Federal Regulations of Medication: Development, Production and Marketing (Law Exam 1)

What does the first amendment have in place to place some limits on regulating drug adversiting?

congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech

What did the Durham-Humphrey Amendment of 1951 do?

created 2 classes of drugs (OTC and Rx) prescription drug labels must contain the statement "Caution: Federal Law prohibits dispensing without a Rx" authorizes PO Rx and refills

What did the Food and Drug Administration Modernization act of 1997 do?

creates a fast-track approval process for drugs intended to treat serious or life-threatening diseases authorizes scientific panels to review clinical investigations expands the right of manufacturers to disseminate information about off-label use of prescription drugs

Food vs drugs; why does the distinction matter?

degree of regulation regulations for both are different drugs have more stringent regulations than food

objectives of VAERS

detect new, unusual, or rare vaccine adverse events monitor increases in known adverse events identify potential patient risk factors for particular types of adverse events assess the safety of newly licensed vaccines determine and address possible reporting clusters recognize persistent safe-use problems and administration errors

Is a drug-eluding stent a drug or device? Why?

device function/purpose: keep vessel open in a non chemical way

What happens if the FDA takes more than 180 days to review an NDA? What happens if the FDA refuses to approve an NDA?

drug companies go to the courts to ask the FDA to review the NDA same with the approval (but its just really reviewing)

What is the rationale for strict liability?

ensure safety of drug chain and public health

The FDA is part of the Department of Health and Human Services, a department of the _______ branch of the federal govement

executive

T/F Dietary supplements require pre-market approval

false

T/F Reporting to VAERS is not mandatory for healthcare professionals but is mandatory for consumers

false: switch

T/F MedWatch is a mandatory adverse event reporting system administered by the FDA

false: voluntary

In order for a new drug to be marketed it must be ______ for use for the _____

generally recognized as safe and effective indications specified in the labeling

What does FDA approval for a drug mean?

generally safe and effective for indications approved in labeling

What happens when a patent expires?

generics come on market

In addition to issuing regulations, the FDA also issues _____ _____ statements that provide guidance on how the FDA intends to carry out its functions

guidance documents- non binding and legally unenforceable

put the phases of drug approval in order

pre clinical testing investigational new drug application filed phase 1 clinical trials phase 2 clinical trials phase 3 clinical trials new drug application filed phase 4 clinical trials

extensive laboratory and animal testing is carried out on the drug

pre-clinical testing

A drug or device is adulterated if its

prepared, packed or held in conditions where it may have been contaminated exposed to a container that may have contaminated it; manufacturered under conditions that do not conform to CGMP

Acts prohibited by the FDCA section 301

producing, delivering, receiving, dispensing, or offering for sale any food, drug, device or cosmetic that is adulterated or misbranded failure to keep and permit access to required records refusal to permit authorized inspections producing, delivering, receiving, dispensing or offering for sale any counterfeit drug alteration, mutilation, destruction, obliteration, or removal of any labeling of any food, drug, device or cosmetic while such article is held for sale which results in such article being adulterated or misbranded producing or delivering a dietary supplement that is unsafe

What did the Drug Price Competition and Patent Term Restoraction Act of 1984 do?

streamlined the generic drug approval process provided 5 years of market exclusivity to innovator drug manufacturers provided patent term extensions for a portion of the time taken up by the FDA approval process

There is no law that says a pharmacist is responsible for knowing drug recalls, so how do we know that pharmacists have this responsibility?

strict liability

The manufacturer S.E. Massengil Co., responding to demand for a liquid formulation, dissolved the drug (what drug?) in diethylene glycol, tested it for _________, ________, and ______, then marketed it as an _______ ______

sulfanilamide appearance taste smell sufanilamide elixir

What is commerical speech?

