Gut Health Day Prepared by Jean Szkotnicki

February 18th, 2016

CANADIAN ANIMAL HEALTH INSTITUTE

u Trade Association representing manufacturers & distributors of animal medications

u Pioneer & generic companies

u Transnational & domestic companies

u Represent approximately 95% of sales

ANTIMICROBIAL RESISTANCE (AMR)

u  Global Issue

u  Canadian Antimicrobial Resistance and Use Action Plan

u  VDD Regulatory & Policy Changes

u  Impacts on Users of Antimicrobials in Agriculture

u  Future Endeavours

AMR a Global Issue

u World Health Assembly resolution May 2014 called for global action to address AMR – Action Plan released May 2015

u World Organization for Animal Health (OIE) Resolution No. 26 on Combatting AMR – May 2015

u Food and Agricultural Organization (FAO): passed a resolution on AMR- June 2015

u “Berlin Declaration on AMR” by the G7 health ministers – Oct 2015

u President Obama’s executive order to combat AMR – Sept 2014

u Need for alignment with US FDA on AMR initiatives given the integrated nature of North American agri-food and pharmaceutical industry

Canadian Antimicrobial Resistance & Use Action Plan

u 3 Pillars u Surveillance – Canadian Integrated Program on AMR & Surveillance

(CIPARS)

u Stewardship

u  Removal of growth promotion claims from medically important antimicrobials used in feed & water plus veterinary oversight of product

u  Controls over Own Use Importation & Importation of Active

Pharmaceutical Ingredients

u Research

Veterinary Drugs Directorate, Health Canada Regulatory & Policy Changes

u  Canadian Animal Health Institute (CAHI) approached VDD in March 2014 agreeing to voluntarily remove growth promotion claims from medically important antimicrobials (MIA) used in feed & water

u  Also agreed to veterinary oversight of these same products

u  Driving force – U.S. Food & Drug Administration move to remove growth promotion claims and have veterinary oversight of MIA used in feed & water by the end of 2016

ELANCO ANIMAL HEALTH

NEGATIVE OUTCOMES OF REMOVING SUBTHERAPEUTIC ANTIBIOTICS Ø  increased incidence of enteric diseases in food-producing

animals Ø  productivity and mortality losses Ø  increased use of antibiotics for therapeutic purposes with

greater relevance to treatment of serious infection in humans (I, II).

Group Category I Category II Category III Total Growth promotion production claims removal

0 22 Erythromycin, Penicillin G, Streptomycin, Tylosin & Virginiamycin

36 Bacitracin , Chlortetracycline Neomycin, Oxytetracycline, & Sulfonamides

58

OTC to Pr 0 48 Erythromycin, Lincomycin, Penicillin G, Streptomycin, Tilimicosin, Tylosin & Virginiamycin

88 Apramycin, Bacitracin, Chlortetracycline, Neomycin, Novobiocin, Oxytetracycline, Spectiomycin, Sulfonamides & Tiamulin

136

WHAT ARE THE MEDICALLY IMPORTANT ANTIMICROBIALS (MIA)?

REGULATORY CHANGES THAT LIE AHEAD u  By 2018…..

u  Prohibition on Own Use Importation of Medically Important Antimicrobials

u  Controls over Importation of Active Pharmaceutical Ingredients (API) u Veterinarian will be required to have a Establishment

License to import API & it must meet GMP for both commercially & non-commercially available product

u Pharmacists will be exempt from having to meet the above requirements for non-commercially available product

POLICY CHANGES THAT LIE AHEAD u  Medically Important Antimicrobials used in feed and water to

move from being over the counter medications to being prescription only

u  Feedmills will be able to manufacture feed in anticipation of a veterinary prescription if mixing on label as listed on the Medicating Ingredients Brochure

u  Manufacture of Extra Label Drug Use of MIA products by Feedmills will still require a prescription

u  Electronic veterinary signatures will be enabled on prescriptions

TIMEFRAME FOR CHANGES

Spring-Summer 2016

Canada Gazette I publication of new regulation for 75 day consultation. Followed by 6-18 months to review comments.

Spring, 2017

Canada Gazette II & subsequent transition period

Dec 2017

Coming into Force. Transition to new labels (AGP and Prescription) New MIA labels required for product distributed by manufacturers including therapeutic claims, duration of use & compatibities.

IMPACTS ON USERS OF MIA ANTIMICROBIALS USED IN FEED & WATER u  Farmers – MIA Antimicrobials Used in Feed & Water will no

longer be available through Livestock Medicines Outlets but available through your veterinarian

u  Veterinarians – Consideration being given to veterinarians being required to meet practice standards that address antimicrobial resistance

u Electronic signatures permitted on feed prescriptions

u  Feedmills – Able to manufacture feed as per the Medicating Ingredients Brochure in anticipation of a prescription but only able to sell product pursuant to a prescription

FUTURE ENDEAVOURS u  Farmers,…

u Expanding Quality Assurance Programs to address AMR e.g. Chicken Farmers of Canada Prohibiting Extra Label Drug Use of MIA Antimicrobials

u Looking at Production Practices to Help Limit Need for Antimicrobials in Production e.g. all in all out production systems, limiting animal exposure to disease challenges at auction sales, pre-conditioning of calves prior to moving into the feedlot

u Stronger relationship with your veterinarian

VETERINARIANS - STANDARDS AROUND AMR

RESEARCH

u  Alternatives to Antimicrobials

Alternative tools to antibiotics

Alternatives Efficacy* Potential for development

Antibiotics +++++ 0

Zinc Oxide ++++ 0

Copper Sulphate +++ 0

Organic Acids + 0

Enzymes +++ +++

Pre-fermentation & Inoculation ? +

Probiotics + +

Fermentable Substrates (Prebiotics) ++ +++

Lactose ++ 0

Zeolites & Clay Minerals ? 0

Nutraceuticals (e.g. ginseng, oregano) ? +

Soya Isolates + +

Immunoglobulins ++ ?

