MPJE Federal Flashcards
- Prohibited foods and drugs to be distributed if adulterated or misbranded
Pure Food and Drug Act of 1906
- New drug cannot be marketed unless it was safe with directions of label
- Required that labels include adequate directions for use and warnings about habit-forming drugs
- First law that applied to cosmetic products
- Drugs marketed prior to 1938 were grandfathered and did not have to be proven safe
Food, Drug, and Cosmetic Act
- Amendment to FDCA
- Established 2 classes of drugs: legend and OTC
- Drugs that required medical supervision required to include “Caution: Federal Law prohibits dispensing without a prescription”
- Legend drugs
o Adequate directions for use = pharmacist putting label with physicians directions - Nonprescription or OTC
- Allowed for oral prescriptions and prescription refills
Durham-Humphrey Amendment of 1951
- Resulted aver concern of thalidomide (birth defects)
- Amendment to FDCA
- Drugs must be safe and effective
- Prescription drug adverting must be regulated by FDA
o OTC advertising is regulated by the FTC (Federal Trade Commission) - Required informed consent for clinical trials, reporting of ADRS, and creating good manufacturing practices
Kefauver-Harris Amendment of 1962
- Amendment of FDCA
- Classification of medical devices by function, establishment of performance standards, pre-market approval requirements, GMP standards, and requirements for reporting
Medical Device Amendment of 1976
- Tax and licensing incentives to make developing orphan drugs more appealing
- Rare disease = <200,000 people in the US
Orphan Drug Act of 1983
- Hatch-Waxman Amendment
- Streamlined drug approval process for generic products
o Only need an abbreviated new drug application (ANDA)
o Does NOT require clinical testing
o Requires proof of bioequivalence with brand name counterpart - Brand name products had incentive by gaining 5 additional years of patent protection
- Patent does not have to expire before researchers begin
Drug Price Competition and Patent-Term Restoration Act
- More stringent controls on distribution of prescription drugs
- Wholesalers by be licensed by states under federal guidelines
- Banning re-importation of prescription drugs produced in the US
- banning the sale, trade, or purchase of samples
- specifying storage, handling, and records of drug samples
- Prohibiting resale of prescription drugs purchased by hospitals or health care facilities
Prescription Drug Marketing Act of 1987
- Touches almost every aspect of FDAs activities
- Fast track NDA for treatment of serious or life-threatening conditions
- Extemporaneous compounding of prescriptions in pharmacies
o States regulate compounding
o Pharmacies are exempt from GMP - Prescription drug legend “Caution: Federal law prohibits dispensing without a prescription” replaced by “Rx Only”
- “Warning- may be habit forming” was eliminated (FDCA)
- Encouraged manufacturers to submit supplemental NDAs for uses
o Can publicly disseminated limited info about unapproved uses – must specify not approved by FDA - Manufacturers get 6 months extra of marketing exclusivity if study in pediatric population
FDA Modernization Act of 1997
- No longer allowed to deny coverage to children with pre-existing illnesses
- Children can stay on parent’s insurance until 26
- No insurance for 6 months and receive subsidy to enroll in high-risk insurance companies by the state
- All new insurance plans must exempt preventative care from deductibles
- Businesses with < 25 employees receive up to 3.5% tax credit for providing health insurance to employees
- Senior citizens in donut hole can get 50% discount on some drugs
- W-2 forms to include cost of health care
- Women’s Preventative Health Care Amendment – STD, contraception, etc
Affordable Care Act
- Not published by the government
- Contains monographs of drugs
- USP and NF are 2 separate entities even though published in 1 book
USP/NF
- Private organization that updates homeopathic products
* *without designation of USP/NF or HPUS the drug is considered misbranded or adulterated
Homeopathic Pharmacopeia of the US (HPUS)
- Find labels for approved drug products
- Find generics for a brand
- Find all drugs with a specific active ingredient
- View regulatory history
- Find consumer information after 1998
Drugs@FDA
- Price pharmacy pays for the drug. Discounted from the AWP
AAC- actual acquisition cost
- Average price paid by wholesaler to manufacturer
AMP- average manufacturer price