"speech" that promotes at least some type of commerce

label the NDC number: 12345-678-90

12345: labeler code: assigned by the FDA; indentifies the manufacturer or distributor 678- product code: assigned by the manufacturer or distributor; identifies the drug, strength, and dosage form of the special product 90- package code: assigned by the manufacturer or distributor; identifies the package size and type

Drugs marketed before ______ are exempt from the safety and efficacy requirement

1938

Manufacturers must be registered with the FDA and are inspected for compliance with CGMP every _____. This includes foreign manufacturing facilities

2 years

What are the new labeling standards for pregnancy?

3 sections: pregnancy: info relevant to the use of the drug in pregnant women, including dosing and potential risks to the fetus lactation: info about using the drug during breastfeeding, including the amount of drug in breast milk and potential effects on the child females and males of reproductive potential: info about pregnancy testing, contraception, and infertility as related to the drug

What is a medical device?

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article which is: - recognized in the USP or NF - intended for use in the diagnosis of disease or other conditions; - intended for use in the cure, mitigation, treatment, or prevention of disease in man or other animals; or - intended to affect the structure or any function of the body of man or other animals and which does not achieve any of its principles intended purposes through chemical action within or on the body..... and which is not dependent upon being metabolized for the achievement of any of its principle intended purposes

What are the MedWatch Forms?

FDA form 3500: healthcare professionals FDA form 3500B: consumers

The FDA is headed by a commissioner who is appointed by the ___________ and confirmed by the ______. The commissioner directly reports to the _______

President of the US senate secretary of health and human services

What did the Orphan Drug Act of 1983 do?

Provided tax and exclusive licensing incentives for manufacturers to develop and market drugs/biologics for the treatment of rare disease or conditions

Who regulates advertising with Rx drugs? non Rx drugs?

Rx drugs: FDA non Rx drugs: FTC

What are the 2 official compenia in the US?

USP-NF HPUS

Advertising is required only to present ______ of side effects, CI and effectiveness. Labeling must include

a brief summary the entire package insert

What is a dietary supplement defined as?

a product that is: - intended for ingestion - intended to supplement the diet and - contains one or more of the following: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by humans to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract or combination of the previous

Whats the main difference between adulteration and misbranding?

adulteration deals with drug misbranding deals with label

Which class of drug recall is this? product not likely to cause adverse health consequences

class 3

Under the FTCA what qualifies as deceptive advertising?

an advertisement containing a statement (or omission) that is likely to mislead reasonable consumers to their detriment (the FTC does not need to prove that consumers were actually misled, only that they are likely to misled)

Healthcare professionals must report the following from VAERS

any adverse event listed by the vaccine manufacturer as a CI to further doses of the vaccines or - any adverse event listed in the VAERS table of reportable events following vaccinations that occurs within the specific time period after vaccination

What are cosmetics?

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 appearnace or articles intended for use as a component of any such articles the term shall not include soap

What are drugs?

articles recognized in the USP, NF, or Homeopathic Pharmacopoeia of the United States (HPUS) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals articles (other than food) intended to affect the structure or any function of the body of man or other animals or articles intended for use as a component of any articles specified above

What is food?

articles used for food or drink for man or other animals chewing gum articles used for components of any such article

What did the Generic Drug Enforcement of 1992 do?

authorizes the FDA to ban individuals or firms from participating in the drug approval process if convicted of related felonies imposes severe civil penalties for false statements, bribes, failures to disclose material facts, and related offenses

What are the benefits of the old pregnancy classifications? Cons?

benefits: easly to apply cons: not a lot of info supplied with it

Certain CI or serious warnings, particularly those that may lead to death or serious injury, may be required by the FDA to be presented in a box. The boxed warning ordinarily must be based on clinical data, but serious animal toxicity may also be the basis of a boxed warning in the absence of clinical

black box warning

For the MedWatch system what does the use of the terms "strongly encourage" and "moral obligation" suggest to you?

