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Excerpt from Upton Sinclair The Jungle (1905)
It was only when the whole ham was spoiled that it came into the department of Elzbieta. Cut up by the two-thousand-revolutions-a-minute flyers, and mixed with half a ton of other meat, no odor that ever was in a ham could make any difference. There was never the least attention paid to what was cut up for sausage; there would come all the way back from Europe old sausage that had been rejected, and that was moldy and white--it would be dosed with borax and glycerine, and dumped into the hoppers, and made over again for home consumption. There would be meat that had tumbled out on the floor, in the dirt and sawdust, where the workers had tramped and spit uncounted billions of consumption germs. There would be meat stored in great piles in rooms; and the water from leaky roofs would drip over it, and thousands of rats would race about on it. It was too dark in these storage places to see well, but a man could run his hand over these piles of meat and sweep of handfuls of the dried dung of rats. These rats were nuisances, and the packers would put poisoned bread out for them, they would die, and then rats, bread, and meat would go into the hoppers together. This is no fairy story and no joke; the meat would be shoveled into carts, and the man who did the shoveling would not trouble to lift out a rat even when he saw one--there were things that went into the sausage in comparison with which a poisoned rat was a tidbit. There was no place for the men to wash their hands before they ate their dinner, and so they made a practice of washing them in the water that was to be ladled into the sausage. There were the butt-ends of smoked meat, and the scraps of corned beef, and all the odds and ends of the waste of the plants, that would be dumped into old barrels in the cellar and left there. Under the system of rigid economy which the packers enforced, there were some jobs that it only paid to do once in a long time, and among these was the cleaning out of the waste barrels. Every spring they did it; and in the barrels would be dirt and rust and old nails and stale water--and cart load after cart load of it would be taken up and dumped into the hoppers with fresh meat, and sent out to the public’s breakfast. Some of it they would make into “smoked” sausage--but as the smoking took time, and was therefore expensive, they would call upon their chemistry department, and preserve it with borax and color it with gelatine to make it brown. All of their sausage came out of the same bowl, but when they came to wrap it they would stamp some of it “special,” and for this they would charge two cents more a pound. Such were the new surroundings in which Elzbieta was placed, and such was the work she was compelled to do.
FEDERAL REGULATION OF MEDICATIONS
I. HISTORICAL OVERVIEW A. Pure Food and Drug Act of 1906 1. United States v. Johnson B. The Federal Food, Drug, and Cosmetic Act of 1938 (FDCA) 1. United States v. Sullivan C. Durham-Humphrey Amendment of 1951 D. Food Additives Amendment of 1958 E. Color Additive Amendments of 1960 F. Kefauver-Harris Amendment of 1962 G. Medical Device Amendments of 1976 H. Orphan Drug Act of 1983 I. Drug Price Competition and Patent Term Restoration Act of 1984 J. Nutrition Labeling and Education Act of 1990 K. Prescription Drug User Fee Act of 1992 (“PDUFA”) L. Dietary Supplement Health and Education Act of 1994 (“DSHEA”) M. Food and Drug Modernization Act of 1997
See Brief History of the Center for Drug Evaluation and Research (CDER) http://www.fda.gov/cder/about/history/default.htm; Milestones in U.S. Food and Drugs Law History http://www.fda.gov/opacom/backgrounders/miles.html
II. DEFINING AND DISTINGUISHING DRUGS FROM FOODS, DEVICES AND COSMETICS A. The Law 1. Statutory definitions of food, drug, counterfeit drug, device, cosmetic are found in 21 U.S.C.
§ 321 and are recited in the textbook
B. Explanation of the Law 1. Crucial issue in determining if a product is a drug is whether the supplier makes a therapeutic
claim (i.e., is the product intended to diagnose, cure, mitigate, treat, or prevent a disease and, for products that are not a food, whether it is intended to affect the function or structure of the body)
2. Action on Smoking & Health v. Harris 655 F.2d 236 (D.C. Cir. 1980) (held cigarettes are not
drugs unless a vendor makes therapeutic claims)
3. FDA v. Brown & Williamson 529 US 120 (2000)2 (after FDA promulgated regulation
designed to reduce youth smoking, court held the FDA does not have jurisdiction over cigarettes)
4. National Nutritional Foods Ass’n v. Mathews 557 F.2d 325 3(high doses of vitamins A& D
are not drugs without therapeutic claims)
http://www.fda.gov/opacom/laws/fdcact/fdcact1.htm http://www.law.cornell.edu/supct/html/98-1152.ZS.html 2
C. Food Versus Drugs 1. Nutrilab, Inc. v. Schweiker 713 F.2d 335 (7th Cir. 1983) (2nd Cir. 1977) 4 Court held that a
starch blocker is a drug because: (i) it was intended to affect the structure and function of the body and (ii) was not a food. It did not fall within the definition of food simply because the active ingredient was derived from kidney beans, which are food.
2. Special Dietary Foods a. Distinguish dietary foods from dietary supplements (i) (ii)
See definition in textbook (also 21 U.S.C. § 350 (c ) (3)(A)) 5 Key aspect of the definition of “special dietary food” is that the food is for persons with a particular “condition” (e.g., disease, convalescence, pregnancy, overweight)—N.B. There is no such requirement for dietary supplements
3. Medical Foods a. Foods formulated for oral use intended for management of a disease requiring specific
dietary NUTRIENTS (H21 USC § 360EEH) (e.g., phenylketonuria)
4. Nutraceuticals and Functional Food a. These terms have no legal meaning but are often used in the dietary supplement industry 5. Health Claims for Foods (i)
In U.S. v. Article of Drug Labeled as Exachol, 716 F.Supp. 787 (S.D.N.Y. 1989) the court held that Exachol (which contained various compounds intended to prevent coronary thrombosis, arteriosclerosis, etc.) could be considered a drug and a special dietary food (ii) Because Exachol was intended for people who already have a heart condition or high cholesterol, it fell within the definition of special dietary food. (iii) Exachol also fell within the definition of a drug (iv) Because the FDA had previously allowed companies whose products were both special dietary foods and drugs to market their product without premarketing approval as a new drug (e.g., Kellogg’s All Bran and fish oil products), the FDA could not treat Exachol differently and Exachol could be marketed with these claims
b. Additional Resources c. GAO Report on Functional Foods and Dietary Supplements @
d. What Can Your Food Do For You? (And Should FDA Let It?): An Overview of the
Regulatory Regime (or Lack Thereof) Surrounding Functional Foods, Julie Melissa Baher @ leda.law.harvard.edu/leda/data/754/Baher06.rtf (you may need to cut and paste this link instead of simply clicking)6
http://www.altlaw.org/v1/cases/480567 http://bulk.resource.org/courts.gov/c/F2/713/713.F2d.335.82-2747.82-2746.html 5 http://www.law.cornell.edu/uscode/21/usc_sec_21_00000350----000-.html 6 For an excellent source of articles by law students on a wide variety of food and drug law topics, see http://www.law.harvard.edu/faculty/hutt/table_of_contents_2002.html
and Cosmetic Act (“FDCA”).D. National Nutrition Labeling and Education Act of 1990 (NLEA): prohibits disease prevention claim in food labeling unless the FDA promulgates a regulation approving the claim and defining the conditions under which the claim can be used. A product intended for ingestion. 1999). defined as dietary supplements. a. Cir. high fiber (cancer prevention). a. Examples: (i) certain high calcium foods can make limited claims regarding osteoporosis. A product that contains one or more of the following ingredients: (i) (ii) (iii) (iv) (v) a vitamin a mineral an herb or other botanical an amino acid a dietary substance for use by man to supplement the diet by increasing the total dietary intake. Dietary Supplements 1.html b. b. Drug. (ii) certain low sodium foods can make claims that a low sodium diet can reduce the risk of high blood pressure.com/lw/19990202/985043. and c. The Food and Drug Administration Modernization Act (FDAMA) changed the requirements of the NLEA so that a food distributor can make claims without an FDA regulation as long as there is “significant scientific agreement” as defined by the FDA.fda.3d 650 (D. constituent. as described above. 164 F. metabolite. (i) In Pearson v. Dietary Supplement Defined a. or (vi) a concentrate. Shalala.bna.cfsan. (iii) certain fiber containing foods may reduce risk of cancer—see the following website for description of permissible claims and citations to the regulation in the CFR: http://www. Summary of Dietary Supplement Health Education Act (DSHEA): Sellers of certain products. A Product to supplement the diet. and folic acid (neural tube defects). The court concluded that the standard for “significant scientific agreement” was too vague and that the FDA could regulate the commercial speech with less burdensome means such as disclaimer that would say something like: “The evidence is inconclusive because existing studies were performed with foods containing antioxidant vitamins and the results could be due to other components in the food. omega-3 fatty acids (coronary heart disease). The FDA promulgated rules for a variety of foods that contain disease prevention claims. Just like with foods.gov/~dms/flg-6c.” 3. can make claims regarding a product’s effect on the structure and function of the body without being considered a “drug” under the Food. extract.htm 4 . a seller of dietary supplements may make “disease prevention” claims under NLEA and FDAMA if there is “significant scientific agreement” about the claim. or combination of the above 7 http://lw. 2. 7the court held that the FDA unlawfully restricted sellers of certain dietary supplements from making disease prevention claims for antioxidant vitamins (cancer prevention).C.
