Uploaded by Jacqueline Go

Federal Pharmacy Law Review 2020 - Student Copy

Federal Pharmacy Law
South College School of Pharmacy
Dr. Tyler Dougherty
[email protected]
Helpful Resources
• 2020 Survey of Pharmacy Law (available on Canvas)
• DEA Pharmacists Manual (available on Canvas)
• List of Controlled Substances (available in RxPrep
MPJE book)
• RxPrep MPJE book with videos
• Reiss B, Hall, G. Guide to Federal Pharmacy Law, 9th
Edition. ISBN-13 9780967633282 (Really good
Federal Law info with questions in various formats)
Multi-State Pharmacy
Jurisprudence Exam (MPJE)
• Combines federal and state specific questions on one exam to
test knowledge of pharmacy jurisprudence
• Serves as the pharmacy law exam in certain jurisdictions and tests
a candidate pharmacist’s knowledge of pharmacy law
• Tests on:
• Pharmacy Practice (83%)
• Licensure, Registration, Certification, and Operational Requirements
• General Regulatory Processes (2%)
• Look at the 2020 Candidate Application Bulletin under
Competency Statements, p36
• I have also provided a competency statement document that I
modified from NABP
• The TN BoP approves questions that are applicable to TN
Multi-State Pharmacy
Jurisprudence Exam (MPJE)
• Federal vs State law: if a question asks you to follow
federal law specifically, do not consider state law. If a
question asks about Tennessee law specifically, do not
follow federal law. If the question does not specify
which to follow, apply both federal and state.
• Exam can be taken every 30 days
• If you fail the exam three times you must seek approval
from the TN BoP to take a fourth time
• Maximum of 5 opportunities to pass the MPJE in any
given state
• Advice: Study hard and pass it the FIRST TIME!
• $250 each time you take the test!!
Multi-State Pharmacy
Jurisprudence Exam (MPJE)
• Computer-based examination that uses adaptive technology
• 120 question exam (100 count toward your score, 20 are pretest
questions and do not count, dispersed throughout the exam)
• 2.5 hours to complete the exam (take the first 15-20 questions
slower, see next bullet)
• The exam is created as you answer questions and your
correct/incorrect answers influence the remainder of the exam
• Cannot skip or omit an answer. Cannot “go back” once you answer
a question
• Must answer at least 107 questions to receive a score
• If you do not complete all 120 questions, you will receive a
penalty that reflects the # of questions remaining
• Scores range from 0-100, with 75 as passing
Question Format
• Multiple Choice
• Multiple Response (bulletin only lists Select all that
apply, but previously use to list “K-type”)
• Ordered Response
Multiple Choice
How many total continuing pharmacy education
hours are required to be completed upon the second
renewal of a pharmacist’s license in this jurisdiction?
A. 15
B. 20
C. 25
D. 30
E. 40
Which of the following medications are classified as
Schedule II controlled substances in this jurisdiction?
Select all that apply
A. Strattera
B. Lisdexamfetamine
C. Meprobamate
D. Amphetamine
E. Dexmethylphenidate
Ordered Response
Place the following in order in which they would
expire according to federal regulations, starting with
the earliest.
A. A partially filled methylphenidate prescription for
a patient not in a long-term care facility
B. A phone-in, emergency oxycodone prescription
C. A written bupropion prescription
D. An electronic alprazolam prescription
E. A partially filled morphine prescription for a
patient in a LTCF
Previous “K-Type” Questions
A legend generic drug which the dose of the active
ingredient is only 60% of the label is:
I. Adulterated
II. Misbranded
III. Illegal to sell
A. I only
B. II only
C. I and III
D. II and III
E. I, II, and III
Major Drug Legislation
• Pure Food and Drug Act of 1906:
• Prohibited drugs passing through interstate commerce to be adulterated or misbranded
• Food, Drug, and Cosmetic Act of 1938 (FDCA)
New drugs must be safe when used as directed on the label
Labels had to have adequate directions/warnings for abuse potential
Result of the sulfanilamide elixir tragedy in 1937
Uses adulteration and misbranding as way to enforce
Adulteration: drug’s purity, strength, quality, manufacturing process, storage
Allows FDA to inspect any facility where drugs are manufactured/stored with a Notice of
Inspection (NOI)
• Durham-Humphrey Amendment of 1951
Created two classes of drugs: OTC vs Rx
OTC: adequate directions for use
Rx: adequate information for use
Created the required legend: “Caution Federal law prohibits without a prescription” or “Rx
• Selling a Rx drug without a rx, or refills is deemed misbranded
• Third class of drugs: “Behind the counter”
• Pseudoephedrine, OTC insulins, Schedule V controlled substance (OTC Robitussin AC,
Cheratussin AC)
Major Drug Legislation
• Kefauver-Harris Amendment of 1962
• All new drugs had to prove efficacy and safety
• FDA now controlled Rx drug advertising (FTC controls non-Rx
drug advertising)
• Required consent of drug test volunteers
• Required reporting of adverse drug reactions
• Created Good Manufacturing Practices (GMP’s)
• In response to the thalidomide birth defects
• Medical Device Act of 1976
• Classified devices by medical use
• Federal Anti-tampering Act of 1982
• Select OTC and cosmetic items should have a tamperresistant seal which readily shows evidence of tampering
• Resulted from Tylenol poisonings
Major Drug Legislation
• Hatch-Waxman Amendment of 1984
• Streamlined the process for new generic drugs
• Innovator drug gets 5 years of market exclusivity or remainder of
patent’s life
• Patent’s last 20 years
• Gives generic companies the authorization to use the innovator’s
data of safety/efficacy to prove bioequivalence (ANDA)
• If innovator drug is on the market for an approved use, and then
receives approval for a new use, the innovator receives 3 years of
exclusivity for marketing purposes. The generic company and can
still sell the generic of the drug for the prior approved use
• Prescription Drug Marketing Act of 1987
• Banned the sale of Rx drug samples (retail pharmacies should never
accept drug samples)
• Drug wholesalers must be licensed by states
• Banned re-importation of drugs into US
• Dietary Supplement Health Education Act of 1994
• Exempts vitamins, minerals, amino acids, herbal products from FDA
controls requiring proven efficacy before marketing
Major Drug Legislation
• Health Insurance Portability and Accounting Act of 1996
• HIPPA: Protects a patient’s private health information
• FDA Modernization Act of 1997
Fast-track process for NDA submissions
Clarified condition for compounding
The prescription legend was replaced with “Rx Only”
Encouraged manufacturers to give pediatric dosing and new uses
for existing drugs
• Methamphetamine Anti-Proliferation Act of 2000
• Place pseudoephedrine, ephedrine, and phenylpropanolamine
behind the counter
• Sales only with a government issued ID
• Requires a log
• Maximum of 3.6 grams/day, 7.5 grams/month mail order, 9
grams/month total (federally)
• Maximum of 3.6 grams/day, 5.76 grams/month, and 28.8
grams/year (Tennessee)
Major Drug Legislation
• Medicare Prescription Drug Improvement and Modernization Act
of 2003
• Added Medicare Part D – prescription drug program (administered by
private insurance companies)
• Part D contains the Donut Hole
• Requires insurance companies to cover MTM services to patients taking
multiple drugs that will exceed a cost
• Other parts of Medicare (administered by the Centers for
Medicare and Medicaid Services, CMS)
• Part A – hospitalization
• Part B – Physician’s services
• Part C – optional Medicare Advantage program
• Dietary Supplement and Nonprescription Drug Consumer
Protection Act of 2006
• Two parallel mandatory reporting systems for serious adverse events,
one for OTC and other for dietary supplements
Orphan Drug Act of 1983
• Designed to encourage drug manufacturers to
develop and market rx drugs for conditions
affecting fewer than 200,000 patients in the United
• Manufacturers are given 7 years exclusivity of
• FDA waives NDA filing fee
• Provides tax credits
Drug Definition – Four Parts
• Part A: article recognized in the official US
Pharmacopoeia/National Formulary (USP/NF) or
Homeopathic pharmacopoeia of the United states
• Part B: article intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in
humans or other animals
• Part C: article (other than food) intended to affect the
structure or any function of the body of humans or
other animals
• Part D: article intended for use as a component of any
articles specified in the above but not including devices
or their components, parts, or accessories
Definition of a Dietary Supplement
• A product that is intended for ingestion and intended to
supplement the diet containing one or more of:
A vitamin
A mineral
An herb or other botanical
An amino acid
Dietary substance for use by humans to supplement the diet
by increasing the total dietary intake
• FDA regulates dietary supplements less stringently than
drugs, but claims by the manufacturer that the dietary
supplement treats a disease (rather than maintaining
health) may bring the product under FDA regulation as
if it were a drug
Drug or Dietary Supplement?