cant be forced to legally to enforce it

Which category of pregnancy classification is this? (A-X) definition: adequate and well controlled studies in pregnant women that have not demonstrated a risk to the fetus application: these drugs are considered safe to use during pregnancy

category A

Which category of pregnancy classification is this? (A-X) definition: there are no well controlled studies in pregnant women, and animal studies have failed to demonstrate a risk to the fetus application: these drugs are considered safe to use during pregnancy

category B

Which category of pregnancy classification is this? (A-X) definition: there are no well controlled studies in pregnany women, but either animal studies have shown an adverse effect or there are no animal reproductive studies application: these drugs should be given only if the potential benefit justifies the potential risk to the fetus

category C

Which category of pregnancy classification is this? (A-X) definition: there is positive evidence of human fetal risk, but benefits from use in pregnant women may be acceptable despite the risk application: these drugs should only be used in pregnancy when the alternatives are worse

category D

Which category of pregnancy classification is this? (A-X) definition: studies in animals or humans have demonstrated fetal risk, and the risk in pregnant women clearly outweighs any benefit application: these drugs are CI in women who are or may become pregnant

category X

Which class of drug recall is this? reasonable probability that the product will cause serious adverse health consequences or death

class 1

Which class of drug recall is this? product may cause temporary or medically reversible adverse health consequences, but probability of serious adverse health consequences is remote

class 2

What did the Prescription Drug Marketing Act of 1987 do?

imposed sales restrictions and record keeping requirements for prescription drug samples permitted distribution of prescription drug samples only upon the request of a physician prohibited re-importation of exported prescription drugs except by the original manufacturer

Criminal penalties for failure to comply with section 301 of FDCA: first offense without intent to defraud

imprisonment up to 1 year fine up to one grand both

Criminal penalties for failure to comply with section 301 of FDCA: second offense without intent to defraud and first offense with intent to defraud

imprisonment up to 3 years fine up to 10 grand both

Manufacturer-to-consumer advertising, also known as direct-to-consumer (DTC) advertising, like manufacturer-to-professional advertising must

include a true statement of the established name of the drug and its formula a brief summary of info relating to side effects, CI, and effectiveness and a fair balance between side effects/CI and effectiveness BUT the level of info required in the "brief summary" is not as stringent as required for manufacturer-to-professional advertising. DTC advertising need only list the most serious and most common side effects

Under the FDCA advertising and other printed matter must

include a true statement of the established name of the drug and its formula a brief summary of information relating to side effects, CI and effectiveness a fair balance betwen side effects/CI and effectiveness

What does the black box warning rule really require?

info about that warning in a black box on that labeling

Put the Brown's Hierachy of drug regulation (please remember that this is fake :) )

information efficacy safety purity (top to bottom)

provides the FDA with info about the drug, the qualifications of the investigators, and on outline of the proposed clinical (human) trials, human trials may begin after 30 days of submission of this unless the FDA rejects it

investigational new drug application (IND) filing

The FDA uses these factors to determine whether a product is a drug or device

is the product intended to deliver drugs to the patient, but is not prefilled by the manufacturer? (e.g. an empty implantable infusion pump) is the drug component included solely to make the product safer? (e.g. a surgical drape impregnated with antimicrobial agents) is the drug component intended to have a therapeutic effect? (e.g. an intrauterine contraceptive device that releases hormone)

What did the Food, Drug, and Cosmetic Act of 1938 do? What did the law NOT do?

it did: - formed the FDA - required that any new drug be proven safe for use under the conditions described on the label - required adequate directions for use - required warnings about habit-forming properties to be placed on labels - applied to food and cosmetics as well as drugs it did NOT: - require proof of efficacy - apply to drugs marketed prior to the implementation of the law

What did the Pure Food and Drug Act of 1906 do? What did it not do?

it ensured strength, quality and purity of food and drugs it did NOT ensure safety of efficacy

A drug or device is misbranded if:

its labeling is false or misleading in any particular its package does not contain (1) the name and place of business of the manufacturer, packer, or distributor and (2) an accurate statement of the quantity of the contents in terms of weight, measure or numerical count any word, statement, or other information is not prominently placed on the label its a nonRx drug and its labeling does not bear adequate directions for use its a Rx drug and its labeling does not bear adequate information for use it purports to be a drug recognized in an official compendium and fails to be packaged and labeled as Rxed by such compendium its container is made, formed or filled as to be misleading its an imitation of another drug its offered for sale under the name of another drug its packaging or labeling is in violation of the Poison Prevention Packaging Act of 1970

