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Dr. Elinor McCartney 1
The post-antibiotic era – innovation & regulation of
feed additives in the EU
Dr Elinor McCartney
President
Pen & Tec Consulting Group
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
2
Dr. Elinor McCartney 3
0
10
20
30
40
50
60
70
80
90
100
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Avilamycin
Broilers
Pigs
Humans
resistant strains (%)
DANMAP 2006
3000
1500
Active substance (kg)
Resistance to avilamycin in Enterococcus faecium	

3
Dr. Elinor McCartney 4
0
50
100
150
200
250
1990 1992 1994 1996 1998 2000 2001 2002 2003 2004 2005 2006
AGPs
Veterinary
Total
Consumption (Tm actives)
Animal antimicrobial consumption (Tm): -15%
1990-2006 (DANMAP 2006)
DANMAP 2006
4
Dr. Elinor McCartney 5
EURL Antimicrobial Resistance Newsletter Nº 2 2007
resistantsensitive
non-
wildtype
inter-mediate
5
Dr. Elinor McCartney 6
Heavy emphasis on AMRs in animals
6
Dr. Elinor McCartney 7
*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
çhospitals & the
çcommunity
AMR is reponsible for ≈25,000 EU deaths per annum*
7
Dr. Elinor McCartney 8
EFSA Journal 2014;12(3):3590
SCIENTIFIC REPORT OF EFSA AND ECDC
The European Union Summary Report on antimicrobial resistance in zoonotic
and indicator bacteria from humans, animals and food in 20121
European Food Safety Authority2,3
European Centre for Disease Prevention and Control2,3
European Food Safety Authority (EFSA), Parma, Italy
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
ABSTRACT
The antimicrobial resistance data among zoonotic and indicator bacteria in 2012, submitted by 26 European Union
Member States, were jointly analysed by the EFSA and the ECDC. Resistance in zoonotic Salmonella and
Campylobacter isolates from humans, animals and food and resistance in indicator Escherichia coli, as well as data on
methicillin-resistant Staphylococcus aureus, in animals and food were addressed. Resistance in human isolates was
mainly interpreted using clinical breakpoints, while microbiological resistance in animal and food isolates was assessed
using epidemiological cut-off values. Resistance was commonly found in isolates from humans, animals and food,
although marked disparities in resistance were frequently observed between Member States. In Salmonella from
humans, high resistance levels were recorded to ampicillin, sulfonamides and tetracyclines, while resistance to third-
generation cephalosporins and fluoroquinolones remained low. In Salmonella and Escherichia coli isolates from fowl,
pigs, cattle and meat thereof, microbiological resistance to ampicillin, tetracyclines and sulfonamides was commonly
detected, while microbiological resistance to third-generation cephalosporins was generally low. High to very high
microbiological resistance to (fluoro)quinolones was observed in Salmonella isolates from turkeys, fowl and broiler
meat. In Campylobacter from humans, resistance to ampicillin, ciprofloxacin, nalidixic acid and tetracyclines was high,
while resistance to erythromycin was low to moderate. High to extremely high microbiological resistance to
ciprofloxacin, nalidixic acid and tetracyclines was observed in Campylobacter isolates from fowl, broiler meat, pigs and
cattle, whereas much lower levels were observed for erythromycin and gentamicin. Increasing trends for ciprofloxacin
resistance was observed in Campylobacter isolates from humans, broilers and/or pigs in several Member States. Multi-
resistance and co-resistance to critically important antimicrobials in both human and animal isolates were presented,
and for the first time, multi-resistance patterns in Salmonella serovars. Very few isolates from animals were co-resistant
to critically important antimicrobials. A minority of isolates from animals belonging to a few Salmonella serovars
(notably Kentucky and Infantis) were resistant to high levels of ciprofloxacin.
© European Food Safety Authority, European Centre for Disease Prevention and Control, 2014
KEY WORDS
antimicrobial resistance, zoonotic bacteria, indicator bacteria
1
On request from EFSA, Question No EFSA-Q-2013-00214, approved on 24 February 2014.
