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‘Probiotic’ on food labels in Europe: Spain adopts a pioneering initiative

By Silvia Bañares, PhD in commercial law, attorney Barcelona Bar Association, Spain; and Miguel Gueimonde, Departamento de Microbiología y Bioquímica de Productos Lácteos, IPLA-CSIC, Villaviciosa, Asturias, Spain. 

The word ‘probiotic’ has been absent from food products in most countries in Europe for years. Authorities there concluded that the word is an implied health claim, which is a reasonable position based on the probiotic definition: live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The argument proceeds: since there are no health claims approved for probiotics by the European Union, the word is not allowed on food labels. However, the logic fails since in 2010 ESFA actually did approve a health claim for probiotics – although they didn’t use the term ‘probiotic’. This claim was for yogurt cultures improving lactose digestion. But nonetheless, restrictions on using the word ‘probiotic’ have endured.

Recently, akin to positions taken by Italy (here and here) and ostensibly the Czech Republic (as stated here), Spanish authorities have determined that the term ‘probiotic’ may be used.

In October 2020 the Spanish Health Authority (AESAN) delivered a new decision related to the use of the term “probiotic” in foodstuffs. According to it:

“until  a uniform criterion is generated on the part of the Member States of the European Union, it is considered that it could be accepted that the term probiotic/s  on the label of foodstuffs, both of national manufacturing as well as from other countries of the European Union. In all cases, these products must meet the safety requirements. However, it should be noted that the use of this term cannot be accompanied by any health claim, unless expressly authorized under the Regulation of the European Union  -Regulation EC 1924/2006[1], [2]

This new decision completely differs from the previous one (February 2020), which forbade the use of “probiotic/s” term in food products. Surprisingly, both documents are extremely similar in their reasoning.

However, the new Guidance contains some points that might be relevant for the future:

  • First, there is a clear statement related to the EU Commission Guidance of 2007 [3]; such Guidance had always been invoked as the rationale in order to forbid the term probiotic in foodstuffs, since according to it, the reference to “probiotic/s implies a health benefit”[4]. But the AESAN communication points out for first time that such Guidance is not binding since it has no legal force.
  • Secondly it recognizes the lack of harmonization at the EU level regarding the “probiotic” term:

 “From the discussions that have been held within the European Commission’s group of experts on nutritional and health claims, it is found that there are different interpretations by State Members regarding the use of the term “probiotic”, which, in turn, implies a non-harmonized situation in the European Union market”[5].

  • Third, there is a clear reference to mutual recognition principle; that is to say, any product legally marketed and sold in any EU country might be, in its turn, marketed in any other European Union Member State. For instance, any foodstuff labelled as “probiotic” in Italy might be legally sold in Spain as far as it fulfils the aforementioned criterion in its country of origin. The AESAN communication recognized such fact, pointing out that:

“In this sense, infant formulas and follow-on formulas are marketed which, as a voluntary added ingredient, contain different live microorganisms. The presence of these live microorganisms is indicated on the product label in the ingredient list. In the field of food supplements, it has been found that there are a large number of food supplements on the market, which include the term “probiotic/s”. These products come from different EU countries, where they are allowed to be marketed under this name and, therefore, they could not be prevented from being marketed in Spain, in application of the “principle of mutual recognition” established in the European Union Treaty”[6].

This statement is clearly aligned with Regulation EU 2019/515 [7] (related to mutual recognition principle) and a recent Commission Regulation (Implementing Regulation 2020/1668), which develops the previous one [8]. According to these dispositions, any competent authority suspending market access should notify the legitimate public interest grounds for such suspension. Therefore, Spain would find quite difficult to reject a foodstuff labelled as “probiotic” in another EU country when it is legally sold as such. Hence, it can be said that Spain has adopted a pioneering initiative that maybe could be followed by other EU Member States.