What are the 3 places the FDA allows the distribution of off label uses?

journal articles reference texts (in their entirety or as individual chapters) clinical practice guidelines

written, printed, or graphic matter upon the immediate container of any article

label

all labels and other written, printed or graphic matter - upon any article or any of its containers or wrappers - accompanying sucy article - may include literature other than the package insert, such material that is deemed to accompany the article is labeling; such material deemed not to accompany the article is advertising

labeling

Examples of adulteration

manufactured not in accordance with CGMP strength, quality or purity differs from compendia standards, unless variations stated on label counting on dirty counting tray in the pharmacy temperature not adequately controlled certain OTC drugs not packaged in tamper-resistant package

formulated for use under supervision of a physician and intended for dietary management of a disease or condition for which distinctive nutritional requirements are established ex: products formulated without phenylalanine for phenylketonuria; folic acid/ B6/B12 combinations for hyperhomocysteinemia

medical foods

The FDA considers the following factors when determining where to inspect:

medical importance of the product market share number of similar products in the marketplace previous compliance record of manufacturer

As with manufacturer-to-professional advertising, failure to comply with manufacturer-to-consumer advertising requirements will cause the drug to be

misbranded

Failure to comply with the FDCA advertising requirements will cause the drug to be ______

misbranded

What are some criticism of permitting the marketing of dietary supplements without prior FDA approval?

more harm than benefit; wont know until its too late dont have to prove claims; false sense of security just need to be safe

VAERS was created by

national childhood vaccine injury act of 1986

The following are examples of what is considered a "new" drug

new chemical entity new ingredient (active, excipient, carrier, coating, etc) in an already approved drug change in the proporation of ingredients in an already-approved combination product new intended use for an already approved drug change in the dosage, method or duration of administration of an already approved drug

a compilation of all the data obtained during the IND process, including pre-clinical and clinical trials, manufacturing processes, labeling and packaging, the FDA has 180 days to review this

new drug appllication filed

Are these black box warnings really effective? Why or Why not?

no; its targeted to pharmacists its effective as legal protection

Pharmacies must provide the medwatch number with each new and refill prescription by any of the following means

on a sticker attached to the container or package on a preprinted vial cap on a separate sheet of paper in patient medication info in a medguide

With respect to the advertising of nonRx drugs the FTC has the authority to

order manufacturers to cease deceptive advertising issue corrective advertising require disclosure of adverse effects of a drug

What happens when exclusivity expires?

other manufacturers can make it sometimes it applies to generic manufacturers

What is the differene between a patent and exclusivity?

patent: federal government grants for anything exclusivity: FDA grants for drugs

Why would society be interested in regulating advertising of drug products?

patient safety

the drug is tested for safety and dosing range on 20 to 80 patients

phase 1 clinical trials

the drug is tested for efficacy on a few dozen to hundreds of patients

phase 2 clinical trials

the drug is tested for efficacy on hundreds to thousands of patients

phase 3 clinical trials

the FDA may also require clinical trials to continue even after a drug has been approved for marketing its also called?

phase 4 clinical trials (post-marketing surviellance)

The federal government regulates advertising and promotional activities of drug products more strictly than other consumer products. Regulators are particularly concerned with the following

promotion of drugs for off label use false and misleading claims unsupported product comparisons overstatement of efficacy understatement of risk

What did the Dietary Supplement Health and Education Act of 1994 (DSHEA) do?

provides a legal definition for the term "dietary supplement" permits claims about dietary supplements that would otherwise be illegal under the FDCA exempts dietary supplement manufacturers from pre-market approval requires the FDA to regulate dietary supplements more as a special type of food than as drugs

What does the distinction of drug vs device matter?

