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

2. Terminology

3. Testing Basics Every winner of every race in the US goes to the test barn Every winner of every race in the US goes to the test barn Depending on the state, one or two additional horses may be selected for testing Depending on the state, one or two additional horses may be selected for testing Typically both urine and blood samples are drawn at the test barn Typically both urine and blood samples are drawn at the test barn Samples are tagged with a unique identifier and sealed to begin a chain of custody Samples are tagged with a unique identifier and sealed to begin a chain of custody

4. Screening test- rapid and sensitive, specificity not crucial. A sample with a positive screening test would be said to be “suspicious” Screening test- rapid and sensitive, specificity not crucial. A sample with a positive screening test would be said to be “suspicious” Confirmation test- sensitive and specific, if the result is positive the presence of a forbidden substance is said to be confirmed. Confirmation test- sensitive and specific, if the result is positive the presence of a forbidden substance is said to be confirmed. Definitions

5. Limit of Detection Limit of Detection—the lowest concentration of a drug that can be detected by a particular laboratory method. Limit of Quantitation Limit of Quantitation—the lowest concentration of a drug that can be reliably quantified by a particular laboratory method. Generally higher than the LOD. Definitions

6. Definitions Withdrawal Time – the time period that must elapse from the time of administration of the last dose of a drug formulation until the drug concentration decreases below some concentration in urine and/or blood. Withdrawal Time – the time period that must elapse from the time of administration of the last dose of a drug formulation until the drug concentration decreases below some concentration in urine and/or blood. –That concentration may be the LOD, the LOQ, or some predetermined concentration. –Factors affecting withdrawal time include dose, route of administration, formulation, number of doses administered, accuracy and precision of the assay, and within-horse and between-horse variability among other factors

7. Definitions Regulatory Limit Regulatory Limit –When a drug and/or its metabolites are found in the urine or blood at a concentration that is at or below the regulatory limit, no administrative action is taken. –Also called a “threshold” or “decision level” –European terminology = “screening limit” –Can be a LOD, LOQ, arbitrary, based on data from administration studies

8. Definitions Zero Tolerance—somewhat Zero Tolerance—somewhat of a myth since no testing methodology can detect down to a concentration of zero. – –Usually suggests that the laboratory calls positive any concentration of drug that is detected – –Entirely dependent on the method being used though

9. Zero tolerance? Screening Method Limit of Detection Detection Time Thin Layer Chromatography ~100 ng/ml ~24 hours ELISA ~1 ng/ml ~72-96 hours Mass Spectral Methods ~25 pg/ml ~7-30 days

10. Zero tolerance? Screening Method Sample contains 150 ng/ml Sample contains 50 ng/ml Sample contains 50 pg/ml State A Thin Layer Chromatography PositiveNegativeNegative State B ELISAPositivePositiveNegative State C Mass Spectral Methods PositivePositivePositive

11. Definitions Hay, oats and water—there is really no definition since the phrase means different things to different people Hay, oats and water—there is really no definition since the phrase means different things to different people. – –No drug administration on raceday? – –No detectable concentrations of drugs on raceday? Since we can’t detect down to zero whose definition of “detectable” is used – –No drugs ever?

12. Hay, Oats and Water Keene Dangerfield, The Blood-Horse, 1979: Keene Dangerfield, The Blood-Horse, 1979: “One things I will say is that people who are talking about going back to racing on hay, oats and water don’t know what they are talking about. We’ve never raced on hay, oats and water…Today we simply are able to find out what they are medicating them with.”

13. U.S. Regulatory Framework

14. State statute enables a state agency to govern pari-mutuel wagering 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 Commission has power to write, enforce and adjudicate rules…executive, quasi-judicial, quasi-legislative Commissioners are usually appointed by the governor Commissioners are usually appointed by the governor Reason…the industry asked for it to eliminate bookmaking competition, state wanted to control since gambling is a vice Reason…the industry asked for it to eliminate bookmaking competition, state wanted to control since gambling is a vice

15. U.S. Regulatory Framework Makeup of commission varies state-by-state 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 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 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

16. U.S. Regulatory Framework— Challenges Commission only quasi-legislative Commission only quasi-legislative –Generally some state legislature oversight which creates another potential hurdle for model rules Commission only quasi-judicial Commission only quasi-judicial –Violations appealed to state court which historically have reduced significant penalties Funding, funding, funding Funding, funding, funding Horsemen/practicing veterinarians have too much influence in some states Horsemen/practicing veterinarians have too much influence in some states