Italy and the Czech Republic have allowed use of the term ‘probiotic’ on foods – perhaps simply because they considered it to be the right thing to do – but they did not make the convincing legal argument made by Spanish authorities. The rationale presented by Spain could likely be easily adopted by other EU countries as well. Perhaps the Spanish initiative will motivate the EU Commission and EFSA to reach a consensus about this word.

Two decades ago, with a rapidly growing list of probiotic-containing products reaching the market worldwide, there was increasing concern by consumers about how to distinguish among the different probiotic strains available and how to know which products have evidence for different health benefits. This, together with the interest of scientist and industry for clear rules and fair competence, prompted the EU Commission to regulate the area and the Regulation EC n° 1924/2006 on nutrition and health claims made on foods was developed. In its preamble this Regulation states, “to ensure a high level of protection for consumers and to facilitate their choice, products put on the market must be safe and adequately labelled” and recognises that  “general principles applicable to all claims made on foods should be established in order to ensure a high level of consumer protection, give the consumer the necessary information to make choices in full knowledge of the facts, as well as creating equal conditions of competition for the food”.  Therefore, consumer protection and facilitating informed purchase choices was in the forefront of the Regulation, in an attempt to satisfy the concerns and demands that consumers had leveraged.

Subsequent interpretation of the Regulation EC n° 1924/2006 led to the conclusion that the term “probiotic” was a health claim and, as a consequence, should not be used in product labelling. Different countries, such as Italy or the Czech Republic, reacted to this by developing national regulations allowing the probiotic food labelling. Now Spain, on the basis of mutual recognition principle, accepts its use as well.

However, this new situation makes relevant again the challenges that consumers had identified two decades ago:  how to differentiate among the different available probiotic products and make an informed, purposeful purchase. This unsolved issue should now be addressed. In this context, we advocate for the development of easy-to-use guidelines targeted to regular consumers, not to clinicians or scientists, to provide consumers with the necessary tools to make their choice.

Related article: Spanish agency approves use of term ‘probiotic’ on food and supplements

References:

[1] https://www.aesan.gob.es/AECOSAN/web/seguridad_alimentaria/subdetalle/probioticos.htm

[2] Translation by the authors

[3] https://ec.europa.eu/food/sites/food/files/safety/docs/labelling_nutrition_claim_reg-2006-124_guidance_en.pdf

[4] Guidance on the implementation of Regulation n° 1924/2006 on nutrition and health claims made on foods conclusions of the Standing Committee on the Food Chain and Animal Health /14/12/2007

[5] Translation by the authors

[6] Translation by the authors

[7] Commission Implementing Regulation (EU) 2020/1668 of 10 November 2020 specifying the details and functionalities of the information and communication system to be used for the purposes of Regulation (EU) 2019/515 of the European Parliament and of the Council on the mutual recognition of goods lawfully marketed in another Member State.

[8] Regulation (EU) 2019/515 of the European Parliament and of the Council of 19 march 2019 on the mutual recognition of goods lawfully marketed in another Member State and repealing regulation (EC) nº 764/2008

EFSA’s QPS committee issues latest updates

By Bruno Pot, PhD, Vrije Universiteit Brussel and Mary Ellen Sanders, PhD, Executive Science Officer, ISAPP

On July 2nd, the European Food Safety Authority (EFSA) published the 12th update of the qualified presumption of safety (QPS) list, a list of safe biological agents, recommended for intentional addition to food or feed, covering notifications from October 2019-March 2020. It was good news to all stakeholders to see that EFSA discussed the recent taxonomic changes within the genus Lactobacillus (see ISAPP blog here) as well as addressed some microbes being considered as potential, novel probiotics.

What is QPS?