Cranberry tablets
increase the acidity of
the urine and help
maintain a healthy
urinary tract
Cranberry tablets prevent
urinary tract infections
Drug or Dietary Supplement?
Probiotics help maintain
healthy intestinal flora.
Probiotics help prevent
diarrhea associated with
antibiotic use.
Items used for food or drink, food/drink components, chewing
Recognized as drugs by USP, NF, HP
Items used to diagnose, cure, mitigate, treat, or prevent disease
Items (other than food) intended to affect the structure or any
function of the body
Product other than tobacco intended to supplement diet that
bears or has one or more of the following: vitamin, mineral, herb,
amino acid (can be in combo)
Instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent or similar recognized by USP
Item intended for diagnosis of disease, or in cure, mitigation,
treatment, or prevention of disease
Item that intended to be rubbed, poured, sprinkled, sprayed on,
applied to human body for cleansing, beautifying, promoting
attractiveness, altering appearance (except soap)
Medical Devices Class I
• Pose least potential harm to users
• General controls are adequate to ensure
• Examples: needles, scissors, exam gloves,
stethoscopes, toothbrushes
21 CFR 860.3(c)(1)
Medical Devices Class II
• General controls are insufficient to ensure
safety/effectiveness – Require special controls
• Req performance standards, post-market surveillance,
patient registries
• Must meet specific performance standards from
• Examples: insulin syringe, infusion pump,
thermometers, diagnostic reagent, tampon, heating
21 CFR 860.3(c)(1)
Medical Devices Class III
• Presents a potential unreasonable risk of illness or
injury, or insufficient information exists to determine its
• Requires premarket approval
• Important in preventing impairment to human health
• Life supporting or life-sustaining devices
• Examples: pacemaker, soft contact lenses, replacement
heart valve
21 CFR 860.3(c)(1)
• A prescription must be signed by the prescriber on the
date it is issued
• A prescription can be communicated to a dispenser
(pharmacy) by an employee or agent of the prescriber
• Once dispensed, the prescription document is the
property of the dispensing pharmacy
• A prescription must be for a legitimate medical purpose
• Proper dispensing of a controlled substance is a
corresponding responsibility of the pharmacy
Tamper-Resistant Prescription Paper
• Tamper-Resistant Prescription law of the US Troop
Readiness, Veteran’s Care, Katrina Recovery, and Iraq
Accountability Appropriates Act of 2007 requires
written prescriptions for Medicaid outpatient drugs to
be issued on tamper-resistant paper
• The paper must be designed to prevent:
• Unauthorized copying of a completed/blank prescription pad
• Erasure or modifications of information written on the pad by
the prescriber
• Use of counterfeit prescription forms
• Does not apply to electronic, oral, or faxed
Written, Oral, Electronic Rxs
• Oral prescriptions authorized under the DurhamHumphrey Amendment of 1951. Oral prescriptions
must be promptly reduced to writing and filed (TN
requires this and requires initialing by whoever receives
• Electronic prescriptions were authorized under the
Medicare Prescription Drug, Improvement, and
Modernization Act of 2003 (Part of Medicare Part D)
• E-prescribing provision preempts any state law that
limits a prescriber’s ability to transmit electronic
prescriptions for Medicare patients.
Prescription Refills
• Refills were authorized by the Durham-Humphrey
Amendment of 1951. Must note the refills on the
back of the written prescription or by a computer
• Pharmacist may not refill a prescription unless
there is a specific authorization (orally or written)
by the prescriber
• Prescribers can limit the number of refills for a
prescription, and the pharmacist must comply with
those directions
• Ex: “can only be refilled every 30 days and not sooner”
Naming New Drugs
• New names of generic drugs is the responsibility of the
United States Adopted Names Council (USANC)
• Secretary of HHS give the final approval
• Name needs to be short, distinctive, and unlikely to be
confused, while also providing indication for
therapeutic class/chemical class
• Brand naming is assigned to the drug by the
• Innovator company: company to first make a
proprietary drug and bring to market
• Receive exclusive rights for marketing
National Drug Code (NDC)
• All drugs must have an NDC
• Drug Listing Act of 1972 requires registered drug establishments
to provide the FDA with current list of all drugs manufactured for
commercial distribution
• 10 or 11 digit, 3-segmented number to identify drugs
• First 4-5 digits: manufacturer or distributor ID (labeler’s code)
• Second 3-4 digits: product ID, identifies strength, dosage form,
formulation for the manufacturer
• Final 2 digits: package ID, identifies the package
• Just because a product has an NDC does not mean the product
has FDA approval. NDC is assigned when an INDA is filed with FDA
National Drug Code (NDC) Number
• 10-digit three segment code (4-4-2, 5-3-2, or 5-4-1)
• Billings and claims submissions require an 11-digit
NDC number.
Definition of Narcotic
• Narcotic: Natural or synthetic opium or opiate and
any derivative, such as poppy straw, coca leaves,
cocaine, and ecgonine
Controlled Substances Act (CSA)
• Certain drugs have a potential for abuse that leads to physical or
psychological dependence
• Federal government has placed these drugs into schedules and
calls them controlled substances
• Comprehensive Drug Abuse Prevention and Control Act =
Controlled Substance Act, created a closed system for distribution
of controlled substances
• Close system: only those persons/entities who are registered with
the DEA may legally engage in manufacturing, distributing,
prescribing, dispensing of controlled substances
• Attorney General of the US has the authority to
add/remove/reschedule a drug from one schedule to another
• Individual states can also schedule drugs, and they identify who
can do this (TN: Commissioner of Health and Commissioner of
Mental Health and Substance Abuse jointly do this)
Drug Enforcement Administration (DEA)
• Enforces the CSA
• DEA is under the US Justice Department
• Justice Department is within the executive branch
of the Federal government
• DEA Pharmacist’s Manual:
Federal vs. State Authority for Controlled Substances
• Controlled Substances can be regulated by both federal
and state laws. Federal law does not preempt state law
in regulating controlled substances
• If a person can comply with one law without violating
the other, the person must comply with the stricter law
• Ex: federal law has no prohibition of using certain stimulants
for weight loss, but state law does (TN), therefore, state law
should be followed
• If a person cannot comply with one law without
violating the other, the person must comply with
federal law
• Ex: state law legalizes a drug that is C-I federally. The person
cannot comply with state law without violating federal law.
(Medicinal marijuana?)
