Pharmacy Law Review 2010

1. Pharmacy Law Review2010 Jesse C. Vivian , RPh, JD Professor of Pharmacy Practice (313) 577-5389 jessevivian@wayne.edu http://jessevivian.net

2. Today’s Agenda:Prepare for MPJE • Discus MPJE, Study Materials and Resources • Reflections by Dr. Kathryn Hurren • Basic Constitutional Law • Review Statutes and Regulations: • Where to find statutes and Regulations • FDA • Michigan • Controlled Substances • DEA • Michigan • Food • Mock Test • Evaluation • Open Discussion

3. MPJE • Computer Adaptive Test • Answer Question • Can’t go back to prior questions • 90 Questions • 60 questions counted • No way to know which 30 questionsx don’t count • Assume every question counts

4. MPJE Study Materials • Michigan Pharmacy Law, 5th ed., 2nd printing • April 2010 • Not cover new e-script CS Rule • Predict Not on MPJE this Summer • DEA and State Boards Not Fully Briefed • Go into effect June, 1, 2010 • Can read about them online • Will post summary article on my website • ASHP’s PharmPrep 3rd ed., Federal Pharmacy Law (online or book; Good for NAPLEX) • Mock Questions • Reiss and Hall, Guide to Federal Pharmacy Law, 6th ed. • Several example questions: mediocre • Feinberg, Pharmacy Law • Practice Test: Pretty Good • Abood, Pharmacy Practice and the Law, 5th ed • Very Detailed, Class Textbook, Example Questions Okay.

5. MPJEhttp://nabp.net Click on PROGRAMS

6. NABP Click on MPJE

7. NABP MPJE • Read entire page and links

8. Constitutional Law • Not on Exam, per se • Need to know for background • Clauses • Supremacy • Duel Jurisdiction • Due Process • Interstate Commerce • Intrastate commerce • Ex Post Facto • Grandfathering • If conflict between Federal and State law exists, • Stricter Law Applies

9. Online Legal Resources • Federal Food Drug and Cosmetic Act • http://www4.law.cornell.edu/uscode/21/ch9.html • Learn to navigate this site to find specific statutes • http://www.law.cornell.edu/topics/food_drugs.html • search database • Do your own search with words like: “food drug and cosmetic act laws and regulations administration” • Federal Regulations • http://vm.cfsan.fda.gov/~dms/reg-2.html

10. Online Resources • Statutes: http://www.lib.umich.edu/libhome/Documents.center/michlaw.html • Regulations: http://michigan.gov

11. First Section Federal Regulation of Drugs Generally Adulteration Misbranding Labeling Antitrust Medicare PPPA USPS

12. History of Drug Regulation • MPJE Questions don’t usually refer to the Names of Acts but focus in on what the Act did at the time. • Pay attention to year law was enacted and effect the law had.

13. Pure Food and Drug Act of 1906 • Prohibited the introduction of adulterated or misbranded drugs and foods into interstate commerce. • Ingredients did not have to be listed • Did not regulate cosmetics of medical devices

14. Example Question • After 1906, it was illegal to introduce drugs into interstate commerce which were: • Misbranded • Adulterated • Made with contaminated materials • Not effective for intended purpose • I only • II only • All of the above • I, II and III only

15. Food Drug and Cosmetic Act of 1938 • 1938: 107 deaths from sulfanilamide elixir mixed with diethylene glycol (anti-freeze) • No “new drug” could be introduced into interstate commerce unless first proven ‘safe’ for labeled indication. • Established New Drug Application/Approval Process (NDA) • Required ‘adequate directions for use’ • Unless dispensed pursuant to prescription from state-authorized prescriber • Required labeling for habit-forming drugs • Applies to Cosmetics and medical devices as well as food and drugs • Established Food and Drug Administration • Labels, labeling, manufacturers label, pharmacy label, patient information label

16. Prohibitions • Its is unlawful to introduce into interstate commerce and article that is • Adulterated or • Misbranded

17. Adulteration Adulterated drugs and devices A drug or device shall be deemed to be adulterated: (1) If it consists in whole or in part of any filthy, putrid, or decomposed substance; or (2)(A) if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health.

18. Adulteration • or (B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess

19. Adulteration • or (4) if (A) it bears or contains, for purposes of coloring only, a color additive which is unsafe within the meaning of section 379e(a) of this title, or (B) it is a color additive the intended use of which in or on drugs or devices is for purposes of coloring only and is unsafe within the meaning of section 379e(a) of this title.

20. Adulteration (b) Strength, quality, or purity differing from official compendium If it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standard set forth in such compendium.

21. Misbranding If an article is alleged to be misbranded because the labeling or advertising is misleading, then in determining whether the labeling or advertising is misleading there shall be taken into account (among other things) not only representations made or suggested by statement, word, design, device, or any combination thereof, but also the extent to which the labeling or advertising fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the labeling or advertising thereof or under such conditions of use as are customary or usual.

22. Label The term ''label'' means a display of written, printed, or graphic matter upon the immediate container of any article; and a requirement made by or under authority of this chapter that any word, statement, or other information appear on the label shall not be considered to be complied with unless such word, statement, or other information also appears on the outside container or wrapper, if any there be, of the retail package of such article, or is easily legible through the outside container or wrapper.