In 2005 EFSA established a generic approach to the safety assessment of microorganisms used in food and feed, prepared by a working group of the former Scientific Committee on Animal Nutrition, the Scientific Committee on Food and the Scientific Committee on Plants of the European Commission. This group introduced the concept of “Qualified Presumption of Safety” (QPS), which described the general safety profile of selected microorganisms. The QPS process was mainly developed to provide a generic pre‐evaluation procedure harmonized across the EU to support safety risk assessments of biological agents performed by EFSA’s scientific panels and units. A QPS assessment is performed by EFSA following a market authorisation request of a regulated product requiring a safety assessment. Importantly, in the QPS concept, a safety assessment of a defined taxonomic unit is performed independently of the legal framework under which the application is made in the course of an authorisation process.

QPS status is granted to a taxonomic unit (most commonly a species), based on reasonable evidence. A microorganism must meet the following four criteria:

1.       Its taxonomic identity must be well defined.

2.       The available body of knowledge must be sufficient to establish its safety.

3.       The lack of pathogenic properties must be established and substantiated (safety).

4.       Its intended use must be clearly described.

Any safety issues, noted as ‘qualifications’, that are identified for a species assessed under QPS must be addressed at the strain or product level. Microorganisms that are not well defined, for which some safety concerns are identified or for which it is not possible to conclude whether they pose a safety concern to humans, animals or the environment, are not considered suitable for QPS status and must undergo a full safety assessment. One generic qualification for all QPS bacterial taxonomic units is the need to establish the absence of acquired genes conferring resistance to clinically relevant antimicrobials (EFSA, 2008).

If an assessment concludes that a species does not raise safety concerns, it is granted “QPS status”. Once EFSA grants a microorganism QPS status, it is included on the “QPS list” and no microorganism belonging to that group needs to undergo a full safety assessment in the European Union.

The QPS list is re‐evaluated every 6 months by the EFSA Panel on Biological Hazards based on three “Terms of Reference” (ToR)*. This evaluation is based on an extensive literature survey covering the four criteria mentioned above.

What happened to the genus Lactobacillus?

In April 2020, based on a polyphasic approach involving whole genome sequencing of more than 260 species of the former genus Lactobacillus, the genus was reclassified into 25 genera including the emended genus Lactobacillus, which includes host-adapted organisms that have been referred to as the L. delbrueckii group, the earlier described genus Paralactobacillus as well as 23 novel genera, named Acetilactobacillus, Agrilactobacillus, Amylolactobacillus, Apilactobacillus, Bombilactobacillus, Companilactobacillus, Dellaglioa, Fructilactobacillus, Furfurilactobacillus, Holzapfelia, Lacticaseibacillus, Lactiplantibacillus, Lapidilactobacillus, Latilactobacillus, Lentilactobacillus, Levilactobacillus, Ligilactobacillus, Limosilactobacillus, Liquorilactobacillus, Loigolactobacilus, Paucilactobacillus, Schleiferilactobacillus, and Secundilactobacillus. Read more in the original paper here or on the ISAPP blog here).

These name changes could have considerable economic, scientific and regulatory consequences, as discussed during an expert workshop organised by the Lactic Acid Bacteria Industrial Platform (LABIP). One of the points discussed during this workshop was the possible implication of the name change on the QPS list in Europe and the FDA’s GRAS list in the USA.

What did EFSA do?

In a 42-page document, which can be found here, amongst others, the species of the former genus Lactobacillus that were already listed on the QPS list, have been formally renamed at the genus level. The species names remained the same, as the taxonomic revision from April 2020 only affected the genus name. As a result, the genus names of 37 former Lactobacillus species on the QPS were updated, and now span 13 different genera. Table 1 delineates these nomenclature updates.

Table 1: Taxonomic revision of the 37 species formerly of the Lactobacillus genus present on the QPS list (published here).