Classification of Controlled
• Placement into one of five (I, II, III, IV, V) schedules
depending on abuse potential and degree to which
drug may cause physical or psychological dependence
• Narcotic vs Non-narcotic
• Scheduled listed chemical products
• Behind the counter products such as pseudoephedrine,
ephedrine, phenylpropanolamine
• Non-Rx C-V products: Robitussin AC, Cheratussin AC
Symbol on Manufacturer Label
• “Schedule” not needed
• Not required if the substance is to be used in
clinical research
• Schedule I = CI or C-I
• Schedule II = CII or C-II
• Schedule III = CIII or C-III
• Schedule IV = CIV or C-IV
• Schedule V = CV or C-V
Controlled Substance Registration
• Every person/entity who manufactures/distributes
controlled substances must register annually with
the Attorney General (DEA registration)
• Every person/entity who dispenses (this term
includes prescribing) controlled substances must
register with Attorney General (DEA registration)
every three years
• DEA does not require individual pharmacists to
register, just pharmacies
• In TN, pharmacist must register and pay a $40 fee
every 2 years to handle controlled substances
Periods of Registration
Business Activity
DEA Form
Chemical Analysis
Schedules I-V
225, 225a
Schedules I-V
225, 225a
Schedules I-V
225, 225a
Schedule I
225, 225a
Schedule II-V
225, 225a
Narcotics in
Schedules II-V
363, 363a
Schedules I-V
225, 225a
Schedules I-V
225, 225a
Schedules I-V
225, 225a
Schedules II-V
224, 224a
DEA Registration Numbers
• Alpha-numerical: two alphabet letters followed
seven digits
• First letter: A, B, F, G, M, P, R
• Second letter: first initial of last name
• Add the first, third, fifth digits = number
• Add the second, fourth, sixth digits and multiple
this number by 2 = number two
• Add number one and two together
• The right most digit should be the ninth digit of the
Example: DEA Number
Dr. Well Done DEA: AD 1257218
Number one = 1+5+2 = 8
Number two = (2+7+1) x 2 = 20
Number one + Number two = 28
This DEA could be legitimate
Could this DEA# be legit?
Practitioners Exempted from DEA
• Agent/employee of hospital or other institution
• All controlled prescriptions must include:
• The hospital/institution’s registration number
• Special internal code number assigned to the
practitioner by the institution
• Name of the physician and signature of the physician
C-I Drugs
• No accepted medical use, as opposed to drugs in the
other schedules
• Cannot be manufactured, prescribed, dispensed, unless
approved by the DEA for investigative purposes
• High potential for abuse and lack accepted information
on safety of use
• Includes:
• Hallucinogenics: marijuana, tetrahydrocannabinol, lysergic
acid diethylamide (LSD), peyote, mescaline, psilocybin
• Dihydromorphine, heroine, morphine methylbromide
• Methaqualone
• Gamma hydroxybutyric acid (GHB)
• Synthetic cathinones (bath salts)
C-II Drugs
• High potential for abuse and abuse may lead to severe
physical or psychological dependence
• Has a currently accepted medical use with severe
• Includes
• opium and many other opiates: morphine, hydrocodone,
codeine, fentanyl, hydromorphone, oxycodone, methadone,
meperidine, dihydrocodeine, diphenoxylate
• Cocaine
• Stimulants: amphetamine, methylphenidate
• Depressants: amobarbital, glutethimide, secobarbital,
C-III Drugs
• Lesser potential for abuse than C-II drugs and abuse may
lead to moderate or low physical dependence or high
psychological dependence
• Current accepted medical use
• Includes many C-II drugs in combination with a
noncontrolled ingredient, or in smaller dosages, or in a
less abusable dosage form:
• aspirin with codeine, acetaminophen with codeine
• Anabolic steroids
• Dronabinol
• Ketamine
• Paregoric
• GHB approved by the FDA
C-IV Drugs
• Lower potential for abuse than C-III drugs and
abuse may lead to limited physical or psychological
• Currently accepted medical use
• Depressants: benzodiazepines, chloral hydrate,
barbital, meprobamate, phenobarbital
• Phentermine
• Carisoprodol
• Tramadol
C-V Drugs
• Low potential for abuse relative to C-IV drug and
abuse may lead to limited physical or psychological
dependence relative to C-IV drugs
• Current accepted medical use
• Includes antitussives containing codeine and
antidiarrheals containing an opiate
• Strength limits of:
• 200 mg of codeine per 100 ml
• 100 mg of dihydrocodeine or opium per 100 ml
• 2.5 mg of diphenoxylate, and not less than 25 mcg
atropine per dosage unit
TN Schedule VI
Criteria: Commissioner determines these substances
should be scheduled but not in C-I-V
• Marijuana
• Tetrahydrocannabinols
• Synthetic equivalents of the substances contained in the
plant or resinous extractives of Cannabis sp.
• Industrial Hemp is excluded
TN Schedule VII
• Criteria: classification of substances that should not
be included in C-I-VI
• Substances: butyl nitrite or any isomer of butyl
Dispensing of Controlled Substance to a
Patient without a Rx
• C-V substances
• Must be sold by a pharmacist or intern
• Purchaser must be at least 18 years old
• Must keep a log book containing:
Date of sale
Name and address of purchaser
Name and quantity of controlled substance sold
Name/initials of pharmacist
Dispensing Non-Rx Controlled Substance
• A controlled substance that is not a prescription under FDCA may be
dispensed by a pharmacist without a prescription to a purchaser at
retail, if:
• Dispensed by a pharmacist (non-pharmacist may complete sale);
• Not more than 240 cc. (8 ounces) of any controlled substance containing opium
[Note: refers to true opium products], nor more than 48 dosage units of any
such controlled substance containing opium nor more than 120 cc. (4 ounces)
of any other such controlled substance [Note: refers to codeine] nor more than
24 dosage units of any other such controlled substance
• may be dispensed at retail to the same purchaser in any given 48-hour period
• The purchaser is at least 18 years of age
• Proper identification
• Pharmacist maintains a bound record book for such dispensing containing all
pertinent information
• A prescription is not required by any other law
21 CFR 1306.26
Controlled Substance Definition: Dispense
• To deliver a controlled substance to an ultimate
user or research subject by or pursuant to a lawful
order of a practitioner
• Dispense includes prescribing and administering of
a controlled substance and the
packaging/labeling/or compounding necessary to
deliver to the ultimate user
• Dispenser: practitioner who delivers a controlled
substance to an ultimate user/research subject
Purpose of the Prescription
• Rx for a controlled substance must be issued for a
legitimate medical purpose by an individual
practitioner in the usual course of his/her practice
• Rx that exceeds the practitioner’s scope are not
• Ex: dentist may not write a rx for a controlled substance
to treat back pain
• Corresponding responsibility
Requirements for Controlled
Substance Rx
The prescription must include:
• The date the prescription was written
• Full name of the patient
• Address of the patient
• Drug name, strength, dosage form
• Quantity
• Directions for use
• Full name, address, DEA registration # of practitioner
• Must be signed by the prescriber
What changes can be made to a
controlled substance Rx?