2
Correspondence: in EFSA: zoonoses@efsa.europa.eu; in ECDC: FWD@ecdc.europa.eu
3
Acknowledgements: EFSA and ECDC wish to thank the members of the Scientific Network for Zoonoses Monitoring Data,
former Task Force on Zoonoses Data Collection (EFSA) and the Food and Waterborne Diseases and Zoonoses Network (ECDC)
who provided the data and reviewed the report. Also, the contribution of EFSA’s staff members: Pierre-Alexandre Belœil, Pia
Mäkelä, Anca Stoicescu, Valentina Rizzi, Anne-Laure Moufle, Roisin Rooney, Kenneth Mulligan, Francesca Riolo, Mario
Monguidi, Saghir Bashir, Angela Cohen, Gina Cioacata and Klaudia Chrzastek, the contributions of ECDC’s staff members:
Scientific support & advice
EFSA and ECDC provide independent scientific support and
advice to risk managers and decision makers on the
possible emergence, spread and transfer of antimicrobial
resistance, EFSA collects data on AMR in food-producing
animals, while ECDC collects data on AMR in humans.
Integrated approach
EFSA and ECDC monitor AMR in animals and humans,
using data reported by Member States. The two agencies
cooperate with the European Medicines Agency to analyse
the relationship between antimicrobial use and the
emergence of resistance in food-producing animals and in
humans.
Europe’s fight
against
ANTIMICROBIAL
RESISTANCE
How do EFSA and
ECDC fight AMR?
8
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
Dr. Elinor McCartney 10
Lies, Damn Lies, Statistics and …
(Consumer) Politics
9
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!
10
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
11
Dr. Elinor McCartney 13
But, every cloud has a silver lining…
12
Dr. Elinor McCartney 14
Innovation – post-AGP ban
•  Probiotics – gut flora stabilisers, immune stimulators
•  Feed enzymes – digestibility enhancers
•  Chelated minerals – better animal welfare & nutrition
•  Selenium yeasts – better nutrition for animals & humans
•  Organic acids/salts – help combat enteropathogens
•  Botanical preparations (herbs, spices, exotic & edible plants)
•  Innovative feed materials
•  Better quality feeds
•  Improved or creative delivery systems
•  TLC è animal health & hygiene
•  Horizon 2020 products?
•  Horizon 2020 teams!
13
Dr. Elinor McCartney 15
A Horizon 2020 team at work ….
Dr. Elinor McCartney 16
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
26
Dr. Elinor McCartney 17
Being a pioneer…. the price of innovation
15
Dr. Elinor McCartney 18
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?
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?
16
Dr. Elinor McCartney 20
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
17
Dr. Elinor McCartney 21
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
18
Dr. Elinor McCartney 22
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?
19
Dr. Elinor McCartney 23
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
20
Dr. Elinor McCartney 24
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
Dr. Elinor McCartney 25
Building successful feed additive dossiers
Best practice: EFSA completeness check list
22
Dr. Elinor McCartney 26
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
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
24
Dr. Elinor McCartney 28
Building a successful feed additive dossier
Being a pioneer….
25
Dr. Elinor McCartney 29
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
26
Dr. Elinor McCartney 30
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?)
27
Dr. Elinor McCartney 31
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
28
Dr. Elinor McCartney 32
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
29
Dr. Elinor McCartney 33
EFSA Evaluations
GUILTY UNTIL PROVEN INNOCENT
30
Dr. Elinor McCartney 34
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
31
Dr. Elinor McCartney 35
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
32
Dr. Elinor McCartney 36
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)
33
Dr. Elinor McCartney 37
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
34
Dr. Elinor McCartney 38
A few botanical examples
44
Dr. Elinor McCartney 39
Non-antibiotic feed additives – e.g. zootechnical
“botanicals”
•  Pioneer feed additives, post-AGP ban
•  Plant-derived, well-researched, & deliver consistent performance
•  Patent protection
•  Innovative delivery to target gut sites
•  Proven quality, purity, stability & guaranteed batch uniformity
•  Safe for animals, consumers, users, & the environment
•  EU/EFSA-approved (2 products in piglets, 1 product in broilers)
•  Under evaluation (≈6 dossiers - 3 broiler, 2 piglet, 1 pig)
•  Several regulatory failures – withdrawn, insufficient safety & efficacy data
•  Many listed as feed “flavours”, but EFSA tough stance on safety – e.g.
