“European Union Risk
Evaluation Process on
Safety of Chemical Additives
used in Animal
Nutrition”
PROFESSOR – EU Risk Expert
Sulhattin Yasar : sulhattinyasar@sdu.edu.tr

Süleyman Demirel University Isparta Turkey
 2005-2010 Formerly worked for EC
JRC IRRM Geel Bellgium
1
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.
Risk management
EC
General
directorate
for
health&consumer
Policy maker
Risk EVALUATION
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
!!!!! Not be marketed - without
authorisation !!!!
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.
8
WHAT is FA ?
feed and animal
products
FEED
ADDITIVES
colour of
ornamental fish and
birds
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 5(3) of 1831/2003
Article 2(a) of 1831/2003
environmental
consequences of
animal production
coccidiostatic or
histomonostatic effect
9
FADs?
Cont.,
10
11
Safety Evalution
Producer
Risk management: Authorisation
Application
OPINION
Risk assessment: Stability -Safety
-Efficacy
Technical
Dossiers
Method of analysis: Safety
Samples + Fee
Member
States’official
laboratory
12
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
13
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-APPLICATIONS1831@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? 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
18
FINAL
AUTHORISATION
http://ec.europa.eu/food/food/animalnutrition/feedadditives/registeradditives_en.htm
19
Example …..Community Register
Example…..Registry Entry
21
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
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.
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/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
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
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
Sel-Plex® 2000,
selenized yeast
Mintrex Zn, Cu,
Mn
Active Substance
Legal limits in feed
selenomethionine and other Total selenium
selenocompounds
Trace elements chelates of Zn or Cu or Mn
the hydroxy analogue of
methionine
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
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
EXAMPLE
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.
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)

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
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.
EMA-european mecidines agency

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.
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
•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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
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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 EUcountries.
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.
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Recommended links
•
•
•

•

•
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