Federal Regulation of the Pharmaceutical Industry- Exam 1 Flashcards
1
Q
******FDCA
A
Food, Drug, and Cosmetic Act
1
Q
******FDCA ADULTERATED
A
- A drug or device is adulterated if:
- it consists of any filthy, putrid, or docomposed substance
- it has been prepared, packaged, or held under unsanitary conditions where it may have become contaminated
- its container is composed of any poisonous or deleterious substance
- it has an unsafe color additive
- its quality or strength has been reduced by the addition or substitution of other substances
2
Q
******FDCA History Continued
A
-
1938: Federal Food, Drug, and Cosmetic Act (FDCA)
- prompted by 107 deaths from sulfanilamide elixir, which was mixed w/ diethylene glycol (antifreeze)
- new drugs must be proven to be safe (to the FDA)
- pre-1938 drugs exempted from “safety” requirement (eg. ASA, warfarin)
3
Q
******FDCA MISBRANDED
A
- A drug or device is misbranded if:
- its labeling is false or misleading
- its labeling is inadequate
- it fails to have required statements prominently displayed & easily understood
- its container is misleading
- the manufacturer/distributor has not included the following in all labeling, descriptive matter, and advertising
- generic name, formula with each ingredient and quantity, information on effectiveness, side effects and contraindications
4
Q
******FDCA- What is a “Drug”?
A
-
DRUG means:
- articles recognized in the US Pharmacopeia. Homeopathic Pharm. or National Formulary
- articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals
- articles intended to affect the structure or any function of the body of man or other animals
- articles intended for use as a component of one of the above 3 categories
- no differentiation between Rx and OTC
- manufacturer’s intent= whether an article is a drug
5
Q
*****FDCA Compounding
A
-
Compounding
- State board regulated
- prepared for 1 patient
- immediate demand
- [advertising of drug = ok] (Freedom of Speech issue)
- exempt from NDA and current GMP
- traditional pharmacy function
6
Q
*****FDCA History
A
-
1906: Pure Food & Drug Act
- prompted by unsanitary practices in food & drug industries
- prohibited adulteration and misbranding of foods & drugs
- amended in 1912 to prohibit false & fradulent efficacy claims
7
Q
*****FDCA Manufacturing
A
-
Manufacturing
- FDA inspected and regulated
- resale to 3rd parties
- future demands
- make inordinate amounts
- distribute out-of-state
- sell wholesale
8
Q
****FDCA History- 1962
A
-
1962: Kefauver-Harris Amendments
- prompted by the “thalidomide disaster”: European antinauseants, which caused 1000’s of birth defects
- drugs must be proven to be EFFECTIVE
- retroactive to drugs approved since 1938
- established Good Manufacturing Practices (GMP)
- required “informed consent” of research subjects in investigational drug trials
9
Q
****FDCA History Continued
A
-
1951: Durham-Humphrey Amendments
- established 2 classes of drugs:
- prescription (Rx)
- over-the-counter (OTC)
- authorized ORAL prescriptions and refills
- established 2 classes of drugs:
10
Q
****FDCA- Prohibited Acts
A
- Most prohibited acts involve misbranding or adulteration
- Violation of FDCA is subject to strict liability
- Applicable to pharmacies
- The mere receipt and subsequent delivery of an adulterated or misbranded drug
- The doing of any act which causes a drug to be counterfeit
- The alteration, mutilation, etc. of the labeling
11
Q
****FDCA- Rx Label Requirements
A
A prescription label MUST contain:
- Name and address of the pharmacy
- Serial number of the prescription
- Date of the prescription filling
- Name of the prescriber
- Name of the patient
- Directions for use
- Cautionary statements if indicated on the prescription
12
Q
****NDA Process- Phase IV Studies
A
-
Phase IV Studies
- FDAAA empowered FDA to require manufacturers to conduct Phase IV studies when adverse event reporting or active surveillance is inadequate
13
Q
****New Drug Application Process- Post Marketing Surveillance
A
-
Post Marketing Surveillance
- Required of manufacturer after NDA approval
- Must submit to FDA reports of serious adverse drug reactions and any new information of safety and efficacy
14
Q
****Out-of-State Rx
A
