The Pharmacy Technician

Chapter 3

Drug Regulation & Control

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.

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.

1906: The original FOOD AND DRUGS ACT prohibits interstate commerce in misbranded and adulterated foods, drinks and drugs. The Department of Agriculture is authorized to seize unsafe substances and prosecute violators. Note that in the good old days, "misbranded" meant that the label did not accurately describe the contents, and "adulterated" meant that the claimed ingredients had been diluted, (as flour might be diluted by pea meal). The intent of the act was to provide penalties for consumer fraud and to prevent injury and death from poisons.

1914: Registered physicians were required only to keep records of drugs dispensed or prescribed. it is unlikely that a single legislator realized in 1914 that the law Congress was passing would later be decreed a prohibition law.The provision protecting physicians, however, contained a joker hidden in the phrase, "in the course of his professional practice only ." 7 After passage of the law, this clause was interpreted by law-enforcement officers to mean that a doctor could not prescribe opiates to an addict to maintain his addiction. Since addiction was not a disease, the argument went, an addict was not a patient, and opiates dispensed to or prescribed for him by a physician were therefore not being supplied "in the course of his professional practice." Thus a law apparently intended to ensure the orderly marketing of narcotics was converted into a law prohibiting the supplying of narcotics to addicts, even on a physician's prescription.Many physicians were arrested under this interpretation, and some were convicted and imprisoned. Even those who escaped conviction had their careers ruined by the publicity. The medical profession quickly learned that to supply opiates to addicts was to court disaster

1927 What would become FDA is formed. This was made possible through the food and drug act of 19061938 - In 1937, an elixir of sulfanilamide containing a poisonous solvent kills 107 persons, mostly children, dramatizing the need to establish drug safety before marketing and to enact the pending food and drug law. 1938 THE FEDERAL FOOD, DRUG, AND COSMETIC (FDC) ACT replaces the 1906 act. It contains new provisions extending control to cosmetics and therapeutic devices; requiring new drugs to be shown safe before marketing--starting a new system of drug regulation; eliminating the pesky Sherley Amendment requirement that intent to defraud must be proved in drug misbranding cases; providing that safe tolerances be set for unavoidable poisonous substances; authorizing factory inspections; and adding the remedy of court injunctions to the previous penalties of seizures and prosecutions

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Timeline continued1950 Alberty 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.

1950 In ALBERTY FOOD PRODUCTS CO. v. U.S., the court of appeals rules that the directions for use on a drug label must include the purpose for which the drug is offered. Therefore, a worthless remedy cannot escape the law by not stating the condition it is supposed to treat. This decision and the amendments of the following year provide FDA the basis for its current policies restricting "unapproved" or "off-label" uses of drugs, as well as the corollary policy of prohibiting health claims for non-drugs. (By FDA logic, non-drugs become "drugs" if a health claim is made for them and, if the provider has not run the regulatory gauntlet, the health claim thereupon becomes an unapproved use and the distribution of the "drug" is prohibited). Discuss Legend drugs (bring example) Kefauver: required drug advertising to disclose accurate information about side effects, and stopped cheap generic drugs being marketed as expensive drugs under new trade names as new "breakthrough" medications66:The identity of the product; The name and place of business of the manufacturer, packer, or distributor; and The net quantity of contents.

PPPA: enacted to prevent young children from accidentally ingesting hazardous substances ordinarily stored about the house. The law requires toxic, corrosive, or irritative substances to be packaged in such a way that it will be difficult for children less than 5 years to open them, yet not difficult for adults to open. The first product to fall under this law was aspirin, on August 8, 1972, with the law gradually encompassing more and more hazardous substances, including some prescriptions and over-the-counter medications.Faulty intrauterine devices and cardiac pacemakers arouse public interest in better regulation of medical devices. (1970s)4

Timeline continued1983 Orphan Drug Act: Research for rare diseases.

1984 Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman) : Quicker introduction of 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.

*The Orphan Drug Act of 1983 provides seven years of exclusive marketing rights for manufacturers of orphan drugs. It also provides tax credits for the cost of clinical research, and grants to support research on new treatments for rare diseases. Manufacturers of orphan drugs do not have to pay FDA user fees, and very often orphan products are given expedited reviews so there are minimal regulatory delays. The law has worked very well: We now have 200 FDA-approved orphan drugs on the American market, and more than 700 designated orphan drugs in the research pipeline. *HatchWaxman: promote generics while leaving in tact a financial incentive for research and development. It allows generics to win FDA marketting approval by submitting bioequivelence studies (clinical-costlier). It also grants a period of additional marketing exclusivity to make up for the time a patented pipeline drug remains in development. This extension cannot exceed five years, and it is in addition to the 20 years exclusivity granted by the issuance of a patent. Grants a 30-month stay to drug companies that file suit against generic manufactures that challenge their patents. *1987: establishes legal safeguards for prescription drug distribution to ensure safe and effective pharmaceuticals. Designed to discourage the sale of counterfeit, adulterated, misbranded, subpotent, and expired prescription drugs. It was passed in response to the development of a wholesale sub-market.*OBRA: 13 different sections/titles. (IV) Provisions related to Medicare A, B, Medicaid. Medicare supplemental insurance policies service provisions, reimbursement, requiring counseling for Medicaid RX patients, reimbursement provisions, for medicaid, nursing home reform, child health initiatives. *HIPPA: The HIPAA Privacy Rule provides federal protections for personal health information held by covered entities and gives patients an array of rights with respect to that information. At the same time, the Privacy Rule is balanced so that it permits the disclosure of personal health information needed for patient care and other important purposes.