Earlier denomination                                                      Updated denomination
Lactobacillus acidophilus                     Lactobacillus acidophilus
Lactobacillus alimentarius Companilactobacillus alimentarius
Lactobacillus amylolyticus Lactobacillus amylolyticus
Lactobacillus amylovorus Lactobacillus amylovorous
Lactobacillus animalis Ligilactobacillus animalis
Lactobacillus aviarius Ligilactobacillus aviarius
Lactobacillus brevis Levilactobacillus brevis
Lactobacillus buchneri Lentilactobacillus buchneri
Lactobacillus casei Lacticaseibacillus casei
Lactobacillus collinoides Secundilactobacillus collinoides
Lactobacillus coryniformis Loigolactobacillus coryniformis
Lactobacillus crispatus Lactobacillus crispatus
Lactobacillus curvatus Latilactobacillus curvatus
Lactobacillus delbrueckii Lactobacillus delbrueckii
Lactobacillus dextrinicus Lapidilactobacillus dextrinicus
Lactobacillus diolivorans Lentilactobacillus dioliovorans
Lactobacillus farciminis Companilactobacillus farciminis
Lactobacillus fermentum Limosilactobacillus fermentum
Lactobacillus gallinarum Lactobacillus gallinarum
Lactobacillus gasseri Lactobacillus gasseri
Lactobacillus helveticus Lactobacillus helveticus
Lactobacillus hilgardii Lentilactobacillus hilgardii
Lactobacillus johnsonii Lactobacillus johnsonii
Lactobacillus kefiranofaciens Lactobacillus kefiranofaciens
Lactobacillus kefiri Lentilactobacillus kefiri
Lactobacillus mucosae Limosilactobacillus mucosae
Lactobacillus panis Limosilactobacillus panis
Lactobacillus paracasei Lacticaseibacillus paracasei
Lactobacillus paraplantarum Lactiplantibacillus paraplantarum
Lactobacillus pentosus Lactiplantibacillus pentosus
Lactobacillus plantarum Lactiplantibacillus plantarum
Lactobacillus pontis Limosilactobacillus pontis
Lactobacillus reuteri Limosilactobacillus reuteri
Lactobacillus rhamnosus Lacticaseibacillus rhamnosus
Lactobacillus sakei Latilactobacillus sakei
Lactobacillus salivarius Ligilactobacillus salivarius
Lactobacillus sanfranciscensis Fructilactobacillus sanfranciscensis

EFSA further specifies that “To maintain continuity within the QPS list, all the strains belonging to a previous designed Lactobacillus species will be transferred to the new species. Both the previous and new names will be retained”. (Emphasis added.)

Impact of the QPS update on the probiotic field

The probiotic field can also take note of this current update for its review of two ‘next generation’ probiotic species evaluated for possible QPS status, Akkermansia muciniphila and Clostridium butyricumAkkermansia muciniphila has been actively researched as a probiotic to help manage metabolic syndrome (Depommier et al. 2019). A probiotic preparation containing both Akkermansia muciniphila and Clostridium butyricum has been studied in a randomized controlled trial for postprandial glucose control in subjects with type 2 diabetes (Perraudeau et al 2020). The committee’s decisions:

  • Akkermansia muciniphila is not recommended for QPS status due to safety concerns;
  • Clostridium butyricum is not recommended for QPS status because some strains contain pathogenicity factors; this species is excluded for further QPS evaluation.

The publication of the next scientific opinion updating the QPS list is planned for December 2020, based on the 6-month assessments carried out by the BIOHAZ Panel.

Conclusion

Due to its scientific rigor and continuous updates, the EFSA QPS efforts provide useful perspective for the global scientific community on safety of candidate microbes for use in foods. Their embrace of the new taxonomic status of lactobacilli signals to other stakeholders that it is time to start the process of doing the same. Further, their assessment of species being proposed and studies as ‘next generation’ probiotics is an important reminder that a microbe’s status as a human commensal is not a guarantee of its safety for use in foods.

 

*QPS Terms of Reference (ToR) (quoted from here):

ToR 1: Keep updated the list of biological agents being notified in the context of a technical dossier to EFSA Units such as Feed, Pesticides, Food Ingredients and Packaging (FIP) and Nutrition, for intentional use directly or as sources of food and feed additives, food enzymes and plant protection products for safety assessment.