• The following may NOT be changed on C II Rx:
• Name of the patient
• Name of the drug (except for generic substitution)
• Name of the prescribing practitioner
• Pharmacist can make the following changes by contacting
the prescriber and getting verbal permission:
• Strength, quantity, directions
• If pharmacist makes a change, they must document what
change was authorized, name/initials of the person granting
the authorization, initials of the pharmacist
• https://nabp.pharmacy/wp-content/uploads/2016/07/DEAmissing-info-schedule-2.pdf
Corresponding Responsibility Doctrine:
Purpose of Controlled Substance Rx
“A prescription for a controlled substance to be effective must
be issued for a legitimate medical purpose by an individual
practitioner acting in the usual course of his professional
practice. The responsibility for the proper prescribing and
dispensing of controlled substances is upon the prescribing
practitioner, but a corresponding responsibility rests with the
pharmacist who fills the prescription. An order purporting to
be a prescription issued not in the usual course of
professional treatment or in legitimate and authorized
research is not a prescription within the meaning and intent
of Section 309 of the Act (21 U.S.C. §829) and the person
knowingly filling such a purported prescription, as well as the
person issuing it, shall be subject to the penalties provided for
violations of the provisions of law relating to controlled
substances.” (21 C.F.R. §1306.04(a))
Labeling Requirements for C-II-V
• Must label the package with:
Pharmacy name and address
Serial number of the prescription (Rx #)
Date of initial filling (and dates of refills)
Name of the patient
Name of practitioner issuing the Rx
Directions for use
Cautionary statements, if applicable
“Caution: Federal law prohibits the transfer of this drug
to any person other than the patient for whom it was
Transferring Controlled Substance Prescriptions
• Pharmacies can transfer refill information between each
other as long as:
• State law allows
• It must be on a one-time basis only, unless the pharmacies share a
real-time, online database. If they do, they can transfer back and
forth up to the maximum number of refills
• The transfer may take place only by direct communication between
two licensed pharmacists
• Transferring pharmacist must write “void” on the face of the invalid
prescription, or add the transfer information to the prescription
record for electronic prescriptions
• Record on the reverse of the invalid prescription the name, address,
and DEA registration # of the pharmacy that is receiving the
prescription, along with he name of the pharmacist receiving
• Must record the date of the transfer and name of the transferring
• From the transferor to the transferee
Transferring Controlled Substance Prescriptions
• The pharmacist receiving the information must write the
word “transfer” on the face of the prescription and reduce
to writing all information required to be on a prescription
Date of issuance of original prescription
Original number of refills authorized
Date of original dispensing
Number of valid refills remaining, dates/location of previous fills
Pharmacy’s name, address, DEA #, prescription #
Name of pharmacist who transferred
• Original and transferred prescriptions must be maintained
for a period of 2 years from the date of last refill
Prescriptions for C-II Drugs
• Written Prescriptions
• Pharmacy may dispense a C-II drug only after receiving a written Rx
by an authorized prescriber except in emergency situations
• Written = paper or electronic
• Oral Prescriptions
• Oral prescriptions for C-II drugs are not permitted except in an
emergency situation. If it is an emergency, the following must be
• Quantity prescribed/dispensed is limited to the amount adequate to treat
the patient during the emergency period
• The rx must be immediately reduced to writing by the pharmacist and
must contain all the required info, except for the prescriber signature
• If the prescriber is not known to the pharmacist, the pharmacist must
make a reasonable effort to determine the oral authorization came from a
valid registered individual practitioner
Emergency Exception for Written Rx
• Pharmacist may dispense a C-II upon ORAL authorization if:
• Quantity prescribed/dispensed is limited to amount adequate to
treat the patient in emergency period
• Rx is immediately reduced to writing and contains all information
required except for signature of prescriber
• PharmD must make reasonable effort to determine if the oral
authorization came from registered practitioner
• Within 7 days of oral emergency prescription, the
prescribing practitioner must provide written Rx to the
dispensing PharmD that contains:
“Authorization for emergency dispensing”
Date of oral order
If delivered by mail, must be postmarked within the 7 day period
If the rx is not delivered within 7 days, the pharmacy must contact
C-II Rx via Fax
• A paper Rx for C-II may be transmitted via FAX,
provided that the original manually signed Rx is
presented to the pharmacist for review prior to the
actual dispensing of the controlled substance
• Pharmacist must file the original, written prescription
• Fax serves as original:
• Substance to be compounded for direct admin to patient
by IV, IM, SQ, intraspinal route
• Resident of LTCF
• Hospice patient
C-II Prescriptions for Institutionalized Patients
• Labeling requirements do not apply if the ultimate user
is institutionalized and the following conditions are
• Not more than 7 day supply of the controlled substance is
dispensed at one time
• The controlled substance is not in the possession of the
ultimate user prior to administration
• The institution maintains appropriate safeguards and records
concerning the proper administration, control, dispensing,
and storage of the controlled substance
• The system is adequate to identify the supplier, product,
patient, and to provide directions for use
• No refills are permitted on a C-II drug
Multiple Prescriptions for C-II Drugs
• A practitioner may use multiple prescriptions
authorizing the patient to receive a total of up to a 90
day supply of a C-II drug if the following are met:
• Each separate Rx is issued for a legitimate medical purpose by
an individual practitioner in the usual course of their practice
• The practitioner provides written instructions on each Rx
indicating the earliest date on which the pharmacy may fill
each Rx. No pharmacist may fill the Rx before that date
• The practitioner concludes that providing the patient with
multiple Rx’s does not create an undue risk of
• The issuance of multiple Rx’s is allowed by state law
What are your thoughts on this?
Partial Filling of C-II Drugs
• Community pharmacy setting, pharmacist may
partially fill if “unable to supply” full quantity
• Balance must be filled within 72 hours after partial filling
• If unable to supply the remainder after 72 hours, the rest
of the Rx is void
Long-Term Care/Terminally Ill Patients
Partial fills
• C-II drugs may be partially filled to permit dispensing of
individual dosage units to patients in LTCF and patients
who are terminally ill/hospice)
• The pharmacist must record on the prescription
whether the patient is “terminally ill or in a “LTCF)
• Total quantity of the C-II drug dispensed in all partial
fillings must not exceed the total quantity prescribed
• Can partial fill in cases of LTCF or terminally ill patients
from the date issued up to 60 days later
CARA 2016
• Allows for partial filling of C-II’s
• Requested by the patient or practitioner
• Total quantity dispensed in all partial fills cannot exceed
total quantity prescribed
• Once a partial fill occurs, the remaining portion
may be filled within 30 days of the date the
prescription was issued
• If not, the prescriber should be notified
• No further quantity can be dispensed after 30 days
without a new Rx
Rx’s for Institutionalized Patients
• Labeling requirements do not apply when a
controlled substance listed in C-III-V are prescribed
for administration to an ultimate user who is
institutionalized, as long as:
• Not more than a 34 day supply or 100 dosage units
whichever is less, of the controlled substance is
dispensed at one time
• The substance is not in the possession of the ultimate
user prior to administration
• Institution maintains appropriate safeguards and records
the proper administration/control/dispensing/storage of
the substance
Refilling C-III - C-V Rx
• For C-III - C-V drugs: limit of six months after date
of issuance or up to five refills, whichever comes
• Practitioner may orally authorize additional refills if
