Federal & Florida Pharmacy Law Review
Check out www.flrules.org
8
Section 1: Federal Food, Drug & Cosmetic Act & etc…
Federal Food, Drug & cosmetic act & major amendments
1. Food, Drug & Cosmetic Act 1983
a. Drugs proven safe
b. Established FDA
c. Specifies only 3 basic illegal acts; adulteration, misbranding, & the placing into interstate commerce of an unapproved new drug
2. Durham-Humphrey amendment 1951
a. 2 classes of drugs (Rx & OTC)
b. Determines “Rx to OTC Switch” (ie: Prilosec, Rogaine, Claritin, etc.)
c. Authorized verbal Rx & refills
3. Kefauver-Harris amendment 1962
a. Drugs safe & effective
b. Established good manufacturing practices (cGMP)
c. FDA jurisdiction over Rx drug advertising
4. Medical Device amendment 1976
a. Safe & effective medical devices
b. FDA can regulate med devices
5. Orphan Drug Act 1983
a. Incentive to manufactures: drugs for rare dz (rare = < 200,000 people)
6. Drug price competition & Patent Term Restoration Act 1984
a. Easier for generic products to be rated “bioequivalent”
b. Provided patent life extensions to brand under certain conditions
7. Prescription drug marketing Act 1987 (PDMA) à samples
a. State licensing of rx drug wholesalers
b. Bans re-import of rx made in US
c. Bans sale, trade, or purchase of samples
d. Mandates storage, handling, & recordkeeping of samples
e. Prohibits, w/certain exceptions, resale of rx drugs purchased by hospitals/facilities
8. FDA modernization act 1997 (FDAMA)
a. Major changes to FDCA
b. From: “Caution: Federal law prohibits dispensing w/o a rx ”; To: “ rx only”
c. Eliminated requirement that certain substances be labeled “Warning- may be habit forming”
Prohibited acts under FDCA
1. Adulteration:
a. Contains filthy, putrid or decomposed substance
b. Prepared/held under unsanitary conditions & possible contamination or injurious to health
c. Methods are not GMP
d. Composed of any poisonous or deleterious substance
e. Unsafe color additives
f. If it purports to be a drug & its strength/quality/purity is different than what is on the label
g. Mixed/packed with any substance that reduces its strength or quality
2. Misbranding:
a. Labeling is false/misleading
b. Rx drug & manufacturers labeling fails to contain:
i. Name & address manufacturer/packer/distributor
ii. Established name of drug
iii. Net quantity (wt, quantity, or dosage units)
iv. Weight of active ingredient per dosage unit
v. Federal legend - “Caution: Federal law prohibits dispensing w/o a “rx” OR “Rx only.”
vi. If not PO, then specific routes of admin
vii. Special storage instructions, if appropriate
viii. Lot #
ix. Expiration date
x. Adequate info for use (PI – for health professional)
c. OTC drug that fails to contain:
i. Statement of identity
ii. Name & address manufacturer/packer/distributor
iii. Net quantity
iv. Cautions & warnings needed to protect
v. Content & format of OTC product labeling in “Drug Facts” panel format:
1. Active ingredient
2. Purpose
3. Use/indications
4. Warnings
5. Directions
6. Other info
7. Inactive ingredients (alphabetical)
8. Questions? Optional w/phone #
d. It is a drug liable to deterioration unless packaged/labeled accordingly
e. Container is made, formed, or filled to be misleading
f. Drug is exact imitation of another drug or offered for sale under the name of another drug
g. Dangerous to health when used in dosage or manner suggested in label
h. Packaged of labeled in violation of the poison prevention act
Advertising or promotion of rx drugs
1. FDA regulates Rx
2. FTC regulates OTCs
3. Advertising of rx drug prices, considered reminder advertising. It is exempt from regulations as long as it meets these requirements:
a. Only purpose is to provide info on price (NOT on safety, efficacy, or indications)
b. Contains the proprietary name of drug, if any; generic name, strength, dosage form, price charged for specific quantity
c. MAY include availability of professional services as long as not misleading
