Injustice - Developers Among Us (SciFiDevCon 2024)
Sponsor Day on animal feeding: The post-antibiotic era – innovation & regulation of feed additives in the EU
1. Dr. Elinor McCartney 1
The post-antibiotic era – innovation & regulation of
feed additives in the EU
Dr Elinor McCartney
President
Pen & Tec Consulting Group
2. Dr. Elinor McCartney 2
Content
• Antimicrobial resistance (AMR) – a driver of regulation & innovation
• EU/EFSA feed additive approval process in context
² Reg. 1831/2003 – definition of a feed additive
² Reg. 429/2008 guidelines, EURL/EFSA guidance – “toolkits”
² Reg. 767/2009 – feed materials
² Dir. 2011/82 – veterinary medicines
• Designing for EU/EFSA success
² Pioneer feed additives, post-AGP ban
² Novelty & EFSA challenges on quality, safety & efficacy
² EFSA-compliant efficacy data & meta-analysis
² Examples of innovation in botanical zootechnical additives
² Horizon 2020 additives & support teams/services
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*ECDC/EMEA Joint Technical Report: The bacterial challenge: time to react 2009
http://ec.europa.eu/transport/road_safety/specialist/statistics/trends/index_en.htm
Most human AMR
problems arise in
çhospitals & the
çcommunity
AMR is reponsible for ≈25,000 EU deaths per annum*
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9. Dr. Elinor McCartney 9
AMR crisis (WHO 2014)
2
Antimicrobial resistance – global report on
surveillance
WHO 2014
Fatal scrapes & scratches in children
Fatal bladder infections in elderly
Fatal sequelae to routine hip replacements
Dr Keiji Fukuda
WHO Director-General
End of safe medicine
Funding needed for new antibiotics
UK experts
AMR travels with infectious disease
Infectious diseases travels globally
Dr Daniel Lo Fo Wong
Senior advisor AMR, WHO
AMR is a global threat
Little is being done to tackle it
AMR turns common infections into untreatable
diseases. Every antibiotic will become useless
Lord Darzi, former UL health
minister
UK funding inadequate (<1% R&D funds)
Worse than 1980s AIDS crisis
Professor Laura Piddock
University of Birmingham
UK AMR is less than elsewhere but we see
patients with infections resistant to antibiotics
Dr Paul Cosford
Public Health England
11. Dr. Elinor McCartney 11
EU votes Population (M) Nº votes
Germany 83 29
UK 60 29
France 60 29
Italy 60 29
Spain 40 27
Poland 40 27
Romania 23 14
Netherlands 16 13
Greece 11 12
Czech Republic 10 12
Belgium 10 12
Hungary 10 12
Portugal 10 12
EU votes Population (M) Nº votes
Sweden 9 10
Bugaria 8 10
Austria 8 10
Slovakia 5 7
Denmark 5 7
Finland 5 7
Ireland 4 7
Croatia 4 7
Lithuania 4 7
Latvia 2 4
Slovenia 2 4
Estonia 1 4
Cyprus (4), Lxburg
(4) Malta (3)
2 11
EU 28 500 M 452
500 M demanding consumers!
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12. Dr. Elinor McCartney 12
EU legislative response to AMR & other “food” issues
• White Paper on Food Safety (2000)
• European Food Safety Authority (EFSA, 2002)
• Rapid Alert System for Food and Feed (RASFF, 2003)
• New Regulations on “Novel” Foods/Feeds (GMOs, 2003)
• Traceability/HACCP “From Farm to Fork” (2006)
• New Regulations on undesirable substances, feed additives, feed
hygiene, official controls in the food chain (2003-2006)
• New Regulations on food enzymes, additives, & flavours (2008)
• New feed regulation (2009)
• Application of the new laws to food and feed imported to the EU
• EU bans antibiotic growth promotors (AGPs) – completed in 2006
• Increased pressure to reduce use of veterinary & human antibiotics
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Dream teams for EC/EFSA dossiers
ü Committed sponsor (cost & time)
ü ISO-17025 accredited analytical labs
ü R&D sites with EFSA “knowhow”
ü Dedicated & modern R&D feed mill
ü Life scientists – used to working with animals, people & data
ü Computer-literacy & statistical skills
ü Passion & perfectionism for work in technical & legal areas
ü Communication skills – written & team-working
ü Fluency in English & attention to detail
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EC/EFSA feed additives – innovation index?