botanical residues of toxicological concern
14
Dr. Elinor McCartney 40
Botanical NICs in weaned piglets: coated
thymol, citric/sorbic acids, vanillin	
  
Study,
duration &
parameters
Control
Product at
3 kg/Tm feed
Probability Improvement
Study 1, 49d
Growth
Feed:gain
437 g/d
1.81
462 g/d
1.76
P<0.05
P<0.05
25 g/d (6%)
-0.05 (3%)
Study 2, 42 d
Growth
Feed:gain
494 g/d
1.75
516 g/d
1.66
P<0.01
P<0.05
22 g/d (4%)
-0.09 (5%)
Study 3, 42d
Growth
Feed:gain
307 g/d
1.86
334 g/d
1.68
P<0.01
P<0.05
27 g/d (9%)
-0.18 (10%)
Dr. Elinor McCartney 41
Botanical NICs in broilers: coated thymol,
citric/sorbic acids, vanillin
35
Parameter T1 Control
(0 g/Tm)
T2 NICs
(200 g/Tm)
P value
AWG (g) 1,932a 1,970b 0.0013
AFI (g) 3,260 3,271 0.6316
FCR 1.688b 1.661a 0.0006
AWG – mean weight gain; AFI – mean feed
intake; abDifferent superscripts within a row
indicate significant differences (P≤0.05).
+2% AWG
-3 points FCR
Dr. Elinor McCartney 42
Botanical “naturals” in weaned piglets:
coated essential caraway/lemon oils
Zootechnicalefficacyinweanedpiglets–meta-analysisof5studies
Productat250g/Tmfeed Control Caraway&
lemonoils
SEM P Difference
Mortality,28-70days(%) 6.21 4.57 1.16 0.299 ~
Liveweight,28days(kg) 7.55 7.56 0.05 0.938 ~
Liveweight,70days(kg) 23.41 24.24 0.19 0.002 +3.6%
Dailygain,28-70days(g/day) 378.2 398.0 4.63 0.002 +5.2%
Feedintake,28-70days(g/day) 553.2 575.3 6.22 0.009 +4.0%
Feed:gain,28-70days 1.47 1.44 0.01 0.204 ~
SEM=standarderrorofthemean;P=probability
35
Dr. Elinor McCartney 43
Botanical “naturals” in broilers (coated essential
thyme/star anise oils): digestibility studies
Zootechnical efficacy in broilers – meta-analysis of 6 studies
Product at 150 g/tm feed Control Thyme &
star anise oils
SEM P Difference
Live weight (g), 21 days 793 819 35.55 0.014 +3.3%
Daily gain (g/d), 1-21 days 35.7 36.9 1.65 0.014 +3.4%
Feed intake (g/d), 1-21days 46.0 46.2 2.10 0.827 ~
Feed:gain, 1-21 days 1.30 1.26 0.03 0.101 ~
Nutrient digestibility
Organic matter (%) 67.2 72.2 0.79 <0.001 +7.4%
Crude protein (%) 77.3 81.5 1.22 <0.001 +5.4%
Crude fat (%) 91.4 93.9 0.83 <0.001 +2.7%
Crude ash (%) 37.5 42.2 2.26 <0.001 +12.5%
Phosphorus (%) 38.4 45.7 2.51 0.002 +19.0%
Calcium (%) 39.8 49.0 5.78 <0.001 +23.1%
Dry matter (%) 78.6 81.2 0.21 <0.001 +3.3%
SEM = standard error of the mean; P = probability
38
Dr. Elinor McCartney 44
Botanicals in broilers è skeletal strength
OM (%) CP (%) CF (%) CA (%) P (%) Ca (%) DM (%)
67.2
72.2
77.3
81.5
91.4
93.9
37.5
42.2
38.4
45.7
39.8
49.0
78.6
81.2
* P<0.001 * P<0.001 * P<0.001
* P<0.001
* P<0.002
* P<0.001
* P<0.001
40
Control vs
Coated essential thyme/star anise oils
Botanical product at 150 g/Tm
Dr. Elinor McCartney 45
Botanical “naturals” – broiler performance
Botanicalperformanceinbroilers–meta-analysisof5studies
Coatedproductat150g/tmfeed Control Thyme&
staranise
oils
SEM P Difference
Mortality,1-42days(%) 5.91 6.32 3.13 0.788 ~
Liveweight,42days(g) 2,710 2,750 113.28 0.316 ~
Dailygain,1-42days(g) 63.5 64.5 2.71 0.315 ~
Feedintake,1-42days(g) 100.2 98.5 4.12 0.288 ~
Feed:gain,1-42days 1.59 1.54 0.11 0.008 -3.1%
SEM=standarderrorofthemean;P=probability
41
Dr. Elinor McCartney 46
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%
Dr. Elinor McCartney 47
Innovation - regulatory push or consumer pull?
Building Horizon 2020 products & teams!