- Published wholesale price that can be used for pricing prescription drugs. Pharmacies usually purchase at a lower price
AWP- average wholesale price
complementary alternative medicine
CAM
department of health and human services
- Includes FDA
DHHS
- Can stand repeated use
- Used for medical purpose
- Appropriate for use in home
DME- durable medical equipment
- Estimated cost of drug to pharmacy based on info collected by DHHS
- Costs are based upon quantity purchased
EAC- estimated acquisition cost
- Highest price allowed under a specific plan for a specific drug
- If a person wants a more expensive drug, they must pay the difference
MAC- maximum allowable cost
- Excipients or adjuvants
GRAS- generally recognized as safe
- Used when considering OTC
GRASE – generally recognized as safe and effective
- Article intended to be rubbed, poured, sprinkled, sprayed or applied to human body for cleansing, beautifying or altering appearance
- Soap is NOT a cosmetic
Cosmetic
instrument, apparatus, implant,
device
Part A
hospital
Part B
medical insurance for physican services
part c
medicare managed care (medicare advantage)
part D
prescription drug
MMA- Medicare Prescription Drug Improvement and Modernization Act
- Part A = hospital
- Part B = medical insurance for physician services
- Part C = Medicare managed care (Medicare Advantage)
- Part D= prescription drug
CMS
centers for Medicare and Medicaid services
covers everything original Medicare covered with lower costs and extra services
MA- Medicare Advantage
- cannot enroll in Part _ and Medicare Advantage
D
PDP- prescription drug plan
- monthly premium, annual deductible, co-payments
o premium and deductable cannot change Jan 1 – Dec 31st but copay can - based upon individual – spouses cannot share a plan
- Tier 1 – least expensive generic
- Tier 2- preferred brand
- Tier 3- nonpreferred brand name
- Tier 4- rarer, high cost drugs
- Donut hole
o Gap between initial coverage and catastrophic coverage - Covers vaccines
Part D
Formulary requirements
- Plans must include drugs within all therapeutic classes in USP
- Companies who want to design their own plan must have P&T Committee
- Insurers do not have to include all drugs, but there are 6 classes where they have to include most
o Anticonvulsants
o Antidepressants
o Antineoplastics
o Antipsychotics
o Antiretrovirals
o Immunosuppressants - Formulary changes must be given within 60 days to CMS
medicare enrollment
3 months before and 3 months after their birthday
o 7 months
- Health insurance sold by private companies
- Cannot sell prescription drug plans
medigap
- Part D sponsors must provide MTM programs
- Targeted quarterly
o 2 or more disease states
o Taking 2-8 drugs
o Predicted to incur part D annual cost - Must target 4/7 core disease states:
o HTN, HF, diabetes, dyslipidemia, respiratory, bone disea/arthritis, mental health - Report outcomes to CMS
- Minimum requirements
o CMR – comprehensive medication review
o Targeted medication review
o Interventions to prescribers- fax, mail, face to face
MTM
- 1st application to FDA before drug can be used on humans
- Intended to protect rights and safety of humans
- IND sponsors: pharmaceutical companies, researcher, academic personnel, organizations
- FDA has 30 days to decide if drug can be tested on humans
IND- investigational new drug application
Clinical Trials
- Phase : small group of healthy individuals
o Test toxicology, PK, and pharmacological properties
phase 1
Clinical trials
- Phase : larger group, 100 or more
o Patients with the disease
o Determine efficacy, info on dosing, relative safety, and adverse events
2:
- Phase : larger groups, sometimes thousands
o Controlled clinical studies
o Efficacy compared to placebo
3
- Can receive drug without being in study if have life-threatening illness
- Drug must be in phase 2 or 3 (need safety and efficacy data)
treatment INDs
New Drug Application (NDA) process
- Submit to FDA with data from phases 1, 2, and 3
- If NDA is approved, manufacturer can market
- After drug is marketed, phase 4 studies are conducted
o Health professionals encouraged to report problems
o Manufacturer must submit yearly reports
o Phase 4 utilized to determine if drug should remain on the market - Manufacturers must describe manufacturering process for cGMPs
FDA expedited review – for
life-threatening diseases or potential to provide large benefit
FDA expedited review:
1)
a. NDA or biologics license application
b. Reduces by 10-6 months
Priority review
