Pharmacy Law Chapter 2

Under the Federal Food, Drug, and Cosmetic act, when can a drug be marketed and sold?

-When is has been proved SAFE and EFFECTIVE for its intended use by the FDA.

Describe the Generic Drug enforcement act of 1992:

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

What did the Federal Food, Drug, and Cosmetic act of 1938 say about medical devices: Who had authority? Why was it lacking?

-Gave FDA authority to regulate med devices -Authority was only to regulate products believed to be adulterated or misbranded.

What did the Drug Price and Patent Term Restoration act of 1984 entail? (what was it informally known as?)

-Waxman-Hatch Amendment -Enacted to streamline the generic approval process while giving patents extension, in certain circumstances, to drug innovators.

Food and Drug Administration Modernization Act of 1997 (FDAMA): 1) what was its intent? 2) what did it do?

-Intent to eliminate backlogs in approval process and ensure timely review of applicators -Fast track approvals for drugs for life threatening diseases, establishes database for clinical trials, authorizes panel to review clinical investigations, and expands rights of manufacturers to disseminate unlabeled info -OTCs required to list inactive ingredients (increases FDA authority)

What was the Prescription Drug Marketing Act of 1987? Why was it put in place?

**There was secondary drug distribution systems threatening public health -Law establishes sales restrictions and recored keeping requirement for SAMPLES of prescription drugs. -Prevented hospitals and other healthcare entities from reselling their pharmaceutical & requires state licensing of drug wholesalers.

Describe the FDA rating and classification system: whats its purpose?

- utilizes priority classifications system that rates new drugs by chemical type and therapeutic potential. -Purpose: determines how rapidly a drug will proceed through NDA process.

What did the amendment of the Pure Food and Drug Act of 1906 entail? Was this Act successful in the end?

-1912: amended to prohibit false of fraudulent efficacy claim. -The act failed to achieve its purpose because it required the federal government to prove fraudulent intent on the part of the ones who made the false statements on the label.

What was Thalidomide?

-1950s: a popular sedative that was being marketed in Europe.

(Broad) FDA approval process for a new drug:

-Applicant must submit evidence to FDA that drug is safe and effective -Conduct animal and clinical studies.

What is a Cosmetic according to the 21 USC sec 321 (i)?

-Articles intended to be rubbed/sprinkled/poured/sprayed on/ otherwise introduced to human body for cleaning, beautifying, prompting attractiveness or altering appearance. -Except such term shall not include soap

According to Section 201 of the FDCA (21 USC sec 321 (f)), what does the term FOOD mean?

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

Why did the Generic Drug Enforcement Act of 1992 come about?

-B/c some FDA staff accepted bribes from generic drug industry personnel in order to facilitate the approval process of certain generic drugs.

What prompted the Pure Food and Drug act of 1906?

-Concern for public health and safety associate with unsanitary and poorly labeled food and drugs.

Describe the Food Additives Amendment of 1958: (2)

-Congress requires that components added to food products must receive pre-market approval and safety. -Delaney's Clause: prohibits food additives that might cause cancer.

What is Tamper Resistant Packaging?

-Defined as one having 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.

What did the Dietary Supplement Health and Education act of 1994 (DSHEA) entail?

-Defines dietary supplements and permit manufacturers to make certain claims that otherwise would have been illegal under FDCA. -FDA regulates dietary supplements more like food then drugs.

What is a drug?

-Definition: Intended use is for therapeutic claims and structure/function claims -There has to be evidence for intended use. -

What is a Label according to the 21 USC sec 321 (k)?

-Display of written, printed, or graphic matter upon immediate container/other article , and a requirement by FDCA that any word/statement/or other info is not considered to be complied unless such info also appears on the outside container/wrapper if there is one or is legible thought the outside container/wrapper.

Prescription Drug User Fee act of 1992: key question: how did this benefit the FDA?