original was written for less than five and
authorization is recorded on hard copy or in
automated system
• Refill quantity cannot exceed quantity originally
21 C.F.R. §1306.22
Oral Refill Authorizations
• Prescribing practitioner may orally authorize
additional refills for the original Rx (C-III-V):
• The total quantity authorized included with the original
amount does not exceed 5 refills/6 months from the
date written
• PharmD must annotate on the back of original Rx the
date, # additional refills, PharmD initials
• Quantity of each refill cannot exceed quantity of initial
• Practitioner must execute a new Rx for any
additional quantity beyond 6 months/5 refills
Recording Refills of C-III and C-IV Rx
• If non-automated system, must record required information on
back of Rx or other readily retrievable document
name and dosage form of the controlled substance
date filled or refilled
quantity dispensed
initials of the dispensing pharmacist for each refill
total number of refills for that prescription
• If the pharmacist merely initials and dates the back of the Rx or
annotates the electronic Rx record, it shall be deemed that the
full face amount of the Rx has been dispensed
• Must be retrievable by Rx number
21 CFR 1306.22
Computerized Refill Records
• Alternative to paper record retrieval
• Must be able to retrieve original Rx information via
computer system
• Computer retrieval of refill history
• Documentation that refill history is correct
• Each pharmacist must sign the bound logbook
• Signing indicates verification of rx’s
• Must be kept for 2 years from last date
• Capable of producing printout of refill data (audit
• Every registrant must keep a complete and accurate record of all
controlled substances
• Three types of records involved
• Inventory
• Drugs received
• Drugs dispersed
• Negligent recordkeeping is a violation of the CSA
Beginning inventory + drugs received – drugs dispersed = inventory
§§827 (a) and (b)
General Recordkeeping Requirements
• Records generally must be kept for two years at the place of
• Centralized records require that DEA be notified
• Records must be able to be delivered to registered location within two
business days per DEA request
• C-I and C-II records must be maintained separately unless readily
retrievable (includes inventory records)
• C-III-V do not need to be maintained separately from noncontrolled records as long as they are readily retrievable from
other records (marked in such a manner to visually distinguish
• Records that must be kept at the registered location:
• Prescription records
• Inventories
• Executed order forms (DEA Form 222)
Records of Dispersal (removal of drug)
• Acceptable records of dispersal include Rx, record books, Form 222,
invoices, records of disposal, theft or loss
• Record keeping options for Rx’s: 2 options
• Two files:
• C-II
• CIII-V and nonscheduled drugs, with controls having stamped red “C”
• If C-III-V are mixed with C-II prescriptions or within non-controlled prescriptions,
a 1 inch red letter “C” must be stamped in the lower right corner of all C-III-V
prescriptions unless the pharmacy has a computer system adequate to retrieve
those prescriptions
• Three files:
• C-II
• Non-controlled substances
• Rx files must contain everything required on a Rx, but also the name or
initials of pharmacist who dispensed
Security Requirements
• C-I drugs must be locked in a cabinet/safe
• C-II-V may be locked up or dispersed throughout
the stock of non-controlled drugs
• Pharmacy cannot hire a pharmacist/intern or
technician who has been convicted of a felony
related to controlled substances
Inventory Records
• Prior to beginning business and subsequently every two
years an inventory must be conducted containing a
complete and accurate record of all controlled substances
“on hand”
• Termed “biennial inventory”: inventory within two years of
previous inventory
• “On hand” means in possession of or under the control of
the registrant
• Inventory may be taken at beginning or end of business day;
records must be written, typed, or printed
• Newly scheduled drugs must be inventoried on date of
• Recent rescheduled drug in TN: Gabapentin
• Exact count must be made of C-I or C-II drugs
• Estimated count permissible for other schedules unless
container holds more than 1,000 units (must make exact
21 C.F.R. §1304.11 (a) and (b)
Distributions from a Pharmacy to Another
• Invoice required for C-III, C-IV, and C-V products
containing all required information:
The name of the substance, dosage form, strength
Number of dosage units or volume in the container
Number of commercial containers distributed
Date distributed
Name, address, and registration number of the person to
whom the containers were distributed
• Form 222 required for C-II products
• Total number of dosage units distributed to another
registrant must not exceed 5% of total units of
controlled substances distributed and dispensed in
one year
Records of Theft or Loss
• Registrant must notify DEA within one day of discovery of
any “theft or significant loss” of any controlled substance
(should also notify police and most likely required to notify
state board of pharmacy)
• DEA has listed several factors to be considered in
determining whether a loss is significant
Quantity lost in relation to type of business
Specific drugs lost or stolen
Whether loss can be attributed to unique individuals or activities
Whether losses are random or fit a pattern
Specific controlled substance is likely to be diverted
• Registrant must complete Form 106
DEA Form 222
• Required for any distribution of C-I or C-II drugs
• Exception: ordering controlled substances through Controlled
Substance Ordering System (CSOS)
• Forms obtained by requesting in writing from nearest DEA
• Forms issued in mailing envelopes containing 7 forms
• Each form is in triplicate titled Copy 1 (BROWN), Copy 2
(GREEN), Copy 3 (BLUE)
• Forms are serially numbered and issued with name, address
and registration number of registrant, authorized activity,
and schedules registrant is authorized to handle
• Registrant may not correct or change any information or
errors on the forms
Who Keeps what copy of 222 Form?
• Purchaser retains Copy 3, and all copies of
unaccepted/defective forms with statement saying
• Supplier retains Copy 1
• DEA retains Copy 2
• All forms must be kept separately from other records
and retained by purchaser/supplier for at least 2 years
at registered location
• The purchaser and supplier can be many different
organizations and depends on who is buying and who is
Example DEA 222
Updated DEA Form 222 – Single Sheet
• Purchaser: “make a copy” and keep it for two years.
• Supplier: purchaser sends the original copy to supplier and keeps
for 2 years
• The DEA will be notified of the order via ARCOS system
• If the pharmacy is acting as a supplier (ie, sending Schedule I or II
medications back to a reverse distributor or selling to another
provider or pharmacy), the top of the instruction form indicates
the following: “If you are not an ARCOS reporter, you are required
to provide a copy of the executed order form to DEA (21 CFR
• Very few, if any, pharmacies would be Automation of Reports and
Consolidated Orders System (ARCOS) reporters unless also
holding a manufacturer, wholesaler/distributor, or outsourcer
license. The DEA order form directs the registrant to email the
copy to dea.order [email protected]
• The triplicate DEA 222 forms are still valid until October 30, 2021
Distributing C II: Supplied by Pharmacy
• Must always use Form 222 when distributing C- I-II
• Pharmacy to another pharmacy
• Pharmacy to individual practitioner
• Practitioner orders from pharmacy
• Practitioner cannot write a Rx for office use
• Reverse distribution: pharmacy to wholesaler
Power of Attorney (POA)
• Authorizes designated individual to obtain and
execute order forms (DEA 222)
• Can be revoked at any time
• Can have an unlimited number of power of
attorney to order C-II’s
• It does not have to be the pharmacist
DEA Forms
• DEA Form 222 – ordering C-II substances
• DEA Form 224 – application for DEA certificate of
• DEA Form 106 – reporting theft or loss
• DEA Form 41 – disposal of out-of-date controlled
substances (reverse distributors)
Disposal of Controlled Substances
• Any person needing to dispose of a controlled substance
may request assistance from the Special Agent in Charge of
the local DEA office for authority/instructions on how to
dispose of the substance
• If the person is a registrant, they must list the controlled
substance desired for disposal on DEA Form 41 and submit
three copies of that form to the local DEA office.