43
•  Education
•  Resources
•  Cutting edge
science
•  Passion for
problem solving
Dr. Elinor McCartney 48
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
Budapest24th – 26th June 2014
Hotel InterContinental Budapest

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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 2
  • 3. Dr. Elinor McCartney 3 0 10 20 30 40 50 60 70 80 90 100 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Avilamycin Broilers Pigs Humans resistant strains (%) DANMAP 2006 3000 1500 Active substance (kg) Resistance to avilamycin in Enterococcus faecium 3
  • 4. Dr. Elinor McCartney 4 0 50 100 150 200 250 1990 1992 1994 1996 1998 2000 2001 2002 2003 2004 2005 2006 AGPs Veterinary Total Consumption (Tm actives) Animal antimicrobial consumption (Tm): -15% 1990-2006 (DANMAP 2006) DANMAP 2006 4
  • 5. Dr. Elinor McCartney 5 EURL Antimicrobial Resistance Newsletter Nº 2 2007 resistantsensitive non- wildtype inter-mediate 5
  • 6. Dr. Elinor McCartney 6 Heavy emphasis on AMRs in animals 6
  • 7. Dr. Elinor McCartney 7 *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 çhospitals & the çcommunity AMR is reponsible for ≈25,000 EU deaths per annum* 7
  • 8. Dr. Elinor McCartney 8 EFSA Journal 2014;12(3):3590 SCIENTIFIC REPORT OF EFSA AND ECDC The European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 20121 European Food Safety Authority2,3 European Centre for Disease Prevention and Control2,3 European Food Safety Authority (EFSA), Parma, Italy European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden ABSTRACT The antimicrobial resistance data among zoonotic and indicator bacteria in 2012, submitted by 26 European Union Member States, were jointly analysed by the EFSA and the ECDC. Resistance in zoonotic Salmonella and Campylobacter isolates from humans, animals and food and resistance in indicator Escherichia coli, as well as data on methicillin-resistant Staphylococcus aureus, in animals and food were addressed. Resistance in human isolates was mainly interpreted using clinical breakpoints, while microbiological resistance in animal and food isolates was assessed using epidemiological cut-off values. Resistance was commonly found in isolates from humans, animals and food, although marked disparities in resistance were frequently observed between Member States. In Salmonella from humans, high resistance levels were recorded to ampicillin, sulfonamides and tetracyclines, while resistance to third- generation cephalosporins and fluoroquinolones remained low. In Salmonella and Escherichia coli isolates from fowl, pigs, cattle and meat thereof, microbiological resistance to ampicillin, tetracyclines and sulfonamides was commonly detected, while microbiological resistance to third-generation cephalosporins was generally low. High to very high microbiological resistance to (fluoro)quinolones was observed in Salmonella isolates from turkeys, fowl and broiler meat. In Campylobacter from humans, resistance to ampicillin, ciprofloxacin, nalidixic acid and tetracyclines was high, while resistance to erythromycin was low to moderate. High to extremely high microbiological resistance to ciprofloxacin, nalidixic acid and tetracyclines was observed in Campylobacter isolates from fowl, broiler meat, pigs and cattle, whereas much lower levels were observed for erythromycin and gentamicin. Increasing trends for ciprofloxacin resistance was observed in Campylobacter isolates from humans, broilers and/or pigs in several Member States. Multi- resistance and co-resistance to critically important antimicrobials in both human and animal isolates were presented, and for the first time, multi-resistance patterns in Salmonella serovars. Very few isolates from animals were co-resistant to critically important antimicrobials. A minority of isolates from animals belonging to a few Salmonella serovars (notably Kentucky and Infantis) were resistant to high levels of ciprofloxacin. © European Food Safety Authority, European Centre for Disease Prevention and Control, 2014 KEY WORDS antimicrobial resistance, zoonotic bacteria, indicator bacteria 1 On request from EFSA, Question No EFSA-Q-2013-00214, approved on 24 February 2014. 