regulated different/ degree of regulation billing insurance

As an administrative agency, the FDA is empowered to issue _____ to carry out the funcitons assigned to it by statute

regulations

The following are types of advertising are exempted from the "true statement" requirement

reminder advertising (cups, pens, basically hey we exist) advertising of drugs used in compounding by pharmacists institutional advertising help-seeking or disease awareness communications

What did the Medical Device Amendments of 1976 do?

required premarket approval for some medical devices required use of GMP during production of medical devices

What did the Kefauver-Harris Amendment of 1962 do?

required proof of efficacy transferred jurisdiction of Rx drug advertising to the FDA established Good Manufacturing Practices (GMP) requirements required informed consent of clinical trial subjects and reporting of adverse drug reactions applied efficacy requirement retroactively to all drugs marketed between 1938 and 1951

What did the Nutrition Labeling & Education Act (1990) do?

requires nutrition labeling on food products authorizes the use of health claims on product labeling as long as the claims comply with FDA regulations

What did the Food and Drug Administration Amendments act of 2007 do?

requires post market clinical studies to assess risks requires implementation of risk evaluation and mitigations strategies (REMS) when necessary

MedWatch is a voluntary adverse event reporting system adminstered by the FDA. The FDA strongly encourages healthcare professionals and consumers to report

serious adverse events potential and actual product use errors product quality problems

supply a special delivery need that exists by reason of a physical, psychological, pathological, or other conditions ex: infant formula, artifical sweetner, caloric supplements

special dietary foods

What did the Prescription Drug User Fee Act of 1992 (PDUFA) do?

speeds up new drug application approval process requires manufacturers to pay user fees for applications and supplements when the FDA must review clinical trials

Manufacturers producing products that comply with this definition may make the following 4 types of health claims about dietary supplements

that the product will benefit a classical nutrient deficiency disease, as long as it discloses the prevalence of the disease in the US the role of the dietary supplement in affecting the structure or function of the body the documented mechanism by which a nutrient or dietary supplement acts to maintain a structure or function the general well-being from consumption of a nutrient or dietary ingredient (e.g. "energizer", " relaxant", or "muscle enhancer")

What if a drug manufacturer refuses an FDA recall request?

the FDA must take seizure or injunctive action to remove the product from the market

If the expiration date of a drug is given only as a month and year, what is the last date on which the drug may be dispensed?

the last day of the month

The Supreme Court set down 4 factors that will be considered when evaluating whether the government may regulate commerical speech?

the speech must be misleading or related to an unlawful activity the government interest in the regulation must be substantial the regulation must directly advance the government interest asserted the restriction of speech cannot be more extensive than necessary to serve that interest

As a result of the Bad Ad program started in 2010 complaints against drug company advertising has

tripled

T/F Manufacturers are not required to respond to 3rd party info

true if a manufacturer chooses to respond, the response must be truthful and misleading, but it need not satisfy the other requirements (i.e. brief statement, fair balance)

The FDA must prove that a dietary supplement is _____ before it can be removed from the market

unsafe

What is an off-label use?

use of a drug not included in package insert or FDA approval

Recalls are one method of removing adulterated or misbranded products from the market. This can be accomplished in 3 ways

voluntarily by the manufacturer by FDA request by FDA mandate (for medical devices, biological products, and foods --- not for drugs)

Examples of black box warnings

warfarin: bleeding to death depo-provera: signficant loss of bone density with long term use antidepressants: increased risk of suicidal tendencies in patients 18-24 YO metformin: lactic acidosis

The FDA may use any of the following when enforcing section 301 of the FDCA

warning letters: for minor violations as a first step to prevent the need for more severe enforcement actions injunctive action: filed in civil court asking the court to order a violator to cease certain activity seizure of adulterated or misbranded food, drugs or cosmetics criminal proceedings

What do we learn from the Nutrilab case?

what food is (articles used by people in the ordinary way most people use food-primarily for taste, aroma, or nutritive value) courts will get involved in answering these questions; if FDA and drug manufacturers cant reach a conclusion