FDA expedited review:
2)
a. May be requested for IND prior to BLA or NDA submission
b. Intended for drugs with unmet need
c. Early reviews/meetings of their product
Fast Track
FDA expedited review:
3)
a. Can request for IND or prior to end of phase 2
b. Must show early clinical evidence
c. Greater emphasis on early meetings
Breakthrough therapy
FDA expedited review:
4)
a. Discuss during development
b. Intended for drugs with long-term endpoints (mortality, etc)
c. Required to confirm efficacy in post-market trials
Accelerated approval
- Require less data but need to show PK data
- 1st applicant to complete formal review will have 6 months of exclusive rights of the generic
- Generic companies cannot be sued for defective design or failing to warn about drugs dangers
Abbreviated New Drug Application (ANDA) - generics
- After marketing changes to synthesis, manufacturing locations, production procedures, labeling
- Do not need a new NDA
Supplemental new drug agreement
- Company that filed original NDA will probably at SNDA
ANDA vs SNDA
- P= priority, no other effective drugs
- S= standard/similar
- P usually get reviewed more rapidly
Therapeutic Classification
- CDC buys at discounted rate and distributes them to health facility for those cannot pay
Vaccines for Children Program
Naming Drugs
- Short, distinctive, not likely confused
- Provide indication of therapeutic class
- 10 or 11 digits
- 4 manufacturer, next 4 specific drug, last 2/3 package
NDC
- Receives reports about bad adversting
OPDP= office of prescription drug promoton
o Filthy, decomposed substance
o Prepared, packaged, or held with unsanitary conditions
o cGMPs not met during manufacturing
o unapproved color additive
o strength, purity, quality lower than standards
o drug not recognized by official compendia
- Adulteration
o false or misleading
o missing name or location of manufacturer, packer, or distributor
o does not contain a word required by law
o does not include name of active drug
o does not have each ingredient identified
o does not say Rx only for legend drugs
o does not contain precautionary statement that it is subject to deteriation
o missing quantity of container
o inadequate directions
o offers sale of the drug
o pharmacy dispensing Rx only rug without legal prescription or authorized refill
- misbranding- labeling
FDCA specified “adequate directions for use” and Durham-Humphrey clarified
- do not need adequate directions for legend drugs if intended to be dispensed by pharmacist
Labeling
Labeling Requirements for Manufacturers Containers
- name and address of manufacturer, packer, or distributer
- established name of drug
- net quantity
- weight of active ingredient in each dosage
o electrolytes require mEq - reads “Rx only” for legend drugs
- routes must be stated IF NOT orally
- storage directions
- lot number
- expiration date by the manufacturer
Special Labeling Requirements
- FD&C Yellow No 5 (tartrazine): allergic rxns
- Aspartame – phenylaniline
- Sulfite – allergic rxn
- Mineral oil – only be used at bedtime and not in infants/pregnancy
- Wintergreen oil – methyl salicylate
- Sodium phosphate – amount in oral solution, no more than 90 mL
- Isoproterenol inhalation – not exceed quantity prescribed
- Ipecac Syrup, fluid extract is 14x as potent as syrup
o Red for emergency use in poisoning, warning to keep out of children and do not use
o 1 oz only
Package Inserts:
- Description
- clinical pharmacology
- Indications and usage
- C/I
- Warnings
- Precautions
- Adverse reactions
- Abuse
- Symptoms
- Dosage and admin.
- Dosage forms
- Most recent revision of labeling
- Usual dose
- Correct problem of drug diversion
- Require distribution records, register in state if shipping, prohibits drugs being reimported in US, state licensing of wholesalers
- Starter packs are not considered samples and can be given to pharmacist
- Retail pharmacist CANNOT possess samples from any source
o Hospitals can if they maintain precise records - Hospitals cannot resell stock
Prescription Drug Marketing Act of 1987
- Thalomid
o Prescriber has to be certified
o Must counsel patient and provide contraception
o Verify negative pregnancy test
o Complete patient-physician agreement form
o No more than 4 week supply
o Send to certified pharmacy
REMS- Risk Evaluation and Mitigation Services
Unit Dose Labeling
- Generic name and trade name
- Quantity of active drug
- Name of manufacturer, distributor, or packer
- Lot number
- Expiration date
Customized patient med packs
BUD?