if product contains an ingredient that is poisonous or deleterious to health if used as directed 11.” a. FDA has burden to prove a dietary supplement is adulterated 10. .htm 5 . gel caps. does . is physically separate from the dietary supplement. .washburnlaw. 7. or c. the active ingredient cannot be marketed as a dietary supplement. . certification. Dietary supplements can be marketed in a variety of dosage forms including tablets. . does not promote a particular manufacturer. Depending on the claims made. is presented with other subject matter to present a balanced view. Secretary of HHS personally declares that an ingredient poses an imminent hazard to public health or safety. . . an article that is approved as a new drug under section 355 of [the FDCA] . if the whole product or the active ingredient of a product has been approved as a new drug.3d 1151 (10th Cir. . . 10th Circuit agreed with FDA’s interpretation of DSHEA and remanded the case to district court for further determination. capsules.” b. In other words. “It presents a significant or unreasonable risk of illness or injury under conditions of use. Shalala 221 F. Labeling for dietary supplements does not include publications printed in their entirety if it: (i) (ii) (iii) (iv) (v) is not false or misleading. definition of “drug” in the FDCA was changed to exclude dietary supplements making certain types of claims. Under DSHEA. etc. Burden of Proof a. The term “dietary supplement . . licensing. . recommended in the product labeling. a single product can be both a dietary supplement and a drug 9. 5. liquids. Pharmanex v. or authorization marketed as a dietary supplement or as a food . Dietary supplement is adulterated if: a.edu/cases/2000/07/99-4087. and does not have appended other information by a sticker or other method 8 http://ca10. Labeling Exemption a. 2000) 8— FDA claimed that red yeast rice containing lovastatin was not a dietary supplement because it contained an “article” that was not marketed as a dietary supplement prior to the time Mevacor was approved as a new drug. . 6. which was not before such approval. include . . .4. Label must explicitly state that product is a “dietary supplement” 8.
illness or disease.J. there must have been a placing of male sperm within the female genitals. U. and. This product is not intended to diagnose. or prevent any disease. Definition of device attempts to distinguish drugs from devices by noting that a device does not achieve any of its principal intended purposes through chemical action or depend on being metabolized to achieve of its principal intended purposes. and (iv) describes general well-being from consumption or a nutrition or dietary ingredient. there must have been thereafter an interruption of the female menstrual cycle. Permissible Claims a. or (ii) describes the role of a nutrient or dietary supplement intended to affect the structure or functions of the body (iii) characterizes the documented mechanism by which a nutrient or dietary ingredient.S. One. burdened with original sin.pdf 6 . v. v.ca10.S. 394 U. 414 F. and The label states prominently and in boldface type “This product has not been evaluated by the Food and Drug Administration.S. and b. is not a test for the diagnosis of disease.12. then. 2006) 9 (held FDA met its burden to show all doses of Ephedra It presents a significant or unreasonable risk of illness or injury under conditions of use. 1975) pregnancy testing kit is not a drug—excerpt from the court’s opinion below: The condition of pregnancy. Drugs vs. A test for pregnancy. cure.3d 1033 (10th Cir. Devices 1. . treat. U. Von Eschenbach. Article of Drug Ova II. All other mortals. 9 http://www. Pregnancy is an execution of an inherent bodily function and implies no ailment. is a normal physiological function of all mammals and cannot be considered a disease of itself.S. recommended in the product labeling) E.. a. Both parties agree that this is so. There is only one widely recognized instance of immaculate conception. 784 (1969) holding antibiotic sensitivity disks are covered by definition of drug b. as such. two. Nutraceutical Corp. .Supp. v.” 13. It is also a fact that there is no occasion for anyone to perform a pregnancy test unless there is a prior factual history to justify it. At least two events must have occurred before any question of a pregnancy can arise. which may be either good news or bad news depending on whether pregnancy is wanted or not. Other conditions for permissible claims (i) (ii) The manufacturer has substantiation that such a statement is truthful and not misleading. 660 (N. must have these two events occur before performing a pregnancy test for any purpose other than an academic one. It is no more than a test for news.uscourts. Safety Issues and Ephedra Products a. A statement regarding dietary supplement may be made if the statement: (i) claims a benefit related to a classical nutrient deficiency disease and discloses the prevalence of the disease in the U. 4459 F. Article of Drug Bacto Unidisk.gov/opinions/05/05-4151.
a.html 7 . The FDA uses several factors to decide whether a product is a device or a drug. United States Pharmacopoeia (USP/NF) 2. AND ENFORCEMENT A. Seizures 3.. 658 (1975) President of national grocery company was criminally liable even though president did not know of the violations because he had a duty to seek out and correct violations of the law b. F. U. v.2d 157 (2nd Cir. Labeling: all labels and other written material either upon container or accompanying an article (broader term than label) a. Label: a display of written. U. PENALTIES. Official compendia 1. FDA can use its seizure authority See FDA Website for recent product recalls. Unlike most criminal statutes that require an intentional or knowing mens rea (state of mind or guilty mind).fda. Enforcement 1. printed. Product Recalls 1. FDA cannot force a recall. but if a manufacturer does not comply with recall request. Cosmetics become drugs when the manufacturer makes therapeutic clams G.S.320 421 U.gov/opacom/7alerts.S. Homeopathic Pharmacopoeia of the United States (HPUS) III.S. C.S. Class II .Reversible effects or remote chance of serious effects c. or graphic matter upon immediate container 2. v. Dotterweich U. Injunctions B. Classifications a. Cosmetics 1. 277 (1943) President of repackaging company was convicted of adulteration and misbranding even though he had no personal knowledge of the wrongful acts. These criteria are in the text. v.10 2. U.2. Label and Labeling 1. Criminal penalties (fines and imprisonment) 2. Class III . Guardian Chemical Corp. the FDCA imposes criminal penalties on corporate officers even if they do not have personal knowledge of violations. Drugs vs.Serious health effects or death b. Corporate Officer Liability 1. H. 410 F.S. Class I . 1969) Court held that dairy machine cleaning product became a drug when manufacturer provided brochures to medical professionals promoting the product because the brochures accompanied the products and constituted labeling even though the brochures were not shipped with the product. PROHIBITED ACTS. Park.Unlikely to cause adverse health effects 10 http://www.
Drug strength or purity differs from what it purports to be h. Key concept for adulteration is to ensure purity 3. Misbranding: a. Decomposed. Contains unsafe color additive f. c. Labeling is false or misleading in any particular (i) Health care economic information presented to formulary committee in the course of selecting drugs for managed care organizations is not considered false or misleading if the information relates directly to an approved indication and is based on competent and reliable scientific evidence.gov/foi/warning_letters/s6873c.gov/scripts/wlcfm/indexdate.fda. b. Label does not state name and address of manufacturer and accurate statement of quantity 11 12 http://www. FDA GMP regulations can be found at: http://www. Not manufactured in compliance with Good Manufacturing Practices (GMP) d. A product packaged in violation of the tamper-resistant packaging regulations is adulterated b.pdf 8 . etc.accessdata. CGMPs do not generally apply to pharmacists unless a pharmacist is manufacturing f.cfm http://www.fda. Misbranded Drugs 1. Unsanitary conditions for packing.html b.D. Intended to ensure that a drug is safe and meets the quality and purity requirements e. if broken. storage. Container consists of poisons that can leach into contents e. Product Tampering a.gov/CDRH/DEVADVICE/32. FDA warning letter index 11 c. Applies to OTC products E. or filthy materials b. Explanation of Adulteration a. Manufacturers generally inspected every 2 years 4. gives visible evidence of tampering 2. Sample FDA warning letter for violation of GMP12 d. putrid. Drug varies from USP or HP unless the label states the deviation from compendial standards g. Adulteration: a.fda. OTC drug not in tamper-resistant container (i) Tamper resistant package contains barrier which. Current Good Manufacturing Practice (“CGMP”) a. Adulterated Drugs 1.
Drug endangers health if used as labeled k. Drug listed in USP. Does not contain the proportion of each active ingredient and the proportion of certain specific compounds listed in the law f. Prescription drug omitting generic “established name” in type not less than one-half the size of trade name e. If at any time prior to dispensing the label fails to bear. but not labeled and packaged by compendial standards h. from advertisements and other descriptive printed matter o. Contains color additive and is not labeled or packaged in conformity with requirements of the FDCA l. the symbol “Rx only” 9 . Drug is subject to deterioration without precautions i. warnings. Advertisement fails to include generic or established name or other required information in type at least half as large as the brand name p. or sold under name of another drug j.c. Inadequate directions for use and inadequate warnings (i) This requirement is not necessary for prescription drugs and forms the distinction between OTC and prescription drugs g. at minimum. etc. Drug and manufacturer not registered with FDA m. Omits summary of side effects. Required information not prominently displayed and written in a way likely to be understood by ordinary individual customer d. Not packaged in accordance with Poison Prevention Packaging Act when applicable n. Misleading packaging or imitation of another drug.
