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

• PROFESSOR EU Risk Expert
• Sulhattin Yasar sulhattinyasar_at_sdu.edu.tr
• 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

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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.

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Community Reference Laboratories
Risk management
National Reference Laboratories
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Elements of Food and Feed Safety
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!!!!! Not be marketed - without authorisation !!!!
FEED ADDITIVE
The General Food Law Regulation (EC) 178/2002
Feed Hygiene Reg. (EC) 183/2005
Feed materials Reg. (EC) 767/2009
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 ADDITIVES
feed and animal products
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
environmental consequences of animal production
animal production, performance or welfare,
enhance digestibility, improve gut flora
Article 2(a) of 1831/2003
coccidiostatic or histomonostatic effect
Article 5(3) of 1831/2003
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FADs? Cont.,
(Annex I of 1831/2003)
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Regulations and Directives
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Safety Evalution
Producer
Application
OPINION
Risk assessment Stability -Safety -Efficacy
Technical Dossiers
Method of analysis Safety
Samples Fee
Member Statesofficial laboratory
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Two types of authorisations

• Regulation 1831/2003, article 6 Categories of
  feed additives
• 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
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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-1831_at_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/feed
  additives/guidelines_en.htm

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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/ef
  sa_locale-1178620753812_FEEDAP.htm

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• 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_ad
ditives/index.htm
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Evaluation
CURRENT WORK since 2004- summary

• 450 1000 Applications to COMMISSION

• 250 Opinions adopted by EFSA

• 50 Opinions in progress at EFSA

• 300 Reports from CRL-FA

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FINAL AUTHORISATION
http//ec.europa.eu/food/food/animalnutrition/feed
additives/registeradditives_en.htm
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Example ..Community Register
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Example..Registry Entry
Authorised by (EC) No 379/2009
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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 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
control Importance of Community/CEN method
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Why we need 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.

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Why we need analytical methods? cont.

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

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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

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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
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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-c
ombination
Examples of Commission and CEN methods Examples of Commission and CEN methods 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
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Active substance legal limits and target
analyte

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

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)
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EXAMPLE
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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
  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

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EXAMPLE
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Residues in food

• 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.

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Example

• Maximum Residue Limits (MRLs) - if appropriate.

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  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

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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

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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 advance
  d therapies are governed by specific rules.

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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 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

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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.

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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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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.

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Recommended links

• EU-Lexhttp//eur-lex.europa.eu/en/index.htm
• CRL web site http//irmm.jrc.ec.europa.eu/html/CR
  Ls/crl_feed_additives/index.htm
• EFSA Web site
• http//www.efsa.europa.eu
• DGSANCO Web site
• http//ec.europa.eu/food/food/animalnutrition/fee
  dadditives/index_en.htm
• Feed additive registerhttp//ec.europa.eu/food/f
  ood/animalnutrition/feedadditives/registeradditive
  s_en.htm

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thank you for your attention