-FDA + Congress took the approach the private industries should pay part of the new drug approval rather than tax payers. -Requires manufacturers to pay fees for applications and supplements when the FDA must review clinical studies. -Fees provide the FDA with resources to hire more reviewers to asses clinical studies and speed up NDA review.

Strategy for determining if a product is a drug: What questions should you consider? What is the critical issue?

-Is the product/article intended to diagnose, cure, mitigate, treat, or prevent a disease OR intended to affect body structure and function? RULE OF THUMB: if therapeutic claims are made, and article is a drug.

What does the Federal Anti-Tampering Act entail?

-It's a federal offense to tamper with consumer products -Requires certain OTC drugs, cosmetics, and devices be manufactured with tampering resisting packaging -violation may result in misbranding, adulterated, or both.

What is the criticism against the DSHEA?

-Law allows marketing of unsafe supplements and prevents the FDA from acting aggressively enough to protect public -Lack of consumer info about interactions between supplements and RX/OTCs -Lack of quality standards and strength of purity.

What is post marketing surveillance?

-Manufacturer required to maintain postmarking record and reports once drug is approved for interstate marketing. -Must submit reports to FDA with any serious adverse reaction and new info relating to drug safety and efficacy.

What is the manufacture, seller, and pharmacist responsible to do if there is a product recall?

-Manufacturer: responsible for notifying seller of the recall. -Seller: responsible for contacting consumers -Pharmacist: responsible for knowing which drug products have been recalled.

What must the Investigation New Drug Application (IND) contain:

-Name of drug, composition of drug, methods of manufacture and QC, info regarding pre-clinical animal testing about pharmacological, pharmacokinetic, and toxicological evaluations. -List of experience/qualifications of clincial investigators -study protocol

What is an NDA? How long does the FDA have to act on an NDA? What happens if they disapprove NDA?

-New drug application that must contain complete evaluation of safety/efficacy. -FDA has 180 days to act: delays are common -If FDA disapproves, they notify the applicant and provide and opportunity for a hearing.

What is a "New Drug"?

-Not generally recognized as safe and effective under condition recommended in labeling -drug made before 1938 is exempt from proving safety/efficacy provided its marketed in accordance with labeling requirements existed.

Why did the Orphan Drug Act of 1983 come about and what did it provide?

-Pharma companies were trying to get congress to recognize the NDA process was too expensive for orphan drugs. -This Act provided tax and exclusive licensing incentives for manufactures and develop these biologicals.

Clinical Studies: Phase IV

-Post marketing surveillance -FDA requires clinical study after drug is approved

What did the Medical Device Amendment 1976 provide?

-Provided extensive regulation administrative authority regarding the safety and efficacy of medical devices.

What is the Federal Food, Drug, and Cosmetic act (FDCA)?What is the intent of the law?

-Provides regulations for all drugs introduce into interstate commerce. -Intent is to protect consumers from adulterated or misbranded foods, drugs, cosmetics, or devices.

What happened with Thalidomide in late 1950s-1960s?

-Pushing towards approval in US by FDA held off approving NDA pending safety info. -1961: confirmed that Thalidomide caused birth defect, phocomelia. -*Birth defects were low in US because FDA did not approve drug.

Describe the Color Additive Amendment of 1960: (2)

-Requires manufacturers to establish safety of color additives in food, drugs, and cosmetics. -The FDA can approve a color for one use but not the other (e.g. external use only)

Why was the Pure Food and Drug Act of 1906 not equipped to deal with the Sulfanilamide tragedy for 1937? How was the issue resolved in the end?

-The 1906 law had not granted the FDA authority to ban unsafe drugs. -FDA removed elixir on a technicality- elixirs contain alcohol and this did not.

How are dietary supplement manufactures able to make claims about the function/effect of their product? What type of claims can they make? Is the FDA strict or relaxed about this?

-They may make limited health claims that describe the relationship between a food substance and a disease. -Must submit and receive approval by FDA based on the "significant scientific claim agreement" -FDA is more relaxed: will approve if the scientific claim is more supported by scientific claims than the evidence against them.

