Chapter 2 Material
Durham-Humphrey Amendment of 1951
Established two classes of drugs - OTC and prescription Provided that the labels of prescription drugs did not need "adequate directions for use" so long as they contained a legend with the statement: "Caution: Federal law prohibits dispensing without a prescription." The inclusion of prescriber directions on the label replaced "adequate directions for use" and helped to ensure safety through medical supervision
Section 201 of the FDCA
Defines and distinguishes drugs from dietary supplements, foods, cosmetics, and devices
What are Medical Foods?
Those specifically formulated (not naturally occurring) to be used under medical supervision in the management of a disease or condition and that provide nutritional requirements that would be otherwise impossible to obtain in a normal diet
Disclaimer for Nutritional Support Statements
"This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."
What are the four nutritional support statements allowed by DSHEA?
1) Statements that the product will benefit a classical nutrient deficiency disease as long as it also discloses the prevalence of the disease in the United States 2) Statements that describe the role of the dietary supplement in affecting the structure or function of the body 3) Statements that characterize the documented mechanism by which a nutrient or dietary supplement acts to maintain structure or function 4) Statements describing the general well-being from consumption of a nutrient or dietary ingredient (e.g., "energizer," "relaxant," "muscle enhancer")
Prescription Drug Marketing Act (PDMA) of 1987
Banned sale, trade, or purchase of prescription drug samples and specified precise storage, handling, and record-keeping requirements for these samples
United States v. Sullivan, 1948
A community pharmacist purchased properly-labeled bottles of sulfathiazole tablets from a wholesaler, but sold the drug without a prescription and without the labeling required by the FDCA The defendant held that the federal law did not apply to his intrastate transactions, but the Court held that the Act did in fact apply to transactions between pharmacist and patient in a pharmacy
What is the Breakthrough Therapy Designation?
A drug intended for a serious or life threatening disease demonstrates substantial improvement on a clinically significant endpoint compared to available therapies
What is adulteration?
A drug is adulterated if it 1) consists in whole or in part any filthy, putrid, or decomposed product; 2) was prepared or held in conditions where it may have been contaminated; or 3) differs in strength, quality, or purity from compendia standards
What is the difference between label and labeling?
A drug label is the display of required information on the container or wrapper Drug labeling includes that label and also "accompanying" information like the package insert
What is misbranding?
A drug or device is misbranded if its labeling is false or misleading or if its HCEI (healthcare economic information) is inaccurate or unreliable Among other things, drug labeling must include a list of active ingredients and the quantities of each OTC drugs must be labeled with "adequate directions for use" and a "Drug Facts" panel
What is the Fast-Track Designation?
A drug that demonstrates potential to address unmet medical needs for a serious illness/condition
What is a Black Box Warning?
A label that is required when a drug may lead to death or serious injury The strongest safety warning a drug can carry and still remain on the market
What is an ANDA?
Abbreviated New Drug Application Created by the PTRA; allows a generic manufacturer to rely on an innovator's safety and efficacy data, provided that the manufacturer can prove bioequivalence
What is Expedited Approval?
Accelerated review pathway for drugs to treat serious illnesses or life-threatening conditions Fast-Track or Breakthrough Therapy designations Approval is conditional on post-marketing or phase IV clinical studies to verify the drug's clinical benefit
What are the two main offenses established in the FDCA?
Adulteration and misbranding
What are Right-to-Try Laws?
Allow patients with life-threatening diseases or conditions who have tried all other available alternatives and are unable to participate in clinical trials to access certain unapproved treatments
1941 Amendment to the FDCA
Allowed the FDA to require batch certification of the safety and efficacy of insulin to ensure uniform potency
What is Priority Review?
Allows the FDA to expedite approval for drugs intended for serious diseases that offer significant improvements in safety and/or effectiveness
Drug Price Competition and Patent Term Restoration Act of 1984
Also called the Waxman-Hatch Amendment Streamlined the generic drug approval process and gave patent extensions to "innovator drugs"
Kefauver-Harris Amendment of 1962
Also known as the "Drug Efficacy Amendment" Strengthened the new drug approval process by requiring that drugs be proven not only safe, but also effective Retroactively included all drugs marketed between 1938 and 1962 Established GMP requirements, transferred jurisdiction of drug advertising from the FTC to the FDA, required the reporting of adverse events
What is a drug?
