Evaluation of probiotics to be used in foods

Brazilian Health Regulatory Agency (Anvisa)

IPA World Congress + Probiota AmericasJune 24 – 26 2019

Vancouver, Canada

Introduction

2002

RDC nº 2/2002 - Resolution onprobiotics and bioactivessubstances

- General Requirements.

- Lack of more specific criteria thatshould be provided to guide thesafety and benefit assessment ofprobiotics.

2018

Resolution on probiotics for use infoods (RDC nº 241/2018)

- The requirements for the proof ofsafety and health benefits of probioticsfor food use are more detailed.

- Convergence with internationalregulations.

2019

Guidelines nº 21/2019 – Guidelinesfor the Processual Instruction of atechnical-scientific dossier forProbiotics in Foods

Indicate the information anddocumentation to be provided aswell as a methodological approachto prove the safety and benefit ofprobiotics, with regard to therequirements established by RDCnº 241/2018.

Alternative approaches arepossible, provided that the legalrequirements are observed.

The use of probiotics in foods requires prior approval from Anvisa

Identity

• The adequate classification,identification and nomenclature ofthe microorganisms is of criticalimportance in the assessment oftheir safety and benefits, beingprimordial elements of thetechnical-scientific dossier.

Safety

• In order to ensure the safety, thedossier should be composed by theidentification of the risk group orclass, history of use, literaturereview, in vitro tests, animal tests,human clinical trials, post-marketsurveillance (if available).

• In silico analysis may be carried outto complement the safetyassessment.

Benefit

• The beneficial effect of a probioticmust be necessarily translated to ageneral or specific functional orhealth claim, related to the provedbenefit for the strain.

• Scientific substantiation of any claimshould be based on the totality andlevel of the evidence.

• Medicinal and therapeutic effectsare prohibited.

Requirements for the Proof of Safety and Health Benefits of Probiotics

for food use

Functional Claim

Generic Claim

• The benefit is related to a general function of the probiotic in some system of the organism.

• Ex.: Contributes to the health of the gastrointestinal tract.

Specific Claim

Benefit: Functional and Health claims

• The benefit is related to a specific physiological or metabolic role in the organism.

• Ex.: Contributes to reduce the time of intestinal transit.

Health Claim

Specific Claim

• Related to the reduction of risk disease or to a healthcondition.

• Ex.: Reduces the risk of urinary tract infection.

Benefit: Specific Health Claims

The type and wording of the claim should be proposed after completion ofthe search and analysis of the studies, based on the outcome of the qualityassessment and the strength of the evidence.

Proof of Benefit

I – Characterization of the probiotic strain: demonstrate that the strain resists the passage through themain chemical and biological barriers of the body and reaches the intestine in living form;

II – Studies for the proof of the benefit (type of studies; criteria for selecting the studies);

III – Totality of the evidence: comprehensive literature search should consider evidence to support thebenefit; evidence that contradicts the benefit; and that is ambiguous or unclear;

IV – Assessment of the methodological quality of each study: Internationally validated methodologies,updated and adapted to facilitate their application;

V – Assessment of the level of the totality of the evidence (consistency and strenght of association);

VI – Conclusion on Scientific Substantiation of functional or health claims (general or specific).

Studies for the proof of the benefit

Essential Requirement: Well-designed human intervention studies.

Types of Studies:- Accepted:• Systematic Reviews and Meta-analysis;• Randomized Clinical Trials;• Cohort prospective studies: Mandatory for health claims.

- Not accepted:• Retrospective studies (case-control, retrospective cohort studies), transversal and

descriptive studies.

Guidelines nº 21/2019

Totality of the Evidence

Comprehensive Literature Search

- Mandatory database: Pubmed

- Complementary database (+1):• EMBASE• BIREME• COCHRANE• LILACS

- The search strategy should be syntheticallydescribed in the technical-scientific dossier.

- The quantitative information of theselection process of the studies should beincluded.

Guidelines nº 21/2019

Level of the totality of the evidence

- The proposed methodology for the assessmentof the level of the evidence considers:

• Totality of the evidence;• Methodological quality of the studies;• Consistency and strengh of the association.

Guidelines nº 21/2019

Conclusion of the Technical-Scientific Dossier

- A conclusion of the level of the evidence should be presented, based on the claimed effect, consideringtwo domains (consistency and strength of the association).

General Functional Claim Specific Functional Claim Health Claim

Consistency

Strengh ofthe

association

Consistency related to decreased riskmust be high in order to prove thebenefit.

Regulation

Guidelines nº 21/2019 – Guidelines for theProcessual Instruction of a technical-scientificdossier for Probiotics in Foods

The Guide is already in force, but it is open tocontributions until March 26, 2020.Contributions should be sent by filling in theelectronic form:https://pesquisa.anvisa.gov.br/index.php/355846?lang=pt-BR.

Resolution RDC nº 241/2018 –Requirements for the Proof of Safety andHealth Benefits of Probiotics for food use

The Resolution is already in force.

Thank you!

Brazilian Health Regulatory Agency - Anvisa

SIA Trecho 5 - Área especial 57 - Lote 200

CEP: 71205-050

Brasília - DF

Phone: +55 61 3462 6000

www.anvisa.gov.br

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Anvisa Atende: 0800-642-9782

ouvidoria@anvisa.gov.br