Law Quiz 1- Food Drug and Cosmetic Act

General Requirements for the "Adequate" Labeling of a Drug

"Adequate" labeling of a drug must include: 1. all conditions, purposes, or uses 2. quantity or dosage for each intended use and for persons of different ages and physical conditions 3. The frequency and duration of administration or application 4. The time of administration or application (with or without meals, at onset of symptoms, etc) 5. Route or method of administration or application 6. Preparation necessary for use (e.g. shaking, dilution)

Cosmetic

(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap.

Misbranding Overview

- Misbranding focuses on representations made by the manufacturer on the label or the labeling -The FDA must approve in the premarketing approval process, the exact wording of a drug's label and labeling -The agency often uses misbranding provisions to prevent manufacturers from marketing products in violation of the law -A label shall not be false or misleading

What are exceptions to the 1970 Poison Prevention Packaging Act enforcement of child-resistant containers for drugs

- Drugs dispensed to institutionalized patients are exempt from child-resistant containers if drugs are administered by employees - Patients or their prescribing physician may request the use of noncompliant containers for their prescriptions

Federal Anti-Tampering Act *yoda slide*

- Passed by congress to make tampering of consumer products a federal offense -Tampering is improper interference with the product for the purpose of making objectionable or unauthorized changes -FDA began requiring certain OTC drugs, cosmetics, and devices be manufactured in tamper-resistant packaging

1970 Poison Prevention Packaging Act

- Protects children from accidental poisonings of household substances - Requires use of child resistant containers for packaging of most OTC drugs and nearly all Rx drugs (w/ some exceptions)

What are household substances defined as

- hazardous substance in federal Hazardous Substances Act - economic poison under the Federal Insecticide, Fungicide and Rodenticide Act - food, drug , or cosmetic under the FDCA - household fuel when stored in a portable container

Safe Medical Devices Act of 1990

-Improved Med Devices Amendment Act of 1976 -gives FDA authority to postmarketing reqs & premarket notification/approval -provides for expedition of premarket device approval process

Prescription Drug User Fee Act of 1992 (PDUFA)

-PDUFA requires manufacturers to pay fees for NDAs and supplements when the FDA reviews clinical studies -PDUFA is reauthorized every 5 years (it was last reauthorized in 2012) -Background: Volume of drugs FDA needed rising w/o rises in fed.budget so this allowed FDA to hire more reviewers to speed up review

FDA Safety and Innovation Act of 2012 (FDASIA)

-Reauthorized PDUFA and added new fees for biosimilars and generic drugs -provisions to: - reduce/detect drug shortages -*reduce drug counterfeiting and block imported adulterated products* -Enhancement of the exchange of Rx diversion information across state lines -Allows FDA to inspect foreign manufacturers regulatory and requires the agency to target problematic manufacturing sites in/out of US

FDA Safety and Innovation Act of 2012 (FDASIA)

-Reauthorized PDUFA and added new fees for biosimilars and generic drugs -provisions to: - reduce/detect drug shortages -reduce drug counterfeiting and block imported adulterated products -Enhancement of the exchange of Rx diversion information across state lines -Allows FDA to inspect foreign manufacturers regulatory and requires the agency to target problematic manufacturing sites in/out of US

Food and Drug Administration Amendments Act of 2007 (FDAAA)

-Reauthorized drug & device provisions - Provided FDA with funding and more authority over drug safety. FDA could require: - labeling changes related to safety -clinical trial data reporting to registries - postmarket clinical studies to assess risks -companies to implement risk evaluation and mitigation strategies when necessary Increased PDUFA fees and more uses allowed to the FDA for funds

FDCA labeling.

-all labels and other written information on any article or containers

Current Good Manufacturing Practices (CGMP)

-establishes minimum requirements for the methods, facilities, or controls used in the manufacture, processing , packaging or holding of a drug product - applies to manufactures, not pharmacies, unless pharmacy is the manufacturer -FDA inspects manufacturers for CGMP every 2 years - FDA looks at public reports to determine when to inspect -.