2 Correspondence: in EFSA: zoonoses@efsa.europa.eu; in ECDC: FWD@ecdc.europa.eu 3 Acknowledgements: EFSA and ECDC wish to thank the members of the Scientific Network for Zoonoses Monitoring Data, former Task Force on Zoonoses Data Collection (EFSA) and the Food and Waterborne Diseases and Zoonoses Network (ECDC) who provided the data and reviewed the report. Also, the contribution of EFSA’s staff members: Pierre-Alexandre Belœil, Pia Mäkelä, Anca Stoicescu, Valentina Rizzi, Anne-Laure Moufle, Roisin Rooney, Kenneth Mulligan, Francesca Riolo, Mario Monguidi, Saghir Bashir, Angela Cohen, Gina Cioacata and Klaudia Chrzastek, the contributions of ECDC’s staff members: Scientific support & advice EFSA and ECDC provide independent scientific support and advice to risk managers and decision makers on the possible emergence, spread and transfer of antimicrobial resistance, EFSA collects data on AMR in food-producing animals, while ECDC collects data on AMR in humans. Integrated approach EFSA and ECDC monitor AMR in animals and humans, using data reported by Member States. The two agencies cooperate with the European Medicines Agency to analyse the relationship between antimicrobial use and the emergence of resistance in food-producing animals and in humans. Europe’s fight against ANTIMICROBIAL RESISTANCE How do EFSA and ECDC fight AMR? 8
  • 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
  • 10. Dr. Elinor McCartney 10 Lies, Damn Lies, Statistics and … (Consumer) Politics 9
  • 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! 10
  • 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 11
  • 13. Dr. Elinor McCartney 13 But, every cloud has a silver lining… 12
  • 14. Dr. Elinor McCartney 14 Innovation – post-AGP ban •  Probiotics – gut flora stabilisers, immune stimulators •  Feed enzymes – digestibility enhancers •  Chelated minerals – better animal welfare & nutrition •  Selenium yeasts – better nutrition for animals & humans •  Organic acids/salts – help combat enteropathogens •  Botanical preparations (herbs, spices, exotic & edible plants) •  Innovative feed materials •  Better quality feeds •  Improved or creative delivery systems •  TLC è animal health & hygiene •  Horizon 2020 products? •  Horizon 2020 teams! 13
  • 15. Dr. Elinor McCartney 15 A Horizon 2020 team at work ….
  • 16. Dr. Elinor McCartney 16 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 26
  • 17. Dr. Elinor McCartney 17 Being a pioneer…. the price of innovation 15
  • 18. Dr. Elinor McCartney 18 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? 16
  • 20. Dr. Elinor McCartney 20 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 17
  • 21. Dr. Elinor McCartney 21 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 18
  • 22. Dr. Elinor McCartney 22 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? 19
  • 23. Dr. Elinor McCartney 23 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 20
  • 24. Dr. Elinor McCartney 24 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 22
  • 26. Dr. Elinor McCartney 26 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 24
  • 28. Dr. Elinor McCartney 28 Building a successful feed additive dossier Being a pioneer…. 25
  • 29. Dr. Elinor McCartney 29 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 26
  • 30. Dr. Elinor McCartney 30 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?) 27
  • 31. Dr. Elinor McCartney 31 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 28
  • 32. Dr. Elinor McCartney 32 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 29
  • 33. Dr. Elinor McCartney 33 EFSA Evaluations GUILTY UNTIL PROVEN INNOCENT 30
  • 34. Dr. Elinor McCartney 34 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 31
  • 35. Dr. Elinor McCartney 35 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 32
  • 36. Dr. Elinor McCartney 36 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) 33
  • 37. Dr. Elinor McCartney 37 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 34
  • 38. Dr. Elinor McCartney 38 A few botanical examples 44