ToR 2: Review taxonomic units previously recommended for the QPS list and their qualifications when new information has become available. The latter is based on a review of the updated literature aiming at verifying if any new safety concern has arisen that could require the removal of the taxonomic unit from the list, and to verify if the qualifications still efficiently exclude safety concerns.

ToR 3: (Re)assess the suitability of new taxonomic units notified to EFSA for their inclusion in the QPS list. These microbiological agents are notified to EFSA and requested by the Feed Unit, the FIP Unit, the Nutrition Unit or by the Pesticides Unit.

 

Probiotics in fridge

The FDA’s view on the term probiotics, part 2: Further down the rabbit hole

By James Heimbach, Ph.D., F.A.C.N., JHEIMBACH LLC, Port Royal, VA

A number of weeks ago I wrote on the ISAPP blog about US Food and Drug Administration (FDA) declining to file Generally Regarded As Safe (GRAS) notices that described the subject microorganism as a “probiotic” or “probiotic bacterium” (see The FDA’s view on the term “probiotics”). Now the FDA’s response to such GRAS notices has developed additional ramifications. Let me put them into two categories: Class 1 misdemeanors that will cause FDA to reject the notice, and Class 2 misdemeanors that will probably not prevent filing, but will cause FDA to raise questions. I should note that these thoughts are based on both my own direct experiences and my repeated telephone conference calls with FDA.

Class 1 Misdemeanors

  1. Using the term probiotic in any way in describing or characterizing the subject microorganism or its past, present, or intended use.
  2. Extended discussion of benefits derived from ingestion of the microorganism in animal or human research.
  3. Any mention, however brief, of the potential for the microorganism to be used in dietary supplements.

Class 2 Misdemeanors

  1. Including brief mentions of the microorganism serving as a probiotic. E.g., if you cite a study of the microorganism that you might previously have reported as “a study of the probiotic benefits” of the microorganism, change it to simply “a study of the benefits” of the microorganism. This same caution is advised when reporting opinions from the European Food Safety Authority (EFSA) or other authoritative bodies.
  2. Using the word “dose” in describing intended use. Also see #4 below.
  3. Virtually any use of the term “dietary supplement,” including in reporting past, current, or intended uses of the strain or the species in Europe or elsewhere, by anyone.
  4. Even relatively brief mentions of benefits. The recommended way of handling reporting of human studies of the species or strain is to avoid any narrative at all. Simply summarize the studies in tabular form, listing the citation, study design (RCT, open-label, etc.) and objective, study population (number, sex, age, characterization such as IBS patients, malnourished children, preterm infants), test article (microorganism binomial and strain), dose (but call it “administration level”—“dose” can be seen as indicating a drug or dietary supplement), duration, and safety-related results. Include methods used to ensure that any adverse events or severe adverse events would have been reported—medical examinations, self-report questionnaires, parental questionnaires, biochemical measures, etc.—and at what time points during or after the in-life portion of the research. Avoid ANY discussion of improvements seen in the test group.

Good luck!

Challenges ahead in the probiotic field – insights from Probiota2019

By Dr. Mariya Petrova, Microbiome insights and Probiotics Consultancy (MiP Consultancy), Bulgaria.

Recently, I attended the Probiota Conference, which brings together representatives from industry and academia on the topic of probiotics and related fields. The goal of many of the speakers at the conference was to provide insight about how to translate scientific discoveries for, and share commercial insights with, end consumers. I would like to share a few points that caught my attention.