Type EC listed –
current legal
status
EFSA listed as
under
(re)evaluation
Comment
Feed enzymes
Zootechnical
Digestibility
50 90 ≅ 100, regulated
since 1990s
Feed probiotics
Zootechnical
Gut flora
40 90 ≅ 100, regulated
since 1990s
Feed flavours
Sensory
600 NICs
(nature identical
components)
200 Botanicals
70 grouped:
50 NICs
70 botanicals
“Flavours” =
most feed
additives!
Zootechnical
Mostly “Other”
≅
5 NICs
≅
1 Botanical
< 10 NICs
<10 botanicals
Room for
innovation?
19. Dr. Elinor McCartney 19
Building EU success
Main dossier reference material
Commercial objectives – how to
achieve within legal framework?
ü EU regulations 1831/2003 & 429/2008
ü EFSA guidance (adminstrative, zootechnical, tolerance/efficacy …)
ü EURL guidance (method validations & verifications)
ü SCAN/recent EFSA opinions on similar products?
ü Previous SCF reports/opinions (e.g. use in foods)
ü EFSA, JECFA, EMEA, CoE reports & literature searches
ü GOOGLE: EFSA, DGSanCo, US FDA/EPA, etc
ü In-house & external research – EFSA-compliant?
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Building successful feed additive dossiers
Consider strategic options - additive groups
1. Technological: Act on feed & feedingstuffs, e.g.
preservatives, anti-oxidants, emulsifiers,stabilisers, thickeners,
gelling agents, binders, anti-radionucleotides, anticakers,
acidifiers, silage additives, denaturants, mycotoxin de-
activators
2. Sensory: Add colour to feed/animals or flavour to feeds
3. Nutritional: Vitamins, pro-vitamins, trace elements, amino
acids, urea
4. Zootechnical: a. Improve feed digestibility, b. gut flora
equilibrium, c. the environment, or d. “other“ (performance
enhancers, animal welfare, food quality ….)
5. Coccidiostats & Histomonostats
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Building successful feed additive dossiers
Planning & data audit
ü Who, what, why, where, when, which, how?
ü Do we need/want a feed additive approval? If yes, why?
ü Which category/functional group/s & why?
ü What do current guidelines/guidance require?
ü What data are available & do they meet current standards?
ü What data must be generated?
ü Time & cost of data generation?
ü What problems will arise & how do we solve them?
ü Can we protect our investment?
ü Iterate until project strategy & plan is clear
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Building a successful feed additive dossier
What is it and what does it do?
• Product specification?
• Administered in feed, water or other route?
• Improve feed, animal products or animal colour?
• Satisfy nutritional needs?
• Improve the environment?
• Improve animal production, performance, welfare?
• Coccidiostat/histomonostat?
• Something else? ( → Comitology)
• Options to market as a feed material, premixture or complementary
feed?
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Planning DATA AUDIT EXPERT ADVICE ITERATE KEY ISSUES
1. Safety e.g. use in foods
e.g. calculate
relative exposure
e.g. assemble
supporting
literature (CoE/
EMEA/JECFA)
e.g. do we need
residue studies?
2. Efficacy
e.g. optimum
range & “claims”?
e.g. EFSA-
compliant studies
e.g. select study
sites
e.g. justify minimum
dose?
