Chapter 3

1. Chapter 3 Drug Regulation & Control

2. Chapter 3Drug Regulation & Control LEARNING OBJECTIVES • Understanding the importance and role of regulation. • Knowledge of the history of drug regulation. • Understanding of the drug development and approval process. • Knowledge of label and labeling requirements. • Knowledge of control substance schedule and requirements for handling cs. • Understanding of recall process. • Understanding of liability.

3. Timeline The safety and effectiveness of food, drugs, medical devices is regulated by legal systems. • 1906 Food & Drug Act : Government pre-approval of drugs is required. • 1914 Harrison Tax Act : Prescribing of narcotics with a license only. • 1927 Food, Drug and Insecticide Administration (FDA) is formed • 1938 Food, Drug and Cosmetic Act: Replaces 1906 Act after poisoning of 107 people; started new system of drug regulation.

4. Timeline continued • 1950Alberty Food Products v. U.S. : Requires indications on a label. • 1951 Durham-Humphrey Amendment: Establishes what drugs are considered prescription(Caution: Federal Law prohibits dispensing without a prescription) • 1962 Kefauver-Harris Amendment : Requires proof of safety before marketing (Thalidomide) and disclosure of accurate information about side effects. • 1966 Fair Packaging and Labeling Act : Requires honest and informative labeling on drugs (product id, name and place of business of mfr, packer or distributor and net qty of contents). • 1970 Poison Prevention Packaging Act : Child-proof packaging. • 1970 Controlled Substances Act: Regulates drug abuse.

5. Timeline continued • 1983 Orphan Drug Act: Research for rare diseases. • 1984 Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman) : Quicker introductionof lower cost generic drugs • 1987 Prescription Drug Marketing Act : Licensed wholesalers, reduced health risks. • 1990 Omnibus Budget Reconciliation Act: Required counseling of Medicaid patients. • 1996 Health Insurance Portability and Accountability Act: Patient confidentiality.

6. New Drug Approval All new drugs require FDA approval before they can be marketed in the United States. The drug must be safe and effective. Center for Drug Evaluation and Research (CDER) Testing process – 8.5 years Laboratory animal humans Clinical trials

7. New Drug Approval Clinical Trials • Phase I: 20-100 healthy volunteers; months; (mainly safety) • Phase II: hundreds of volunteers; up to 2 years; (short-term safety but mainly effectiveness) • Phase III: up to thousands of volunteers; 1-4 years; (safety, dosage and effectiveness) • Discovery: 2 to 10 years • FDA review/approval • Post-marketing testing • Approved by FDA: 17 years • Five year extension on patent (Hatch-Waxman Act of 1984)

8. Marketed Drugs Drug patents provide an exclusive right to market for specific periods of time (20 years). Once the patent is expired, other manufactures may copy the drug and release it under the generic name (must be pharmaceutically and therapeutically equivalent). Pharmaceutically equivalent – contain the same amount of drug in the same dosage form. Therapeutically equivalent – when administered to the same individual, in the same dosage regimen, it will provide the same therapeutic response.

9. Marketed Drugs • Once approved by the FDA, a new brand drug is entered into the market. When all of the money for the research and development is paid back, a generic drug will be marketed by other companies. • Generic drugs are required to be identical to the brand-name product listed in the orange book (FDA’s Approved Drugs Products publication) in terms of active ingredient and dosage form as well as route of administration and strength.

10. National Drug Code (NDC Number) • The National Drug Code System was originally established by Medicare as part of an outpatient drug reimbursement program and was used as a method to identify drugs during commercial distribution. • Comes in two formats, a 5-3-2 format and a 5-4-1 format. Each manufacturer/packager selects which format they wish to follow and uses that format for its products

11. National Drug Code (NDC Number) EXAMPLE: 01234-5678-45 • 1st set (five digits): manufacturer • 2nd set (four digits): drug info (i.e. medication strength and dosage form) • 3rd set (two digits): package size

12. OTC Labeling Requirements • Product name • Name and address of manufacturer or distributor • List of all active and other ingredients • Amount of contents • Adequate warnings • Adequate directions for use Text p. 39

13. FDA Proposed OTC label

14. Prescription Drug Label • Name and address of dispenser • Prescription serial number • Date of RX filling • Expiration date • Prescriber name • Patient name • Directions for use • Cautionary statements Text p. 43

15. Controlled Substances Regulations • Labels (classifications) • Record keeping (inventory, Sch II are kept separately) • Security (Sch. II in the locked cabinet) • Joint responsibility (prescriber and pharmacist) • DEA number (must be used for controlled drugs Rxs) • DEA form 222 to order C I and C II drugs. (p.45)

16. DEA Form Used to order controlled substance I and II Must be signed by a registered person. Three copies: Green copy is sent to the DEA. Brown copy is kept for your records. Blue copy is kept by the company issuing the form. Must be kept in a separate file from other invoices.