d. Price stated MUST include all charges; mailing fees & delivery fees may be stated separately
Special warning requirements
4. FDC – Yellow # 5 (tartazine) & #6
a. Must disclose presence & provide warning in “precautions” b/c poss. allergic rxn
5. Aspartame
a. Must disclose presence & provide warning in “precautions” for Phenylketonurics: contains phenylalanine __mg per dosage unit
6. Sulfites
a. Rx drugs containing sulfites must contain allergy warning in “warnings” section
7. Mineral Oil
a. Warning to only be taken at HS & NOT used in infants unless directed by MD. Label can NOT encourage use during pregnancy
8. Wintergreen oil
a. Any drug containing > 5% methyl salicylate (flavor) include warning: use other than directed may be dangerous & drug should be kept out of reach of children
9. Sodium Phosphates
a. Limits amount in oral soln to <90mL per OTC container; requires specific warning
10. Isoproterenol inhalation preperations
a. Requires warning not to exceed dose prescribed & to contact MD if difficulty breathing persists
11. Ipecac Syrup:
a. Statement in boxed & red letters: “For emergency use to cause vomiting in poisoning. Before using, call physician, the poison prevention center, or hospital emergency room immediately for advice.”
b. Warning “Warning: keep out of reach of children. Do not use in unconscious persons.”
c. Dosage of med must appear (15mL (1 tsp) in individuals > 1y/o)
d. May only be sold in 1 oz containers
12. Phenacetine ( acetophenetidin )
a. Warning: possible kidney damage (taken in large amounts/for long period of time)
13. Salicylates :
a. ASA & others: warnings about Reye’s syndrome
b. Retail containers of 1? grain (81mg; pediatric) ASA cannot be sold in containers holding > 36 tablets
14. Alcohol warning
a. Internal analgesics & antipyretics including APAP, ASA, IBU, Naproxen, Ketoprofen, ect – required to have warning for persons consuming > 3 bev/day & to consult with MD before taking
FDA drug & devices recall classifications: (descending order of importance)
1. Class 1 (BAD!): reasonable probability will cause serious AE or death
2. Class 2: may cause temp/medically reversible AE or probability of serious AE is remote
3. Class 3: not likely to cause serious AE
Pt Package inserts: (MANDATORY)
1. Supplied by manufacturer & written for lay person
2. Required upon initial filling for certain products
3. Hospitalized/ institutionalized pts: provided at first admin & then q 30 days. Required for:
a. Oral contraceptives
b. Estrogen products
c. Progesterone products
4. Failure to provide would be MISBRANDING
Medication Guides (voluntary)
5. Similar to PPI
6. FDA will require for drugs when:
a. Pt labeling could prevent serious AE
b. Product has serious risks relative to benefit
c. Pt adherence to directions is crucial
7. Med Guides written in standard format & for lay person
8. Manufacturers à obtain FDA approval before distributing med guides.
9. Meds Guides required for:
a. Epzicom (abacavir/lamivudine); Ziagen (abacavir); Trizivir (abacavir/lamivudine/zidovudine)
b. Soriatane (acitretin)
c. Lotronex (alosteron HCL)
d. Cordarone (amiodarone)
e. Antidepressants in child/teen
f. Strattera (amoxetine)
g. Tracleer (bosentan)
h. Palladone (hydromorphone HCL)
i. Roferon-A (interferon alpha-2A); Rebif (interferion beta-1A); Infergen (interferon alfacon-1); Avonex (interferon beta-1A)
j. Accutane (isotrentinion)
k. Relivid (lenolidamide)
l. Lindane
m. Lariam (mefloquine HCL)
n. Mifepex (mifepristone)
o. Viramune (nevirapine)
p. NSAIDS
q. Pegasys (peginterferion alfa-2A); PEG-intron (peginterferion alfa-2B)
r. Elidel (pimecrolimus)
s. Symlin (pramlitidine)
t. Ribavirin (all brands)
u. Servent (salmeterol)
v. Advair (salmeterol/fluticasone)
w. Emsam (selegeline)
x. Xyrem (Na oxybate)
y. Soltamox or Nolvadex (tamoxifen)
z. Forteo (teriparatide)
aa. Protopic (tacrolimus)
Restricted distribution systems:
1. Isotretinoin ( Accutane ) – iPLEDGE
a. Only MD registered in iPLEDGE may prescribe.