• The Special Agent in Charge will authorize and instruct the
applicant to dispose of the controlled substance in one of
the following ways:
• Transfer to a person registered under the act and authorized to
possess the substance
• Deliver to an agent of the DEA or to the nearest DEA office
• Destroy in the presence of an agent of the DEA
• According to the Special Agent in Charge
Opioid Treatment Programs (OTPs)
• Congress first authorized narcotic treatment programs (now
OTPs under Substance Abuse and Mental Health Services
Administration, SAMHSA) in 1974
• Legalized administering methadone to addicts as medically
alternative to heroin
• Practitioner must be separately registered with the DEA as
an opioid treatment program
• Detoxification: dispensing an opioid agonist in decreasing
doses incident to withdrawal and as a method to bring the
individual to a narcotic drug-free state
• Short term: <30 days
• Long term: 30 days – 180 days
• Maintenance: dispensing of opioid agonist for a period in
excess of 21 days for the treatment of dependence of
heroin/morphine-like drugs
Approved Drugs in OTP’s
A practitioner may administer or dispense directly,
but not prescribe, a narcotic drug listed in any
schedule to a narcotic-dependent person for the
purpose of maintenance or detoxification, if the
product is approved for use:
• Methadone
• Buprenorphine sublingual tablets (Subutex)
• Buprenorphine-naloxone tablets/films (Suboxone)
• Levo-alpha-acetyl-methadol (LAAM)
Drug Addiction Treatment Act (DATA)
• Enacted in 2000 with intent of allowing addicts to be treated for
addiction in office-based settings (outside of OTPs)
• Only permitted drugs are buprenorphine SL (Subutex) and
buprenorphine-naloxone (Suboxone) tablets/films
• Treatment must be by a “qualifying physician”
• Board certified in addiction psychiatry from American Board of Medical
• Addiction certification from American Society of Addiction Medicine
• Board certified in addiction medicine from American Osteopathic
• Or 8 hours of authorized training in treatment and management of
opioid-dependent patients
• Special DEA Identification number (DATA 2000 Waiver ID or “X”
• Number of patients:
• 1st year: max of 30 patients at one time
• 2nd year: max of 100 patients at one time
• 3rd year: max of 275 patients at one time
Combat Methamphetamine Epidemic Act of 2005 and
Methamphetamine Prevention Act of 2008
• Places restrictions on OTC drugs used to manufacture
methamphetamine including pseudoephedrine
• “scheduled listed chemical products”
• Law limits sale to no more than 3.6 g of ephedrine, PSE, or
PPA base to a single purchaser per day
• No consumer may purchase more than 9 g within a 30-day
period or 7.5 g within a 30-day period by mail order
• Products must be stored behind counter or in a locked
cabinet where customers do not have direct access
• Sales must be recorded with required information
• Many states have stricter laws
Pseudoephedrine Purchases
• The product must be placed behind the counter within
25 feet, and visible
• Written or electronic logbook must contain
Name of product, quantity sold
Date/time of sale
Full name, address of purchaser
Buyer must sign the logbook
• Requires photo identification to purchase
• Electronic logbook scans the ID
• Name entered must be the name of the buyer and it is
the responsibility of the seller to determine that
• Patient must be 18 years or older
Federal Limits on the Number of Tablets of Methamphetamine Precursor Drugs That Can Be Sold
Number of tablets = 3.6 g Number of tablets = 9 g of Number of tablets = 7.5 g
25 mg ephedrine HCl
175 tablets
439 tablets
366 tablets
25 mg ephedrine sulfate
186 tablets
466 tablets
389 tablets
mg pseudoephedrine HCl
146 tablets
366 tablets
305 tablets
mg pseudoephedrine HCl
73 tablets
183 tablets
152 tablets
mg pseudoephedrine HCl
36 tablets
91 tablets
76 tablets
Pseudoephedrine Sulfate
mg pseudoephedrine sulfate
mg pseudoephedrine sulfate
155 tablets
389 tablets
324 tablets
77 tablets
194 tablets
162 tablets
mg pseudoephedrine sulfate
38 tablets
97 tablets
81 tablets
mg pseudoephedrine sulfate
19 tablets
48 tablets
40 tablets
Phenylpropanolamine (PPA) FDA issued a voluntary recall as being unsafe for human consumption. Veterinary use
is by prescription only
Base ≠ Salt
• The number of dosage units are calculated on the
base of pseudoephedrine, NOT salt
• 18% of the MW of a 30mg tablet of
pseudoephedrine HCl is the salt
• 23% of the MW of a 30mg tablet of
pseudoephedrine sulfate is the salt
Drug Product Substitution: Orange Book
• Approved drug Products with Therapeutic Equivalence
• Evaluates pharmaceutically equivalent products on the basis
of bioequivalence (ADME process)
• Pharmaceutical equivalence—products contain same active
ingredients and are identical in strength and dosage form
• Bioequivalent pharmaceutical equivalents are generally
presumed therapeutically equivalent—having same clinical
safety and efficacy
• Orange Book uses 2-letter rating system; some products use
two letters and a number
• Pharmacists must comply with state law when substituting
and exercise professional judgment substituting B-rated
• https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm?
Bioequivalence of Generic and Brand
Name Drugs
• “A” rated products:
• Bioequivalent and therapeutically equivalent to brand
name/reference product
• Substitutions of same strength/dosage forms allowed
• “B” rated products:
• NOT bioequivalent
• NOT to be substituted for the reference product
• “AB” rated products:
• Equivalency problems originally, but since resolved
• Substitutions of same strength/dosage forms allowed
Generic vs Therapeutic Substitution
• Therapeutic Substitution is the substitution of a
different drug than the one designated on the
prescription or medical order without contacting
the prescriber
• Example – Substitute dicloxacillin for penicillin
• Generally limited to institutions that use a drug
• Collaborative Pharmacy Practice Agreements may
give pharmacists a significant role in medication
therapy management (MTM) that allow them to
make therapeutic substitutions
Generic vs Biosimilar Drugs
• Generic drugs must be the same drug, strength,
dosage form
• Biosimilars are “similar” to the reference product,
but not interchangeable
• Interchangeable biologics are so similar that they
can be interchanged between the referenced
Different “Books”
• Bioequivalence/generic substitution: ORANGE BOOK
• Biosimilars: PURPLE BOOK
• Vaccine information: PINK BOOK
• Traveler’s information/healthcare: YELLOW BOOK
Label vs. Labeling
• Display of written, printed, or graphic matter upon the
immediate container of any article
• Must appear on the outside container or wrapper of the
retail package OR
• Must be easily legible through the outside container or
• All labels and other written, printed, or graphic matter
upon any article or its containers or wrappers, or
accompanying such article
• All must be approved by the FDA
• Includes package inserts
Manufacturer Prescription Drug Labeling: labeled for the health care
professional, not the patient!
