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

PROFESSOR – EU Risk Expert Sulhattin Yasar : [email protected]

  Süleyman Demirel University Isparta Turkey

2005-2010 Formerly worked for EC JRC IRRM Geel Bellgium

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Content

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 2

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.

EC General directorate for health&consumer Risk EVALUATION Policy maker EUROPEAN FOOD SAFETY AUTHORITY EXECUTIVE AGENCY FOR HEALTH&CONSUMER EUROPEAN MECIDINES AGENCY Community Reference Laboratories National Reference Laboratories COMMUNITY PLANT VARIETY OFFICE

Elements of Food and Feed Safety

FEED ADDITIVE

The General Food Law

Regulation (EC) 178/2002 Feed Hygiene Reg. (EC) 183/2005 Feed materials Reg. (EC) 767/2009

!!!!!

Not be marketed - without authorisation !!!!

Feed Additives Reg. (EC) 1831/2003 A scientific evaluation needed:

•

SHOWING no harmful effects, on human, animal and environment

.

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WHAT is FA

?

colour of ornamental fish and birds

feed and animal products

FEED ADDITIVES

nutritional needs of animals

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

Legally classified by Cat/Func groups

animal production, performance or welfare, enhance digestibility, improve gut flora Article 2(a) of 1831/2003

environmental consequences of animal production coccidiostatic or histomonostatic effect

Article 5(3) of 1831/2003

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FADs? Cont.,

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Producer

Application

Safety Evalution

Risk management: Authorisation

OPINION

Risk assessment: Stability -Safety Efficacy Technical Dossiers Samples + Fee

Member States’official laboratory

Method of analysis: Safety

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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

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Specification in the authorisation regulation

Who does what?

COM DG 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 [email protected]

.

◦ ◦ ◦ 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?

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

CURRENT WORK since 2004 summary •

450 – 1000 Applications to COMMISSION

Evaluation

•

300 Reports from CRL-FA

•

50 Opinions in progress at EFSA

•

250 Opinions adopted by EFSA

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FINAL AUTHORISATION

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

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Example …..Community Register

Example…..Registry Entry

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

in 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 control Importance of Community/CEN method

•

Why we need analytical methods?

Official feed laboratories the content of the are enabled to enforce

active substance

in feedingstuffs .

•

Why we need analytical methods? cont. Official feed laboratories

use

are enabled to enforce of the authorised product regarding

conditions of

•

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

•

…(2) the determination of impurities – if approproate

•

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

Undesirable 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: Examples

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

The cascade approach

Food and feed control regulation 882/2004

Community methods CEN methods Ring trial validated methods Single 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 ANALYTE

Vitamin A

Examples of Commission and CEN methods SOURCE

Regulation 152-2009 Official Methods

STATUS

in force Amino Acids Trace Element EN 15510 Probiotics Regulation 152-2009 Official Methods CEN standards in force approved approved

Active substance – legal limits and target analyte:

 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)

EXAMPLE

Identification Limitations of the use of analytical methods

 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  Identification may be possible when working on the product itself.

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

EXAMPLE

Residues in food



The conditions of use contain:

◦

Limits for residues/metabolities products, food, tissues.

in animal

◦

Officially controlled by the official methods

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

Example

•

Maximum Residue Limits ( MRLs ) - if appropriate.

 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

Residues of Veterinary Medicinal Products

 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

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

EMA-european mecidines agency



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

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Volume 3 - Scientific guidelines for medicinal products for human use

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

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

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

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



Volume 10 - Guidelines for clinical trial

 Medicinal products for

products

and

paediatric use advanced therapies

,

orphan

,

herbal medicinal

are governed by specific rules.

Pre-authorisations -guidelines

 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.

Post-authorisation

Official control

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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 38

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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.

 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

MRL – established - example

Conclusion

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. 41

Recommended links

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EU-Lex:

http://eur-lex.europa.eu/en/index.htm

CRL web site:

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

EFSA Web site:

http://www.efsa.europa.eu

DGSANCO Web site:

http://ec.europa.eu/food/food/animalnutr ition/feedadditives/index_en.htm

Feed additive register:

http://ec.europa.eu/food/food/animalnutritio n/feedadditives/registeradditives_en.htm