New user friendly labeling regulations for OTC products went into effect in 1999 and have been modified from time to time since then b. ephedrine.gov/cder/otc/label/quesanswers. the drug is a prescription drug and the labeling must contain Uinformation directed to the prescriber. Professional Labeling (i) This is a type of labeling provided to health professionals for use of OTC products that are not safe for lay diagnosis or treatment 13 http://bulk. Kenzia Note the 3 factors that the court in U. but package insert must describe drug abuse and dependence when applicable. Habit Forming Drugs (i) No longer required after FDAMA. Adequate “Information” for use (i) (ii) Distinguish from adequate “directions” for use If a drug cannot meet the “adequate directions for use” standard. False or Misleading Labeling b. Articles of Drug (Midwest Pharmaceuticals).1238.html 10 . Established Names of Drugs (i) (ii) (i) (ii) Requires list of active ingredients for prescription and OTC products Must also list inactive ingredients d. c. Batch Certification (i) No longer required (previously required for insulin and antibiotics) 3.org/courts. Explanation of Misbranding (concerns representations made by manufacturer) a. and phenylpropanolamine were imitation drugs g. Note the 6 pieces of information that are necessary for a drug to have adequate directions for use (p. Nonprescription Drug Labeling a. The general requirements are described in the text on pp.F2d.S. 825 F.59-60 of the text. 58-59) f. 1987) 13used to determine that tablets containing caffeine. not the patient (iii) Note the 6 categories of information that must be included in the labeling to meet the “adequate information for use” standard (p.2d 1238 (8th Cir.resource. v.2.gov/c/F2/825/825. Adequate “Directions” for Use This means the directions under which a layperson can a drug safely and for the purpose for which it was intended.86-1438.fda. Helpful websites for the rules and for questions and answers about OTC labeling are: (i) OTC Labeling: Questions and Answers www. Imitation Drugs (i) (ii) See People v. 58 of text) e.htm d. c.
3922-3997.55.1. §201. The Package Insert (a) (b) 71 Fed.access.gov/ora/compliance_ref/cpg/cpgdrg/cpg430-100. 3999-4000 20 New inserts are supposed to reduce preventable adverse drug events by making drug information more easily accessible.gpo.57.access.gov/2006/pdf/06-544. Reg.gpo.fda. § 201. e.pdf http://edocket.1016 See 21 CFR § 201. Reg.56. (vi) Black Box Warnings (vii) Pregnancy Warnings Categories A ->D and X 22 (v) 14 15 http://edocket.14 § 201. Drugs that are both OTC and Rx (i) (ii) Some drugs are available in different strength with an Rx than when provided OTC Some drugs are OTC with certain indications.1.gpo. 3998-3999.100 c. Reg.100 17 FDA finalized new requirements for package inserts in 2006 d.pdf 21 http://www.100. but prescription for additional indications 4.gov/cfr_2001/aprqtr/pdf/21cfr201.gov/2006/pdf/06-543.html 17 http://edocket. Unit Dose Labeling (i) (ii) (i) (ii) The amount of information on the label of unit dose packages is more limited than for regular stock bottles. 2006 (a) Changes include: (1) (2) (3) (4) Table of contents Highlights section Black Box Warnings Patient Counseling Information (iv) Daily Med 21is an online clearinghouse for providing health professionals access to drug information Package insert intended to give the “learned intermediary” (the prescriber) sufficient information to use the drug safely and effectively for individual patients. more memorable. See FDA Compliance Policy Guide 71132b.55.gpo.18 71 Fed. See 21 CFR § 201.pdf 20 http://edocket.access. (iii) Applies only to drug applications submitted after June 30. this labeling is provided to health professionals in the mail or in a communication that does not reach the public (iii) Although a pharmacist can legally recommend an OTC product for a non-indicated use. The required information is sufficient to provide an audit trail of what the drug is and where it came from in case of a recall. 2006 and will be phased in for drugs approved 5 years prior to June 30.(ii) Normally.gov/cder/news/FactsatFDA.access.19 71 Fed.access.pdf 19 http://edocket.15 §201. and less complex.gov/2006/pdf/06-545.gpo.pdf 16 http://www.access.gov/cfr_2001/aprqtr/pdf/21cfr201.gov/cfr_2001/aprqtr/pdf/21cfr201. Prescription Drug Labels and Labeling a.htm 11 .gpo. Commercial Container Label b. a pharmacist should not give a patient professional labeling unless the patient asks for it.pdf 18 http://edocket.fda.
. or Any drug . 5. otherwise than in such investigations. has become so recognized. drug manufacturers. among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs.gov/bbs/topics/NEWS/2005/NEW01272. UexceptU that such a drug not so recognized shall not be deemed to be a ''new drug'' if at any time prior to June 25. but which has not. and others. . NDC number identifies: (i) drug manufacturer or distributor (labeler code) (ii) drug name (product code) (iii) package size (package code) c. wholesalers. New FDA Drug Labeling Regulations— See FDA Press Release FDA Announces New Prescription Drug Information Format to Improve Patient Safety 23January 18.htm http://www. Drug Listing Act of 1972 required NDC for all drugs covered by FDCA e. National Drug Code Number (NDC) a. 1906.html 12 . Ten character code d.5. 3.the composition of which is such that such drug. b. been used to a material extent or for a material time under such conditions.com/exposures/Drugs/FDACategories. Understanding the meaning of new drug is essential to understanding the overall FDA regulatory scheme. or suggested in the labeling thereof. “New Drug” means: 2. private insurers. 2006 IV. Intended to facilitate automated processing of drug data by government agencies. recommended. as a result of investigations to determine its safety and effectiveness for use under such conditions. the composition of which is such that such drug is not generally recognized. Summary of definition: a drug that is not generally recognized as safe and effective by qualified experts for use under the conditions recommended in the labeling.fda. . Grandfathered drugs: Drugs marketed before 1938 are exempt from proving either safety or efficacy provided that it is marketed in accordance with the labeling requirements as then existed.perinatology. Now required as part of manufacturer’s prescription and OTC label (i) (ii) NDC is required to be part of a linear bar code with the intention to reduce medication errors Drug may have an NDC without an approved NDA f. Any drug . and if at such time its labeling contained the same representations concerning the conditions of its use. it was subject to the Food and Drugs Act of June 30. . 22 23 http://www. 4. as safe and effective for use under the conditions prescribed. 1938. NEW DRUG APPROVAL 1. as amended.
F2d. Notice of Claimed Investigational Exemption for a New Drug (also called Investigational New Drug Application (IND)) 3. d. reporting other distribution information to FDA (i) d.89-2088. Clinical Investigators.89-2087.S. 1990) 24 C.1401. If FDA does not reject the IND within 30 days of submission.fda.html http://www.org/courts.fda. c.gov/cder/handbook/phase2. f. 2.gov/c/F2/901/901. IND is an exemption to FDCA law prohibiting interstate shipment of drugs unless proven safe and effective 5. Participants must know the risks. Road to Approved New Drug Application 1.htm 13 .gov/cder/handbook/phase3.gov/cder/handbook/phase1. controlled studies. Drug is also considered a new drug if it is: a.B. Investigational Review Board (IRB) must approve studies conducted in institutions.fda. See FDA Information Sheet Guidances for IRBs. Approved Drugs as “New Drugs” 1. Evidence of safety and efficacy must come from animal and human clinical studies. and Sponsors at HUhttp://www. 901 F. metabolism. and alternative course of treatment. U. new intended uses) 2. or e. An established drug with new medical claims (i.gov/oc/ohrt/irbs/U 24 25 http://bulk. but new drugs cannot move in interstate commerce. clinical trials may begin c. Baxter Healthcare Corporation. absorption.htm 27 http://www. Investigational New Drug Application a.resource.fda. IND necessary before a manufacturer can ship drug in interstate commerce for clinical trials 4. v. Phases of clinical drug testing Phase I:25 small number of subjects. Contents of an IND (i) (ii) (iii) (iv) (v) (vi) Name of drug Composition of drug Methods of manufacturing and quality control Information from preclinical (animal)studies Outline of proposed clinical trials Experience and qualifications of clinical investigators b. test for safety and efficacy—usually doubleblinded and compared with a placebo control group (iv) Postmarketing: information on further adverse effects. investigate toxicity. elimination. and route of administration (ii) Phase II:26 initial trials on limited number of subjects for specific disease to determine the efficacy of the drug and the dosages at which efficacy occurs (iii) Phase III:27 large number of subjects. b.2d 1401 (7th Cir.htm 26 http://www. possible benefits. Drug contains a new substance New combination of approved drugs The proportion of ingredients change An established drug that is available in new dosage forms or at new dosage levels or is packaged in novel materials such as plastic.e. Informed Consent e.
