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“European Union Risk Evaluation Process on Safety of Chemical Additives used in Animal Nutrition”

PROFESSOR – EU Risk ExpertSulhattin Yasar : sulhattinyasar@sdu.edu.tr

Süleyman Demirel University Isparta Turkey 2005-2010 Formerly worked for EC JRC

IRRM Geel Bellgium

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ContentContent EUROPEAN UNION – LAW, SAFETY RISKS

FOOD AND FEED SAFETY REGULATIONS

Feed Additives (FA)

◦ Regulations, Directives, Guidelines – authorisation

◦ Safety Evaluation

◦ Who does what?

◦ Summary – Opinion & Authorisation

◦ Method of analysis - Official control of FADs

Chemical Residues

Conclusion

GENERAL FOOD LAW

Regulation (EC)178/2002 ◦laying down the General Principles and requirements

of Food Law covering all stages of food/feed production and distribution..

◦The aim to provide a framework to ensure a coherent approach in the development of food legislation.

◦At the same time, provides the general framework for those areas not covered by specific harmonised rules but where the functioning of the Internal Market is ensured by mutual recognition.

Community Reference Laboratories

ECGeneral

directorate for

health&consumer

EUROPEAN FOODSAFETY

AUTHORITY

EUROPEAN MECIDINES

AGENCY

COMMUNITY PLANT VARIETY OFFICE

EXECUTIVE AGENCYFOR

HEALTH&CONSUMER

Risk EVALUATION

Risk management Policy maker

National Reference Laboratories

Risk management

Elements of Food and Feed Safety

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!!!!!!!!!! Not be marketed - without Not be marketed - without authorisationauthorisation !!!!!!!!

A scientific evaluation needed:

• SHOWING no harmful effects, on human, animal and environment.

FEED ADDITIVE

The General Food Law Regulation (EC) 178/2002

Feed Hygiene Reg. (EC) 183/2005

Feed Additives

Reg. (EC) 1831/2003

Feed materialsReg. (EC) 767/2009

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FEED ADDITIVES

feed and animal products

colour of ornamental fish and birds

nutritional needs of animals

environmental consequences of animal production

animal production, performance or welfare, enhance digestibility, improve gut flora

coccidiostatic or histomonostatic effectArticle 5(3) of 1831/2003

substances, m.o. or prep., other than feed material and premixtures, intentionally added to feed or water

Article 2(a) of 1831/2003

WHAT is FA ?

Legally classified by Cat/Func groups

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FADs? Cont.,FADs? Cont.,(A

nn

ex I

of

1831

/200

3)

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Safety EvalutionSafety Evalution

Risk assessment: Stability -Safety -Efficacy

Risk management: Authorisation

Member States’official laboratory

Application

Technical Dossiers

Method of analysis: Safety

OPINION

Producer

Samples + Fee

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Two types of authorisations

• Regulation 1831/2003, article 6: Categories of feed additives:

a) technological additives: any substance added to feed for a technological purpose;

b) sensory additives: any substance, the addition of which to feed improves or changes the organoleptic properties of the feed, or the visual characteristics of the food derived from animals;

c) nutritional additives;

d) zootechnical additives: any additive used to affect favourably the performance of animals in good health or used to affect favourably the environment;

e) coccidiostats and histomonostats

• Authorisation is granted for an additive without mentioning a producer

• Authorisation is granted for a specific additive produced by the holder of the authorisation, placing a specific product on the market: Holder specific authorisation

Specification in the authorisation regulation

Who does what?Who does what? COM- COM- DG SANCODG SANCO

Applications submitted following the procedures specified in Reg. 1831/2003 and Reg. 429/2008.

Once the application is electronically submitted, send a copy to the functional mailbox SANCO-APPLICATIONS-1831@ec.europa.eu.

◦ Application form in accordance with Annex I of Regulation (EC) No 429/2008 ◦ Public summary; ◦ List of the confidential parts of the dossier

These particulars and documents to be submitted to the Commission are in addition to the information to be submitted to EFSA and the CRL-FA

http://ec.europa.eu/food/food/animalnutrition/feedadditives/guidelines_en.htm

Who does what?Who does what? EFSA EFSA

The FEEDAP Panel, independent scientific board: advising on safety and/or efficacy of FADs

The 21 members expertise covering :

◦ animal physiology, biochemistry, pharmacology,

◦ toxicology, microbiology, (animal) nutrition (including fish),

◦ veterinary sciences,

◦ feed materials and technology,

◦ husbandry, product quality,

◦ ecotoxicology.

http://www.efsa.europa.eu/EFSA/ScientificPanels/efsa_locale-1178620753812_FEEDAP.htm

EFSA is assisted by a Community Reference Laboratory for additives for use in animal nutrition (CRL for Feed Additives).