i. Must agree to assume responsibility of preg counseling
ii. Must obtain & enter results into iPLEDGE BEFORE prescribing
b. Only pts registered in iPLEDGE can be prescribed this drug
i. Must comply with: complete informed consent form; obtain counseling about risks/requirements for safe drug use; comply with preg tests & use of contraception
c. Only pharmacies registered in iPLEDGE can dispense
i. Must attest to: knowing risks; training other Rphs, comply/seek all others comply with program; obtain isotretinion from iPLEDGE registered wholesalers; return unused product; not fill for any party other than qualified pt
d. To dispense – RPh must obtain authorization from iPLEDGE (ipledgeprogram.com) via internet or telephone
2. Lotronex ( alosetron HCL)
a. Indicated only for women w/severe diarrhea-predominate chronic (>6mo) IBS who have failed every other therapy
b. Prescribing program requires sticker to be affixed to ALL rx for Lotronex
c. Telephone, fax, or electronic rx NOT valid
d. Rx dispensed in original retail pack (included med guide; package insert & follow-up survey enrollment
3. Clozaril ( clozapine )
a. Used for schizophrenia –monitoring for potentially fatal agranulocytosis
b. Only dispensed by pharmacies registered w Clozaril National Registry
c. May only dispense enough tablets until next blood test
4. Thalomid (thalidomide)
a. System for Thalidomide education & prescribing safety (STEPS) program requires registration of all prescribers, pts, & RPhs
b. Requires preg testing, informed consent, authorization, validation prior to dispensing, compliance with measures to prevent pregnancy, education materials, pt counseling, & required reporting of fetal exposure
c. Rx limited to 28 days in blister packs w/safety info
d. NO telephone rx or automatic refills
5. Tikosyn ( dofetilide )
a. Tx of AF; only available in retail pharmacies in Tikosyn in Pharmacy System (TIPS) program
b. RPh must verify prescriber is qualified by checking database (tikosynlist.com) or telephone prior to dispensing
c. RPh must initial & date each rx & stamp with special TIPS stamp
6. Tracleer ( bosentan )
a. Tx of pulmonary arterial HTN – needs monitor for liver tox
b. Only available through designated pharmacies participating in Tracleer Access Program (TAP)
7. Xyrem (sodium oxybate or also known as GHB)
a. Tx of narcolepsy – schedule III
b. Available only through a single centralized pharmacy
National Drug Code (NDC) Number
1. 10 or 11 digit # that identifies particular drug by manufacturer, product, & package
a. First 4-5 digits = manufacturer - LABELER
b. Next 4 digits = specific drug - PRODUCT
c. Last 2 digits = package size - PACKAGE
2. FDA does NOT mandate that drug manufacturers place NDC codes on labels!!! (Most manufacturers do though)
Compounding vs Manufacturing
1. FDA issued compliance policy guide 1992
2. FDA Modernization Act (FDAMA) 1997
a. Compounding in pharmacy ≠ manufacturing
b. Pharmacy may NOT advertise compounding of any particular drug, class of drug, or type of drug ***US Supreme court ruled in 2002 that entire compounding provisions of FDAMA were invalidated
FDA 2002 Policy on Compounding:
1. FDA defers to state authorities regarding the less significant violations of the act related to pharmacy compounding of human drugs
2. FDA will work with state if needed for investigations, ect
3. If FDA gets suspicious that pharmacy is manufacturing à they need to consider whether the pharmacy is engaging in the following acts considered manufacturing:
a. Compounding drugs in anticipation of receiving rx (except in limited quantities in relation to amounts of drugs compounded after receiving valid prescriptions)
