EXAM 1 Flashcards
Why do we study law?
- Tells us the minimal competency and actions that are acceptable
- if we dont meet what is acceptable, we need to be held accountable
Laws enacted by Congress?
Federal
Laws enacted by Legislature?
State
What do regulations do?
administration enactments authorized by statutes (DEA, FDA, etc.)
What is common law?
-Body of principles based on custom and usage (UK)
- Basis for American Law
What is Judicial or Case Law derived from?
judicial decision and interpretations of statutes
What does the Federal Government regulate?
Manufacturing, packaging, storage, labeling, and labels, distribution and authorized use of pharmaceuticals
Why do we regulate drugs?
- continue new drug development and creation of drugs that are public good
-safe production and use of drugs
-mitigate information asymmetry
What does the federal government require?
Label requirements; auxiliary labels and definitions
-clarify, provide additional information or reinforce primary label
- “shake well”, “refrigerate”, etc.
What does the federal government define?
Control substances act of 1970:
-defines agents, authorized possession and acquisition, storage and inventory, and limitations on distribution
-enforced by the DEA
-pharmacies needing to be registered with the DEA
What do the state governments do?
Defines the personnel and conditions for the storage and distribution of pharmaceuticals on an individual basis
-pharmacists, technicians, interns, assistants
What is the USP?
-United States Pharmacopoeia
Information for USP
-founded: 1820’s by M.D.s
-initial goal: standardized names and formulations of medicines
-effort: defined 217 products (today > 3200)
mission of USP?
promote public health by disseminating:
-standard of quality
-authoritative information
What is the “Standard of Quality”?
-strength, quality, purity, packaging and labeling of “drug products”
–inclusive of drug entity, dosage form, medical devices, diagnostic products
-information disseminated through official compendia: USP-NF
What is authoritative information?
1978-2004: The USP dispensing information series
Now: Periodic monographs
in authoritative information, what is the model guidelines for the medicare prescription drug act (medicare part d) for?
focus: establishing/monitoring outcomes in disease states where intervention/prevention can make a difference
What is the Basis of Authority?
-Vested in the Federal Law
–Federal food drug and cosmetic act of 1938 (OBRA ‘90); Medicare prescription drug, improvement and modernization act 2003
-adopted by individual state pharmacy acts
What is the APhA?
American pharmacist association
-oldest of pharmacy professional societies
represents all aspects of pharmacy
-established “mission” for pharmacy practice which sets the basis for “Pharmaceutical Care”
-involved in establishing policy for pharmacy practice and federal legislative and regulatory initiatives
What is the “Pure food and drug act of 1906”?
prohibited foods and drugs that were distributed though interstate commerce to be adulterated or misbranded
what wasn’t required according to the “pure food and drug act of 1906”?
-manufacturers listing ingredients
-manufacturers labeling directions for use
-regulation of cosmetic products and medical devices
Why was the “Food, drug and cosmetic act of 1938” written?
a result from 107 deaths that occurred from the liquid SULFANILAMIDE in 1937
What does the Food, drug and cosmetic act of 1938 require?
-any NEW DRUG can’t be marketed unless it’s been proven to be safe when used according to directions on the label
-labels needing adequate directions for use
-warnings about habit-forming drugs contained in the product
What does the food, drug and cosmetic act of 1938 apply to?
-medications
-cosmetic products
-medical devices
What drugs were “grand fathered” before 1938 (before the food, drug, and cosmetic act of 1938)?
-levothyroxine
-digoxin
-nitroglycerin
-phenobarbital
What is the Durham-Humphrey Amendment of 1951?
-Amendment of FDCA
-2 classes of drugs:
–Legend drugs
–Over-the-counter drugs
What are legend drugs?
-required medical supervision
-don’t have to list “adequate directions for use”
-required to include the legend “Caution: federal law prohibits dispensing without a prescription” on the label
what are over-the-counter drugs (non-prescriptions)?
-don’t require medical supervision
-required label to have “adequate directions for use”
Why was the Kefauver-Harris Amendment of 1962 created?
resulted from public concern about birth defects from thalidomide
What is the Kefauver-Harris amendment of 1962?
all new drug marketed in the U.S. had to be SAFE and EFFECTIVE (new and all drugs approved between 1938-1962)
-regulation of RX drug advertising under the authority of the FDA
-creation of good manufacturing practices (GMP)
What does the Kefauver-Harris Amendment of 1962 require?