3. Quality
i.e. analytical
method validation
& verification
e.g. product
specification
e.g. role & legal
status of coating
agents &
excipient/s
e.g. stability &
compatibility
4. Generate data SAFETYè EFFICACYè QUALITYè
e.g. EFSA/EURL
compliance
5. Reports Review in detail Check raw data
Check & rerun
statistics
e.g. meta-analysis
6. Annexes Safety Annexes Efficacy Annexes Quality Annexes Bibliography
7. Text Safety Text Efficacy Text Quality Text
Summary Text
(coherence)
8. Administration EURL EU EFSA SUBMIT
Building EU success
Best practice – planning ahead
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EURL EU EFSA: (1 paper copy, 2 CDs)
Cover letter &
declaration form &
EU Annex I
Cover letter &
application form
(EU Annex I)
Part 1
Administrative
Part 2
Technical
Part 3
Confidential
3 ref. samples
(same lot)
3 ref. standards
Administrative data Cover letter
Section I
PubSum, ScSum,
List.Doc, ConfInfo
Confidential parts
Certificate of ID/
analysis
Section I
Public summary
Application form
(EU Annex I)
Section II Quality
II Annexes
From Section II
Pay EURL fees
EU MSDS
Section I
Scientific summary
Contact details
(Annex E)
Section III
Safety
III Annexes
From Section III
PubSum &
ScSum
Section I
Dossier Index
Descript. Add
Annex A
(Register entry)
Section IV
Efficacy IV
Annexes
From Section IV
Obtain proof of
payment or
fee waiver
Section I
Confidential Parts
Completeness
Checklist (Annex
B)
Section V
PMMP
Notes
ê
English
NB: Multi-tasking
dossiers OK!
EURL fee proof of
payment or fee
waiver
Declaration
E-copy = paper
NB Bibliography to
Sections II, III, IV.
PDFs
<20 MB
25. Dr. Elinor McCartney 25
Building successful feed additive dossiers
Best practice: EFSA completeness check list
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Austria
Bulgaria
Belgium
Croatia
Cyprus
Czech Republic
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Ireland
Italy
Latvia
Lithuania
Luxembourg
Malta
Netherlands
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
UK
Natugro Inc.
Natugr
o
25 kg
WhizzGro®
Dossier
EFSA
“6-month
evaluation”
Public Summary
WGs & Plenary/s
EFSA opinion
published
28 Member States:
Comitology, QMV (≥3 m)
→ Regulation (+2-3m)
Building successful feed additive dossiers
The evaluation & authorisation process
27. Dr. Elinor McCartney 27
EU votes Population (M) Nº votes
Germany 83 29
UK 60 29
France 60 29
Italy 60 29
Spain 40 27
Poland 40 27
Romania 23 14
Netherlands 16 13
Greece 11 12
Czech Republic 10 12
Belgium 10 12
Hungary 10 12
Portugal 10 12
EU votes Population (M) Nº votes
Sweden 9 10
Bulgaria 8 10
Austria 8 10
Slovakia 5 7
Denmark 5 7
Finland 5 7
Ireland 4 7
Croatia 4 7
Lithuania 4 7
Latvia 2 4
Slovenia 2 4
Estonia 1 4
Cyprus (4), Lxburg
(4) Malta (3)
2 11
EU 28 500 M 452
Building successful feed additive dossiers
QMV, EU 28, ≥50% Member States (> 60% EU population), 74% votes
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Building a successful feed additive dossier
Being a pioneer….
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Building successful feed additive dossiers
Best practices – learning from experience
ü Start at the beginning – if possible
ü Collect all relevant & current
EURL/EU/EFSA documents
ü Focus on key EFSA documents (e.g. sensory guidance for
botanicals)
ü Check (& challenge?) product positioning & claims with the
client/marketing department
ü PLAN the dossier – problems, solutions, budgets, & time to
market
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Building successful feed additive dossiers
Do’s
ü If in doubt, consult the EU Commission &/or EFSA by
e-mail/telecon
ü Follow EU guidelines to the letter (!) (Reg 429/2008)
ü Follow relevant EFSA guidance/s to the letter (!), BUT è
ü Check legal loopholes for opportunities to reduce costs/time (read the
small print in Reg. 429/2008)
ü Be ruthless with studies that are not EFSA-compliant
ü Use standard templates for efficacy & tolerance study protocols &
reports
ü Monitor all studies – visit & communicate with study directors & barn
crews
ü Check all study raw data & statistics!
ü Blood samples (& tissues?) in all tolerance studies! (store spare sets?)