6. For therapeutic potential . NDA contains all of the information that the manufacturer has acquired during its investigations b.178. the FDA uses a two letter system: (i) Priority (P) represents a therapeutic advance (a) (b) (c) No other effective drug available It is more effective or safer than current drugs Drug has an important advantage (ii) Standard (S) represents standard (i. The New Drug Application (NDA) a.030 8.fda.fda. replacing currently available agent) (iii) The S & P system replaces the old A.000 $589. d. benefit of drug e. Lowest priority: Drug is a product previously marketed by the same firm (used primarily for new indications) d. Termination by FDA: The FDA may terminate a clinical trial any time if it appears too dangerous.gov/cder/regulatory/applications/ c. Prescription Drug User Fee Act (PDUFA) has decreased the review time for NDAs— new drug applicant pays fees (i) See http://www.e. but delays often occur. FDA reviews the application and is required to act on it within 180 days.700 $65.000 $392. FDA Drug Rating and Classification a. During its review FDA determines risk vs. System to classify drugs by chemical type and therapeutic potential b.gov/CBER/pdufa.htm for details about PDUFA Fee Category Fee Rates for FY 2008 72 Federal Register 58103-58106 APPLICATIONS Requiring clinical data Not requiring clinical data Supplements requiring clinical data ESTABLISHMENTS PRODUCTS $1. Six designations for chemical type (i) (ii) Highest priority: Active moiety is a new molecular entity.B. 14 . Priority (P) and Standard (S) c. 7.000 $589. See FDA (CDER) website Drug approval Application Process http://www. C ratings.
. See FDA Postmarketing Surveillance Programs at http://www. change in manufacturing facility where the new facility does not differ materially from the previous facility).g.fda. 28 http://www. Review of several thousand drugs approved between 1938 and 1962 to determine (i) Remember: The definition of “new drug” means drugs “not generally recognized as safe and effective. Drug Efficacy Study Implementation (“DESI”) 1. (ii) New drug definition excludes drugs used prior to 1938 if such drugs are marketed in accordance with the labeling requirements prior to 1938. Manufacturer must maintain post marketing records and reports and must submit reports of serious adverse drug reactions and new information about safety and efficacy to the FDA. V. Studies required by FDA and conducted to obtain additional data of a drug’s safety and efficacy and to determine new uses for the drug.htm 10. b.gov/cder/regulatory/applications/Postmarketing/surveillancepost. FDA commissioned National Academy of Sciences/National Research Council (NAS/NRC) See Marketed Unapproved Drugs—Compliance Policy Guide 28for more details about DESI efficacy for indicated uses a. (iii) “Reported changes” are minor changes that the manufacturer only needs to report in its annual report. Three categories (i) “Prior approval” from the FDA is required for changes in production (e. or for certain changes in manufacturing (e. but no requirement to prove efficacy. Supplemental NDAs have lower priority than new NDAs 9.g. manufacturing process) and most labeling changes (ii) “Change being effected” supplement allows manufacturers to implement a change before the FDA approves the change. (iv) Thus. Examples of such changes include editorial changes in labeling and changes in container size.htm 15 . Changes in this category include changes that strengthen warnings or dosage and administration information.e.. Supplemental New Drug Application f. these 1938 to 1968 drugs were new drugs and had to be shown to be effective. Phase IV Studies a. g.gov/cder/regulatory/applications/Postmarketing/surveillancepost. (iii) Drugs approved after 1938 and before 1962 had to be safe. GENERIC DRUGS AS NEW DRUGS A. Postmarketing Surveillance a.fda. synthesis.
Generix. 640 (1973) 29 Weinberger v. Weinberger.lp. 1975). U. the court held that FDA could not allow marketing of generic drugs until after the ANDA process had been completed.S.2d 221 (4th Cir.pl?court=us&vol=460&invol=453 33 http://www. v. 103 S.. Drug Competition and Patent Restoration Act (Hatch-Waxman Act) 1984 1.lp. 412 U. Allows a manufacturer of a generic drug to obtain approval based on bioequivalence and bioavailability studies.findlaw. 412 US. v.pl?court=US&vol=412&invol=655 32 http://caselaw.b. 2. The FDA approved generic drugs with only bioavailability studies and eventually allowed some manufacturers to market generic drugs while final approval was pending. d. Cir.C.Ct.com/scripts/getcase. 4.org/v1/cases/533850 16 . Inc. Innovator company can obtain an additional 2 to 5 years of patent term extension for some of the time the drug was in FDA review.findlaw. 1298 (1983) 32 (the term “drug” was intended by Congress to include the entire drug product. v. Supreme Court cases together held the FDA had authority to determine which drugs were new drugs and upheld FDA’s authority to retroactively require proof of efficacy for pre-1962 drugs. 1981) 33 –The court held the FDA had authority to create guidelines allowing paper NDAs that allow generic manufacturers to receive approval of their drugs based on previously published studies of safety and efficacy. a.S. c.S.S. Shalala. 890 (D.com/cgi-bin/getcase.Supp. Burroughs Wellcome Co.com/scripts/getcase. The first generic drug company to market a drug has a 180-day exclusivity period. therefore a generic drug is a drug under the FDCA and subject to the requirements for new drugs) HU U H B. Schweiker. 1996).findlaw. Cir.altlaw. Paper New Drug Application a.C. v. Panel classified drugs according to efficacy (i) (ii) (iii) (iv) (v) (vi) U U U U U U Effective : Evidence justifies claim Probably Effective : More evidence is needed to support claim Possibly Effective : Substantially more research needed to support claim Ineffective : (no acceptable evidence) Effective but : Other more effective or safer drugs available Ineffective as a Fixed Combination : No added benefit of combination over single ingredient U U U U U U 2. Weinberger 425 F. Extent and rate of absorption cannot be significantly different from innovator drug 3. Bentex Pharmaceuticals.lp. Ciba Corp.findlaw. HU UH HU U HU U 3.lp. 645 (1973) 30 USV Pharmaceutical Corp. 655 (1973) 31 FDA conducted DESI review for generic and for innovator drugs. b. In Hoffman LaRoche.pl?court=us&vol=412&invol=645 31 http://caselaw. HU U H C. v. Three U. Weinberger. complete with active and inactive ingredients. 4. In Bristol-Myers Squibb Co. 649 F. 29 30 http://caselaw.com/cgi-bin/getcase. Inc. 5.3d 1493 (D.pl?court=US&vol=412&invol=640 http://caselaw. the court held that FDA can approve a generic drug even if the innovator manufacturer had an additional indication that the generic company cannot include in its labeling. 412 U. 91 F.
00 OTC products on the market. v. the FDA can approve an investigational drug for Uwidespread access outside the controlled clinical trialsU to treat “serious” or “life threatening” diseases only if it meets the following criteria: a. If an ingredient was safe and effective.g. Under FDAMA. warnings.fda.gov/ohrms/dockets/AC/07/slides/2007-4323s1-02-FDA-Chang. Category II: Ingredients not GRAS c. The widespread use will not interfere with ongoing clinical trials f. 5.ppt. 442 U. Despite the FDA’s efforts. The FDA evaluated OTC products marketed between 1938 and 1962 to evaluate whether the products were effective. even for terminally ill patients. the safety and efficacy requirements of the FDCA have meaning.gov/cder/drug/unapproved_drugs/ 2. F. Sponsor is actively pursuing FDA approval e. Marketed Unapproved Drugs 1. Category I: ingredients generally recognized as safe and effective (GRAS) b. Instead the FDA evaluated “therapeutic categories. See e. Supp 838 (D.” 4. Category III)) E. Rutheford. Patient Treatment with Investigational Drugs (§ 561) 1. Defendants had argued that the safety and efficacy standards had no meaning for terminally ill patients because they would certainly die without the drug.fda. Drug is under investigation in clinical trials for the disease or the clinical trials have been completed d. Because there were between 100.S. 1979) (court held FDA could not promulgate regulations allowing drugs to stay on the market without evidence of safety and efficacy (i. Cutler v. 2.D. there are still thousands of drugs being marketed without FDA approval.findlaw. Its use is for a “serious” or “immediate life threatening” disease b. There is sufficient evidence of safety and effectiveness for use in a “serious” disease 34 http://caselaw.com/scripts/getcase.lp. Category III: Insufficient data to determine if GRAS d.e. 3. 6. No comparable or satisfactory treatment is available c. Kennedy. Regulatory History of Pediatric Cough and Cold Products at http://www. etc. The FDA published monographs for each ingredient in the Federal Register. the FDA did not conduct a product-by-product review—instead the FDA evaluated the 200 active ingredients on the market. the monograph specified the permissible labeling for the drug including the indication.. Over-the-Counter Drug Review 1. U.S.D. 475 F. See FDA website Drugs Marketed in the United States That Do Not Have Required FDA Approvalhttp://www.pl?court=US&vol=442&invol=544 17 .C. 544 (1979):34 Court held that a compound intended to treat cancer (laetrile) was a drug because. Case law a. dosage.000 and 500.. FDA created three categories of OTC products a.
