Risk Management and the Controlled Substances Act: The FDA Perspective

1. 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 CDER/CSS ALSDAC September 9-10, 2003

2. 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 CDER/CSS ALSDAC September 9-10, 2003

3. 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. CDER/CSS ALSDAC September 9-10, 2003

4. 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 CDER/CSS ALSDAC September 9-10, 2003

5. 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 CDER/CSS ALSDAC September 9-10, 2003

6. 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 CDER/CSS ALSDAC September 9-10, 2003

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

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

9. 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 CDER/CSS ALSDAC September 9-10, 2003

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

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

12. 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 CDER/CSS ALSDAC September 9-10, 2003

13. 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 CDER/CSS ALSDAC September 9-10, 2003

14. 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 CDER/CSS ALSDAC September 9-10, 2003

15. 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 CDER/CSS ALSDAC September 9-10, 2003

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

17. 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 CDER/CSS ALSDAC September 9-10, 2003