  • 39. Dr. Elinor McCartney 39 Non-antibiotic feed additives – e.g. zootechnical “botanicals” •  Pioneer feed additives, post-AGP ban •  Plant-derived, well-researched, & deliver consistent performance •  Patent protection •  Innovative delivery to target gut sites •  Proven quality, purity, stability & guaranteed batch uniformity •  Safe for animals, consumers, users, & the environment •  EU/EFSA-approved (2 products in piglets, 1 product in broilers) •  Under evaluation (≈6 dossiers - 3 broiler, 2 piglet, 1 pig) •  Several regulatory failures – withdrawn, insufficient safety & efficacy data •  Many listed as feed “flavours”, but EFSA tough stance on safety – e.g. botanical residues of toxicological concern 14
  • 40. Dr. Elinor McCartney 40 Botanical NICs in weaned piglets: coated thymol, citric/sorbic acids, vanillin   Study, duration & parameters Control Product at 3 kg/Tm feed Probability Improvement Study 1, 49d Growth Feed:gain 437 g/d 1.81 462 g/d 1.76 P<0.05 P<0.05 25 g/d (6%) -0.05 (3%) Study 2, 42 d Growth Feed:gain 494 g/d 1.75 516 g/d 1.66 P<0.01 P<0.05 22 g/d (4%) -0.09 (5%) Study 3, 42d Growth Feed:gain 307 g/d 1.86 334 g/d 1.68 P<0.01 P<0.05 27 g/d (9%) -0.18 (10%)
  • 41. Dr. Elinor McCartney 41 Botanical NICs in broilers: coated thymol, citric/sorbic acids, vanillin 35 Parameter T1 Control (0 g/Tm) T2 NICs (200 g/Tm) P value AWG (g) 1,932a 1,970b 0.0013 AFI (g) 3,260 3,271 0.6316 FCR 1.688b 1.661a 0.0006 AWG – mean weight gain; AFI – mean feed intake; abDifferent superscripts within a row indicate significant differences (P≤0.05). +2% AWG -3 points FCR
  • 42. Dr. Elinor McCartney 42 Botanical “naturals” in weaned piglets: coated essential caraway/lemon oils Zootechnicalefficacyinweanedpiglets–meta-analysisof5studies Productat250g/Tmfeed Control Caraway& lemonoils SEM P Difference Mortality,28-70days(%) 6.21 4.57 1.16 0.299 ~ Liveweight,28days(kg) 7.55 7.56 0.05 0.938 ~ Liveweight,70days(kg) 23.41 24.24 0.19 0.002 +3.6% Dailygain,28-70days(g/day) 378.2 398.0 4.63 0.002 +5.2% Feedintake,28-70days(g/day) 553.2 575.3 6.22 0.009 +4.0% Feed:gain,28-70days 1.47 1.44 0.01 0.204 ~ SEM=standarderrorofthemean;P=probability 35
  • 43. Dr. Elinor McCartney 43 Botanical “naturals” in broilers (coated essential thyme/star anise oils): digestibility studies Zootechnical efficacy in broilers – meta-analysis of 6 studies Product at 150 g/tm feed Control Thyme & star anise oils SEM P Difference Live weight (g), 21 days 793 819 35.55 0.014 +3.3% Daily gain (g/d), 1-21 days 35.7 36.9 1.65 0.014 +3.4% Feed intake (g/d), 1-21days 46.0 46.2 2.10 0.827 ~ Feed:gain, 1-21 days 1.30 1.26 0.03 0.101 ~ Nutrient digestibility Organic matter (%) 67.2 72.2 0.79 <0.001 +7.4% Crude protein (%) 77.3 81.5 1.22 <0.001 +5.4% Crude fat (%) 91.4 93.9 0.83 <0.001 +2.7% Crude ash (%) 37.5 42.2 2.26 <0.001 +12.5% Phosphorus (%) 38.4 45.7 2.51 0.002 +19.0% Calcium (%) 39.8 49.0 5.78 <0.001 +23.1% Dry matter (%) 78.6 81.2 0.21 <0.001 +3.3% SEM = standard error of the mean; P = probability 38
  • 44. Dr. Elinor McCartney 44 Botanicals in broilers è skeletal strength OM (%) CP (%) CF (%) CA (%) P (%) Ca (%) DM (%) 67.2 72.2 77.3 81.5 91.4 93.9 37.5 42.2 38.4 45.7 39.8 49.0 78.6 81.2 * P<0.001 * P<0.001 * P<0.001 * P<0.001 * P<0.002 * P<0.001 * P<0.001 40 Control vs Coated essential thyme/star anise oils Botanical product at 150 g/Tm
  • 45. Dr. Elinor McCartney 45 Botanical “naturals” – broiler performance Botanicalperformanceinbroilers–meta-analysisof5studies Coatedproductat150g/tmfeed Control Thyme& staranise oils SEM P Difference Mortality,1-42days(%) 5.91 6.32 3.13 0.788 ~ Liveweight,42days(g) 2,710 2,750 113.28 0.316 ~ Dailygain,1-42days(g) 63.5 64.5 2.71 0.315 ~ Feedintake,1-42days(g) 100.2 98.5 4.12 0.288 ~ Feed:gain,1-42days 1.59 1.54 0.11 0.008 -3.1% SEM=standarderrorofthemean;P=probability 41
  • 46. Dr. Elinor McCartney 46 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%
  • 47. Dr. Elinor McCartney 47 Innovation - regulatory push or consumer pull? Building Horizon 2020 products & teams! 43 •  Education •  Resources •  Cutting edge science •  Passion for problem solving
  • 48. Dr. Elinor McCartney 48 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
  • 49. Budapest24th – 26th June 2014 Hotel InterContinental Budapest