-informed consent by research subjects in clinical investigations
-reporting of adverse drug reactions
What is the Medical Device Amendment of 1976?
provides better classification of medical devices:
-according to specific function
-establishment of performance standards
-pre-market approval requirements
-conformance of GMP standards
the medical device amendment of 1976 is a requirement for?
adherence to record and reporting requirements
What is the Orphan Drug Act of 1983?
-used to treat diseases that affect relatively few people
-has limited potential for profitability
-provided various tax and licensing incentives to manufacturers to make development of orphan drugs more appealing
What is the “Drug Price Competition and Patent-Term Restoration Act of 2984”? What is it for?
-“Waxman-Hatch Amendment”
-attempted to resolve a dispute between generic and brand name
-streamlined drug approval process for generic drugs
-provided innovative drug manufacturers with incentives to develop new drugs
What is the “Prescription drug marketing act of 1987”?
-control distribution of prescription drug samples
-prevent hospitals and other healthcare entities from reselling pharmaceuticals to other businesses
what is the “FDA Modernization Act of 1997”?
-far-reaching piece of legislation
-nearly all of FDA activities
-for FAST-TRACK REVIEW of some NDA submissions (for serious or life-threatening conditions - AIDS, more modern, Covid)
How does the “FDA modernization act of 1997” affect compounding of prescriptions?
-indicating that individual states should regulate compounding
-pharmacies are exempt from the strict regulatory federal GMP standards and requirements for submission of new drug applications
What changes occurred due to the “FDA modernization act of 1997”?
-change of prescription drug legend:
–old: “Caution: federal law prohibits dispensing w/o a RX”
–new: “RX only”
-“Warning - May be habit forming” was eliminated
How did the “FDA modernization act of 1997” make changes for manufacturers?
-Encouraged to conduct research for new uses of current drugs and submit supplemental NDA’s for new uses
What is the Affordable Care Act (ACA)?
-require all individuals have health insurance
-require standards for financial and administrative transactions
-stop agreements between brand name and generic drug manufactures that limit or delay
-phase elimination of the catastrophic threshold
What is the “Inflation Reduction Act of 2022”?
-Required the federal government to negotiate prices for some drug coverage
-require drug companies to pay rebates to medicare
-cap out-of-pocket spending
-limit monthly cost sharing for insulin to $35 for people with medicare
-eliminate cost sharing for adult vaccine
-expand eligibility for full benefits under the Medicare Part D
What is the Official Compendia?
-US Pharmacopoeia/National Formulary (USP/NF)
-published by the U.S. pharmacopoeia convention (USPC)
-Contains monographs of recognized
What is the Investigational new drug application (IND)?
-extensive testing process to assure that a new drug is SAFE AND EFFECTIVE
-must be submitted to FDA before new drug is marketed
-Completed by sponsor (manufacturer)
-before drug given to humans
How long does the FDA have to decide if the IND is suitable for clinical trials in humans?
30 Days
What does the IND application include?
-all preclinical data on safety and use
-clinical protocols for human testing
Why do we need to have a process to bring new drugs to market?
-FDA finalized rule in December 1998 requiring information on safe and effective use in children to prevent problems
Phase 1 of clinical trials
-SMALL groups
-HEALTHY subjects
-direct supervision of sponsor
Purpose:
-evaluation of TOXICOLOGY, PHARMACOKINETICS, and PHARMACOLOGICAL PROPERTIES
-assessment of SAFETY
Phase 2 of clinical trials?
-LARGE group (>100)
-patients have DISEASE or CONDITION
-direct supervision of sponsor
purpose:
-determine:
–EFFECTIVENESS
–DOSAGE
–RELATIVE SAFETY
–ADVERSE EFFECTS
Phase 3 of clinical trials?
-LARGE group
-multiple locations
-double-blind
-done by independent investigators at multiple locations
-COSTLY
-long time
purpose:
-obtain data on EFFECTIVENESS vs. placebo
What is important about treatment INDs?
-allow administration of IND to patients not enrolled in the new drug clinical trial program
-patients must be in an imminent life-threatening stage of illness
-drugs MUST be in phase 2 or 3!!
“treatment protocol” -> designated patients must be approved by FDA
What is important about the New Drug Application (NDA) process?
-thousands of pages of data and information
-very COSTLY and TIME-CONSUMING
-review: 6 months
-FDA provides opportunity for comment to experts and other interested parties
-approved? yes? drug can be marketed
Phase 4 of clinical trial?