What happened during the Sulfanilamide elixir tragedy of 1937?

-Thought to be a miracle anti-infective sulfa drugs marketed. -Marketed as an elixir but was manufacture with diethylene glycol (anti-freeze) -No toxicity tests were conducted. Solvent was found deadly and 107 people lost their lives.

Section 505 (d) of FDCA: safety/efficacy

-applicant submit enough info to demonstrate drugs safety under conditions prescribed or recommended/suggested in labeling. -Efficacy: substantial evidence that the drug will have the effect it purports under the conditions or use prescribed, or suggested in labeling.

When can an approved drug become a "New Drug"?

-drug contains a new ingredient -there is a new combination of approved drugs -proportion of ingredients in combination change -new intended use for drug -dosage/method/or duration of admin. or application has changed

Clinical Studies: Phase III

-hundreds-thousand of patients -testing drug efficacy/safety -clinical setting -double blind & compared with other groups

Clinical Studies: Phase II

-limited # of patients with disease intended for drug -Purpose: to determine efficacy of the drug and dosage that efficacy occurs--> determine the drug safety with pharmacological testing

Section 505 (a) of FDCA: application

-no new drug should be introduce into interstate market unless application has been approved by FDA.

What shall a label be?

-not be false or misleading -provide established name of drugs- listing any active ingredients for both Rx and OTC -adequate directions for use -adequate info for use -not be an imitation drug

Informed Consent:

-required by all study subject or representative -informs subjects of risks, benefits, and alternative treatments -IRB approval of study

What are Current Good Manufacturing Practices (CGMP)?

-set of regulations that establishes minimum requirements for methods, facilities, controls used to manufacture, processing, packaging, and holding of a drug product. -A drug is adulterated if it does not comply

Clinical Studies: Phase I

-small # of subjects -examine drug toxicity, metabolism, bioavailability, elimination and other pharmacological actions. -Purpose: to detect adverse effects, not efficacy.

What are the 2 major offenses under FDCA?

1) Adulteration 2) Misbranding

What did the Food, Drug, and Cosmetic Act (FDCA) of 1938 entail? How did it amend the old law? (4)

1) No new drug could be marketed unless proven safe for use under conditions described and approved by FDA (aka NDA) 2) expansion of the definition of misbranding/adulteration. 3) Labels must contain adequate directions and warnings about habit-forming properties. 4) applies to cosmetics and devices.

What are the categories of Supplemental New Drug application: (3) What types of changes fall under each category.

1) Production: changes to synthesis of drug/ manufacturing process 2)Labeling changes: changes to dose/strength/admin info or manufacturing methods 3)Minor changes: editorial changes in labeling or container sizes.

What did the Kefauver- Harris Amendment establish (5):

1) Strengthen drug approval process by saying they needed to proven both SAFE and EFFECTIVE (required IND before NDA) 2)Retroactive for drugs between 1938-1962 3) Jurisdiction of drug advertising to Federal Trades Committee 4) Established GMP requirements. 5) More controls in clinical investigations (informed consent, reporting adverse reactions)

What does the Medical Device Amendment require for approval of device:

1) classification of device according to function 2) premarket approval 3) Establishment of performance standards 4) Conformance with GMP regulations 5) Adherence to record and reporting requirements.

What are prohibited acts, penalties, and enforcement under the FDCA?

1) introduction of any drug/food/cosmetic/device into interstate commerce that is adulterated or misbranded. 2)Adulteration/Misbranding of " " in interstate commerce. 3)Adulteration/misbranding of receipt for delivery and payment of " " 4)Introduction/delivery of any product in violation of FDCA 5) Failure to supply copy of record, failure to maintain record, or failure to permit access or verification of required record. 6) refusal of inspection 7)handling any counterfeit drug 8)introduction of unsafe dietary supp. to interstate commerce. ....see slide show for rest

What were the 1938 FDCA requirements for a new drug? What did the 1962 Kefauver-harris amendment require of drugs?

