Drug Control in Horse Racing in the U.S.

1. Drug Control in Horse Racing in the U.S. Scot Waterman, DVM Executive Director Racing Medication & Testing Consortium

2. U.S. Regulatory Framework

3. U.S. Regulatory Framework • State statute enables a state agency to govern pari-mutuel wagering • Commission has power to write, enforce and adjudicate rules…executive, quasi-judicial, quasi-legislative • Commissioners are usually appointed by the governor • No US federal government counterpart to the CPMA

4. U.S. Regulatory Framework • Makeup of commission varies state-by-state • Some states do not allow those involved in the industry day-to-day to serve as commissioners • Number of commissioners (as low as 1, as high as 13) • Funding for operations varies state-by-state • Majority of states funded through general funds but some based on revenue sources from handle • Rulemaking process varies state-by-state • NJ, NY, CA from start to finish process can take over one year. Some states also have regulations encoded in statute…need to involve legislature to change

5. U.S. Regulatory Framework—Challenges • Commission only quasi-legislative • Generally some state legislature oversight which creates another potential hurdle for model rules • Commission only quasi-judicial • Violations appealed to state court which historically have reduced significant penalties • Commission budgets always at risk • Local politics more important than national politics

6. Racing Medication & Testing Consortium

7. RMTC History • Formation: • Began with the AAEP Medication Summit, December 2001 • Summit designed to determine level of consensus on uniform medication policy • All organization that participated in original meeting are still involved nine years later • Organization has moved beyond rule uniformity as a singular goal • Incorporated as a 501 (c) (3) charitable organization since 2003

8. RMTC Board • Horsemen—THA, HBPA, CTT • Tracks-Magna, Churchill, Oak Tree, Del Mar, HTA, TRA, NYRA, Keeneland • Owners/Breeders—TOBA, TOC, KTA • Veterinarians—AAEP • Security—TRPB • Regulatory Association—RCI • Breed Registries/Other—AQHA, The Jockey Club, NTRA, USTA, Hambeltonian Society, Arabian Jockey Club • Jockeys—Jockey’s Guild

9. Goals and Objectives • Uniform medication rules • Uniform testing procedures and laboratory accreditation • Uniform thresholds and withdrawal guidelines for therapeutic medications • Unbiased source of information on medication issues for state racing commissions • Develop intelligence on new threats to integrity • Better communication regarding medication issues

10. RMTC Goals and Objectives • Generally successful in the development of model medication policies and encouragement of adoption at state level • Large board viewed as an “industry consensus” once language is completed • Have been able to overcome some of the parochial issues as state level • Able represent RMTC in person at state commission meetings when requested • Development of a network of individuals within commissions to assist in the adoption process

11. RMTC Goals and Objectives • US closer to uniformity than ever before • Challenges still remain: • Penalties • Difficult to get stewards/commissions to depart from status quo • How to make smaller states relevant, part of process • Commissions that want to look tougher than anyone else • Grinding process, impatient industry

12. RMTC Pharmacokinetic Program

13. Uniform thresholds and withdrawal times • First step…create a priority list of drugs for study: • AAEP was asked to put together a committee of veterinarians to identify “most essential” therapeutic medications • List was then prioritized based on the number of positive tests caused in the USA over a five year period and survey results of practitioners

14. Uniform thresholds and withdrawal times • Second step…fund administration studies on each drug at relevant doses • FDA formula used for drug residues in milk used to calculate threshold at a given withdrawal period • Minimum of twenty horses used for each study to reduce the k factor of the formula • Withdrawal time based on end of pharmacologic activity when known

15. Study Design • Test substance • Blood primary • Urine secondary • Laboratory methods • LC-MS at lowest attainable limit of detection (LOD) using latest instrumentation and methodology • Drug Administrations • Drugs were administered IV as single dose except for select drugs • Blood and urine samples were collected at specific times after drug administration – samples were sent to testing laboratories for analysis • “Cheater doses” studied when intelligence on dose/route/time is available

16. University of Florida Equine Performance Laboratory • Director • Pat Colahan, DVM • Horses • Breeds • Thoroughbred • Standardbred (specific studies) • Gender • Geldings and mares • Age • 3-10 years • Fitness • Trained on treadmill and fitness assessed periodically

17. Equine Performance Laboratory • Training and Fitness Assessment • Exercised 3 times per week on high-speed treadmill • Trot for 0.6 km at 4.0 m/s, gallop for 2 km at 8 m/s, and trot for 0.6 km at 4 m/s • Treadmill horizontal on Monday and inclined 6 degrees on Wednesday and Friday • Incremental Exercise Test to Exhaustion • Warm up on the treadmill at 4 m/s for 5 min before the start of the test; exercise for 1 min each at 9, 10, 11, 12, 13 and 14 m/s until they are unable to maintain the speed. • Blood samples collected for lactate and pH • Require lactate > 20 mM and pH <6.95

18. Equine Performance Laboratory • Sample collections • Blood – individual venipuncture into lithium heparin tubes – plasma harvested and stored at – 70 °C • Urine – collected by free catch method – urine aliquotted and stored at – 70 °C • Sample distribution • Samples are sent by overnight courier to participating laboratories

19. Process for sample analysis • ISO 17025 accredited laboratories used • Instrumentation is LC-MS or LC-MS-MS. • Develop and validate methods for each analyte before testing experimental samples. • Schedule sample collection for a drug study after the proposed method has been suitably validated and approved for use in the study.

20. Priority Group 1 Acepromazine Butorphanol Detomidine Glycopyrrolate Lidocaine Mepivacaine Methocarbamol Pyrilamine Priority Group 2 Boldenone Dantrolene Firocoxib Fluphenazine Hydroxyzine Nandrolone Stanozolol Testosterone Withdrawal Times Research

21. Glycopyrrolate Example • Quaternary amine • Anti-cholinergic • FDA approved as a pre-anesthetic but used in racing as a respiratory “aid” due to bronchodilatory effect and reduction in airway secretions • Rapidly eliminated making detection more difficult • 20-horse administration using 1 mg/horse IV and 10 mg/horse orally (n=6)

22. Plasma Threshold

23. Firocoxib Example • Non-Steroidal Anti-Inflammatory Drug • FDA-approved for use in the horse as an oral paste • Drug has an exceptionally long half life • Clinical effects compare favorably to phenylbutazone with fewer side effects • 20-horse administration using 0.1 mg/kg orally for 7 days • Merial funded the research

24. Firocoxib threshold considerations • Plasma concentrations after a single dose are less than those after a multiple dosing regimen. • Clinical effects are likely during a single dose administration. • Therefore, a threshold must be able to detect single dose administration. • A threshold of 20-50 ng/mL would detect race day administration of a single dose. • The withdrawal period after a multiple dosing regimen using a threshold of 40 ng/mL is one week.

25. Uniform thresholds and withdrawal times • Other recommendations: • Methocarbamol threshold of 1 ng/ml in plasma, withdrawal guideline of 48 hours based on single 15 mg/kg IV dose • Anabolic steroid screening and confirmatory limits • Drugs complete by our next Board meeting • Acepromazine • Detomidine • Lidocaine • Mepivacaine • Pyrilamine • SOPs and method validation data will be made available to all labs free of charge

26. General Industry Challenges • Funding for RMTC to continue research • Funding from states for commissions to increase spending on testing, investigatory capabilities, adjudication • “Silver bullet” thinking on complex issues • Dealing with issues that may be strictly based on perception and misinformation • Culture of medication use • Competition for horses which encourages overnight extras instead of condition book races

27. RMTC: Contact Us • www.rmtcnet.com