-post-marketing surveillance
-health professionals encouraged to report issues
-manufacturer MUST submit annual reports to FDA
-this data will determine if drug can stay on the market
When can we use an FDA Expedited review program?
-therapy that treat serious or life-threatening diseases
-priority review
-fast track
-breakthrough therapy
accelerated approval
what does the Abbreviated New Drug Application (ANDA) do?
-for after patent protection expires
-secondary companies may use the generic game or brand
-secondary can submit ANDA
What does ANDA require?
-less data
-pharamcokinetic data
-bioavailability
-proof of similar clinical activity to innovator’s product
What is the Supplemental New Drug Application (SNDA)?
-ABBREVIATED application
-after marketing a drug product
-for changes in drug’s synthesis, production procedures, manufacturing, etc.
What happened after the Waxman-Hatch Amendment/Drug price competition and patent-term restoration act?
-Brand Manufacturers were granted longer patent protection (5 years)
-generic manufacturers given easier access to approval of ANDAs
What is the Good Manufacturing Practices (GMP)?
-regulations that specify the minimum requirements to manufacture products
-registered with FDA
-describe making process
FDA inspects facilities approximately once every 2 years (more if history of deficiencies)
When is a drug considered “adulterated”?
-contains any filthy, putrid, or decomposed substances
-prepared, package, etc. under unsanitary conditions
-doesn’t meet GMP standards
-unapproved color additive
What is the Prescription Drug Marketing act 1987?
-used to correct problem of drug diversion from normal distribution channels
-require proper storage of drugs and maintenance of appropriate distribution records
-restrict sale, purchase, or trade of prescription
Why does REMS exist?
Established to regulate potential harmful side effects where benefits could outweigh risks
-FDA administrative amendments act of 2007
What are the 5 levels of risk mitigation?
- Professional label and package insert
- REMS - medication Guide
- REMS - communication Plan
- Elements to assure safety use
- Implementation system
What are the specific requirements for Thalidomide REMS?
-females MUST undergo pregnancy testing and use BCP
-males - use condoms
-MD and pharmacies registered to prescribe or dispense
-mandatory patient surveys
How can Thalidomide be dispensed?
-28 day supply
-no refills
-filled within 7 days of being written
How can Accutane be dispensed according to iPLEDGE?
-30 day supply
-no refills
-filled within 7 days of being written for females
T/F: FDA considers prescribing and dispensing drugs for unapproved uses or doses illegal.
False
What does the federal law prohibit in regards to off-label use?
prohibits anyone in the chain of distribution from suggesting to a patient or prescriber that an approved drug maybe used for an unapproved purpose
What are the requirements for unit-dose packaging and labeling?
-generic and/or trade name
-amount of active drug/drugs
-manufacturer, packer, etc.
-re-packager’s lot number
-expiration date
-special storage requirements
What is the expiration dates for customized patient med paks?
-no more than 60 days from when med pack was prepared
What happens for drug recalls for class 1?
-stocks in pharmacies removed and notification of patients who were given the drugs
(cause serious, adverse health consequences)
What happens with class 2 drug recalls?
-pharmacy stock removed
(cause temporary or reversible effects)
What happens with Class 3 drug recalls?
-unlikely cause any adverse health consequences
What are expiring dates for compounded prescription?
non liquids and solids: not more than 25% of time remaining on the product OR <6 months (whichever is less)
aqueous: 14 days if refrigerated
anything else: time of therapy use but <30 days
What is the Drug Quality and Security Act of 2013?
requirements for trading partners regarding TRACING OF RX PRODUCTS
-interoperable, electronic tracing systems
What are 2 types of facilities for compounding that follow the drug quality and security act of 2013?
503A: traditional pharmacy settings
503B: “outsourcing centers”; don’t require prescriptions
What is the main difference between federal and state regulations when dispensing medications?
-restrictions on what is considered non-controlled and controlled may differ
-follow more strict regulations
Who can prescribe RX?
each state varies who can or cant prescribe outside of MDs
(NPs, PAs, etc.)
Can MDs self prescribe? what about controlled?
yes
some states PROHIBIT self-prescribing controlled meds
What is important about RX refills?
-controlled: tight limitations
-non-controlled: MD must indicate # of refills/time limit (no indication = NO REFILLS)
What is the duration of RX refills?
usually < 1 year
Who owns the RX after its filled by a pharmacy?
legally owned by dispensing pharmacy
-can’t remove from files unless for court order
-if MD or PT wants prescription, we can ONLY GIVE COPY
How long do we store the RX in the pharmacy?