Regulation (EC) No 1831/2003 on additives for use in animal nutrition nominates the Joint Research Centre (JRC) as the CRL for Feed Additives and its Institute for Reference Materials and Measurements (IRMM) has taken up the task.

Regulation (EC) No 378/2005, as last amended by Regulation (EC) No 885/2009, details the rules for the implementation of Regulation (EC) No 1831/2003 and provides the practical conditions for the duties and tasks of the CRL.

Additional tasks are assigned to the CRL by Regulation (EC) No 882/2004 on official controls performed to ensure the verification of compliance with feed and food law, animal health and animal welfare rules.

In accordance with this regulation, sampling and analysis in the context of official controls are carried out by official laboratories designated by competent authorities in each Member State.

http://irmm.jrc.ec.europa.eu/html/CRLs/crl_feed_additives/index.htm

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EvaluationEvaluation

• 300 Reports from CRL-FA

•450 – 1000 Applications to COMMISSION

•250 Opinions adopted by EFSA

•50 Opinions in progress at EFSA

CURRENT WORK since 2004- summary

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FINAL AUTHORISATIONFINAL AUTHORISATION

http://ec.europa.eu/food/food/animalnutrition/feedadditives/registeradditives_en.htm

Example …..Community RegisterExample …..Community Register

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Example…..Registry Entry

Focus is on the concentration of the active substance in feed, premixtures, feed additive per se, and ITS RESIDUES/metabolites in animal food and tissues.

Feed additives are authorised via a European regulation specifying the conditions of use (register entry)

Target concentrations of the active substance as defined in the register entry are legal limits

The CRL together with the NRLs evaluate methods that are suitable to enforce the legal limit in the frame of the official control purposes

The analytical methods are applied in the frame of official controlImportance of Community/CEN method

OFFICAL CONTROL OF FA

Why we need Why we need analytical methods?analytical methods?

• Official feed laboratories are enabled to enforce conditions of use of the authorised product regarding the content of the active substance in feedingstuffs.

Why we need analytical methods? cont.

• Official feed laboratories are enabled to enforce conditions of use of the authorised product regarding

• …(1) the identification of the additive – if approproate .

• …(2) the determination of impurities – if approproate

• …(3) Maximum Residue Limits (MRLs) - if appropriate.

Undesirable substances/impuritiesUndesirable substances/impurities

• Impurities in additives:

• Limits for lead, cadmium and dioxins are established in Directive 2002/32

Other CRLs have been established for these elements

Undesirable substances: Undesirable substances: ExamplesExamples

Directive 2002/32: Setting legal limits for undesirable substances in feed additives

Legal limits for impurities set in the authorisation regulation of the feed additive

Food and feed control regulation 882/2004

Community methodsCEN methodsRing trial validated methodsSingle laboratory methods

This principle is applied whatever the applicant proposes !!

Not evaluate applicants’ methods, if there is a standard method available

The standard should cover all “analyte/matrix/concentration”-combination

The cascade approach

Examples of Commission and CEN methods

ANALYTE SOURCE STATUS

Vitamin A Regulation 152-2009 Official Methods in force

Amino Acids Regulation 152-2009 Official Methods in force

Trace Element EN 15510 approved

Probiotics CEN standards approved

Not in all cases the active substance and the target analyte are identical

Feed additive, active substance and analyte to measure

Additive Active Substance Legal limits in feed Sel-Plex® 2000, selenized yeast

selenomethionine and other selenocompounds

Total selenium

Mintrex Zn, Cu, Mn

Trace elements chelates of the hydroxy analogue of methionine

Zn or Cu or Mn

The analytical method does not measure the active substance, but an important

“component” – here the elements

The concentration of the target element is influenced by the background level

The legal limit applies, regardless of whether the target element has been introduced via the feed additive or not (specificity)

Active substance – legal limits and target analyte:

EXAMPLEEXAMPLE

The identification of the feed additive when present in feed

Identification important holder specific authorisations (e.g. coccidiostats, ‘zootechnical additives’)

Non-holder authorisations may subject of the specific restrictions

In most cases no analytical methods to show the active substance is added via a feed additive

Identification may be possible when working on the product itself.

Identification of the additive in feed is possible in the case of probiotics

Limitations of the use of analytical methods

Identification

EXAMPLEEXAMPLE

The conditions of use contain:

◦ Limits for residues/metabolities in animal products, food, tissues.

◦ Officially controlled by the official methods

◦ EFSA proposes to set MRLs for the sum of various residues, if no legal limits are proposed/established.

Residues in food

ExampleExample• Maximum Residue Limits (MRLs) - if appropriate.