- Usually Rx from other states is honored as a professional courtesy
- Usually illegal to fill a Rx from a foreign country
- Texas allows written Rx for non-controlled medications from Canada and Mexico
15
Q
****Rationale for Federal Drug Regulation
A
- Protection of the public against adulterated and misbranded drug products
- Necessity of balancing “direct regulation” and “indirect regulation”
15
Q
***Drug Price Competition (DPC) & Patent Term Restoration Act (PTRA) of 1984
A
- Expedited generic approval process
- Generic manufacturer must demonstrate:
- same active generic ingredient
- bioequivalence
- acceptable manufacturing and control
- Concessions to innovator drug companies included
- patent extensions
- market exclusivity
15
Q
***Controversies
A
- Bioequivalence of generics to the parent and each other
- Whether a drug without market exclusivity for a particular indication could be prescribed and dispensed for that indication
- Whether FDA can approve and ANDA for a generic when the labeling will not include one or more of the indications contained on the innovator drug product’s labeling
16
Q
***FDCA History: 2009
A
-
2009 FDA Guidance
- off-label use: indications other than approved by the FDA
- Manufacturers’ promotion of drugs for off-label use subject to FDA restrictions
- unabridged peer-reviewed articles published in scientific/medical journals not influenced by drug company
- accompanied by: approved labeling, comprehensive bibliography, contrary publication, any known safety risk, conflict of interest
17
Q
***FDCA- Label Requirements- Side Effects
A
- Effective 7/1/09, Rx labeling must contain a “side effects statement”
“Call your doctor for medical advise about side effects. You may report side effects to the FDA at 1-800-FDA-1088”
- The statement may be:
- On a sticker attached to the vial
- On the vial cap
- On a separate piece of paper
- In consumer medical information
- In the FDA-approved Medication Guide
17
Q
***FDCA- Label Requirements- MedGuides
A
- MedGuides are required handouts to be given to patients for certain high-risk drugs each time the drug is dispensed
- to help prevent serious adverse effects
- to assist patient decision making
- to assist patient adherence
- FDA now requires about 200 drugs to have MedGuides, including
- NSAIDS
- Anti-depressants
- Narcotics
18
Q
***NDA Process- Risk Evaluation & Mitigation Strategy (REMS)
A
-
Risk Evaluation & Mitigation Strategy (REMS)
- FDAAA granted FDA authority to require REMS as a condition for approval of an NDA or postmarket when the FDA believes it necessary to ensure benefits outweigh risks
- Under REMS authority FDA can require a variety of procedures ranging from Medication Guides to limiting the drug to specified settings for dispensing
18
Q
***NDA Process- Postmarket Labeling
A
-
Postmarket Labeling
- FDAAA gave FDA the authority to require manufacturers to add safety information or warnings postmarket
20
Q
***Nonprescription Drug Labeling
A
- User friendly format including pharmacological category or principal intended use, cautions and warnings, adequate directions for use, and a “Drug Facts” panel
- Pharmacies that re-label or repackage must conform to the same labeling requirements as manufacturers
- Professional OTC labeling may be published by manufacturers for indicaions not appropriate for lay diagnosis or treatment
- Drugs that are both OTC and prescription exist when some indications can be labeled with adequate directions for use and some cannot
21
Q
**FDCA- Prohibited Acts Continued
A
- FDA enforcement of the FDCA
- Injuctions
- Criminal proceedings
- Drug seizure
- Warning letter
22
Q
**Functions of FDA
A
- Rulemaking
- Issue guidance documents
- Incorporate advice from standing advisory committees of outside experts
23
Q
**New Drug Application Process
A
-
New Drug Application (NDA)
- all “new drugs” must be FDA approved
- Initiated by IND Request/ investigational new drug
- preclinical animal incestigations re: toxicity, kinetics
- Phase I: detect adverse effects; low # of subjects
- Phase II: determine efficacy; limited # of subjects
- Phase III: determine safety & efficacy in large # of subjects
- double blind; control group w/ placebo