Patient package inserts (PPIs)
• Information for the patient
• Although the FDA originally had wanted PPIs required
for most drugs, it applies to very few, including
estrogen-containing drugs, DES, and oral
• Written in lay person language
• Applies to new prescriptions and refills
• Duty of manufacturers and pharmacists to distribute
to patients
• Law applies to institutional pharmacy as well as
Package Insert Requirements
• Information for the healthcare professional
• Highlight section summarizing important info
Access to benefit/risk
Boxed warning
Table of contents
Full prescribing info
Patient counseling info
Inclusion of date of initial product approval
Toll-free reporting number for adverse side effects
Consumer medication information (CMI)
• Also known as “useful” written patient information
• Law required 95% of patients receiving a new Rx receive
useful written information about their medications by
• 2008 study showed that 94% of patients were receiving
the information but only about 71% meet the minimum
standard for usefulness
• Flaws in current CMI: formatting, word counts, lack of
clear action for patients, priority of information
Risk Evaluation and Mitigation
Strategies (REMS)
• Black box warnings (BBW)
• Medication Guides (Med Guides)
• Education for prescribers, dispensers, patients
• Manufacturing standards for opioid abuse
• Required in labeling when use of a drug may lead to
death or serious injury
• Required for about 450 prescription drugs
• Considered dramatic step for a drug
Medication guides (MedGuides)
•Required for drugs FDA has determined as posing
“serious and significant concerns”
•Required for new and refill prescriptions
•Generally required for outpatients not under direct
supervision of healthcare professional
•Content of MedGuide must be approved by FDA
•Every new MedGuide approved since 2007 has been in
conjunction with a REMS
Drugs with MedGuides
• Accutane (isotretinoin)
• Antidepressants in children and
• Avonex (interferon beta- 1a)
• Amiodarone
• Methylphenidate
• Warfarin
• Elidel Cream (pimecrolimus)
• Epzicom (abacavir & lamivudine)
• Forteo (teriparatide)
• Infergen (interferon alfacon-1)
• Lariam (mefloquine)
• Lindane shampoo and lotion
Lotronex (alosetron)
Mifeprex (mifepristone)
Pegasys (peginterferon alfa-2a)
PEG-Intron (pegylated interferon
Protopic Ointment (tacrolimus)
Rebetol (ribavirin)
Rebetron (ribavirin & interferon
Rebif (interferon beta-1a)
REMS Drugs
• STEPS Program for Thalidomide
• Birth control necessary
• All prescribers and pharmacies must be registered –
Mandatory patient surveys
• Prescriptions limited to 28-day supply, no refills
• Prescriptions must be filled within 7 days of being written
• iPLEDGE Program for Isotretinoin (Accutane)
Mandatory computerized patient registry
Prescribers, pharmacies, and wholesalers must be registered
Informed consent
Patient identifying code number
Female patients must have pregnancy test within 7 days of
filling prescription
REMS Drugs
• Prescribing Program for Lotronix (PPL)
Prescriber must be enrolled in Program
Prescriber must affix sticker to prescription
Medication Guide, Package Insert, follow-up survey
NO telephoned, faxed or electronic prescriptions
• Tracleer Access Program (TAP) – Limits availability of bosentan to
specialty distributor pharmacies participating in program
• Clozaril National Registry (Clozapine)
• Prescribed ONLY by physicians and dispensed ONLY by pharmacists who
are registered
• Quantity dispensed limited to provide drug until next blood test
• Prescribers must supply pharmacist with current blood work
• Tikosyn in Pharmacy System (T.I.P.S.) Program
• Pharmacies must enroll to stock or dispense dofetilide
• Prescribers must be enrolled and qualified to prescribe
REMS Drugs
• Exjade Patient Assistance and Support Services (EPASS)
• Verifies prescription and reimbursement information
• Provides education materials and facilitates the filling of
prescriptions for defasirox (Exjade)
• Available only through specialty pharmacies
• Fosamax Paget’s Patient Support Program
• 40 mg tablets only to patients with Paget’s disease of the
• Available only through specialty pharmacies
• Extended-release opioid products
• Prescriber education
Pregnancy Warnings Prior to 6/30/15
Category A
• Clear evidence of no risk to fetus
Category B
• Animal studies failed to show risk to fetus
Category C
• Risk to fetus is undetermined
Category D
• Positive evidence of risk to fetus
Category X
• Risk to fetus outweighs any possible benefit
21 CFR 201.5
Pregnancy Warnings
• A 2014 regulation replaces the above system. For
drugs approved after June 30, 2015, labeling will
require the inclusion of three subsections to
describe risks: “Pregnancy,” “Lactation,” and
“Females and Males of Reproductive Potential”
• “Pregnancy”: pregnancy, labor, delivery
• “Lactation”: level of drug secreted in breast milk, effects
on infant
• “Reproduction”: pregnancy testing, contraception,
• Drugs approved prior to June 30, 2015, will be
gradually phased into the new labeling standards
New Drug Application (NDA) Process
• Investigational New Drug Application (INDA)
• 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 risk–
benefit criteria; the decision is not subject to appeal or
judicial review
• FDAAA requires NDA sponsors to publish summary
information regarding phase 1 trials on a public registry
• https://clinicaltrials.gov/
New Drug Approval
• New Drug Application (NDA)
• Submitted to FDA after Phase III trials completed
• Includes proposed label, package insert, manufacturing
• If FDA finds the drug to be safe and effective, the drug is
approved for sale
• Abbreviated New Drug Application (ANDA)
• Generic manufacturers need not do all the
safety/efficacy testing as the innovator drug did
• Must establish the generic version is bioequivalent to
innovator drug
Informed Consent
• Informed consent required in all three phases
• Research subjects required to know risks, possible
benefits, and alternative courses of treatment
• Institutional Review Board (IRB) approval required
in some settings
Clinical Trials
Phase 1
• A small group of healthy individuals are given the drug
• Evaluate toxicity, metabolism, F, elimination (kinetic data)
• Doses typically low, assess safety
• Participants don’t usually have the disease
Phase 2
• A larger group (100 more) of participants that have the disease
or symptom in question that is being treated
• Testing efficacy and safety of the drug
Phase 3
• Hundreds or most likely thousands of participants
• Clinical settings such as physician offices/hospitals
• Typically double blinded compared against placebo
• Continue to focus on safety while honing in on doses for efficacy
Phase 4
• Postmarketing clinical studies
• Determine new uses, abuses, additional
safety/efficacy data
Drug Rating and Classification
• Priority classification system rates new drugs by
chemical type and therapeutic potential; this
determines how quickly drug will move through
IND/NDA process
• A number designates chemical type, and a letter (S,
P, or O) designates therapeutic potential
NDA Chemical Types
New molecular entity (NME)
New active ingredient (salt, noncovalent derivative, ester… etc)
New dosage form
New combination
New formulation/manufacturer
New indication
Drug already marketed without an approved NDA
OTC switch
New indication submitted as distinct NDA, consolidated with
original NDA after approval
10. New indication submitted as distinct NDA – not consolidated
Therapeutic Potential
• Type P = Priority
• Priority review drug
• Appears to more advanced over available therapy
• No other effective drugs are available
• Type S = Standard
• Similar to other drugs already on the market
• Type O = Orphan
• A product that treats a rare disease affecting fewer than
200,000 Americans
Orphan Drugs
• Developed for treatment of rare disease
• < 200,000 people in the US
• Cost of development may exceed anticipated
market sale
• Orphan Drug Act of 1983
Supplemental New Drug Application (SNDA)
• SNDA generally required when a manufacturer
makes any change in an approved drug or in its
• Production process, packaging, labeling, indications
• Three categories of SNDA
• A “change being effected (CBE)” SNDA allows the
sponsor to make the change before FDA approval
and is important for labeling changes.
• Voluntary reporting system to allow healthcare professionals to
report any serious adverse events, product use errors, and
product quality issues
• FDA emphasizes the importance of reporting by healthcare
• Pharmacists report the most
• Can report drug product issues: labeling, particulate matter, abnormal
color/taste, stability
• FDAAA requires pharmacies to provide patients with the
MedWatch number and a statement about reporting side effects
• “Call your doctor for medical advice about side effects. You may report
side effects to the FDA at 1-800-FDA-1088”
• Must be with each new and refill prescription
• https://www.fda.gov/safety/medwatch/
• A report is not a legal claim, information is confidential
Other Reporting Mechanisms
Medical Device
Post Marketing
Safety of Drug
Veterinary Product
• Hospital reporting of medication errors
• Health care facilities must report medical
device related deaths to FDA and manufacturer
• FDA/CDC Vaccine Adverse Event Reporting
System (VAERS)
• Health professionals can report to FDA Adverse
Event Reporting System (FAERS)
• Reported to FDA’s Center for Veterinary
Nonprescription Drug Labeling
• User friendly format including pharmacological category or
principal intended use, cautions and warnings, “adequate
directions for use”, and “Drug Facts” panel
• Pharmacies that relabel or repackage must conform to the
same labeling requirements as manufacturers
• Professional OTC labeling may be published by
manufacturers for indications 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
• FTC controls advertising for nonprescription drugs, but FDA
approves the drug product
Nonprescription Drug Labeling
Active ingredients
Other information as required
Inactive ingredients (in alphabetical order)
Questions? Comments? with telephone number
Adequate directions for use
A “Drug Facts” panel
Poison Prevention Packaging Act
• Intent of act to protect children (<5) from accidental
poisonings due to “household substances”
• Administered by the Consumer Product Safety Commission
• The law establishes the standards for child-resistant
• Not child resistant if more than 20% of group can open the package
in a total of 10 minutes
• Adults 50-70 years of age: 90% of a 100 person adult panel must be
able to open and close the package in five minutes and again for a
second time within one minute
• Container may not be reused unless glass or threaded
plastic and then only with new closure
• Misbranded if it does not comply
• Do not confuse this with Anti-Tampering Act
Poison Prevention Packaging Act
Rx drugs
Hazardous household products
All new and refilled rx’s must be dispensed in a childresistant closure, unless:
Prescriber requests – cannot make a blanket waiver
Patient requests – have them sign a waiver
Institutionalized patients
Certain drug products such as SL nitroglycerin and SL and
chewable isosorbide dinitrate
• For manufacturer: May market one size in noncompliant package
with appropriate statement - “This package for households
without young children.”