  Residues of Veterinary Medicinal Products

Animals (cattle, pigs, poultry, fish) treated with medicines

Their residues could remain in tissues and foods (meat, milk, egg)

No hazards to be guaranteed by toxicologic evaluation

If necessary they are banned when the established MRLs are exceeded

 Regulation (EC) No 470/2009 by DG-ENTERPRISE

EMA-european mecidines agency

Opinions and reports on MRLs

the Committee for Medicinal Products for Veterinary Use (CVMP) The European public MRL assessment report provides an overview

of the assessment carried out by the CVMP on an application submitted for the establishment of MRLs. 

EU Legislation – Eudralex

The body of European Union legislation in the pharmaceutical sector is compiled in Volume 1 and Volume 5 of the publication "The rules governing medicinal products in the European Union".

Volume 1 - EU pharmaceutical legislation for medicinal products for human use

Volume 5 - EU pharmaceutical legislation for medicinal products for veterinary use

Pre-authorisations -guidelines

Volume 2 - Notice to applicants and regulatory guidelines for medicinal products for human use

Volume 3 - Scientific guidelines for medicinal products for human use

Volume 4 - Guidelines for good manufacturing practices for medicinal products for human and veterinary use

Volume 6 - Notice to applicants and regulatory guidelines for medicinal products for veterinary use

Volume 7 - Scientific guidelines for medicinal products for veterinary use Volume 8 - Maximum residue limits

Volume 9 - Guidelines for pharmacovigilance for medicinal products for human and veterinary use

Volume 10 - Guidelines for clinical trial

Medicinal products for paediatric use, orphan, herbal medicinal products and advanced therapies are governed by specific rules.

Post-authorisation

 Aim of EMA is to support the work of Health Authorities outside the European Union.

The legal bases are Art. 127 of Directive 2001/83/EC (medicinal product for human use) and Art. 93 of Directive 2001/82/EC (veterinary medicinal products).

As foreseen by the legislation, the Agency's certification scheme is based on World Health Organisation recommendations .

Certificates are issued by the Agency, on behalf of the EC, to confirm the Marketing Authorisation status of products either authorised by the EC through the centralised procedure or products for which a centralised application has been submitted to the Agency, and products pursuant to Art. 58 of Regulation 726/2004/EC.

The certificates also confirm the Good Manufacturing Practice (GMP) compliance status.

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Official controlOfficial control

•Council Directive 96/23/EC 

•measures to monitor certain substances and residues thereof in live animals and animal products

•establishes that Member States should draft a national residue monitoring plan for the groups of substances detailed in Annex I.

•These plans must comply with the sampling rules in Annex IV to the Directive Directive 96/23/EC

European Union Reference Laboratories The EU's network of laboratories for the control of residues

includes: EU Reference Laboratories (EU-RLs) designated by the

Commission; National Reference Laboratories (NRLs) designated by each

EU-countries; Official control laboratories under the responsibility of EU-

countries. EU and national reference laboratories contribute to high

quality and uniformity of analytical results. Functions Provide analytical and reference methods to NRLs; Coordinate the application by NRLs of the methods Conduct training for NRL staff Provide the Commission with scientific and technical

assistance Collaborate with laboratories that analyse feed and food in

non-EU countries.

MRL – established - example

Active agent: Benzylpenicillin

Marker residue: Benzylpenicillin

Animal Species: All food producing species MRLs – target tissues: 50 μg/kg -muscle 50 μg/kg - Fat 50 μg/kg - Liver 50 μg/kg - Kidney 4 μg/kg -Milk

Other provisions: MRLs for fat, liverand kidney do not apply to fin fish. For porcine and poultry species the fat MRL relates to ‘skin and fat in

naturalproportions’. Not for use in animals from which eggs are produced for human consumption.

Classification: Anti-infectiousagents/Antibiotics

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ConclusionConclusion- Chemical Additives must be safe before placing on the market: farm to fork.

- Risks managed by EC and assessed by respective Agencies and CRLs

- Safety Evaluation - Human, animal, health, welfare, consumer, environment, end-user benefits (Efficacy)

- Official controls of significant importance to monitor the practical aspects of consumer concerned safety.

Recommended linksRecommended links• EU-Lex:

http://eur-lex.europa.eu/en/index.htm• CRL web site:

http://irmm.jrc.ec.europa.eu/html/CRLs/crl_feed_additives/index.htm

• EFSA Web site: http://www.efsa.europa.eu • DGSANCO Web site:

http://ec.europa.eu/food/food/animalnutrition/feedadditives/index_en.htm

• Feed additive register:http://ec.europa.eu/food/food/animalnutrition/feedadditives/registeradditives_en.htm