23. Labeling • The term ''immediate container'' does not include package liners. • The term ''labeling'' means all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article.

24. Generally • If a drug is mislabeled— • It is Misbranded • If drug not manufactured according to CGMPs • It is adulterated • If Drug does not conform to compendial standards and is labeled “USP” • It is adulterated • Drugs can be both misbranded and adulterated at the same time

25. Solid Oral Drugs • Must be marketed with an imprint that permits identification • Applies to Rx-only and OTC drugs • Exceptions where ‘impracticable’ • Sublingual Nitroglycerin tablets • Drug is misbranded without required identification

26. FDCA of 1938 • Grandfather Clause • Drugs on market before 1938 were not subject to review and NDA requirements • Avoided ex post facto clause • Did NOT establish prescription-only/OTC status of drugs • Some drugs were considered ‘safe’ only when used under medical supervision • Did not required drugs to be ‘effective’ for intended purposes

27. Distinguish “drug” and “new drug” and Grandpa The term ''new drug'' means - (1) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof, except that such a drug not so recognized shall not be deemed to be a ''new drug'' if at any time prior to June 25, 1938, it was subject to the Food and Drugs Act of June 30, 1906, as amended, and if at such time its labeling contained the same representations concerning the conditions of its use.

28. FDCA of 1938 • Recognized “Official Compendia,” privately published, that standardized drug quality • USP/NF Monographs • Chemical characteristics and quality standards of listed drugs • USP/NF merged • Homeopathic Pharmacopoeia of the United States • Anything published in official compendia is a drug

29. Articles in the FDCA • Food • Drug • Cosmetic • Dietary Supplements • Soap • An Article may be a food, a drug, a cosmetic and/or a dietary supplement • Depends on distributor’s CLAIMS

30. Foods and Cosmetics • The term ''food'' means (1) articles used for food or drink for man or other animals, (2) chewing gum, and (3) articles used for components of any such article. • The term ''cosmetic'' means (1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.

31. Drug The term ''drug'' means (A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C).

32. Dietary Supplement • A food or dietary supplement for which a claim, subject to sections 343(r)(1)(B) and 343(r)(3) of this title or sections 343(r)(1)(B) and 343(r)(5)(D) of this title, is made in accordance with the requirements of section 343(r) of this title is not a drug solely because the label or the labeling contains such a claim. A food, dietary ingredient, or dietary supplement for which a truthful and not misleading statement is made in accordance with section 343(r)(6) of this title is not a drug under clause (C) solely because the label or the labeling contains such a statement.

33. Dietary Supplements • The term ''dietary supplement'' - (1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described here. • Except for purposes of paragraph (g), a dietary supplement shall be deemed to be a food within the meaning of this chapter.

34. Important Amendments to FDCA • Durham-Humphrey Act of 1951 • Created 2 Classes of Drugs • Prescription-only (Rx only, prescription legend) • Rx-only legend must appear on manufacturer label • Safe only when used under medical supervision • ‘adequate directions for use not required if dispensed pursuant to prescription using a pharmacy label in its place • OTC • Safe to use without medical supervision and when accompanied by ‘adequate directions for use’ • Allowed oral transmission of prescriptions • Allowed prescription refills

35. Durham-Humphrey • Created § 503(b)(1) drugs (b)(1) A drug intended for use by man which— (A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or (B) is limited by an approved application under section 505 {New Drug} to use under the professional supervision of a practitioner licensed by law to administer such drug; shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.

36. Kefauver-Harris Act of 1962 • a/ka/ ‘Drug Efficacy Amendment’ • Thalidomide in Europe caused birth defects in children of pregnant mothers • All new drugs put on market after 1962 must be proven ‘effective’ for intended purposes • Now ‘new drugs’ must be safe and effective before given an NDA • Applied to drugs marketed between 1938 and 1962 • Established Drug Efficacy Study Initiative (DESI) • Burden on FDA to prove 1938-1962 drugs not effective • Established Informed Consent for Human Research Subjects • Implemented Good Manufacturing Practices • GMPs, CGMPs

37. Kefauver-Harris • Established DESI class of drugs for those marketed between 1938 and 1962. • Drug Efficacy Study Implementation • The DESI program was intended to classify all pre-1962 drugs that were already on the market as either effective, ineffective, or needing further study. The Drug Efficacy Study Implementation (DESI) evaluated over 3000 separate products and over 16,000 therapeutic claims. By 1984, final action had been completed on 3,443 products; of these, 2,225 were found to be effective, 1,051 were found not effective, and 167 were pending. • http://en.wikipedia.org/wiki/Drug_Efficacy_Study_Implementation • One of the early effects of the DESI study was the development of the Abbreviated New Drug Application (ANDA). More about this later

38. Kefauver-Harris Act • Another aspect of this act is that it gave authority to regulate Advertising and Marketing of: • Rx-Only and OTC drugs to the FDA • Dietary Supplements to the FTC • Federal Trade Commission • The Federal Trade Commission is the nation's consumer protection agency. The FTC's Bureau of Consumer Protection works For The Consumer to prevent fraud, deception, and unfair business practices in the marketplace. • http://www.ftc.gov/bcp/index.shtml