Individual Patient Access to investigational Drugs for serious Diseases (Parallel Track Policy) (§ 561) 1. toxin. expanded access to investigational drugs for treatment use would be available to individual patients. The drug is intended for treating a life threatening or serious disease and demonstrates a potential to address an unmet need b. or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound). antitoxin. e. including in emergencies. may provide an investigational drug for treating a serious disease if the FDA determines: a.S. FDA issued Proposed Rules for Charging for Investigational Drugs and Expanded Access to Investigational Drugs for Treatment Use 36 “Under the proposal.edu/uscode/uscode42/usc_sec_42_00000262----000-. Von Eschenbach 445 F.5. or cure of a disease or condition of human beings. applicable to the prevention.com/us/cfr/title21/21-5. Expedited Approval of Drugs Intended to Treat Life-Threatening Disease (“Fast Track Approval”) (§ 506) (See http://law. upon request of an individual acting through a physician. intermediate-size patient populations. or analogous product. There is no constitutional right to receive drugs in phase I or II trials.htm 37 http://www4. A manufacturer.uscourts. The patient has no comparable or satisfactory alternative treatment and the risks from the investigation drug are no greater that the probable risks from the disease b.gov/docs/common/opinions/200611/04-5350b. The drug has an effect on a clinical endpoint or surrogate endpoint VI.C. treatment. significant risk h.D. Approved by the FDA 2.A. There is sufficient evidence of safety and effectiveness for use in a “serious” disease c. The manufacturer submits a protocol for treating individual patients.fda. See Abigail Alliance v.C. and larger populations under a treatment protocol or treatment investigational new drug application. FDAMA provided statutory language that provides for expedited approval of drugs intended to treat a life-threatening disease under the following conditions: a. blood component or derivative. who lack other therapeutic options and who may benefit from such therapies. Licensed by the Public Health Service 3. 35 36 http://pacer. allergenic product.0. It is intended to improve access to investigational drugs for patients with serious or immediately life-threatening diseases or conditions.cornell. “Biological product” means a virus.gov/Cder/regulatory/applications/IND_PR.cadc. For “life-threatening” disease.html 18 . No generic process. BIOLOGICALS A. vaccine.html) 1. See 42 U.law.1. therapeutic serum.justia. 2006) 35 f.3.37 1.1. there is a reasonable basis to conclude the drug may be effective and would not expose patients to unreasonable. The use of the drug will not interfere with clinical investigations being conducted to gain approval d. 262(i). blood.pdf http://www.3d 470 (C.g.” H. Sponsor has submitted a protocol to the FDA for this widespread use G.
This means a device manufacturer does not have to obtain a PMA if it can show the new 38 39 http://www. 2. intended to affect the structure or any function of the body of man or other animals. Class III: These devices are most regulated because they are life supporting and pose a serious risk of injury. scissors. Voluntary Adverse Drug Reaction Reporting (MedWatch Program) 1.fda. 510K notification: A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective. Class I: Least regulated and “general controls” are adequate to ensure safety. substantially equivalent. Since the early 1970s. recognized in the official National Formulary. in vitro reagent.htm http://www. machine. 2. which encourages health care professionals to voluntarily report observed or suspected defects or quality problems with marketed drug products. the product is usually a drug.VII. The law requires premarket approval.gov/CDRH/DEVADVICE/312. treatment. and toothbrushes. stethoscopes. or the United States Pharmacopoeia. The agency receives reports through the MedWatch Program. FDA MedWatch Home Page 39 VIII. Drug Quality Reporting System (DQRS)38 a. Classifications: a. the FDA has operated the Drug Quality Reporting System (DQRS). and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes. implant. Examples include insulin pumps and syringes. or in the cure. or any supplement to them. or prevention of disease.gov/cder/Offices/CRMS/DQRS. that is. MEDWATCH VOLUNTARY REPORTING PROGRAMS A.fda. implement.92(a)(3)) that is not subject to Premarket Approval (PMA). Class II: Must meet specific FDA performance standards. or accessory which is: b. in man or other animals. apparatus. Definition (see http://www. to a legally marketed device (21 CFR 807. MEDICAL DEVICE ACT (AMENDMENTS) OF 1976 A. FDA states: “This definition provides a clear distinction between a medical device and other FDA regulated products such as drugs.html#link_2)40 1. (i) (ii) Note that there is an important process by which device manufacturers may market medical devices without premarket approval.html#link_2 19 . thermometers. Examples include needles. If the primary intended use of the product is achieved through chemical action or by being metabolized by the body. and electric heating pads.gov/CDRH/DEVADVICE/312. A device is: a. intended for use in the diagnosis of disease or other conditions.fda. or d. including a component part. mitigation. c.fda. c. tampons. [A]n instrument. or other similar or related article.” 3.html 40 http://www.gov/medwatch/index. contrivance. b.
3. 2.42 B.43 The U.S.fda. 557 (1980). Important First Amendment cases: a.pdf http://www.for cleansing.(iii) devices is substantially equivalent to a device already on the market. beautifying. serious injury. 5. or sprayed on. See Riegel v. the manufacturer can be sued for product liability or negligence if the device injures a patient.gov/opinions/07pdf/06-179. a “device-user facility” (which includes hospitals. 41 42 http://www. poured.com/scripts/getcase. S. (iv) An important.gov/opacom/laws/fdcact/fdcact1.. Under the 1990 Amendments.fda. and outpatient treatment facilities) must report any death.S.supremecourtus..gov/cdrh/devadvice/314. and Is not more extensive than is necessary to serve that interest. Articles intended to be rubbed. Compliance with GMPs is not necessary.gov/cdrh/devadvice/ IX. See http://www. Central Hudson Gas v. 321 (2008)41 4. or altering the appearance" See 21 USC §201(i). Medical device manufacturers must report deaths and serious injuries to the FDA. COSMETICS A. Overview 1. see http://www. introduced into. The Court held that truthful commercial speech that does not promote unlawful activity can be limited only if it: (i) (ii) (iii) (iv) Is not misleading or related to an unlawful activity. 4.lp. X. the manufacturer cannot be sued under state law tort claims. Supreme Court articulated the test for determining when the government can regulate commercial speech. Manufacturers must substantiate the safety of products and ingredients. Public Service Comm’n. recent U. Constitution 1. Is in support of a substantial government interest. The First Amendment to the U. For additional information about Medical Devices. Medtronic. If a device comes to market by the 510K process.S. 6. If the device has received a PMA.S. sprinkled.html. Know the test for determining if government action infringes on the First Amendment right in the context of commercial speech. 447 U. Premarket approval not necessary 2.htm 43 http://caselaw. or otherwise applied to the human body.fda. or serious illness related to a product. 200 U.pl?navby=CASE&court=US&vol=447&page=557 20 . Supreme Court case held the Medical Device Act and regulations preempts state laws (including tort lawsuits) that conflict with PMA requirements. ambulatory surgical facilities. nursing homes. Definition 1. Directly advances the government interest asserted. DRUG ADVERTISING AND PROMOTION A. promoting attractiveness.findlaw. Cosmetics may be misbranded or adulterated.
” which contains the following: (i) Established name of the drug (ii) Formula.3d 331 (D.47 c. but that do not state the indications or dosage.gov/c/F3/202/202.bna. books.aspx 47 http://edocket. That no advertisement shall be considered to be in violation of this section if the presentation of true information relating to side effects and contraindications is comparable in depth and detail with the claims for effectiveness or safety.com/lw/19990810/941306. 202 F.R.gov/cfr_2003/aprqtr/pdf/21cfr202.F.1.org/speech/advertising/cases_resources_summary.resource. Prescription Drug Advertising: Manufacturer to Professionals 1.access. See 21 C. Friedman.2d 51 (D.gpo. showing quantitatively each ingredient (iii) “Brief summary” of other information related to side effects.99-5304. 44 45 http://lw. HWashington Legal Foundation v.1(e)(2)(i).pdf 21 . A drug is misbranded unless the manufacturer includes a “true statement.331.Supp.html 46 http://www. or detail than is required by section 502(n) of the act and this information is not fairly balanced by a presentation of a summary of true information relating to side effects and contraindications of the drug. Applicable Statute and Regulations a.46 B. §202. or lack of side effects that have not been approved by the FDA (ii) Suggest that a drug is better than other drugs unless such a claim is based on substantial evidence (iii) Contain favorable information from an inadequate study f. etc. “Advertising” includes ads in journals and other periodicals. and effectiveness as required by regulations b. 1998)44 Court held the FDA cannot prohibit distribution of peer-reviewed publications and textbooks that discuss off-label use of drugs.C.htm http://bulk. media. 2000). however. Fair Balance: An ad does not present a fair balance if: It fails to present a fair balance between information relating to side effects and contraindications and information relating to effectiveness of the drug in that the information relating to effectiveness is presented in greater scope.C. An advertisement cannot: (i) Contain any representations or suggestions about effectiveness.45 c. 13 F. indications. Not applicable to “Reminder Advertisements”: True statement does not apply to reminder ads that mention the drug. A manufacturer does not meet the true statement standard if the advertising: (i) (ii) Is false or misleading Does not present a “fair balance” between effectiveness and side effects and contraindications (iii) Fails to reveal a material fact d. Provided.b. For more information see First Amendment Center.firstamendmentcenter. for use by health care professionals. e. Heney.F3d. depth. contraindications. See also Washington Legal Foundation v.org/courts.