- BUD of 60 days
Form FDA 3500 – Med Watch Form, 3500A is for IND researchers
- Vaccines should go to VAERs
Drug Recalls
- Class I: serous ADR, pharmacy stock and require notification to patients
- Class II: temporary, pharmacy stock
- Class III: unlikely to cause ADRs
- Manufacturers responsibility to send written notice
- For prescription or anticipated based on habits
- Do not sell to third parties
- Compounded are not commercially available
- Ingredients are approved by USP
- Pharmacy cannot solicit but can advertise that they compound
- Interstate distribution cannot be more than 5% of total prescriptions
- No requirement to register, but a pharmacy may register as an outsourcing facility
Compounded
Once prescription has been filled and dispensed, belongs to the pharmacy
true
Medicare modernization act- keep records for 10 years
true
Expiration dating established by manufacturer
- Homeopathic products are exempt
true
Expiration for unit dose/repackaged
- 12 months or 25% of time remaining on the bottle
true
- Under control of CPSC (consumer product and safety)
- Child resistant for the following: ASA, methyl salicylate, controlled substances, prescription drugs, iron (≥250 mg elemental per package), APAP (≥1g), diphenhydramine (66 mg), ibuprofen (≥1g), loperamide, mouth wash (≥3 g of ethanol), lidocaine (5mg), naproxen, ketoprofen, fluoride, minoxidil
- If OTC is made in multiple sizes, one does not have to be resistant but must contain label that not for household with children
- All new and refilled rx’s with exemption:
o Prescriber specifies – only 1 Rx at a time
o Patient requests
o Hospitals when drug is being used by health care professionals
Poison Prevention Packaging Act
What drugs are exempt from Poison Prevention Packaging Act
o SL Nitroglycerin
o SL or chewable isosorbide dinitrate 10 mg or less
o Erythromycin ethyl succinate granules for suspension ≤8 mg
o Erythromycin ethyl succinate tablets no more than 16 mg
o Powder cholestyramine
o K supplements in unit dose, less than 50 mEq
o Sodium fluoride less than 264 mg
o Betamethasone in manufacturer
o Methylprednisolone ≥64mg
o Colestipol
o Oral contraceptives
o Pancrealipase
Poison Prevention Packaging Act
Testing protocols for children ≤5 and adults 50-70
o Fails if ≥__% of children can open OR if 90% of adults cannot open
20%
Tamper Evident required for
OTC oral
- Required for Accutane, statins, estrogen and progesterin products
- Applies to physicians and patients in hospitals
- Can receive within 30 days
- Must have summary of important info and table
Patient Package Inserts
- Language easy to understand by patients
- Required when: labeling could prevent ADRs, product has serious risks relative to benefits, adherence to directions is crucial
- Manufacturers must get FDA approval before submitting
MedGuides
- Must be similar for ADME
- Products must show similar time to peak, peak concentrations, and AUC
- Pharmaceutical alternatives = same therapeutic but may have different salts, esters, dosage forms, or strengths
o Not allowed, must be equivalent - If a product is AB1 can substitute for another AB1, but cannot substitute for AB2
Drug Substitution
- Less then 2 fold difference between LD50 and ED50
- Less than 2-fold difference between minim toxic conc. And minimum effective conc.