Food and Drug Administration Modernization Act of 1997 (FDAMA)

-passed to streamline regulatory procedures & expedite availability of safe& effective drugs/devices -requires FDA mission statement - fast-track approval process for NDAs for treatments of serious/life threatening diseases - priority review for breakthrough tech in med devices and allowed FDA to contract w/ outside experts to review med device applications -databank of info on clinical trials, authorized scientific panels to review clinical investigators, expanded rights of manufactures to share info on unlabeled uses -replaced federal legend w/"Rx only"; eliminated provision for certain substances to be labeled : " Warning- may be habit forming" -expanded FDA uthority over OTC drugs & required labeling for inactive ingredients - prevented states from creating labeling reqs for OTC drugs and cosmetics when fed requirements exist -encouraged manufactures to research new uses of drugs & submit supplemental NDAs for these uses. These uses may be publicaly shared with a statement clarifying that the use has not been FDA-approved -pediatric drugs received an additional 6 months of marketing exclusivity to encourage pediatric research by manufacturers

FDCA Definition of "Drug" *yoda*

1. Articles recognized by official pharmacopoeia in the US (USP/NF) 2. And used for the diagnosis, cure, mitigation, treatment, or prevention of disease 3. And intended to affect the structure or any function of the body 4. In man or other animals

Order of "Drug Facts" panel in non-prescription drug labels

1. active ingds (dosing unit & quantiy/unit) 2. purpose 3. use(s) 4. warnings 5. directions 6. Other info (as req. by monograph, by regulatio, or in approved labeling) 7. inactive ingredients (alphabetically) 8. Questions or comments ->(phone number)

FDCA Label definition *yoda*

321k: display of written, printed or graphic matter on immediate container of any article of product

Definition of dietary supplement under DSHEA

A product that is intended for ingestion, is inteded to supplement the diet and contains ONE or more of the following -vitamin -mineral -herb/botanical -amino acid -dietary substance to supplement diet -concentration, metabolite, constituent, extract, or combo

Adulteration (poison/insanitary provisions) Part A

A)Poisonous, insanitary, etc., ingredients; adequate controls in manufacture 1. consists of filhy, putrid or decomposed substance 2a.prepared, packed or held under insanitary conditions 2b. if drug's use, processing, packing or holding are not in compliance w/ good manufacturing practice 3. consists of any poisonous r deleterious substance 4. contains an unsafe color additive for the purposes of coloring only

What groups supported Dr. Wiley

APhA, AMA

Medical Device Amendments of 1976

All devices after '76 are classified into 3 classes Class I- least harm, least regulation, general controls sufficient for safety & efficacy Class II- intermediate class, general controls insufficient; specific performance standards required Class III- life supporting, life sustaining, or resent a potential unreasonable risk of illness or injury, must have premarket approval

Drug

Articles used in diagnosis, cure, mitigation, treatment or prevention of dsisease by affecting function of the body

New Drug *yoda*

As per FDCA, a drug that is not generally recognized as safe and effective by qualified experts for use under the conditions recommended in labeling

Prescription Drug Marketing Act of 1987

Bill enacted to place more controls on distribution of prescription drug products and samples -sale restrictions -precise storaging, handling, records for Rx drug samples -prohibits hospitals/HC institutions from reselling pharma purchases to other businesses -requires state licensing of Rx drug whole sales -bans re-importation of Rx drugs made in US

After the Hatch-Waxman Amendment, what is the difference between brand and generic approval processes

Brand medications require a new drug application while generics only have to submit an abbreviated new drug application (ANDA) which requires proof of bioquivalence

What class of medical devices do needles, elastic bandages and exam gloves belong?

Class 1 Class 1 devices are subject to general controls that require device manufacturers to register their facility and list their products with he FDA, provide premarket notification in some cases, maintain records and reports, and adhere to good manufacturing practices Most common type of med device scissors, enema kits and toothbrushes are also examples

Classes of Recalls

Class I : reasonable probability that the product will cause serious, adverse health consequences or death (ADC) Class II: remote probability of temporary or reversible ADCs Class III recall: not likely to cause ADCs

What class of medical devices do insulin syringes, tampons, powered wheel chairs and thermometers belong?

Class II Class II are devices which general controls are insufficent and products must meet specific performance standards established by FDA before marketing Other examples: infusion pumps, diagnostic regents, electric heating pads, some pregnancy testings kits

What happens when a manufacturer violates CGMP?

Companies who distribute drugs that defective may recall them or the FDA may seize them or bring an injunction to have the court order the company to stop violating CGMP

Sulfanilamide Tragedy of 1937 *yoda*

Company added diethylene glycol and caused 107 deaths and FDA removed it on misbranding violation. Led to Food, drug, Cosmetic Act 1938

What is a child-resistant container per the Poison Prevention Packaging Act

Containers must be manufactured such that 80% of children <5 yo cannot open them, but 90 & of adults can

Kefauver-Harris Amendment of 1962

Created after thalidomide defects Drugs had to be proven not only safe, but also effective - efficacy requirement was retroactive to all drugs 1938-62 - required informed consent of research subjects and report of ADRs

Federal Food, Drug, and Cosmetic Act of 1938 *yoda*

Current law: 5 points -no new drug marketed until proven safe -expands definitions of misbranding and adulteration (active ingredients) -factory inspections -applies to devices and cosmetics -Pre 1938 drugs exempted