b. Compounding drugs removed/w/drawn from market for safety reasons
c. Compounding from “bulk active ingredients” that are not components of FDA approved drug w/out FDA investigational new drug application (IND)
d. Receiving, storing, or using drug substances w/out first obtaining written assurance from supplier that each lot made in FDA-registered facility
e. Receiving, storing, or using drug components not meeting official compendia requirements
f. Using commercial scale manufacturing/testing equipment for compounding
g. Compounding for 3rd parties or offering drugs for wholesale for resale
h. Compounding drugs commercially available (essentially copies)
i. Failing to operate w/in compliance to state law
Pregnancy Categories (ascending order of importance)
1. Category A – Adequate, well-controlled clinical studies IN preg
a. No evidence of risk in last two trimesters
2. Category B – Adequate, well-controlled clinical studies NOT in preg - animal studies showed no risk; OR animal studies show AE but human studies have not shown risk in 1st trimester
a. No evidence of risk in last two trimesters
3. Category C – safety of drug not determined.
a. Drug should NOT be used unless benefit > risk to fetus
4. Category D – positive evidence of risk to fetus
a. ONLY admin if benefits > > > risk to fetus
5. Category X – indicate risk of damage caused by drug - outweighs ANY possible benefit
FDA Orange Book
1. Official name: “Approved drug products w/therapeutic equivalence evaluations”
2. Primary source for determining generic equivalency
3. Uses 2 letter coding system w/1st letter being the key:
a. A = pharmaceutically & therapeutically equivalent
b. B = NOT pharmaceutically & therapeutically equivalent
4. Products w/no known or suspected bioequivalence issues:
a. AA – conventional dosage forms
b. AN – solutions & powders for aerosolization
c. AO – injectable oil soln
d. AP – injectable aqueous soln
e. AT – topical products
5. AB rating à Products w/actual or potential bioequivalence problems, but for which adequate scientific evidence has established bioequivalence
FDA classification system for New drugs
1. Therapeutic Classification:
a. Type P (Priority) – Drug represents major therapeutic gain b/c no other effective drugs available for tx certain illness OR it has significant advantages to currently marketed drugs (“Fast tracked”)
b. Type S (Standard) – drug similar to others on market
2. Chemical Classification:
a. Type 1 – new molecular structure; must not be currently marketed in US
b. Type 2 – new derivative of molecular structure already approved in US
c. Type 3 – new formulation of drug already marketed in US
d. Type 4 – new combo of two or more drugs
e. Type 5 – drug manufactured by new company
f. Type 6 – new therapeutic indication for already approved drug
Poison Prevention Act***
1. Administered by Consumer Product Safety Commission (CPSI)
2. Requires child-resistant containers for rx & OTC
3. Exemptions:
a. Request of pt or MD
b. Bulk containers not intended for household use
c. Drugs distributed to institutionalized pts
d. 1 package size of OTC designed for elderly
e. *Specific drugs*:
i. Oral contraceptives, conjugated estrogens & norethindrone acetate in manufacturers package
ii. Medroxyprogesterone tablets
iii. SL nitroglycerin
iv. SL or chewable isosorbide dinitrate 10 mg or less
v. ASA or APAP in effervescent tablets or granules
vi. Potassium supplements in unit dose packaging
vii. Sodium fluoride (not more than 264mg per package)
viii. Anhydrous cholestyramine & colestipol packets
ix. Aerosol products
x. Erythromycin ethylsuccinate granules for oral suspension & oral suspensions w/ < 8g erythromycin