25
Q
*Black Box Warning
A
- Required in labeling when use of a drug may lead to death or serious injury
- Required for about 450 prescription drugs
26
Q
*FDA Drug Recalls
A
-
FDA Drug Recalls
- Class I: product causes serious adverse effects or death
- Class II: product causes temporary adverse effects on health
- Class III: product not likely to cause adverse effects on health (ex: labeling problem)
28
Q
*FDCA- Penalties
A
- Penalties
- 1st offense: 1 year in prison & $1000 fine
- 2nd offense or fraud: 3 years in prison & $10,000 fine
- Civil penalties: $50,000- $1M (after 2nd offense)
29
Q
*NDA Process- Postmarket Drug Safety Info for Patients and Providers
A
-
Postmarket Drug Safety Information for Patients and Providers
- FDAA required FDA to develop and maintain website for patients and providers including labeling, safety information, REMS, guidance documents, etc
- FDAAA also established “Sentinel Initiative” designed to detect early signs of a drug’s risk
31
Q
*Pregnancy Warnings
A
- Currently 5 categories of risk: A, B, C, D, X
- Proposed regulation would eliminate these categories and replace with risk summaries and relevant clinical information
32
Q
Biologics
A
- Products derived from living organisms
- Licensure by PHSA but subject to FDCA and FDA requirements
- Congress considering allowing generic versions
33
Q
FDA Summary: 2
A
- “Adulterated” drugs= containing filthy, putrid, or decomposed material or held under unsanitary conditions
- “Misbranded” drugs= not containing necessary labeling (including Rx drugs dispensed by pharmacists)
- Drug manufacturers/processors must be FDA registered
34
Q
FDA Summary: 3
A
- Rx drugs & refills can only be dispensed pursuant to a Rx from a licensed practitioner
- FDA can seize misbranded or adulterated drugs
- Employer/ responsible person liable for employee FDCA violations
- Lack of knowledge/ criminal intent will NOT excuse violation
35
Q
FDCA History: 1997
A
-
1997: FDA Modernization Act
- prescription labels must contain the symbol “Rx only”
- Streamlined approval process
36
Q
FDCA Summary
A
- Drugs must be safe, effective, and properly labeled
- Manufacturing, packaging and distribution pf drugs must comply w/ Good Manufacturing Practices (GMP)
- OTC (non-Rx) drugs must be labeled for safe use
37
Q
Insulin: OTC vs. Prescription
A
- Insulin 1st marketed in 1920s and Rx not required
- FDA allowed insulin to remain OTC (needed by many people whose lives depended on it)
- Some states require a prescription for insulin and the devices used to administer it
- Older insulins: “naturally” created & remain OTC
- Newer insulins: synthetically based & FDA requirement for a prescription
39
Q
FDCA Miscellaneous Issues: New Drug Application (NDA) Process
A
- IND- Investigational New Drug Application
- Sponsor must receive approved Notice of Claimed Investigational Exemption for a New Drug in order to ship drug in interstate commerce to conduct phase 1, 2, and 3 clinical studies
- FDA may terminate testing at any time under a benefit to risk ratio criteria and the decision is not subject to appeal or judicial review
- FDAAA (Food and Drug Administration Amendments Act) requires NDA sponsors to publish summary information regarding phase 1 trials on a public registry
40
Q
New Drug Application Process- Informed Consent
A
- Informed consent
- informed consent required in all 3 phases
- research subjects required to know risks, possible benefits and alternative courses of treatment
- Institutional Review Board (IRB) approval required in some settings
41
Q
Orphan Drug Act
1983
A
- 1983
- Created incentives for pharmaceutical companies to create drugs for rare conditions
- >200,000 people affected
- 50% R&D tax credit to the manufacturer
- Longer patent exclusivity
42
Q
OTC Drug Review
A
- OTC drug review process approves drugs on the basis therapeutic category and conformance to a monograph rather than on a drug by drug basis like prescription drugs
43
Q
Structure of FDA
A
- National headquarters and extensive field force
- Five centers
- Biologics Evaluation & Research
- Food Safety and Applied Nutrition
- Drug Evaluation & Research
- Veterinary Medicine
- Devices & Radiological Health