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New Drug ApprovalAll 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

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New Drug Approval

Clinical TrialsPhase 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 yearsFDA review/approvalPost-marketing testingApproved by FDA: 17 yearsFive year extension on patent (Hatch-Waxman Act of 1984)

Marketed DrugsDrug 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.

The length of these patents varies in different countries, though they are usually between 15-20 years. In the U.S., a pharmaceutical patent is valid for 20 years. Drug companies usually apply for patent protection before they actually begin producing the drug, opting instead to secure their rights to a particular compound at the beginning of the testing process. By the time a drug comes to market, there may only be 8-10 years of patent protection remaining, which is significantly less than the 20 offered by the patent. Companies often attempt to extend these patents by making slight reformulations of the original compound or proving its effectiveness at treating a condition other than the one for which it was originally granted a patent. This is referred to as "evergreening", a practice which many criticize.8Marketed DrugsOnce 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 (FDAs Approved Drugs Products publication) in terms of active ingredient and dosage form as well as route of administration and strength.

*bioequivalence : the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study

9National 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

National Drug Code (NDC Number)EXAMPLE: 01234-5678-45 1st set (five digits): manufacturer2nd set (four digits): drug info (i.e. medication strength and dosage form)3rd set (two digits): package size

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

FDA Proposed OTC label

Prescription Drug LabelName 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

Controlled Substances RegulationsLabels (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)

DEA FormUsed to order controlled substance I and IIMust 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.

DEA Form 222

Prescription FraudScrutinize 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?

6 months for controls, one year for non controls, C2: 21 days. 18Prescription FraudTypes of fraudulent prescriptions:Stolen prescription padsQuantities altered for larger amountsTelephone number for verification changed on prescription padUses computer to duplicate padsUses acetone to remove ink and rewritesCalled in by patient or other unauthorized personnelPrescription FraudPatterns of possible diversion:Prescriber writes unexpectedly large quantitiesDiverter returns too frequently for refillsPresents prescriptions for multiple drugs with abuse and written in names of other peopleDoes not use insurance cardsPays cashPrescription FraudPreventing 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 policeDEA NumbersAssigned 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)

PASS OUT ACTIVITY22Exempt narcoticsAre medications that contain habit-forming ingredients but can be sold without a RxOnly the pharmacist can dispenseLimited dosage unitsPurchasers are at least 18 years oldTransactions are documented in a record book to track who/what/how much/whenDoes not apply in Texas23RecallsReports of adverse effectsManufacturing problems

Class I: serious adverse effects or deathClass II: cause temporary but reversible effectsClass III: not likely to cause adverse effects

Recalls1. 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 aresent to customers.5. Recalls are listed publicly.6. Listed in the weekly FDA enforcement report.

25Investigational DrugsInvestigational 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).

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration for sale in the United States (see Question 1). The most common way patients receive investigational drugs is by taking part in clinical trials (see Question 2). Patients sometimes receive investigational drugs through mechanisms such as expanded access protocols and special exception programs (see Question 3). Specific criteria must be met to receive an investigational drug outside a clinical trial (see Questions 3 and 7). Patients interested in receiving investigational drugs should talk to their physician (see Question 8). In general, investigational drugs are provided free of charge (see Question 9).

26Emergency ContraceptivesDual 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.

No conscious clause in place in Texas that allows RPH to refuse to sell on the grounds of their beliefs. 27PHARMACY LAWSFederal and State Laws

Federal LawsA prescription for a controlled substance must meet the following requirements:

Patients full name and addressPractitioners name, address, and DEA#Drug name, strength, dosage form, quantity, directions, and refillsMust be written in ink or typewritten and signed by prescriberControlled substance must be dated on the date of issuance

Federal LawsSchedule III, IV, and V prescriptions:

May be verbal, written, or faxed and may be refilled if authorized by the prescriberSchedule III and IV may be refilled up to five times within six monthsSchedule V may be refilled as directed by the prescriberSchedule II requires a written prescription by the prescriber that is signed and may not be refilled

Federal LawsRecord keeping: C-II need to be ordered on DEA form 222C-II hard copies needs to filed separately from all other hard-copy prescriptionsAll hard-copy prescriptions need to be kept for two years from the date of the last refillSecurity for controlled substances: locked cabinet, dispersed, other secure storageTheft or loss: Report immediately and file DEA form 106d

State LawsEach 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.

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.

Regulating AuthoritiesAmerican 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.

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