2-5 years depending on state
NYS: 5 years
medicare modernization act of 2003: RX need to be kept for 10 years
T/F: lot numbers and expiration dates are NOT required on the RX label (according to federal law).
True
What is the purpose of Poison Prevention Packaging Act of 1970?
-provide special packaging to protect children < 5 years
-most RX, non-RX, and household products
What is the Federal anti-tampering act of 1982?
-a barrier or indicator to limit access
-if disturbed, this is evidence of possible entry
T/F: Individual states not regulate substitution for one drug product for another.
False
Why would we want to have drug substitutions?
Provide lower cost drug products in place of the drug product prescribed
what does it mean to dispense a PHARMACEUTICALLY equivalent drug in place of the original prescribed drug?
SAME:
-active ingredient
-dosage form
-route of administration
-strength or concentration
different:
-excipients
What does it mean to be THERAPEUTICALLY equivalent?
pharmaceutically equivalent AND bioequivalent
-clinically evaluated and have been shown to have similar pharmacokinetic properties
-similar blood concentration vs. time curves (time to peak, peak concentrations, AUC)
when will the FDA approve marketing of competing drug products?
-no problems with bioequivalence
OR
-if there is problems, they shown to meet appropriate bioequivalent standards
What makes a drug a pharmaceutical alternative?
-drug contains same therapeutic moiety
BUT different in:
–salts
–esters/complexes
–dosage forms
–strengths
T/F: most state DON’T allow substitution between pharmaceutical alternatives
True
When can a therapeutic substitution be allowed?
pharmacy has a right to substitute a different drug for the one designated on the RX without contacting the prescriber
-limited to drug formulary
What is the difference between closed and open formulary?
Closed: formulary where only the drug product listed may be used
open: formulary that permits some unlisted drugs to be dispensed
What is a generic name?
-single specific name given by the USAN
-Each specific drug structure is given only one generic name in this country
What is a trade/brand name?
-unique name is selected by a pharmaceutical company for its own brand of generic drug
-encourages prescribers to prescribe a specific company’s product exclusively
What is a patent protection?
-new drug product have protections for a few years
-manufacturers right to market the drug
-“single source product” - no one else can market the same drug
What is a multisource product?
-after patent expires
-other companies can submit ANDA to gain approval to market the same drug
-may use the generic name or make a brand name
What is the Orange Book for?
-approved drug products with therapeutic equivalence evaluations
-bioequivalence info. from the FDA
-monthly supplements
What 2 categories are part of the Orange Book?
“A” rated: bioequivalent AND therapeutically equivalent to brand name; MAY BE SUBSTITUTED FOR ONE ANOTHER
“B” rated: NOT bioequivalent; DON’T SUBSTITUTE
T/F: most states limit substitution to interchanges between products that are the same dosage from.
True
cap can’t sub for tab;
ointment cant sub for cream, etc.
Subcategories of “A” code?
-generally designate different dosage FORMS
Subcategories for “AB” categories?
-have actual or potential bioequivalence problems
-may be acceptible substitutes if the equivalency problems has been resolved by in vivo and/or in vitro studies
“B” codes?
-drugs that the FDA doesn’t currently consider to be therapeutically equivalent to other equivalent products
-bioequivalence problems often stem from dosage form problems
what isn’t required to be in the orange book?
“Grandfather” Drugs
-drugs marketed before 1938
-codeine, ephedrine, levothyroxine, phenobarbital, peudoephedrine, quinine, etc.
T/F: pharmacist can “generally” substitute more expensive products
False
What does the narrow therapeutic index/ratio refer to ?
-drugs where the multiple between the minimum toxic concentration and minimum effective concentration is relatively low
T/F: The federal government have regulation limiting the free substitution of different manufacturers’ prodcuts.
False
SOME STATES
what does it mean to be “biosimilar”?
same route of administration, mechanism of action, strength, dosage form
Definition: Reference Drug product.
biologic product that is the original innovator’s product
Definition: Biosimilar product.
Approved by FDA as highly similar to product, but have allowable difference b/c they are made from living organisms
Definition: Interchangeable agent.
-expected to produce the same clinical result as the reference product in any given patient
What is the use of the Purple Book?
-lists biological products
-to determine if a product approved through 351(k) pathway is biosimilar/interchangeable to reference product approved through 351(a) pathway