17. DEA Form 222

18. Prescription Fraud Scrutinize prescriptions: • Do quantities, directions, or dosage differ from usual medical usage or practice? • Are the directions written in full with no abbreviations? • Is it a photocopy? • What is the date on the prescription? • Does the prescription look as though it has been wet?

19. Prescription Fraud Types of fraudulent prescriptions: • Stolen prescription pads • Quantities altered for larger amounts • Telephone number for verification changed on prescription pad • Uses computer to duplicate pads • Uses acetone to remove ink and rewrites • Called in by patient or other unauthorized personnel

20. Prescription Fraud Patterns of possible diversion: • Prescriber writes unexpectedly large quantities • Diverter returns too frequently for refills • Presents prescriptions for multiple drugs with abuse and written in names of other people • Does not use insurance cards • Pays cash

21. Prescription Fraud Preventing Diversion: • Encourage physicians to use tamper-resistant prescription pads • Suggest to physicians to write the quantity and strength in both numbers and letters • Know the prescriber, signature, and DEA# • Request proper identification if in doubt • If you believe forgery, do not dispense; call your local or state police

22. DEA Numbers Assigned to prescribers for dispensing controlled drugs. Ex: AR4342793 • add 1st +3rd +5th number = X • add 2nd+4th +6th number = Y • multiply by 2 = Z • then add X+Z =__ __ • The total should be a number whose last digit is the same as the last digit of the DEA number. • (4+4+7=15 3+2+9=14 14x2=28 then 15+28=43)

23. Exempt narcotics • Are medications that contain habit-forming ingredients but can be sold without a Rx • Only the pharmacist can dispense • Limited dosage units • Purchasers are at least 18 years old • Transactions are documented in a record book to track who/what/how much/when

24. Recalls • Reports of adverse effects • Manufacturing problems Class I: serious adverse effects or death Class II: cause temporary but reversible effects Class III: not likely to cause adverse effects

25. Recalls 1. Report adverse effect to the FDA. 2. FDA will contact the manufacturer. 3. Manufacture contacts wholesalers, retailers, and all consumer levels. 4. Personal phone calls are made or letters are sent to customers. 5. Recalls are listed publicly. 6. Listed in the weekly FDA enforcement report.

26. Investigational Drugs • Investigational drugs are in the final stages for approval from the FDA. • Used in patients with a life-threatening disease before marketing. • When the drug is expired, the product is returned to the sponsor (for example, the prescriber).

27. Emergency Contraceptives • Dual marketing status – both Rx (17 years and under) and OTC status • In Texas the pharmacist is not eligible to prescribe Plan B to the patient under 17.

28. PHARMACY LAWS Federal and State Laws

29. Federal Laws A prescription for a controlled substance must meet the following requirements: • Patient’s full name and address • Practitioner’s name, address, and DEA# • Drug name, strength, dosage form, quantity, directions, and refills • Must be written in ink or typewritten and signed by prescriber • Controlled substance must be dated on the date of issuance

30. Federal Laws Schedule III, IV, and V prescriptions: • May be verbal, written, or faxed and may be refilled if authorized by the prescriber • Schedule III and IV may be refilled up to five times within six months • Schedule V may be refilled as directed by the prescriber • Schedule II requires a written prescription by the prescriber that is signed and may not be refilled

31. Federal Laws • Record keeping: • C-II need to be ordered on DEA form 222 • C-II hard copies needs to filed separately from all other hard-copy prescriptions • All hard-copy prescriptions need to be kept for two years from the date of the last refill • Security for controlled substances: locked cabinet, dispersed, other secure storage • Theft or loss: Report immediately and file DEA form 106d

32. State Laws • Each state enacts laws governing the manufacturer, distribution, prescription, and dispensing of controlled substances; pharmacists must comply with both federal regulations and regulations in the state(s) in which they practice. • Such regulations may reside in different departments of the state, such as the board of pharmacy, the department of health, or consumer affairs.

33. Law and the Technician Liability (can be prosecuted for misconduct) Negligence – failing to do what you should have done: • Incorrectly labeling the Rx; • Failing to maintain patient confidentiality; • Failing to recognize expired drugs; • Calculation errors; • Dispensing the wrong medication; • Incorrect handling of controlled substance; • Inaccurate record keeping.

34. Regulating Authorities • American Society of Health-System Pharmacists, • United States Pharmacopeia – sets standards for the manufacture and distribution of drugs and related products in US. • Joint Commission on Accreditation of Health Care Organizations – establishes standards and monitors compliance for health care programs in US. • The American Society for Consultant Pharmacists – sets standards for practice for pharmacists.