17. U.S. Regulatory Framework— What actually happens RMTC develops a model rule on a therapeutic medication RMTC develops a model rule on a therapeutic medication RCI Model Rules Committee and Board of Directors approve model rule RCI Model Rules Committee and Board of Directors approve model rule The adoption of the model rule will be more restrictive than what is allowed under state “A” current rule The adoption of the model rule will be more restrictive than what is allowed under state “A” current rule State “A” begins adoption process State “A” begins adoption process RMTC and sometimes RCI show up at a public commission hearing and present rationale RMTC and sometimes RCI show up at a public commission hearing and present rationale Local horsemen and veterinarians say adoption of rule will hurt racing in state “A” Local horsemen and veterinarians say adoption of rule will hurt racing in state “A” You are the commissioner…who do you listen to? The guy from out of town or the local guys who say racing in your state will suffer? You are the commissioner…who do you listen to? The guy from out of town or the local guys who say racing in your state will suffer?

18. Racing Medication & Testing Consortium

19. RMTC History Formation: 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 Incorporated as a 501 (c) (3) charitable organization since 2003

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

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

22. RMTC Goals and Objectives Generally successful in the development of model medication policies and encouragement of adoption at state level 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

23. Model Rules V. 2005 Permitted Therapeutics: Permitted Therapeutics: –IV administration of furosemide 4 hours prior to post –Anti-ulcer medications permitted 24 hours prior to post –One of three NSAIDS – Bute, Banamine & Ketoprofen – 24 hours prior to post Prohibited Practices Prohibited Practices –ESWT restrictions –Possession of blood doping agents

24. Language adopted Language in the process of being adopted Process require legislative action Process has not been started No horse racing or harness racing commission Salix/NSAID Adoption Progress

25. Androgenic Anabolic Steroids Unregulated in US (except Iowa) up until 2007 Unregulated in US (except Iowa) up until 2007 Model rule developed proactively by RMTC in 2007 Model rule developed proactively by RMTC in 2007 Rule set thresholds for 4 anabolic steroids and prohibits presence of any others Rule set thresholds for 4 anabolic steroids and prohibits presence of any others Adopted the international thresholds for endogenous anabolic steroids Adopted the international thresholds for endogenous anabolic steroids Thresholds for stanozolol and nandrolone based on the LOD using GC/MS in urine (best science at the time) Thresholds for stanozolol and nandrolone based on the LOD using GC/MS in urine (best science at the time)

26. Language adopted Language in the process of being adopted Process pending completed administration studies Process has not been started No horse racing or harness racing commission AAS Adoption Progress

27. RMTC Goals and Objectives Industry closer to uniformity than ever before Industry closer to uniformity than ever before Very few in industry thought RMTC would be this successful in driving uniformity Very few in industry thought RMTC would be this successful in driving uniformity Organizations involved standing behind rules Organizations involved standing behind rules Challenges still remain: Challenges still remain: –Penalties Difficult to get stewards/commissions to depart from status quo 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

28. RMTC Goals and Objectives Improving Communication Efforts—Successful Improving Communication Efforts—Successful –Industry Presence at conferences and organizational board meeting Presence at conferences and organizational board meeting Respected source of information for industry trades Respected source of information for industry trades Withdrawal times database on website Withdrawal times database on website Regular newsletters, annual report Regular newsletters, annual report –Wagering Public Regular spot on Steve Byk show on Sirius Regular spot on Steve Byk show on Sirius Educational materials on website Educational materials on website Database of positive tests with explanation of drug in development Database of positive tests with explanation of drug in development Source for mainstream press Source for mainstream press

29. RMTC Goals and Objectives Development of Uniform Withdrawal Times and Thresholds—Too Early To Tell Development of Uniform Withdrawal Times and Thresholds—Too Early To Tell –Accomplished: Identified drugs with legitimate therapeutic uses Identified drugs with legitimate therapeutic uses Prioritized drugs into five groups based on number of violations over 5 year period Prioritized drugs into five groups based on number of violations over 5 year period Collected previous science on each drug Collected previous science on each drug –Ongoing: Administration of each drug at relevant doses to 20 horses for maximum statistical power Administration of each drug at relevant doses to 20 horses for maximum statistical power Analyze drug concentrations and determine withdrawal time Analyze drug concentrations and determine withdrawal time Ultimate goal: uniform withdrawal time with a corresponding concentration of drug which regulates the withdrawal time Ultimate goal: uniform withdrawal time with a corresponding concentration of drug which regulates the withdrawal time