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2. TOC (Table of Contents)
Item Page
1. Title page
2. Table of Contents
3. Summary (insert in final report)
4. Quality statement
5. Target dates/reporting requirements
6. Materials & methods (inc. statistical technique/s)
7. Results (tables)
8. Discussion & conclusions (text/bullet points)
9. References
10. Appendices: CVs, CoAs., external laboratory reports, raw data,
statistical outputs
11. Addenda (e.g. late additions to report)
12. EFSA Annex C (tolerance/efficacy)
Building successful feed additive dossiers
Do use standard templates for study protocols & reports
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Building successful feed additive dossiers
Don’ts
x Assume that commercial trials from 1985 will meet current
EFSA standards
x Run studies without an EFSA-compliant, written protocol
x Finalise reports without a careful review against EFSA
requirements
x Submit a dossier without double-checking both e-copies &
paper copies against each other
x Assume that EURL/EFSA/EU guidance/guidelines will be the
same as for the last dossier submitted, hence
è do not:
x Copy & paste from the previous dossier to the current dossier
(e.g. species extension) without checking & updating to fit new
EURL/EFSA/EU requirements
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EFSA FEEDAP evaluations
EFSA feed additive dossier validation process
² Informal/formal letter of receipt
² EFSA completeness check (30 working days)
² EFSA MiP – Missing Information Parts
² EFSA validation letter è Clock Zero (6 months evaluation)
² EFSA circulates dossier to EURL, EU & Member States
² EFSA requests confirmation that the Public Summary does not
contain confidential information
² EFSA publishes the Public Summary of the dossier
² All this will be managed by the EFSA Applications Help Desk
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EFSA FEEDAP evaluations
EFSA working groups (WG) & plenary meetings
² Dossier evaluation is mainly undertaken by WG of independent experts –
listed on EFSA web page – not all are FEEDAP panel members
² EFSA Sins!
² WGs supported by EFSA FEEDAP scientific officers (Secretariat)
² Plenary meetings consist of 21 EFSA FEEDAP scientific panel members
– also listed on EFSA web page
² EFSA opinion is first drafted by WG, then discussed & adopted at EFSA
plenary meetings
² EFSA plenary may request reworking of WG draft or raise additional
questions for the applicant (!)
² Hence dossier usually appears at least twice on EFSA FEEDAP agenda
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EFSA FEEDAP Evaluations
EFSA SIns – Supplementary Information requests
² = “Clock-Stop”
² 30 working days to reply or
² Applicant requests time extension/s
² In theory only 1 EFSA clock-stop (SIn) with all questions from WG
² In practice, several SIns are more common è
² (Depends on applicant’s answers & EFSA plenary)
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EFSA FEEDAP Evaluations
Best practices, must do’s, recipes for success:
ü Answer all EFSA questions to the letter
ü Be realistic about time frames & request time
extension/s as necessary
ü Stick to sound technical arguments & avoid anecdotal data
ü EFSA want DATA not fairy tales!
ü Use legal arguments if necessary (Reg. 429/2008!)
ü Be prepared to yield on less important points (e.g. minimum
effective dose)
ü Generate essential additional data (DTW!)
ü Keep EFSA secretariat informed by e-mail
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Kidney bean lectins in piglets for gut maturation
41
Oral lectins at 11,
12, 13 days of age
T1 Control T2 Lectins P value %
change
ADG, 28-70
days of age
g/day
378.4 412.5 0.004 +9%
ADFI, 28-70
days of age
g/day
515.7 542.5 0.0149 +5%
Feed:gain,
28-70 days of
age
1.367 1.319 0.186 -4%
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Innovation - regulatory push or consumer pull?
Building Horizon 2020 products & teams!
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• Education
• Resources
• Cutting edge
science
• Passion for
problem solving
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Dr Elinor McCartney
EU Food Chain Legislation Expert
Thank you – any questions?
President
Pen & Tec Consulting
Pl. Ausiàs March, 1, 4th floor D01
Mirasol, Sant Cugat del Vallès
08195 Barcelona, Spain
E-mail: elinor@pentec-
consulting.eu
Tel: +34 93 675 80 15
www.pentec-consulting.eu