Store in refrigerator in a tightly closed container (Liu 2009; Juarez Thomas 2004; Shillinger 1999).

Specifications

The medicinal ingredients must comply with the requirements outlined in the NHPID and the following requirements are expected to be met by each live microorganism attesting to this monograph:

Regarding risk information:

The finished product specifications must be established in accordance with the requirements described in the Natural and Non-prescription Health Products Directorate (NNHPD) Quality of Natural Health Products Guide. In the case of live microorganisms, this includes the following:

Note
Information on the manufacturing process, including but not limited to the above, must be maintained by the applicant or the manufacturer and provided to Health Canada upon request.

References Cited

References Reviewed

Appendix I

Table 6. Excluded live microorganisms from this monograph
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