1) required drugs to be proven safe before FDA approves them for market. 2) Required drugs to be proven not only safe by effective.

What are the penalties for violators of FDCA? First vs second offenses?

1) violators shall be imprisoned for more than 1 years, fines not more than $1000, or both fines and imprisonment 2) second offense or intent to defraud/mislead: imprisonment for up to 3 years, fines up to $10,000

Describe the Durham-Humphrey Amendment of 1951. What did is accomplish? (4)

1-Law established two classes of drugs: prescriptions and over the counters. 2-Prescriptions need to contain the legend "Caution: Federal Law Prohibits dispensing without prescription" or the Rx label. 3-Directions from prescriber on Rx needs to be on label for pharmacist to dispense 4- Oral/Verbal prescriptions and refills of prescription drugs

When is a drug considered an Adulterated Drug under the FDCA even if it is pure?

A drug can be adulterated even if it is pure if: 1) prepared/packed/held in conditions where it may have been contaminated 2)exposed to a container that may be contaminated 3) manufactured under conditions that do not conform to CGMP

Hypothetic issue 1: Is a product that prevents pregnancy considered a drug?

A product claimed to by a manufacturer to prevent pregnancy may not be a drug under B, since pregnancy is not a disease, however, under C it may be a drug preventing pregnancy which means the product intends to affect the function of the bodys.

What is an imitation drug?

A product is an imitation if it is: identical shape/size/color, similar or virtually identical in gross appearance, similar in effect to controlled substances.

What is a dietary supplement?

A product that is intended: -for ingestion -to supplement a diet -Contains one or more of the following: vitamin, mineral, herb, amino acid, used for humans to supplement diet by increasing dietary intake, a concentrate/metabolite/constituent/extract/combination of previous

What conditions must be met for an article to be considered a drug? (4)

A) Must be recognized in US Pharmacopeia, official Homeopathic Pharmacopeia of US, Official National Formulary, or any supplement of them B) intended for the diagnosis, cure, mitigation, treatment, or prevention of disease in man/animal C) (other than food) intended to affect the structure or any function of body D) intended for use as component of articles specified above

Can changes occur after NDA is approved?

After NDA is approved, manufacturer cannot make any changes unless they submit supplemental new drug application to FDA and its approved.

What is Labeling according to the 21 USC sec 321 (m)?

All labels and other written, printed, or graphic matter upon any article or any of its container accompanying (Labeling) such article (Package Insert).

What is a Device according to the 21 USC Section 321 (h)?

An instrument, apparatus, implement, machine, contrivance, implant, invitro reagent, that is: 1)In National Forumlary OR US Pharmacopeia or supplement of them 2)intended for use to diagnose, cure, mitigate, treatment, or prevention 3) intended to affect structure/function of body and does not do so using chemical/biological processes.

Overall, what is the BrOAD overview of what is a drug?

Broad Meaning: Addresses products intended for use with disease and recognizes that even when products are not intended for use with disease, they make a structure/function claim. ***DRUG IF IT IS MEANT TO AFFECT THE STRUCTURE OR FUNCTION OF THE BODY

What is tampering?

Defined as an improper interference with product for the purpose of making objectionable or unauthorized changes.

What types of med devices require Pre Market Approval (PMA)

Devices that are: -life sustaining -implantable -classified as high risk by FDA -not substantially equivalent to another device -requires manufacturer to conduct pre-clinical and clinical studies to show safety and efficacy.

Why did the Dietary Supplement Health and Education Act of 1994 (DSHEA) come about?

Dietary supplement manufacturers felt that NLEA left too much authority with the FDA and unduly restricted the promotion of dietary supplements.

When can you ship an IND?

FDA exempts a drug if its being shipped for clincial investigation, otherwise only drugs with approved NDA can be shipped.

What did the Medical Device Amendment of 1976 include? What was gained about FDA authority to regulate med devices? what 2 routes were given to manufacturers to get approval for med device?