Epidermal Growth Factors ? ?

Colostrally Derived Growth Factors ? ?

* Efficacy & development based on a subjective score 0 to ++++ (very high) or ? (unknown)

Husbandry /Management Techniques

Efficacy* Potential for Development*

All-in-All Production ++++ ++++

Hygiene ++++ +++

Later Weaning ? +

Outdoor Production ++ 0

Colostrum Quality & Intake +++ ++

Immunisation +++ ++

Drinking Water Quality & Provision ++ +++

Education – Owner & Stockperson ++++ ++++

* Efficacy & development based on a subjective score 0 to ++++ (very high) or ? (unknown)

Acknowledgements : Dr. Pinder Gill, Dr. Vernon Fowler, British Society of Animal Science, 2005

REGULATORY PATHWAYS TO SUPPORT COMMERCIALIZATION OF NEW PRODUCTS

u  Regulatory Pathway in support of feed additives with physiological claims & health claims

PRESSURE TO DETERMINE USE OF ANTIMICROBIALS IN AGRICULTURE

u  CAHI provides data to the Public Health Agency of Canada

CIPARS 2014 REPORT

1)  The change nationally in the use of antibiotics was 4.74% for 2014 compared to 2013.

2)  Companion animal represents under 1.0 % of the total kg active.

3)  The largest antibiotic category continues to be tetracyclines followed by ionophore and chemical coccidiostats.

4)  The classifications with the largest growth in 2014 compared with 2013 are: 1) chemical coccidiostats, 2) aminoglycosides, 3)macrolides.

5)  The classification with the largest decline in 2014 compared with 2013 was tetracyclines.

6)  Provincially, Quebec leads in the volume of total antibiotics used in animal medicine.

7)  “ 3 company rule” is established to comply with the EU and US anti-competition regulations, and we added in some cases a “90% rule” on top to be sure not to infringe the regulations in the USA.

CIPARS 2014 REPORT

0

50,000

100,000

150,000

200,000

250,000

300,000

350,000

400,000

450,000

500,000

550,000

600,000

650,000

700,000

CHEMICAL COCCIDIOSTATS,

ARSENICALS

IONOPHORE COCCIDIOSTATS

AMINOGLYCOSIDES ß-LACTAMS / PENICILLIN

CEPHALOSPORINS FLUOROQUINOLONES LINCOSAMIDES MACROLIDES TETRACYCLINES SULPHONAMIDES OTHERS

Kilo

gram

s (K

G)

of A

ntib

ioti

cs

Antibiotic Class

Active Kilograms of Antibiotic Class of Veterinary Products in Canada Canadian Integrated Program for Antimicrobial Resistance Surveillance (C.I.P.A.R.S.)

KG Active 2014 KG Active 2013

Total 2014: 1,548,585 kg Total 2013: 1,478,492 kg

Difference: 4.7%

CIPARS 2014 REPORT

0.00

100,000.00

200,000.00

300,000.00

400,000.00

500,000.00

600,000.00

AB BC MB NB NF NS ON PEI QC SK

Kilo

gram

s (K

G)

of A

ntib

ioti

cs

Province

Active Kilograms of Antibiotic Class of Veterinary Products in Canada by Province Canadian Integrated Program for Antimicrobial Resistance Surveillance (C.I.P.A.R.S.)

KG Active 2014 KG Active 2013

Total 2014: 1,548,585 kg Total 2013: 1,478,492 kg

Difference: 4.7%

CIPARS 2014 Report

24

-200,000

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

1,400,000

2014 vs 2013 KG Active by Route of Administration

Chemical Coccidiostats, Arsenicals Ionophore Coccidiostats Aminoglycosides ß-Lactams / Penicillin

Cephalosporins Fluoroquinolones Lincosamides Macrolides

Tetracyclines Sulphonamides Others

CHALLENGE – MARKET PRESSURES & ACCUMULATING SCIENTIFIC EVIDENSE WILL CONSTRAIN THE SECTORS ACCESS TO ANTIMICROIBIALS

Source: Friends of the Earth 2015

IMPROVED UNDERSTANDING OF AMR u  MANAGEMENT - Consider livestock production practices to reduce use &

potential impact on human medicine

u  DEVELOPMENT OF ALTERNATIVES - Design/test therapeutic approaches against veterinary or zoonotic diseases

u  SURVEILLANCE - Monitor the emergence of resistance (genes) & potential for transfer between livestock – the environment & consumer products

u  RESEARCH -Study the kinds & flow ofresistance (genes) & zoonotic potential of microbes

QUESTIONS & DISCUSSION