Assessment of the safety of “probiotics” in food supplements
Authors: O'Connell Motherway Mary , O'Connor Lisa , Smith Shaun , Bolton Declan , Cormican Martin , De Waal Theo , Gutierrez Montserrat , Part Ms Ann Marie , Walsh Fiona , Duffy Geraldine 
Published: November 2024

Executive summary
Food supplements are defined in European Union (EU) food law (Directive 2002/46/EC, S.I. No. 506 of 2007) as “foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form, namely forms such as capsules, pastilles, tablets, pills and other similar forms, sachets of powder, ampoules of liquids, drop dispensing bottles, and other similar forms of liquids and powders designed to be taken in measured small unit quantities”. Directive 2002/46/EC provides for the setting of maximum safe levels of vitamins and minerals in food supplements. Other substances, including live microbes (“probiotics”) and their products, can be included in food supplements provided they are safe (Regulation (EC) No 178/2002, S.I. No. 747 of 2007). In the absence of EU guidance, the Food Safety Authority of Ireland (FSAI) through this document will provide guidance to food supplement producers and food business operators (FBOs) on assessing the safety of “probiotics” used in food supplements in Ireland.
To facilitate efficient monitoring of food supplements, Directive 2002/46/EC allows EU Member States (MS) to require the food supplement producer, or the person placing a food supplement product on the market, to notify the competent authority for that country. Ireland requires this notification. In Ireland, notification is not an approval or authorisation procedure. A notification is made by completing an online notification form, which includes submitting a copy of the product label to the FSAI.
The most widely used “probiotics” in food supplements are strains of lactic acid bacteria (LAB), bifidobacteria, Bacillus sporogenes and the yeast Saccharomyces boulardii. The potential risks from consuming “probiotics” in food include infection, ill effects from microbial toxins produced by the microbial strains or contaminants, transmission of antimicrobial resistance and immunological effects. Reported adverse events resulting from consuming “probiotics” are few. Where opportunistic infections associated with “probiotics” in foods or food supplements are reported, they are usually in people at increased risk of infection where various underlying factors such as damage to the skin or mucous membranes, indwelling medical devices, alterations to the gut microbiome or impaired immune response may enable infection by organisms that are rarely or never associated with infection in otherwise healthy people.
The European Food Safety Authority (EFSA) introduced the concept of Qualified Presumption of Safety (QPS) to standardise its own safety evaluation of microorganisms used in “regulated products” (i.e. feed additive, food additive, food flavourings, food enzymes, novel foods and plant protection products). The QPS assessment is conducted separately from and independently of the safety assessment of a regulated product submitted for market authorisation. Therefore, having QPS status does not guarantee market authorisation. The first list of biological agents with QPS status was established in 2007. The QPS list is described at the species level for bacteria and yeasts, and at family level for viruses. EFSA performs an extensive literature search and then updates the QPS list every 6 months. In addition, the EFSA Panel on Biological Hazards (BIOHAZ panel) publishes a Scientific Opinion on the updated QPS list every 3 years. The FSAI uses the QPS list as a point of reference when assessing the safety of microbes or their by‐products in foods.
In 2018, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) published “Guidance on the characterisation of microorganisms used as feed additives or as production organisms”. There is currently no EU guidance on the criteria to be used for the safety assessment of “probiotics” in food supplements, or the evidence a food supplement producer should use to assess the safety of “probiotics” in food supplements.
This Scientific Committee report addresses two questions and makes the following recommendations:

Question 1. What is the committee's view on the most appropriate safety criteria to use when assessing the safety of “probiotics” in food supplements?

The Committee considers the most appropriate safety criteria to be that:

There is long experience of use of the organism(s) in food or food supplements without substantiated report of harm in otherwise healthy people.
Credible reports of infection or intoxication associated with the organism are isolated or rare and limited to those people at highest risk of infection.
The organism(s) is readily identifiable to at least species level.
There is an antimicrobial agent available for treatment of infection with the organism(s).
The organism(s) has no known association with environmental harm.
If the organism(s) was not used in food in the EU prior to 15 May 1997, its use has been authorised under the novel food Regulation (EU) 2015/2283.
If the organism(s) was genetically modified, it has been authorised under Regulation (EC) No 1829/2003 on genetically modified food and feed, and under Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms.
The organism(s) has been rigorously characterised as follows:

The definition of species and strain level is adequate to facilitate comparison in the event of suspected link to human infection.
There is evidence of the absence of properties associated with an increased potential to cause infection.
There is evidence of the absence of acquired (transferable) antimicrobial resistance genes.
There is evidence of the absence of a capacity for biogenic amine production.

Question 2. What evidence should a food supplement producer use to demonstrate the safety of “probiotics” when producing a food supplement?

The Committee considers that a food supplement producer should be able to demonstrate that:

The organism(s) used meets the criteria set out above.
The culture has been deposited in a recognised and accessible culture collection if not obtained from a culture collection.
If cultures are stored, they are stored at ‐80 °C to ensure that they remain stable in storage.
If cultures are propagated, the characterisation of the organism should be repeated at defined intervals to ensure that the organism has not significantly altered or been inadvertently displaced by, or contaminated with, another organism.
The production process does not result in substantial change to the properties of the microorganism(s) between start of production and the end product.
The production systems have adequate quality management systems to ensure consistent properties of the organism(s) in the final product.

In addition, the Scientific Committee made the following recommendations:

Food supplement producers should document the food safety management system adopted to ensure consistent safe manufacture of the food supplement.
The individual microbial strains used should be stored and accessible (either from the food supplement producer or from a culture collection) in the event of a suspected link to human infection.
In line with the requirements of the Regulation on the provision of food information to consumers (Regulation (EU) No. 1169/2011), accurate information should be provided to the consumer on the label. It is recommended that this information includes the type and number of organisms present as well as appropriate storage advice. In addition, the viability of the organism(s) throughout the shelf life of the product should be determined to ensure that the information on the product label is accurate throughout the shelf life. Furthermore, where it is known that there are groups of people for whom the strain or strains used may not be suitable, this should be indicated on the label.
If an Enterococcus faecium strain is included as a “probiotic” in a food supplement, the label should clearly indicate the presence of Enterococcus faecium in the food supplement.