Do good science. End-consumers rely on news coverage of science, which unfortunately is too often more sensationalist than accurate. Prof. Gregor Reid’s talk, “Disentangling facts from fake news,” noted that news article titles such as “Probiotics labeled ‘quite useless’” and “Probiotics ‘not as beneficial for gut health as previously thought’” – after research was published last year in Cell (here and here) – were misleading to end-users and of great concern to people in the field of probiotics who are familiar with the totality of the data. Researchers have a responsibility to situate their results in the context of existing evidence. However, Prof. Reid also observed that “too many products are called probiotics with strains not tested in humans”; “too many products are making un-verified claims”; “too many journalist don’t have expertise in science”; “too many rodent studies making association with human health”; “researchers making up their own terms without defining them”. So how do we solve this? Do good science and communicate results clearly, accurately and without bias – to journalists, to peers and to end-users. (See related ISAPP blogs here and here).

Understand the probiotic mode of action. Understanding probiotic modes of action may be the most challenging issues ahead of us. Currently, we have too little understanding of mechanisms by which probiotics provide health benefits. Probiotic strains are living microorganisms, which most likely work through multiple mechanisms and molecules, but we indeed need more in-depth research. When I reflect on my own experience and the struggles to do molecular studies, I can appreciate how difficult this research is. Although others may be focused on screening the microbiome and developing bioinformatics tools, I applaud the researchers trying to develop deeper understandings of how probiotics function, which will enable more rational approaches to probiotic selection and use. (See related ISAPP blog here.)

New names, new glory. The forthcoming reclassification of the Lactobacillus genus was discussed. We are faced with the largest taxonomic upheaval of this genus in history, including many economically important species. The current Lactobacillus genus will be split into at least ten genera. The species and strain names will not change, but many species will have different genus names. Researchers are expected to propose that all new genera names will begin with the letter “L.” The reclassification can help us better understand the mode of action of industrially important probiotics and help tailor probiotic applications. The changes will be communicated with regulatory bodies such as EFSA and FDA. Name changes could also have consequences for medical stakeholders and may lead to potential issues with intellectual properties. Consumers of probiotic products will likely be less affected by this change, but an educational website targeted to consumers could be beneficial. (See related ISAPP blog here.)

EFSA claims as expected. EFSA claims and regulations were also discussed. To date, approximately 400 health claims applications have been submitted to EFSA without any approved. Experts advised to keep the claims simple and easy. EFSA’s strict approach to claims may have the advantage of compelling industry to conduct studies that better support health claims. Responsible companies are adapting to regulatory requirements and are developing good products, and they will probably succeed in meeting claim standards. Nevertheless, it seems that although health claims are deemed important to companies and medical representatives, end-users of probiotics obtain information from other sources. Obtaining health claims is only one piece of the puzzle. Also important is providing science-based information to end-users, especially those keen on keeping their good health through nutrition.

Be transparent. Don’t forget to disclose the strains you use on product labels. Strains designation is one key way to distinguish your product and it is an important way to communicate to your consumer exactly what is in your product. Surprisingly still, some scientific papers fail to report the strains they used to perform their clinical trials. The field is moving towards more transparency with high-quality clinical trials, the best-selected strains for certain condition and clear designation of the probiotic strain on the label. (See related ISAPP infographics here, here and here)

Educate, educate and again educate. Often discussed at the conference was the subject of educating the end consumers. Companies should take a proactive approach to engage consumers and promote understanding of the available evidence where probiotics can promote health. It is difficult for consumers to differentiate science-based evidence from journalistic sensationalism or researcher self-aggrandizement. A major obstacle is also the ready availability in the marketplace of unproven products containing strains that have been tested only in animal models or not proven experimentally at all. Taking the need for reliable communications on probiotics and probiotics to end-users very seriously, ISAPP has developed a range of science-based videos and infographics. The infographics include topics such as how to read the labels of the probiotics products (USA and EU versions) and a probiotic checklist. Thanks to the enthusiastic work of many volunteers, some ISAPP infographics can now be found in 10 different languages.

Despite having great discussions, one thing keeps troubling my mind: Where is the field of probiotics going and how will it look like in 10 or 20 years? The fight for probiotics is not over, despite the progress we have made so far.