Article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals Article (other than food) intended to affect the structure or any function of the body of man or other animals
What is a cosmetic?
Articles intended to be applied to the human body for the purpose of cleansing, beautifying, promoting attractiveness, or altering appearances Does not include soap
What is a food?
Articles used for food or drink for man or other animals, chewing gum, and articles used for components of any such article
What is a CBE SNDA?
Changes to the labeling of the drug, such as those that strengthen warnings, that can be implemented before FDA approval of the SNDA only if the labeling changes reflect "newly acquired information"
What are the three classes of drug recalls?
Class I -> reasonable probability that the product will cause serious adverse health consequences or death Class II -> product may cause temporary or reversible adverse health consequences Class III -> product is unlikely to cause adverse health consequences
What is the Expanded Access Program?
Compassionate Use -> potential pathway for a patient with a serious illness or immediately life-threatening condition to gain access to an investigational medical product outside of clinical trials if no other comparable or satisfactory therapies are available
Dietary Supplement Health and Education Act (DSHEA) of 1994
Defined dietary supplements and forced the FDA to regulate them more as foods than as drugs Permitted manufacturers to make claims which were otherwise illegal under the FDCA
True or False? Cosmetics are regulated similarly to drugs.
False -> cosmetic regulation is less strict Registration with the FDA is voluntary and cosmetic manufacturers do not have to conform to cGMP Pre-market approval is not required for cosmetics, except for color additives
True or False? A hair dye is adulterated if it contains coal tar.
False -> hair dyes containing coal tar are exempt from the adulteration and color additive provisions of the FDCA
True or False? The 1938 FDCA gave the FDA authority to review the safety and efficacy of medical devices before marketing
False -> this authority was granted in the Medical Device Amendment of 1976
Family Smoking Prevention and Tobacco Act of 2009
Granted the FDA the authority to regulate tobacco products, including the disclosure of their contents, requirement of more effective warnings, and strict control over their marketing
Pearson v. Shalala, 1999
Held that dietary supplement manufacturers could make health claims not approved by the FDA, so long as they are not false or misleading and are accompanied by a disclaimer
United States v. Johnson, 1911
Held that the misbranding provision of the Pure Food and Drug Act of 1906 did NOT prevent false or misleading claims of EFFICACY (only of identity)
What are the required sections of a package insert?
Highlights Table of Contents Full Prescribing Information Patient Counseling
How is it determined if a product is a drug?
If a supplier makes a therapeutic claim or a structure/function claim, their product is considered a drug, no matter what disclaimers are in the labeling
When might a cosmetic product be misbranded?
If it is not labeled with a list of ingredients in descending order of prominence
Sulfanilamide Elixir Tragedy of 1937
In an attempt to produce the "miracle" anti-infective sulfanilamide as an elixir, a manufacturer used diethylene glycol as a solvent, which killed 107 people The 1906 Pure Food and Drug Act did NOT grant the FDA the authority to ban unsafe drugs, so the product was removed on the technicality that it was marketed as an elixir but did not contain alcohol
What does DSHEA mean for pharmacists?
In patient counseling, pharmacists should direct patients to products which are labeled as conforming to USP or NF standards and should NOT promote supplements on the basis of unapproved health or disease claims (could violate FDCA)
What is an IND?
Investigational New Drug Application Request that the FDA authorize the administration of an investigational drug or biologic product to humans Based on safety and efficacy evidence form animal studies, required to begin clinical (human) trials
What are the labeling requirements for risk warnings of drug use during pregnancy and lactation?
Labeling must include the detailed subsections "Pregnancy", "Lactation", and "Females and Males of Reproductive Potential" Replaces the prior 5-letter category grading system
Nutrition Labeling and Education Act (NLEA) of 1990
Mandates nutrition labeling on food products and authorizes health claims on product labeling that are in line with FDA regulations
What is the NDC Number?
National Drug Code -> 10-digit (11-digit when used in billing), 3-segment code used to identify drug products, does NOT mean that the drug has received an NDA
What is an NDA?