FDA was granted authority to regulate med devices for safety and efficacy prior to marketing. -Gave manufacturers 2 routes to obtain approval based on risk potential and product complexity

What does the Food and Drug Administration act of 2007 (FDAAA) provide?

FDA with increased responsibilities and authority to regulate drug safety, label changes related to safety, clinical drug data reporting and registries, *requiring post market clinical studies to asses risk and requires companies to establish risk evaluations and mitigation strategies (REMS)

What is the national drug code number?

Identifies a drug/device/OTC

Section 505 (B) of FDCA: content of application

Includes what application needs to contain: reports showing safety and efficacy, drugs components and composition, methods/facilities and controls in manufacturing/processing and packing of drug, sample of drug and its components, proposed labeling.

What gives the federal government authority to regulate?

Interstate Commerce clause in the Constitution

What amendment did congress enact after the Thalidomide problems?

Kefauver-Harris Amendment of 1962

What are considered Adequate Direction for Use?

Labeling must include: drug indication, side effects, dosage, routes/methods/frequency/and duration of administration, contraindications, other warnings

Nutrition and Labeling Education Action of 1990 (NLEA):

Mandates nutrition labeling on food products and authorizes health claims on product labeling, as long as they are made in compliance with FDA regulations.

FDC Act %510 (K): What does it say regarding med devices? What types of devices does it apply to?

Manufacturers can market a device that they can show is substantially equivalent to a legally marketed device that is not subjected to premarket approval. *only for low or medium risk devices

Was there any medical device regulations before 1938?

NOPE

What did the Pure Food and Drug Act of 1906 prohibit?

Prohibited the adulteration and misbranding of foods and drugs in interstate commerce.

What defines a Counterfeit Drug according to the 21 USC sec 321 (g)?

Really and drug in which the labeling contains a mark/label/identifying that is anything but the manufacturer/processor/distributor that originally developed/made/and distributed the drug.

What does the FDA approve to avoid misbranding?

The FDA must approve as part of the premarket approval process, the exact wording of a drug's label and labeling.

What came out of the Sulfanilamide tragedy?

The Food, drug, and cosmetic act of 1938

Name the special food categories (2):

Thought: are these exclusions from food definition? -Specialty Dietary Foods -Medical Foods -Nutraceuticals and Functional Foods

What was the intent of the Drug Price and Patent Term Restoration act of 1984?

To make generic drugs more readily available while proving incentives for manufacturers to develop new drugs.

What is the official compendia? what happens there?

United states Pharmacopeia Convention/ Homeopathic Pharmacopeia of the USP -where they work on the organization and function of these documents, as well as the role and legal authority of each.

What does accompanying vs not accompanying mean when talking about labeling?

accompanying= labeling not accompanying= advertising

What is substantial evidence?

adequate and well controlled investigations by experts qualified in scientific training and experience to evaluate drug's effectiveness.

more slides with little INFO afterwards. look at written notes if any after lecture

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When are pharmacies considered manufacturers? In this scenario, what is another condition that a drug is considered adulterated?

if it repackages or compound medication for sale under certain conditions. It is considered adulterated if it contains an unsafe color additive, or if its strength/quality/purity differs from standards, unless stated on label.

Class 1 Recall:

issued when there is a reasonable probability that the product will cause serious, adverse health consequences or death.

Class 2 Recall:

occurs when the product may cause temporary or medically reversible health consequences, but the probability of serious adverse reaction is remote.

What was the Food and Drug Administration Act of 2007 (FDAAA) in response to?

post market problems with certain drug products.

What is the purpose of IND application?

protect safety of humans inc lincial trials and to ensure the clinical trials are design properly to prevent problems during NDA review.

Class 3 Recall:

recalls apply to products that are not likely to cause adverse health consequences.

look at slides after post marketing surveillance. was not alot of info on them but they hadnt been lectured on yet

yay