1. CDER/CSS ALSDAC September 9-10, 2003 Risk Management and the Controlled Substances Act: The FDA Perspective Deborah B. Leiderman, M.D., M.A. Director Controlled Substance Staff Center for Drug Evaluation and Research Food and Drug Administration

2. CDER/CSS ALSDAC September 9-10, 2003 Controlled Substances Act (CSA) 1970 Enacted to comply with international treaties and efforts to combat drug trafficking and to assure drug availability for legitimate medical use Established five schedules and levels of control, CI-V Drug classes: opioids, depressants, stimulants, hallucinogens

3. CDER/CSS ALSDAC September 9-10, 2003 CSA 1970 Schedule I (CI) –Most restrictive –Reserved for drugs with high abuse potential and no recognized medical use –Examples: heroin, LSD Schedule II-V (CII-V) –Descending abuse potential and restrictions –Drugs have medical use in U.S.

4. CDER/CSS ALSDAC September 9-10, 2003 Schedule II Opioid Analgesics Highest level of control for drugs with recognized medical use Highest potential for abuse; abuse potential comparable to CI drugs Pose the greatest risk to the public health

5. CDER/CSS ALSDAC September 9-10, 2003 Schedule II Opioid Analgesics Health care system, medical practice, and prescribing patterns – significant change since 1970 CII drugs in past – operating room and inpatient settings Advances in science, medicine, and pharmacotherapy have transformed much disease and trauma into chronic illness Care moved to outpatient setting

6. CDER/CSS ALSDAC September 9-10, 2003 Schedule II Opioid Analgesics Oxycodone, morphine, fentanyl, hydromorphone classified as CII under the CSA Schedule II designation applies to all strengths and dosage forms of the drug No differentiation between 5 mg oxycodone and 160 mg OxyContin, fentanyl injectable 20 µg, 2 mg patch, morphine 5 mg tablet CII encompasses broad range of drug classes, potencies, and dosages. Comparable to range CIII-CV

7. CDER/CSS ALSDAC September 9-10, 2003 Range of Schedule II Drugs Fentanyl 100-250 µ g/2mL 2.5-10 mg/patches Morphine 10mg/mL inj. 15-30 mg tabs MS Contin 15-200 mg tabs Secobarbital Amobarbital Pentobarbital Oxycodone comb. 5-10 mg tabs OxyContin 10-160 mg tabs Hydrocodone Substance Methylphenidate 5-54 mg caps & tabs Hydromorphone 2-8 mg tabs Oxymorphone 1-1.5mg/mL inj. Methadone 5-40 mg tabs Methamphetamine Amphetamine 5-30 mg caps & tabs Cocaine Topical Solution 4%, 10% OPIATESBARBITURATESSTIMULANTS

8. CDER/CSS ALSDAC September 9-10, 2003 Range of Schedule III-V Drugs Codeine & Hydrocodone (comb.) Dihydrocodeine Buprenorphine Anabolic Steroids Codeine (comb.) Dihydrocodeine Diphenoxylate Schedule III Schedule IVSchedule V OPIATES STIMULANTS Dextropropoxyphene Pentazocine Butorphanol Gamma hydroxybutyrate (GHB) DEPRESSANTS Zaleplon Zolpidem Sibutramine Modafinil OTHER Alprazolam Diazepam Midazolam Quazepam BENZODIAZEPINES Dronabinol

9. CDER/CSS ALSDAC September 9-10, 2003 What does Schedule II require? Manufacturing quotas set by DEA (input on medical need from FDA) Distribution tracking Import and export controls Registration of prescribers and dispensers No refills

10. CDER/CSS ALSDAC September 9-10, 2003 Schedule II does not require: Physician/practitioner education Limits on drug quantity prescribed or dispensed Prescription monitoring

11. CDER/CSS ALSDAC September 9-10, 2003 Regulation of Controlled Substances Manufacturer Prescribers & Dispensers Patients & Community FDA DEA State Regulatory Authorities Approval & Labeling Licenses Quotas Licenses

12. CDER/CSS ALSDAC September 9-10, 2003 DEA Role CSA requires DEA to: - Register drug manufacturers - Establish quotas - Register dispensers and prescribers CSA does not provide for: - Prescriber education - Knowledge assessment - Active surveillance

13. CDER/CSS ALSDAC September 9-10, 2003 FDA Role Regulates drug manufacturers Reviews and approves drug products - -“safe and effective” Drug label – primary method for communicating information to prescribers and dispensers Post-marketing Safety/Pharmacovigilance FD&C Act does not distinguish between controlled and other drug products

14. CDER/CSS ALSDAC September 9-10, 2003 State Role Boards of Pharmacy and Medicine – primary regulators of physicians and pharmacy practice States may impose additional drug controls Authority, regulations, practices, and resources vary across states

15. CDER/CSS ALSDAC September 9-10, 2003 Prescription Drug Monitoring Programs (PDMPs) State purview Goal to reduce illicit use of prescription drugs –Deter and identify “doctor shopping”, illicit sales of prescriptions and drugs, forged prescriptions Collect, review, analyze prescription data from pharmacies –Variable structure, resources –Database query; some electronic –Active surveillance –15 States – active PDMPs 2002

16. CDER/CSS ALSDAC September 9-10, 2003 Regulation of Controlled Substances Manufacturer Prescribers & Dispensers Patients & Community FDA DEA State Regulatory Authorities Approval & Labeling Licenses Quotas Licenses

17. CDER/CSS ALSDAC September 9-10, 2003 Risk Management and Drug Scheduling High-dose, extended-release Schedule II opioid analgesic products not distinguished from other Schedule II drugs in CSA Scheduling under the CSA does not manage all risks of misuse, abuse, and overdose of prescription drugs Drug scheduling alone cannot address challenges posed by high-dose opioid analgesics in context of the modern health care system with the current patterns of medical practice and ease of access to information and drugs