pdf 3. In other words.fda. Educational: Does not mention the name of the drug. The policy contained a number of factors that the FDA would apply to industry sponsorship of programs to determine if the program was serving as a mouthpiece for the company and if the speakers were agents and representatives of the company. 3. DTC ads fall into two categories: a. h.fda. C.gov/cgi-bin/getrpt?GAO03-177 2. prescription drug advertising in broadcast media only include information about major risks instead of the entire “brief summary” as long as there is adequate provision for providing labeling. booklets. There are no specific regulations for Direct-to-Consumer advertising. Prescription Drug Advertising: Manufacturer to Consumer 1. mailing pieces. Product Specific: These are subject to regulations.gov/cder/guidance/isse. The FDA encouraged the dissemination of information to treat inadequately treated conditions.fda. the FDA clarified the distinction between product specific and educational ads in a draft guidance document: “Help-Seeking” and Other Disease Awareness Communications by or on Behalf of Drug and Device Firms http://www.pdf 22 . The following websites contain useful information for anyone interested in more detail: http://www. etc. safety. but the information in labeling must be more comprehensive. Advertisers can provide summary of risks in audio or video form as long as the adequate provision standard is met by providing consumer with full information from other sources: (i) (ii) (iii) (iv) Toll-free number Internet address Referral to currently running advertisement in a publication. Industry-Supported Educational Programs 1. FDA Guidance 2004 Disclosing Risk Information in Consumer-Directed Print Advertisements http://www. “Labeling” includes brochures. etc. The following summarizes the status of guidelines for DTC ads: a.gov/cder/guidance/5669dft. Specifically. The FDA promulgated a guidance policy for industry sponsored programs in 1997.gao. could any statements about indications. Office of Inspector General (OIG) issued guidance for pharmaceutical industry that included advice that when a drug company provides funds to influence an educational program it may violate antikickback laws D.gov/cder/guidance/6019dft.g. be attributed to the company and evaluated under the FDCA? 2. Final Guidance on Industry Supported Scientific and Educational Activities 1997 at http://www. efficacy.gov/cder/ddmac/globalsummit2003/ and www. Same standards apply to both advertising and labeling.fda. Referral to a health care provider b. just the manufacturer b.htm.
and other products promising health benefits. ISPs and other high-tech products and services. F. Prescriber can prescribe for unapproved uses and dosages a. Health care practitioners b. the GAO issued a report in 2006 criticizing industry advertising.pubmedcentral. Prescription Drug Advertising by Manufacturers 1. 48 49 http://www. Promoting Prescription Drugs for Off-Label Uses 1.48 c. 2003 October. Its law enforcement activities focus on: (i) Claims for foods. The FTC regulates OTC advertising by manufacturers 2. (iii) Weight-loss advertising (iv) Advertising and marketing directed to children. In order to provide this information. From the FTC website: a. dietary supplements. FTC is the Federal Trade Commission.pdf E. See Package inserts and the standard of care. PRESCRIPTION DRUGS Improvements Needed in FDA’s Oversight of Direct-toConsumer Advertising http://www. the company had to: (i) have filed an application for the new indication. FDAMA allowed dissemination of certain off-label uses to the following entities under several conditions: a. drugs.gov/new. Perhaps increased liability. The information had to be in unabridged peer-review articles in scientific or medical journals that had not been influenced by the company.items/d0754. Government agencies 3. (ii) Health fraud on the Internet.gao. The Division of Advertising Practices 3. Bureau of Consumer Protection: The Division of Advertising Practices49 is the nation’s enforcer of federal truth-in-advertising laws.nih. Med Cent). Farr in the text. 16(4): 502–504. Law was not intended to limit MD’s ability to treat patients b. PBMs c. a.shtm#bcp 23 . 2. (v) Performance claims for computers.gov/articlerender. Group health plans e. Friedman.fcgi?artid=1214572 http://www. Finally. (ii) submit the information to the FDA 60 days before dissemination for approval.ftc. Proc (Baylor Univ. Review Ramon v. Some of these restrictions were unconstitutional under Washington Legal Foundation v.gov/bcp/edu/pubs/consumer/general/gen03. and (iii) include a disclaimer on the material when disseminated b.c. Health insurance plans d.
This is the federal law that creates trademark rights. 1977) Court ordered company to stop making claims that Listerine was effective for preventing colds. Federal Trade Comm’n. The federal law that prohibits false advertising or representations 2.C. a. G. names. (vii) Protecting children’s privacy online. advertising and promotion.” c. Bureau of Competition seeks to prevent anticompetitive mergers and other anticompetitive business practices in the marketplace 4. The Lanham Trademark Act 1. or on the Internet. can be renewed forever as long as they are being used in commerce. Werner-Lambert v. 24 . If a mark by company “A” creates confusion about the source of a product so consumers think it is produced by company “B” and company “B” has an existing trademark for its product. including monitoring for unfair practices or deceptive claims and reporting to Congress on cigarette and smokeless tobacco labeling. A trademark protects words. or colors that distinguish goods and services from those manufactured or sold by others and to indicate the source of the goods. (viii) Claims about product performance made in national or regional newspapers and magazines. unlike patents. Key to a trademark is that it informs the consumer of the source of product. company “A” likely infringes the trademark of company “B.(vi) Tobacco and alcohol advertising. FTC enforces the Lanham Act. through direct mail to consumers. in radio and TV commercials. b. b. 562 F. sounds.2d 749 (D. symbols. Trademarks. including infomercials.
.. excessive belching . The Law 1..g. Article of Drug—Decolin (involved dehydrocholic acid to be used for “indigestion . Oral. 25 . the purpose of the Amendment was to allow the oral transmission of prescriptions and to allow pharmacists to honor refill information on the original prescription. . a. Prescription Versus Over-the-Counter Drugs a. Dispensing Written. method of use. adequate warnings) are required for the OTC package the consumer receives. The law created this distinction by creating two classes of drugs. b. . In fact. the labeling required by the FDA for manufacturers need not be on the package the consumer receives. c. .S. The Amendment granted the FDA with authority to categorize drugs as prescription only if the drugs are: (i) (ii) Unsafe for use except under the supervision of a practitioner based on toxicity. d. The Amendment allows for oral transmission f a prescription drug order if the order is promptly reduced to writing. v. Creates the distinction between prescription (legend) drugs and OTC drugs by exempting certain drugs from some labeling requirements 2. after-meal discomfort and fullness(particularly after fatty meals) . and Electronic Prescriptions a. In other words. DURHAM-HUMPHREY AMENDMENT A.FEDERAL REGULATION OF MEDICATION: DISPENSING XI. or collateral measurements necessary to use the drug Subject to the new drug application process b. OTC drugs were safe for use without medical supervision because the instructions and warnings on the label of the product were adequate for the intended use. if a taking a drug causes delay in seeking treatment for a serious condition that the drug cannot cure) 2. constipation”) (i) Court held FDA must prove two facts to change the status of a drug from OTC to prescription: (i) toxicity and method of use require supervision of a practitioner and (ii) collateral measures necessary to use the drugs require supervision (e. Prescription drugs must contain the legend “Rx only. the Amendment created a labeling exemption for prescription drugs such that the package the consumer receives is not required to bear the information manufacturers must provide with their products. . All the requirements for labels and labeling (e. Explanation of the Durham-Humphrey Amendment 1. U.g. . Because a physician or other prescriber decides whether a patient receives the drug.” (The term legend drug derives from the old legend that was required on prescription drug labels” “Caution: Federal law prohibits dispensing without a prescription”) B. Prescription (Legend) Drugs: are Uunsafe without medical supervisionU.
Electronic signatures are now considered valid by passage of the Electronic Signatures in Global and National Communications Act (E-Sign”). For nonsterile solid and liquid drugs repackaged into containers. it may be confusing when one manufacturer labels the same drug as Rx Only while another company distributes the same drug as an OTC product. Minimum federal standards for information on prescription drug label Prescriber’s name Name and address of dispenser (pharmacy) Serial number (Rx number) Date of filling UorU date of prescription c. D. Switch of Prescription Drugs to Over-the-Counter Drugs 1.b. a. Thus. the pharmacist should include a beyond use date that is the earlier of one year from the date of repackaging o the expiration date on the original bulk container. USP sets the standards for expiration and beyond use dating. whichever is earlier.gov/os/2001/06/esign7. the beyond use date “shall not be later than (a) the expiration date on the manufacturer’s container. Prescription label must include if stated on prescription: (i) Name of patient (ii) Directions for use (iii) Cautionary statements C. Most states. but not the FDA. 2. require expiration or beyond use dating. Petition FDA 3. See FTC web page at http://www.ftc.” b. Labeling Requirements a. or (b) 1 year from the date the drug is dispensed. like prescription containers. Note: Each company must receive approval of a switch to an OTC status.htm 3. OTC drug review process (monograph is published if the ingredient is approved as an OTC) 26 . 2. For multiple-unit containers. The Amendment exempts pharmacists from labeling prescriptions drugs except: (i) (ii) (iii) (iv) (v) (vi) (i) (ii) (iii) (iv) Label cannot be false or misleading Drugs cannot be imitation drug Drug cannot be sold under name of another drug Packaging and labeling must conform to compendial standards Drug must be packaged and labeled appropriately if subject to deterioration Drug packaging must conform to Poison Prevention Packaging Act b. which allows electronic signatures that meet certain requirements to be considered the same as physical signatures. Expiration or Beyond Use Dating 1. Request switch with supplemental NDA a.
