1. Istanbul April 2011 Dr Joe Collins MVB PhD CBiol FSB MRCVS CertEP CertVR VMPs: - Availability - MUMS - Cascade

2. Veterinary medicines policy within MS’s To protect animal health and welfare –Wide range of safe, efficacious medicinal agents –Clinical freedom exercised in the patient’s interest –Harmonised licensing rules –Managed efficient route of supply –Policing of illicit use To protect the food chain and user safety –Responsible professions (vets, pharm., tox., medic) –Treat as ‘companion animals’? –Policing of supply and use –Residue testing

3. Issues regarding Import From Third Countries vs. Internal Market Import of –live animals –disease –people –skills / techniques –carcases –meat products Medicines!

4. Availability & Access Availability of effective, affordable, safe medicines where they are most needed Legacy vs. Generic Protection of the investment of the developer of a medicine and the MAH Promote innovation Balance

5. Medicines Directive 2001/82/EC as amended by Directives 2004/28/EC; 2009/9/EC and 2009/53/EC. Directives not Regulations Transposed E.g. ROI: European Communities (Animal Remedies) (No 2) Regulations 2007 Current review of Directive 2001/82 –No single market - harmonisation –Heavy bureaucratic burden –Lack of availability

7. Medicines Directive 2001/82/EC as amended by Directive 2004/28/EC. Article 5 (1) No veterinary medicinal product may be placed on the market of a Member State unless a marketing authorisation has been granted issued by the competent authorities of that Member State in accordance with this Directive ….

8. Marketing Authorisation Article 6 (1) A veterinary medicinal product may not be the subject of a marketing authorisation for the purpose of administering it to one or more food-producing species unless the pharmacologically active substances which it contains appear in Annexes I, II or III to Regulation (EEC) No 2377/90

9. Marketing Authorisation Article 6 (3) By way of derogation, …, a veterinary medicinal product containing pharmacologically active substances not included in Annexes I, II or III … may be authorised for particular animals of the equidae family that have been declared,,…, as not being intended for slaughter for human consumption. Not Annex IV Not conflict with Authorised Medicinal Products

10. EMA Policy no. 429080/2009 The availability of safe and effective veterinary medicinal products will improve both animal welfare and public health – Zoonoses; Food. … considerable concern …, about the lack of veterinary medicines for minor uses, and for minor species – MUMS; and for Limited Markets. Article 79 of Regulation (EC) No 726/2004 [1] requires the EMEA to introduce measures to assist applicants at the time of submitting applications for products for limited markets.

11. MUMS – Limited markets Minor use Low prevalence Limited geography Minor species= not major (pharma) Cattle, sheep, pigs, poultry, salmon dog, cat Importance? Severity Licensed alternatives Public health/zoonosis Food supply issue Limited market (financial return) Volume Regional distribution Legislative (control)

12. Potential MUMS Assistance - EMA More advice Free scientific advice Reduced data requirements Fee reductions Translation of documents

13. The cascade Linked with availability of VMPs The ability to resort to the cascade under specified circumstances – where there is no VMP authorised in the MS for that species and clinical indication Directive 2001/82/EC as amended by Directive 2004/28/EC. Article 10 – cascade for non-food animals Article 11 – cascade for food animals

14. General policy objective …to ensure animal health and welfare Improve availability of veterinary medicinal products for food producing animals Avoid illegal use of substances… … to continue to limit consumer exposure to pharmacologically active substances … used in veterinary medicinal products for food producing animals...

16. Cascade for food-producing animals – article 11 … the veterinarian responsible may, under his direct personal responsibility and in particular to avoid causing unacceptable suffering, treat the animals … with: (a) a VMP authorised in the Member State concerned ……for use with another animal species, or for another condition in the same species; or (b) if there is no product as referred to in point (a), either: (i) a medicinal product for human use authorised in the Member State concerned in accordance with Directive 2001/83/EC ….or (ii) a veterinary medicinal product authorised in another Member State in accordance with this Directive for use in the same species or in another food-producing species …; or (c) if there is no product as referred to in subparagraph (b), and within the limits of the law of the Member State concerned, a veterinary medicinal product prepared extemporaneously by a person authorised to do so…

17. … provided that pharmacologically active substances included in the medicinal product are listed in Annex I, II or III to Regulation (EEC) No 2377/90, and that the veterinarian responsible specifies an appropriate withdrawal period.

19. Cascade for Non-Food Producing Animals …by way of exception, the veterinarian responsible may, under his/her direct personal responsibility and in particular to avoid causing unacceptable suffering treat the animals concerned with: (a) a veterinary medicinal product authorised…for use in another animal species, or for another condition in the same species; or (b) if there is no product as referred to in point (a), either: (i) a medicinal product authorised for human use in the Member State concerned …..or (ii) in accordance with specific national measures, a veterinary medicinal product authorised in another Member State ….or (c) if there is no product as referred to in subparagraph (b) and within the limits of the law of the Member State concerned, of a veterinary medicinal product prepared extemporaneously by a person authorised to do so …. Identified as ‘not being intended for slaughter for human consumption’

21. Cascade no authorised veterinary medicinal product … another animal species, …another disease condition … human use … another MS … prepared extemporaneously In addition: –Specify an appropriate withdrawal period –Or ensure exclusion from the food chain

23. Essential Substances Article 10 (3)...the Commission shall establish a list of substances essential for the treatment of equidae …and for which the withdrawal period shall be not less than six months. Essential substances may be used only in accordance with Article 10(1) of Directive 2001/82/EC The details … must be recorded … in Section IX of the identification document for equidae

24. ‘Essential’ Substances Commission Regulation 1950/2006 established a list of substances essential for the treatment of equidae Positives list not a negatives list The cascade applies, i.e. exceptional use, protect the welfare of the animal, under the direct responsibility of the veterinarian. Non-annex medicines (EC 2377/90) “Essential” to protect health / welfare Subject to change – MS’s +/- professions

25. Essential Medicines Sedatives 9 Cardio-respiratory medicines 12 Analgesics and anaesthetics 8 Muscular function 4 GI Tract 4 Antimicrobial agents 10 Anticonvulsants 2 Ophthalmic 13 Misc. 9

26. Medicines Directive 2001/82/EC as amended by Regulation EC 470/2009 The Commission shall establish a list of substances: which are essential for the treatment of equidae, or which bring added clinical benefit compared to other treatment options available for equidae and for which the withdrawal period shall be not less than six months according to the control mechanisms laid down in Commission Decisions 93/623/EEC and 2000/68/EC.

27. ‘New’ Terms of Reference Cascade provisions apply – YES Annex IV medicines - NO Purely economic considerations – NO Multiples in same class – YES Different modes of action – YES ‘Chronic therapies’ - NO Different routes of action – YES Different pharmacokinetic profile – YES

28. CVMP proposal 2009 21 additions; 1 replacement; 3 removals One extra antimicrobial – Polymyxin B ‘Chronic therapies’ – Cyproheptadine Radiopharmaceutical – Tc99 Not halothane – ‘existing user-safety concerns’ Not phenylbutazone – ‘outstanding information on the teratogenic and carcinogenic potential’

29. Balance Availability (theoretical) –MUMS –Cascade –Essential Substances –‘Added Clinical Benefit’ Access (practical) –Innovation & protection –Routes of sale & supply –Labelling problems –Recording problems Safety –Animals –Users –Consumers