Misbranding setting, reporting, advertising, packaging

Drug made in a nonregistered establishment Failure to include contact information to report ADR Prescription drug promoted in violation of advertising provisionslacking: - established drug name - strength of the drug - brief summary requirement drug breaks USF/NF specifications, sold under another drug name or misrepresents drug violates PPA/ FATA and/or REMS Health endangering when used as prescribed and lacks precautionary statement for drugs subject to deterioration

Adulteration even if drug is pure

Drug may still be considered adulterated under Adulteration act if: 1) Prepared, packed or held where it could've been contaminated -exposed to contaminated contained -manufactured under conditions that do not conform to current good manufacturing practices (CGMP)

NDC *The NDC number is listed in the MPJE blueprint as potentially being on the MPJE, so definitely know this

Drug products are identified with an 11 digit, 3 segment number called a National Drug Code First segment assigned by the FDA: identifies manufacturer or distributor Second segment identifies strength, dosage form and formulation Third segment is package size

Adultering (strength, quality purity) Part B, C, D

Drug/ device adulterated if: B)Strength, quality, or purity differs form official compendium - standards determined with tests methods seth forth in compendium -no drug in compendium will be considered adulterated if it is stated on the label Misrepresentation of strength, etc where drug is unrecognized in compendium C) if not in compendium (Part B ^^)and its strength differs or purity/quality falls below what it is represented to possess D i) Mixture w/ or substitution of another substance to reduce quality/strength in part or wholly

Family Smoken Prevention and Tobacco Control ACT 2009 *yoda* *KNOW THIS

FDA regulates tobacco -bans flavored tobacco -stops youth marketing -companies must provide info about amount of nicotine in product to FDA and public -FDA must review if products claims to be light -warning label must cover 50% -FDA regulates advertising -Creates tobacco product scientific advisory committee to give advice to FDA

Who enforces the Poison Prevention Packaging Act

FDA was in charge of enforcing the law until it was passed to the Consumer Product Safety Commission in 1973 (CPSC)

T/F Prescribers may issue blanket waivers for non-resistant containers for all of their patient's medications

False Patients may request a blanket waiver for all of their prescriptions Prescribes can only request a waiver on an individual Rx and its refills, not all of their patient's medications.

T/F Requests for non resistant containers must be documented in writing by the pharmacist per the 1970 Poison Prevention Packaging Act?

False Requests are permitted under the law to be oral It is encouraged, however, for pharmacists to keep documentation for their protection

Why was Federal Anti-Tampering Act created *yoda slide*

In Chicago in 1982, Tylenol capsules on pharmacy shelves were laced with cyanide killing seven people - the tamperer was never caught and 270 copycat incidents occurred soon after

Misbranding Habit-forming drugs

It is required to have a *Drug Abuse and Dependence* section in package insert w/ description of habit-forming characteristics FDAMA eliminated the requirement that any drug containing a habit-forming substance must have a warning on the label to this effect Inclusion is up to manufacturer

Which amendment established Good Manufacturing Practices requirements

Kefauver-Harris Amendment of 1962

What constitutes a misbranded label?

Label is false and misleading Label is missing: -"Established Name" of the drug -Each active drug ingredient listed -Quantity of container ingredients -Adequate information for use (Rx drugs only) -Words, statements, information as required by law conspicuously and prominently displayed, eg: Prescription drugs required to contain "Rx only" - *labeling lacks adequate directions for use, adequate warnings, or address/phone number of manufacturer to report serious adverse effects *

Misbranding Generally Active & Inactive Ingredients

Law requires : -listing of any active ingredient for both prescription and non-Rx drugs -quantity of each active ingredient -a *separate* list of each *inactive* ingredient in *alphabetical* order by established name for both Rx/non-Rx drugs -flavors and fragnances are inactive ingredients that do not need to be listed

Hatch- Waxman Amendment

Made generic drugs more readily available to the public and provide incentives for the manufacturer to develop new drugs Streamline approval process for generics Gave patent extensions to innovator drugs

Requirements for non-prescription drug labeling

OTC drugs are safe and effective for self-tx by pt Label must contain in part the follow (21 CFR part 201 A/C) - established drug name and drug class or principle intended actions - name & address of manufacturer, packer or distributor - net quantity of content of pkg - cautions and warnings - adequate directions for use (general labal req)

Definition of tamper- resistant packaging

Packing has an indicator or barrier to entry which if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred

T/F: If a brand device is reclassified, the reclassification applies to the generic device as well

True The FDA can reclassify devices if there is new information on safety and efficacy Hundreds of devices have been reclassified from Class III to Class II; and from Class II to Class I