- Most drugs can have limit of 90-110% but NTD must have 95%-105%
o Carbamazepine, cyclosporine, digoxin, ethosuximide, levothyroxine, lithium, phenytoin, procainamide, tacrolimus, theophylline, warfarin
Narrow Therapeutic Drugs
- Manufactueres can mail if they addressee is enrolled with DEA
- Can mail CS if:
o Inner label is packaged and labeled following CS Act
o Place in plain container
o Out wrapper free form markings
- Medicaid Prudent Pharnaceutical Purchase Provisions requires DUR that has a prospective and retrospective component
- Info required on profile
o Patient’s name, address, phone
o Age or DOB
o Sex
o Disease state info if known
o Any allergies
o List of medications previously dispensed
o Pharmacists comments when necessary - Requires to offer counseling- since under states they decide
o Federal law does not include what should be discussed - Pharmacist does not counsel only when patient refuses
- Objective to reduce cost of state Medicaid costs
- Pharmaceutical manufacturers are required to offer Medicaid programs the lowest or best price
Obra 90 and Patient Counseling Act
- Assure privacy and security of records
- Ever provider to submits electronically is a covered entity
- Fines if broken
- Medical groups must provide written notice
o Must be kept for a minimum of 6 years from when service OR last date prescription was dispensed
o No requirement for future signatures - Pharmacies must provide a notice of privacy when patients first start- no expiration
o Can still provide services if patient refuses - Patients can report perceived breakings to HHS/OCR
- Pharmacies must post notice of privacy in public site as well as website if they have one
HIPPA
- Exportation o Shipment of drugs to foreign country - Importation o Brought in from another country o Must be labeling and cGMP standards - Reimportation o Drug in US shipped to foreign country and then shipped back to US o Only legal if the original manufacturer does it
International Commerce Involving Drugs
Should only purchase drugs from website if it contains VIPPS (Verified internet pharmacy practice)
true
FDA prohibits shipment of unapproved drugs by interstate shipment
true
Can be biosimilar with difference in molecular structure
true
DEA is under supversion of the
attorney general
- “enone”, “testosterone” “olone” “estrenol” “ulone” “erone”
Anabolic steroid
- Short term is 30 days, long term is 30-180 days
Detoxification treatment
- Opium, opiates, derivatives
- Poppy straw
- Coca leaves except where cocaine, ecgonine, and salts have been removed
- Cocaine, salts, iosmers
- Ecgonine and its derviatives
Narcotic drug
Registrations of Manufacturers, Disributers, and Dispensers with DEA for CS
- Business activity shall be assigned to month
- Initial registration expires 36 months
DEA Registration for Applicants
- Pharmacies – DEA form 224
- Manufacturers, disributors, importers, exporters, or researchers – form 225
- Narcotic treatment Programs – Form 363
- Registration forms are sent 60 days before expiring
Schedule 1 drugs
- Bufotenine
- Diethylyamide
- Heroin
- Lysergic acid
- Marijuana
- Mescaline
- Methaquinolone
- Peyote
Purchasing or transferring a CI or CII – DEA form 222
- Not required when transferring products from central fill to retail pharmacy
- Only one item on the line
o Each product must be on a different line - Name and address of supplier
- Signed and dated by person authorized
- Unused forms must be delivered when any federal, state, or local inspects site
- Purchaser’s name must be on form, even if it is one of the power of atterny completing the form
- Purchaser submits copy 1 and 2 and retains copy 3
o Must record on copy 3 cotainers received and dates - If an order cannot be completely filled it may be partially and balance is owed within 60 days
- Supplier retains copy 1 and forward copy 2 to DEA
- Copy 1- brown, supplier
- Cop 2- green- supplier forwards to DEA
- Copy 3- blue retained by purchaser
- Keep records for 2 years
Endorsing an Order
- Supplier who cannot fill all or part within specified time may be ednored to another supplier
- Can only be made by supplier to whom order was frist made
o Name and address of second supplier
o Signature of person authorized on behalf of first supplier - 1st supplier cannot fil any part of the order
Lost forms
- Statement with serial numbers
- Immediately report to special agent charge of DEA
Controlled Substance Ordering Systems (CSOS)
- Electronic DEA form 222
- Allowed once for Schedule I and 2, can also use for schedule iii-v
- Paper has limit of 10 items per form, this has no limit
- Faster trasnactions and smaller inventories
- Accurate orders
- Decreased cost
- Can include non controlled
If compounding CS must register as a manufacturer except
- Compounded as aqeous, oligenous, or solid form
- Does not contain more than 20% of CS