39. Points to Remember • Not all drugs on US market have an NDA • Pre-1938 drugs grandfathered • Examples: • digoxin, nitroglycerin, levothyroxine (thyroid products), phenobarbital • Important because not all drugs have an Orange Book rating even though there may be equivalents available • All drugs on US market must be manufactured according to GMPs (CGMPs) • Drugs put on market in US between 1938 and 1962 are safe and effective for labeled indications • “Adequate Directions for Use” applies to ALL drugs • Can remove and replace by prescription labeling on pharmacy label

40. Poison Prevention Packaging Act of 1970 • Not Part of FDCA • Administered by Consumer Product Safety Commission (CPSC) since 1973 • Purpose to prevent accidental poisoning of children under age five • Requires “Hazardous Household Products” to be marketed in child-resistant packaging • Immediate container or wrapping • With exceptions, ALL DRUGS are ‘hazardous household products’ subject to special packaging requirements

41. PPPA • Know drugs to which Act applies • Examples: • All oral dosage forms of • Aspirin • Controlled substances • Prescription drugs • Know drugs that have limited application: • Examples • Packages with more than 250 mg of non-injectable iron • Packages with more than 50 mg elemental fluoride or 0.5% • fluoride

42. PPPA • Know ALL Exceptions for drugs not required to be in child-resistant packaging • Examples: • Packages of less than 8 grams of erythromycin ethylsuccinate • Sublingual nitroglycerin tablets • Oral contraceptives dispensed in manufacturer’s mnemonic packaging • Packages of less than 105 mg prednisone tablets • One size of OTC line with label indicating package is not child-resistant

43. PPPA • Failure to Comply with PPPA is an act of misbranding • Patient may ASK for blanket waiver of child-resistant packaging for all dispensed prescription medication • Physician may ASK for non-child-resistant packaging only for single prescriptions • Request does NOT have to be in writing • BUT: “if its not documented, it didn’t happen’

44. Federal Anti-Tampering Act of 1982 • Not part of FDCA • Somewhat related to, but independent of PPPA • Enacted after intentional cyanide contamination of OTC products on drugstore shelves • Tylenol (TYMURS), Chicago • http://en.wikipedia.org/wiki/Chicago_Tylenol_murders • Most ORAL OTC drug products and many dietary supplements must have tamper-proof indicator or barrier that shows if package has been opened or tampered with

45. Medical Device Act of 1976 • Pre-Market Approval • GMP manufacturing standards • Performance Standards • Classified according to intended Use • Records and Reporting Requirements • Not a major focus of exam

46. Orphan Drug Act of 1983 • Limited reasons for manufacturers to invest in research and development because potential for return on investment limited or non-existent • Rare Disease < 20,000 persons in US • Tax incentives to manufactures • Not a major focus of exam

47. Drug Price Competition and Patent Term Restoration Act of 1984 • a/k/a “Hatch-Waxman Act” • Established Standards for marketing of ‘generic’ drugs without necessity of NDA process • Replaced with Abbreviated New Drug Application/Approval (ANDA) • Generics have to be ‘therapeutically equivalent’ to pioneer drugs • Generally, adds about 5 years of exclusivity (patent) rights to pioneer (innovator) company

48. Hatch-Waxman Act • FDA published “Orange Book” “Approved Drug Products with Therapeutic Equivalence Evaluations.” • Is Guideline Only • Some States Require Following it • Positive Formularies • Negative Formularies • Michigan is NOT and Orange Book State • If generic is chemically/pharmaceutically equivalent to Brand name prescribed generic interchange is permitted • DO NOT use term ‘generic substitution’ for DPS • Substitution is illegal in Michigan • Means to dispense a drug other than the drug prescribed • i.e., a different chemical entity • erythromycin vs. erythromycin ethylsuccinate • E-Par vs. EES

49. Prescription Drug Marketing Act of 1987 PDMA—Very Important • Prohibits re-importation of drugs produced in the US after they have left the US • Wholesalers must be licensed under state law according to federal standards • Bans the sale, trade or purchase of ‘drug samples • In Michigan, term is “complimentary starter doses” • Hospital pharmacies may ‘hold’ samples and ‘dispense’ them at request of a staff physician • Community pharmacies can NEVER have samples on premises or face large fine. • Distribution of samples are strictly regulated • Record-keeping and storage mandates • Institutions (hospitals) cannot sell drugs to community pharmacies unless there is a ‘bone fide’ emergency • Hospitals usually get special discount pricing

50. Robinson-Patman Act of 1936 • NOT an amendment to FDCA • Is part of the Antitrust Laws • a/k/a/ ‘Anti-Price Discrimination Act’ • Prohibits institutions (hospitals) that buy drugs at favorable discounted rates from selling drugs at cost to others—primarily community pharmacies • “Own Use” Doctrine • ‘Bone fide emergency’ exception • http://uwacadweb.uwyo.edu/PHARMACYNOTES/Casey%20Wood/unit%205%20core%20ctw.pdf