Two advisory boards approved the switch. Plan B has been available since 1999 as a prescription drug.50 4. (i) Morr-Fitz.gov/CDER/DRUG/infopage/planB/planBQandA. In 2006.E. Plan B contains a high dose of levonorgestrel. In 2004 Barr again submitted its application and the FDA initially rejected it. which is normally used in lower doses in oral contraceptives. 2007) b. but only to be sold in pharmacies by a pharmacist to a person who is at least 18 years old. Prescriptive Authority a. v. the following have prescriptive authority (i) Nurse practitioners & nurse midwives (CIIs and CIII in consultation with MD) (ii) Dentists (iii) Physician assistants (dependent on physician to prescribe) (iv) Podiatrists (v) Veterinarians (vi) Osteopaths (vii) Physicians (viii) Optometrists (limited) (ix) Naturopathic physician (limited to specific formulary) c. 2003 Barr submitted SNDA to switch Plan B to OTC d. Brownfield v.E.fda. State law governs who can prescribe b. 2006. 256 Cal. How should pharmacists verify that the prescriber has actually authorized the refill? 2. but the FDA rejected the application. Daniel Freeman Marina Hospital. Prescriptions must be within scope of practice of the prescriber (scope of authority) 3. 50 http://www. b.htm 27 . There have been several cases litigated where states have passed laws or regulations to govern dispensing post-coital contraceptives. f. g. In Utah. Only a prescriber can authorize refills. See FDA Website FDA’s Decision Regarding Plan B: Questions and Answers August 24. Emergency Contraceptives (Plan B) a. e. 240 (1989) (court concludes morning after contraception does not constitute abortion services under a law that protects religious organizations from providing services that are contrary to their teachings). March 19. Inc. Prescription Refill Authorization a. App. b. 867 N. Conscientious Objection a. the FDA finally approved the switch to OTC. Professional Practice Considerations 1. Blagojevich.2d 1164 (Ill. Rptr. but an employee can communicate or transmit refill authorization with the pharmacist (Utah regulations have also specifically allowed for this process). c.
changes in the endometrium may affect survival of a blastocyst within the uterus or prevent implantation. and prevention of ovulation.c. Thus. Patient Package Inserts 1. Controversial proposed rule51 from HHS would define “abortion” to include IUDs and.gpo. The labeling for these drugs must include special patient labeling and must be given with each package dispensed 51 52 53 http://www. Finally.F. An overview of oral contraceptives Mechanism of action and clinical use.516)54 2. including thickening of cervical mucus. whereas decreased tubal mobility inhibits ovum transport and fertilization and may affect sperm migration and activity. Collaborative Practice Agreements (basically a state law issue that will be addressed in the Utah law portion of the course) 6.gov/cgi-bin/get-cfr.pdf http://frwebgate. 66:S29-S36.F. decreased tubal mobility.cgi?TITLE=21&PART=310&SECTION=501&YEAR=1999&TYPE=PDF http://frwebgate. The FDCA is silent about who can dispense drugs and leaves the decision to the states F. changes in the endometrium. if abortion is defined broadly. thus inhibiting ovarian activity and preventing development of an ovum.access. perhaps. d.rhrealitycheck. whether before or after implantation. § 310.R. and administration of any drug or the performance of any procedure or any other action—that results in the termination of the life of a human being in utero between conception and natural birth.access.R. Neurology. 2006.gov/cgi-bin/get-cfr.gpo. Authority to Dispense Prescription Drugs a. Their primary mechanism of action is believed to be prevention of ovulation. FDA regulations require PPIs for certain hormonal products are required for (See www.gpo. Mechanism of action of hormonal contraception.org/emailphotos/pdf/HHS-45-CFR. Thickening of cervical mucus hinders sperm penetration. providers will be able to refuse providing services for a broader range of services.htm) a. oral contraceptives.gov/cder/guidance/6932dft. § 310. The regulation is intended to give health care providers the right to object to providing abortion services.access.gov/cgi-bin/get-cfr. § 310.cgi?TITLE=21&PART=310&SECTION=515&YEAR=1999&TYPE=PDF 54 http://frwebgate. c.105)52 Oral postcoital contraceptives (DES) Injectable contraceptives (Medroxyprogesterone acetate) Estrogens (12 C. Estrogen prevents release of follicle-stimulating hormone (FSH). Progestin has a variety of effects. “Abortion” means any of the various procedures—including the prescription.fda. Excerpt from Frye CA. b. Estrogen and progestin are active components of hormonal contraception.cgi?TITLE=21&PART=310&SECTION=516&YEAR=1999&TYPE=PDF 28 . Oral contraceptives (21 C.515)53 Progestational drug products (21 C.F. 5.R. e. dispensing.
lawfully prescribe a different dosage for a patient. b. Mulder v.pdf http://www. Med Guides are required for drugs when: (i) (ii) Patient labeling could help prevent serious adverse effects The drug has serious risks relative to its benefits which the patient should know about when deciding whether to use the drugs. Parke Davis: court held that a physician’s deviation from recommendations of a drug manufacturer in the package insert is prima facie evidence of negligence 3. XII. Reg. or may otherwise vary the conditions of the use from those approved in the package insert. but Congress eventually passed a law that prohibited the FDA from doing so if private industry could achieve a plan whereby 95% of patients receive useful written information about their drugs by 2006).accessdata. A 2005 study found only1 of 25 pharmacies actually distributed the Med Guide for celexocib. Ramon v.gov/scripts/cder/drugsatfda/index.htm) 50% of the time. clinically justifiable uses even if such uses are not indicated by the manufacturer 2.gov/cder/offices/ods/medication_guides.gov/cder/reports/prescription 3.htm can be found at H. 22 P. See www.cgi?dbname=1998_register&docid=98-31627-filed. Farr see text for summary 55 56 http://frwebgate. without informing the FDA—that is.3. FDA Consumer website to learn about drugs Drugs@FDA56 APPROVED DRUGS FOR UNLABELED INDICATIONS 1. List of drugs required to have a Med Guide http://www. the prescriber may.M. In 1993. Medication Guides 1. See Schlieter v. 5. 3. and (iii) Patients’ adherence to the directions is crucial to the drug’s effectiveness. Hospitals need only give information once every thirty days after first dose.fda. Risk Management Programs for Very High Risk Drugs 1.fda. 2001 study showed only 89% of patients received written information and the information was useful only Info/default.gpo.3d 682 (N. a. 2. 6637855H (Final Rule for Medication Guide Requirements). prescribers are free to prescribe drugs for legitimate.access. Accutane (iPledge – requires patients to register) Plan B Clozapine (Clozaril) Olosetron (Lotronex) Alendrinate (Fosamax) I. Carlos.fda. See 63 Fed. 2001) (giving PPIs to a physician in a hospital does not meet the pharmacy’s duty to give each patient a PPI when patient received Premarin) G. as part of medical or professional practice. c. the FDA issued a regulation that required manufacturers to provide information for certain drugs.gov/cgi-bin/getdoc. 2. The FDA has tried to create regulations that would require PPIs for every drug.cfm 29 . General Rule: Once a drug is in the pharmacy after shipment in interstate commerce. which each pharmacist must then provide to patients. 4.
S. wrapper. or (viii) Failing to operate in conformance with applicable state law regulating the practice of pharmacy. storing or using drug substances from sources unapproved by FDA or that do not meet official compendia requirements (iv) Compounding with commercial scale manufacturing or testing equipment (v) Compounding amounts of drugs far in excess of valid prescriptions (vi) Offering compounded drugs at wholesale to others for resale (vii) Distributing inordinate amounts of compounded products out of state. Spensieri v. propagate. § 360(g)58 1.edu/nyctap/search/display. or labeling of the products must register as a manufacturer B.C. 94 N. The FDA stated that in determining whether to initiate an action against a pharmacy for failing to register as a manufacturer it would consider whether the pharmacy engages in certain activities: (i) Soliciting business to compound specific drug products or therapeutic classes of products (ii) Compounding inordinate amounts of drugs that are commercially available (iii) Receiving.: Court listed a number of factors to consider in determining whether pharmacy qualifies for the exemption b. D.law. or process drugs or devices for sale other than in the regular course of their business of dispensing or selling drugs or devices at retail 21 U.exe?getdoc+uscview+t21t25+181+1++21%3Acite%20w%2F3%20360 30 .Y. Pharmacies that repackage OTC products or in any way change the container. FDAMA exempted pharmacists from 3 provisions of the FDCA (i) The adulteration provision that requires compliance with CGMP (ii) The misbranding provisions that require labeling with adequate directions for use (iii) The new drug provisions 57 58 http://www. Lasky. In other words. FDAMA’s Compounding Provisions 1.htm http://uscode. upon prescriptions of practitioners licensed to administer such drugs or devices to patients under the care of such practitioners in the course of their professional practice. pharmacies are exempt from registering as a manufacturer if they engage in the traditional practice of pharmacy.57 XIII. and which do not manufacture.2d 231 (1999). compound.html?terms=physician&url=/nyctap/I99_0168. prepare. 2. Chronology of Compounding Laws and Guidance C.S. Cedar Towers Pharmacy v.4. U.gov/uscode-cgi/fastweb. (ix) Other factors may be appropriate for consideration in a given case. Pharmacies are exempt from registration as manufacturing if they maintain establishments in conformance with any applicable local laws regulating the practice of pharmacy and medicine and which are regularly engaged in dispensing prescription drugs or devices. FDA 1992Compliance Guidelines 1. PHARMACY COMPOUNDING VERSUS MANUFACTURING A. Based in part on judicial decisions a.cornell.house.