- Only distributed to a practitioner who is authorized to dispense
Control substances – need DEA when writing
Auditor must approve application for DEA and writing CS
Need 2 factor identity proofing to sign for electronic CS:
something you know, something you have, something you are
Detoxification and maintenance programs
- To DISPENSE must register separate with DEA
- Without license, physician can administer for withdrawal why they are waiting for a recovery program
o Only one day at a time
o Not more than 3 days
Central fill pharmacies CANNOT fill emergency oral CS II drugs
true
faxing of CII
- LTCF
- Home infusion for parenteral administration
- Hospice
Contol substances– “caution, federal use prohibits transfer of drug to any other person”
true
- Transimitted electronically or fax
- Write CENTRAL FILL on original and record name, address, DEA of cnetra lfill and name of pharmacist and date of transmission
- Indicate # of refills
- Maintain original from 2 years from date it was last refilled
Retail and central fill pharmacies for Schedule 3-5
Disposal of Controlled Substances
- Reverse distributer
- DEA form 222
- Schedule 3-5
o Maintain dosage form, strength, quantity, and date - Reverse distributer will destroy, and reverse distributor will fill out DEA FORM 41
Pharmacists may transfer up to 5% total dosage units of controlled substances in a calendar year
- If more, need wholesaler license
- Use DEA form 222 for Controls 1-2 when transferring
If pharmacy goes out of business OR gets a new owner
- Use DEA form 222 for transferring
- Schedule 3-5 also must be documented with name, strength, dosage form, quantity, date transferred, and DEA
- If going out of buissness and going to another pharmacy
o Must do inventory that day
o Will serve as final inventory
o Both parties need records
o Do not need to send copy to DEA
Physicians are not required to keep records of CS unless its for a detox program, written in their practice, or regularly dispense
Mid level need to keep records for DEA
true
Pharmacies when organizing scripts keep CSII sepearte, then c3-5, then non controlled
- Need red C for Schedule 1 or 2 if records are not maintained by electronic system
theft
- Notify DEA immediately
- Complete DEA form 106
- Breakage, damage, or spill report to DEA form 41
Mailorder limited to 7.5g/30 days of PSE
all non-liquid PSE must be packaged in blister packs
true
Drug Addiction Treatment Act -DATA
- Dispense qualified CS 3-5 drugs to pharmacy
- Can treat 30 in first year, then 100 if apply
Opioid Treatment Programs
use what meds
- Methadone, buprenorphine, naltrexone,
Prevention of drug diversion
- Can receive ____ dose for days clinic is closed
single
OTC drug facts
- Active ingredient and amount
- Uses
- Warnings
- Inactive ingredients
- Purpose
- Directions: 1) age 2) how much 3) how often and how long
Need OTC warning for pregnancy and nursing
true
OTC require to include sodium content if amount exceeds ___mg/dose
- very low sodium: 35 mg or less - low sodium :140 mg
5mg
OTC labeling requirements for electrolytes - Calcium: - Mg: - K: - Warnings of on electrolyte diet and exceed o Na: o Ca: o Mg: o K:
- Calcium: 20mg
- Mg: 8 mg
- K: 5mg
- Warnings of on electrolyte diet and exceed
o Na: 140
o Ca: 3.2 g
o Mg: 600
o K: 975
OTC tamper except
- Aersol
- Lozenges and drugs in first aid kits
- 2-piece gelatin capsules sealed using tamper-evident technology with one tamper-evident feature
Medicaid Tamper-Resistant Rx Requirement
- Prevent unauthorized copying
- Prevent modification
- Prevent counterfeit rx forms
- Does not apple to DME
Prescription to OTC Reclassification
- NDA requesting OTC to FDA
- Must not require prescription only status to protect the public
- May recommend an ingredient be removed/changed
- Category 1: safe
- Category 2: not safe
- Category 3: insufficient evidence
Dietary supplement health education act (DSHEA)
- Herbals, amino acids, vitamins, minerals, and supplements
- Products do not have to prove efficacy
- Products currently on market to have to prove safe
- Dietary supplement = final ingredient
Herbal labeling
- Include common name, latin name is optional
- Cannot make claims or statements
food products including dietary supplements, herbals, and process foods that provide health or health benefits including prevention or treatment of disease
Nutraceuticals
- Do not need cGMPs but need to manufactured in sanitary conditions
- Labeling and advertising by FTC
- Ingredients need to be in USP/NF or CTFA Cosmetic Ingredient Dictionary
Cosmetics
- Used for compounding by using Form ATF-11
- Cannot be sold or loaned
- May not be sold to outpatients, store in lock
- Physicians can write order
Alcohol
Specially Denatured Alcohol
- Tax exempt
- Unsuitable for beverage
Americans with Disabilities Act
- Prevents discrimination if can preform functions of a job
- Any company with 15 or more are covered