Requirements for the "Adequate" Labeling of a *Prescription* Drug

Prescription drugs cannot be labeled adequately to protect the consumer and meet the "adequate directions for use" requirements under Section 502(f) "Adequate" labeling of a Rx drug must include: 1. Indications 2. Side effects 3. Dosage 4. Routes, methods, frequency, and duration of administration 5. CI 6. Other warnings and precautions that enable a practitioner to administer, prescribe, or dispense the drug safely

Shirley Amendment of 1912

Prevented fraudulent therapeutic claims by drug manufacturers

Key Prohibited Acts in the FDCA

Prohibits: -intro, delivery into. receipt of interstate commerce of any adultered or misbranded food, drug or cosmetic, including dietary supplements deemed unsafe -manufacturing of ^^^ - no articles in violation of section 344 (contaminated food products) or 355 (a new drug that does not have an approved application filed) of this title. - refusal to permit access to or copying of any record as required -refusal to permit: entry of FDA inspectors or FDA inspection - creation, sale, dispensing, hold for dispensing or sale of a counterfeit drug -alteration/ removal of the whole or any part of the labeling of a food, drug, device, tobacco product, or cosmetic

What are some examples of medications that are recent exceptions to the Poison Prevention Packaging Act?

SL nitroglycerin SL/chewable isosorbide dinitrite Some packages of steroids with dosing limits Cyclic oral contraceptions Medroxyprogesteroneacetate talets Some powders/ suspensions Hormone Replacement Therapy Full list slide 57

What mucraker publications brought awareness

The Jungle and the Great American fraud

Pure Food and Drug Act of 1906

The wiley act prohibits adulteration and misbranding of foods and drugs

What class do devices not marketed before 1976

These devices initially fall into class III, unless FDA determines that they are equivalent to a Class I or II device

Orphan Drug Act of 1983

This act provided tax and exclusive licensing incentives for manufacturers to develop treatments for rare diseases or conditions (<200,000 Americans have condition)

Thalidomide Tragedy 1961

Used in pregnant women to treat morning sickness and caused birth defects in Europe. FDA didn't allow it. Approved in 1998 for myeloma

Recall

When adulterated or misbranded products are removed from the market - FDA/ or manufacturer independently may intiate recall -Manufacturers are responsible for notifying sellers of the recall and sellers contact consumers if necessary

Misbranding safety provisions

a drug/ device is misbranded if: a) deteriorative drug b) misleading container, sold another the name of another drug c) health-endangering when used as prescribed d) color additives-must comply w/ packaging/ labeling req applicable under section 379e if intended use is solely for purpose of color

Qualified health claim

allowed when there is more evidence of the claim than against it

What is an example of a medical device that is available by prescription only?

contact lenses

Durham-Humphrey Amendment of 1951 "prescription drug amendment" *yoda*

created prescription and OTC created Rx legend allows oral prescriptions and refills standards for info on labels and labelling

Misbranding label provisions

drug or device is misbranded if: a) false or misleading label b) package form- should have name/place of manufacturer, accurate statement of quantity (exceptions exist), c) prominence of info on label d) designation of drug by established names e)drug/ingredient should be printed prominently and in type at least half as large as that used for brand name f) directions for use and warnings on label g) purports to be a recognized drug

Misbranding Generally: Adequate Directions for Use

drugs labeling must contain adequate directions for use and adequate warnings against use by children and others for whom use may be dangerous -must be directions under which the layperson can use a drug safely and for the purposes for which it is intended (21 CFR § 201.5)

Dietary Supplement Health and Education Act of 1994 allowed for the FDA to regulate them as a drug T/F *yoda*

false; it allowed them to regulate it as a food instead of a drug. Under the act: the FDA cannot require permarked approval (like drugs) -also prohibited the marketing of supplements as food additives

Pure Food Movement

grassroot movement of the 1870s led by Dr. Harvey Washington illey

Device

instrument intented for diagnosis of disease or in cure/ prevention

Unqualified health claim

is supported by significant scientific agreement; also known as an authorized claim.

What are examples of Class I Medical Devices that are exempt from a premarket notification application and FDA clearance?

manual stethoscopes, mercury thermometers and bedpans. However, the manufacturer is required to register their establishment and list their generic product with FDA.

What are examples of Class III devices

pacemakers, soft contact lenses, replacement heart valves, silicone gel-filled breast implants, and implanted cerebella stimulators Class III devices must have premarket approval

Food

raw, cooked, or processed edibile subtance, ice, bevarage and chewing gum

Safe Medical Devices Act of 1990

requires device-user facilities (treatment facilities that are not physician's offices) to report to the Secretary of HHS any death, serious injury, or serious illness that may be related to the product Distributors must maintain records of adverse events but are not required to submit adverse event reports to the FDA or to device manufacturers