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

31. RMTC Goals and Objectives Challenges: Challenges: –Has taken much longer than anticipated Good science takes time but frustrating since we wanted answers yesterday Good science takes time but frustrating since we wanted answers yesterday No dedicated laboratory to analyze the significant number of samples generated No dedicated laboratory to analyze the significant number of samples generated Discrepancies in data between labs due to methodology differences Discrepancies in data between labs due to methodology differences –How do we determine desired withdrawal time? Pharmacodynamic markers Pharmacodynamic markers Best educated guess Best educated guess –How to present data to reach goal of uniformity

32. RMTC Goals and Objectives Uniform Testing Procedures—Too Early To Tell Uniform Testing Procedures—Too Early To Tell –Post-race testing in the United States: Currently 18 laboratories conducting testing in US…too many labs chasing too few dollars Currently 18 laboratories conducting testing in US…too many labs chasing too few dollars Only 5 labs ISO 17025 accredited Only 5 labs ISO 17025 accredited –30% of samples were tested by an accredited lab in ‘08 Funding is state-by-state and many times is under state procurement laws which reward low bidder or is statutorily directed Funding is state-by-state and many times is under state procurement laws which reward low bidder or is statutorily directed No industry standards for US testing labs No industry standards for US testing labs Not enough attention being paid to sample collection strategies Not enough attention being paid to sample collection strategies

36. RMTC Drug Testing Initiatives Task Force formed in September 2008 Task Force formed in September 2008 First meeting…design the best system for US Drug Testing irrespective of funding and political concerns First meeting…design the best system for US Drug Testing irrespective of funding and political concerns Consensus that we should utilize laboratory standards developed by the World Anti-Doping Association where applicable and work towards the development of a performance-based system Consensus that we should utilize laboratory standards developed by the World Anti-Doping Association where applicable and work towards the development of a performance-based system Other related topics discussed…next generation of lab directors, sample selection strategies and the use of frozen samples Other related topics discussed…next generation of lab directors, sample selection strategies and the use of frozen samples

37. RMTC Drug Testing Initiatives Creation of Industry Standards for Labs: Creation of Industry Standards for Labs: –Edited version of the Lab Standards document created by the World Anti-Doping Association has been developed by the committee Standards rely on ISO 17025 accreditation as the first step Standards rely on ISO 17025 accreditation as the first step An external proficiency program is then conducted An external proficiency program is then conducted Labs failing proficiency cannot conduct testing Labs failing proficiency cannot conduct testing A percentage of the laboratory budget is mandated to be directed towards research A percentage of the laboratory budget is mandated to be directed towards research –Working on a truly external quality assessment program for testing laboratories…hope to have in place during Q2 in 2010

38. RMTC Drug Testing Initiatives Creation of Industry Standards for Labs (continued): Creation of Industry Standards for Labs (continued): –Result will create the first set of industry standards for post-race testing labs in US –Result will create the first ever external QAP in the US –States/industry will have a document to “sell” in order to provide incremental funding for lab to meet standards –Will need funding for the industry organization that takes on the role of WADA

39. RMTC Drug Testing Initiatives Possible outcomes Possible outcomes –Incremental funding by states in order to allow their labs to meet the standards –Reduction/consolidation of testing labs due to inability to meet standards and/or failure in proficiency If implemented will lead to greater uniformity in laboratory procedures and methodologies If implemented will lead to greater uniformity in laboratory procedures and methodologies

40. General Industry Challenges Funding for RMTC to continue research Funding for RMTC to continue research Funding from state for commissions to increase spending on testing, investigatory capabilities, adjudication Funding from state for commissions to increase spending on testing, investigatory capabilities, adjudication “Silver bullet” thinking on complex issues “Silver bullet” thinking on complex issues Dealing with issues that may be strictly based on perception and misinformation Dealing with issues that may be strictly based on perception and misinformation Culture of medication use Culture of medication use Indirect issues that affect medication use Indirect issues that affect medication use

41. RMTC: Contact Us www.rmtcnet.com www.rmtcnet.com www.rmtcnet.com