4. 421 F. Western States Medical Center. Prescriptions could not be solicited f.3d 263 (3rd Cir.fda. 4. Western States decision 2. This summer (2008). adulteration. 122 S. but that the FDA could not conduct a more thorough inspection if the initial inspection reveals the compounding exemption applies.uscourts.html. In order to qualify. the federal court held the FDA could inspect pharmacies to determine if the compounding exemption applied.cornell. A copy of this compliance policy is included in the reading materials and can be found at http://www.gov/opinarch/041175p.40) http://www. A federal court agreed with this position in a footnote in the 1995 case Professionals and Patients for Customized Care v.edu/supct/html/01-344. Thompson v.60 F.gov/OHRMS/DOCKETS/98fr/02D-0242_gdl0001. 1497 (2002):59 The Supreme Court held that these final two conditions (e & f above) were unconstitutional restrictions on free speech E. Shalala.Ct.ca3. but that FDAMA provides an exemption from the new drug provisions of the FDCA if 59 60 http://www. Limited quantities could be prepared in anticipation of legitimate prescriptions c. Products must be for individual an individual patient and cannot be resold b. FDA’s authority to inspect pharmacies was challenged by a compounding pharmacy where the FDA obtained a warrant and conducted an inspection. the FDA as a matter of policy has not historically brought enforcement actions against pharmacies engaged in traditional compounding 3.ZS. 56 F.2.law. or misbranding provisions. the Fifth Circuit held that compounded drugs are new drug. 2.fda. Remember the definition for “new drug” and consider whether a compounded drug is a new drug. No advertising for individual products 3.gov/ora/compliance_ref/cpg/cpgvet/cpg608-400. 2005). and Cosmetic Act does not expressly exempt “pharmacies” or “compounded drugs” from the new drug. See Wedgewood Village Pharmacy v. The FDA has taken the position that all compounded drugs are new drugs. Compounded product must be made from approved ingredients and not from products that appear on an FDA list of products withdrawn from the market e. United States. FDA drafted new compliance guidelines in reaction to the Thompson v. New Drug Issue 1.html http://www. FDA 2002 Compliance Policy Guide 1. 3. Cannot compound commercially available products d.pdf 31 .pdf. See also Compounding of Drugs for Use in Animals (CPG 7125. Drug. In the subsequent litigation. FDAMA would have extended an exemption from the new drug provisions of the FDCA.3d 592 (5th Cir. pharmacists had to meet certain conditions: a. 1995): Although the Food.
and counterfeit drug products that infiltrate the legitimate drug market through the drug diversion market B. 4. “[T]o restore the integrity and control over the pharmaceutical market necessary to eliminate actual and potential health and safety problems before serious consumer injury results. Form must contain practitioner’s name. 06-51583 (July 18. amount and identity of sample. See FDA statement of its interpretation of Medical Center Pharmacy v.5. http://www. Except the following may receive drug samples upon written request: (i) (ii) Prescribing Practitioners Pharmacies of hospitals or health care entities b. title. pharmacies comply with state laws governing compounding. purchase.gov/cder/pharmcomp/medical_center_pharmacy. Web links: a. Patent Issues XIV.gov/cder/ob/default. 2. Samples can be provided only to prescribing practitioners who request them in writing a. Retail pharmacies cannot possess drug samples. B. 3.pdf (includes entire text) 2. Intent 1. mere presence of a sample is evidence of illegal acquisition 2. 2008). 6. See text for coding system. Medical Center Pharmacy v. FDA Approved Drug Products with Therapeutic Equivalents 1.” 2.htm (search version) b.fda. See Therapeutic Equivalence of Generic DrugsResponse to National Association of Boards of Pharmacy at www. Narrow Therapeutic Index (NTI) Drugs 1. misbranded. name of manufacturer. G. or trade of samples a. No. address. Most states use the Orange Book to determine whether a generic drug can lawfully be substituted. Mukasey. Regulation of Prescription Drug Samples 1. PRESCRIPTION DRUG MARKETING ACT OF 1987 A. and date 32 . “A” rated drugs are generally bioequivalent and can be substituted. 1.fda. Prohibits sale. Drug where there is less than a two-fold difference between the median lethal dose and the median effective dose or less than two-fold difference between minimum toxic concentration and minimum effective concentration in the blood. THE ORANGE BOOK A. http://www.htm XV.fda.gov/cder/orange/obannual.gov/cder/news/ntiletter. Mukasey at http://www.fda.htm. To reduce public health risks from adulterated.
Manufacturers & distributors: a. pharmacies were confused about whether and how to make returns to wholesalers. Intended to stop the flow of foreign counterfeits G. Wholesalers must be licensed in every state in which it distributes drugs (Utah now regulates wholesalers pursuant to this federal law) F. Violations can be punished by fines or incarceration in accordance with penalties under the FDCA 2.civil fine of $100.000.” or charitable organizations from selling or trading drugs a. Reimportation of Prescriptions Drugs 1. cannot be reimported. Manufacturers are required to keep complete and accurate inventory and records C. Because the wording of the PDMA is so broad. except by manufacturer a.000 33 . Purchases and Releases by Hospital and Health Care Entities 1. See also FDA Guidance on return and disposal of drugs at http://www. Eventually. resales. New regulations for wholesalers a.com/pharmacist/FDA_Drug_Return_Policy. samples. Part 205. Penalties 1. Failure to maintain proper records .uspharmd. “health care organizations.S. Product Returns 1. Violation of sample provisions carries up to $50.html E. the FDA issued regulations that allowed returns with proper documentation. 21 C. Violation of provisions dealing with reimportation. Exceptions (i) (ii) (iii) (iv) Dispensing and distributing drugs pursuant to prescription Purchases from buying group or from other member hospitals Sales or purchases to nonprofit affiliates Sales or purchases among hospitals or health care entities under common control b. Sales or purchase for emergency medical situations D.F. Prescription drugs manufactured in the U.000 b.R. Wholesale Distributors 1.000 4. Prohibits hospitals.3.000 civil penalty Uper offense c. Authorized and unauthorized wholesalers 2.000 fine 3. Snitcher provision: informer can collect half of criminal fine up to $125. or wholesalers punishable by up to 10 years in jail or $250. Subsequent offenses punishable up to $1.
A package fails if more than 20% of test group of children can open after visual demonstration. Dietary supplements containing iron: same as for iron containing drugs c. PPPA requires that most prescription drugs be packaged in child-resistant containers. PPPA applies to APA with more than 1 gram in single package b. POISION PREVENTION PACKAGING ACT A. Best to have written waiver c. All prescription drugs and all controlled substances must be packaged in child-resistant packaging a. Ibuprofen: oral dosage forms containing more than 1 gram in single package 8. Diphenhydramine: oral dosage forms containing more than 66 mg of diphenhydramine in single package d. Patient can make a blanket request that all prescriptions be dispensed in noncomplying containers d. More than 10% of a test group of adults cannot open container c.” the Act is intended to extend packaging requirements for household substances to prescription and certain nonprescription drugs 1. INSPECTIONS UNDER THE FEDERAL FOOD. Excludes effervescent tablets or granules containing less than 15% of drug c.XVI. Other OTC substances subject to the Act a. Physician’s blanket request cannot be honored 34 . Resale of plastic child-resistant containers is prohibited 3. Exemptions a. Requires “household substances” to be packaged for consumer use in “child-resistant containers. AND COSMETIC ACT XVII. 3Exceptions to the packaging requirements are listed in the texts 4. Iron containing drugs: if preparation contains a total amount of elemental iron equivalent to 250 mg or more in single package b. or b. Rules for aspirin and acetaminophen products a. Each manufacturer can produce one single size package of an OTC drug if it bears the warning “This package for households without young children” 7. DRUG. Unit does fails if one child can open more than eight individual units or the number of units representing the toxic amount 2. Excludes powdered ASA and APAP containing less than 13 grains of drug per unit dose 6. Patient or physician can request non-child-resistant container b. however when many drugs move from prescription to OTC child-resistant packaging is no longer required 5. USE OF ALCOHOL IN PHARMACY PRACTICE XVIII.
State Advertising Case: The Virginia Case and the First Amendment 1. Virginia Citizens Consumer Council. Advertising: Strict Liability B. Supreme Court held that the laws prohibiting the advertising prescription drug prices were unconstitutional. The Court noted that the Board of Pharmacy cannot protect “its citizens by keeping them ignorant. the U.XIX. In Virginia State Board of Pharmacy v.” 35 .S. DRUG ADVERTISING BY PHARMACISTS A.