New Drug Application Proposal that the FDA approve a new pharmaceutical for sale and marketing in the U.S. Contains a complete evaluation of a drug's safety and efficacy, based on clinical trials, manufacturing processes, labeling, and drug chemistry
What is a "new drug"?
One that is not generally recognized by qualified experts as safe and effective for use under the conditions recommended in the drug's labeling
Dietary Supplement and Non-Prescription Drug Consumer Protection Act of 2006
Passed as a result of issues surrounding ephedra-containing dietary supplements (EDS) Established two mandatory serious adverse event reporting systems, one for non-prescription drugs and one for dietary supplements
What is a Paragraph IV Certification?
Patent certification of an ANDA that certifies that the patent of the innovator is invalid or will not be infringed by the approval of a generic product The patent holder is notified of this, and if they sue, the ANDA cannot be approved for 30 months If the generic manufacturer prevails, they get 180 days of market exclusivity
What is the Parallel Track Policy?
Policy created by the FDAMA by which an individual patient acting through a physician may request an IND in phase II or III of the NDA process for the treatment of a serious disease or condition outside of a clinical trial
What is a dietary supplement?
Product that is intended for ingestion to supplement the diet and that contains any one or more of the following: vitamin, mineral, herb/botanical, amino acid, metabolite, or substance which increases total dietary intake
1912 Amendment of the Pure Food and Drug Act
Prohibited false and fraudulent efficacy claims, but was ineffective because it required the government to prove fraudulent intent on the part of the labeler
Pure Food and Drug Act of 1906
Prohibited the adulteration and misbranding of food and drugs in interstate commerce Did not include cosmetics or devices
Orphan Drug Act of 1983
Provided incentives (tax benefits and licensing exclusivity) for the development of orphan drugs for treatment of rare diseases Defined a "rare disease" as one which affects fewer than 200,000 Americans
Federal Food, Drug, and Cosmetic Act (FDCA) of 1938
Provided that no new drug could be marketed until it was proven safe for use under the conditions defined on the label and was approved by the FDA Required that drug labels contain "adequate directions for use" and warnings about the habit-forming properties of certain drugs Exempted drugs marketed before 1938 from the "proven safe" requirement
Food and Drug Administration Amendments Act (FDAAA) of 2007
Provided the FDA with increased authority to regulate drug safety, including requiring REMS when necessary
Prescription Drug User Fee Act (PDUFA) of 1992
Requires that manufacturers seeking NDAs pay a fee for application and supplement when the FDA must review clinical studies Helped to speed up NDA reviews
What is REMS?
Risk Evaluation and Mitigation Strategy Created by the FDAAA; a strategy to manage a known or potential serious risks associated with a drug or biological product
What do the segments of an NDC mean?
Segment 1 -> manufacturer or distributer Segment 2 -> strength, dosage form, and formulation Segment 3 -> package size and drug type
Food and Drug Administration Modernization Act (FDAMA) of 1997
Streamlines regulatory procedures to ensure the expedited availability of safe and effective drugs and devices Reauthorized the PDUFA with the intent to eliminate backlogs in the NDA approval process Expanded the FDA's authority over OTCs and established ingredient-labeling requirements for inactive ingredients
What are Special Dietary Foods?
Substances that serve a special dietary need (infant formula, artificial sweeteners, caloric supplements) that exists by reason of a physical, physiological, pathological, or other condition
What is an SNDA?
Supplemental New Drug Application When a manufacturer makes a change in an approved drug for anything from the production to labeling
Action on Smoking and Health v. Harris (1980)
The FDA ruled that the drug definition applied only to brands of cigarettes for which the vendor made a therapeutic claim, which was upheld by the Court
Thalidomide Tragedy of 1961
The popular sedative thalidomide was being marketed in Europe in the late 1950s and distributed experimentally in the US in 1960 The FDA withheld an NDA due to pending safety information about the drug, which was soon proven to cause very serious birth defects Led to the Kefauver-Harris Amendment of 1962
What is a device?
any instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or related article/component that is: Intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals Intended to affect the structure or any function of the body of humans/animals but is not food