Products Required to have ChildResistant Packaging
Controlled substances
• Methyl salicylate
• Rx drugs
• https://www.govinfo.gov/co
• Certain medications are
• 16 CFR 1700.14
Rx Drugs Exempted from PPPA
• Sublingual dosage forms of nitroglycerin
• Sublingual and chewable forms of isosorbide dinitrate
in dosage strengths of 10 milligrams or less
• Erythromycin ethylsuccinate granules for oral
suspension and oral suspensions in packages containing
not more than 8 grams of the equivalent of
• Cyclically administered oral contraceptives in
manufacturers' mnemonic (memory-aid) dispenser
packages that rely solely upon the activity of one or
more progestogen or estrogen substances
• Anhydrous cholestyramine in powder form.
Rx Drugs Exempted from PPPA
• All unit dose forms of potassium supplements, including
individually-wrapped effervescent tablets, unit dose vials of liquid
potassium, and powdered potassium in unit-dose packets,
containing not more than 50 milliequivalents of potassium per
unit dose
• Sodium fluoride drug preparations including liquid and tablet
forms, containing not more than 110 milligrams of sodium
fluoride (the equivalent of 50 mg of elemental fluoride) per
package or not more than a concentration of 0.5 percent
elemental fluoride on a weight-to-volume basis for liquids or a
weight-to-weight basis for non-liquids and containing no other
substances subject to this Sec. 1700.14(a)(10)
• Betamethasone tablets packaged in manufacturers' dispenser
packages, containing no more than 12.6 milligrams
• Pancrelipase preparations in tablet, capsule, or powder form and
containing no other substances subject to this Sec.
Rx Drugs Exempted from PPPA
• Prednisone in tablet form, when dispensed in packages
containing no more than 105 mg of the drug, and containing
no other substances subject to this Sec. 1700.14(a)(10)
• Mebendazole in tablet form in packages containing not
more than 600 mg of the drug, and containing no other
substance subject to the provisions of this section
• Methylprednisolone in tablet form in packages containing
not more than 84 mg of the drug and containing no other
substance subject to the provisions of this section
• Colestipol in powder form in packages containing not more
than 5 grams of the drug and containing no other substance
subject to the provisions of this section
• Erythromycin ethylsuccinate tablets in packages containing
no more than the equivalent of 16 grams erythromycin.
Rx Drugs Exempted from PPPA
• Conjugated Estrogens Tablets, U.S.P., when dispensed in mnemonic
packages containing not more than 32.0 mg of the drug and containing
no other substances subject to this Sec. 1700.14(a)(10)
• Norethindrone Acetate Tablets, U.S.P., when dispensed in mnemonic
packages containing not more than 50 mg of the drug and containing no
other substances subject to this Sec. 1700.14(a)(10)
• Medroxyprogesterone acetate tablets
• Sacrosidase (sucrase) preparations in a solution of glycerol and water
• Hormone Replacement Therapy Products that rely solely upon the
activity of one or more progestogen or estrogen substances
• Colesevelam hydrochloride in powder form in packages containing not
more than 3.75 grams of the drug
• Sevelamer carbonate in powder form in packages containing not more
than 2.4 grams of the drug.
Rx Drugs Exempted from PPPA
• Acetaminophen. Preparations for human use in a dosage
form intended for oral administration and containing in a
single package a total of more than one gram
acetaminophen shall be packaged in accordance with the
provisions of Sec. 1700.15 (a), (b), and (c), except the
• Effervescent tablets or granules containing acetaminophen,
provided the dry tablet or granules contain less than 15 percent
acetaminophen, the tablet or granules have an oral LD-50 of 5
grams or greater per kilogram of body weight, and the tablet or
granules contain no other substance subject to the provisions of
this section
• Unflavored acetaminophen-containing preparations in powder form
(other than those intended for pediatric use) that are packaged in
unit doses providing not more than 13 grains of acetaminophen per
unit dose and that contain no other substance subject to this act.
Rx Drugs Exempted from PPPA
• Aspirin. Any aspirin-containing preparation for human
use in a dosage form intended for oral administration
shall be packaged in accordance with the provisions of
§1700.15 (a), (b), and (c), except the following:
• Effervescent tablets containing aspirin, other than those
intended for pediatric use, provided the dry tablet contains
not more than 15 percent aspirin and has an oral LD-50 in rats
of 5 grams or more per kilogram of body weight
• Unflavored aspirin-containing preparations in powder form
(other than those intended for pediatric use) that are
packaged in unit doses providing not more than 15.4 grains of
aspirin per unit dose and that contain no other substance
subject to the provisions of this section.
Product Tampering
• Federal Anti-Tampering Act of 1982
• Result of Tylenol Scare
• Tampering: act as improper interference with the product
for the purpose of making objectionable/unauthorized
• Tamper-resistant package: “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.”
• Directions to consumer on how to determine if tampered
• Exceptions: dermatologics, dentrifice, insulin, lozenges
• Products cannot have “tamper-proof” packaging
Pharmacy Compounding
• Pharmacies compounding for their patients pursuant to
prescription are exempt from FDCA manufacturing provisions
as long as they do not manufacturer, prepare, compound or
process drugs/devices for sale other than in the regular course
of their business
• FDA 1992 compliance guide
• Published by FDA over concern that some pharmacies were crossing
the line from compounding to manufacturing and were not
compounding properly
• FDAMA (§ 503A) 1997
• Defined compounding and delineated nine activities that might cross
the line from compounding to manufacturing; added other
requirements regarding compounding
• Stripped FDA of authority to consider compounded drugs as “new
Compounding Quality Act of 2013
• Passed as part of Drug Quality and Security Act in
response to New England Compounding Center
• FDA expects BoP to conduct oversight and
regulation of pharmacy compounding
• Allows compounders of sterile products to
voluntarily register as “outsourcing facilities.”
Products exempt from misbranding provisions
Compounding FDCA 503A
• Defines compounding: “combining, admixing, mixing,
diluting, pooling, reconstituting, or otherwise altering a
drug or bulk drug substance to create a drug”
• Exempts a pharmacy from misbranding/CGMP
requirements if:
Individual patient based on valid prescription
“limited quantity” if prepared in anticipation of receiving Rx
Not a copy of commercially available product
Compounded in compliance with USP
Pharmacy does not distribute >5% of total prescriptions
dispensed or distributed without a MOU between the state,
FDA, and pharmacy
Rx Requirements for 503A
• Prohibits pharmacies from compounding for “office
• “Limited quantity”:
• History of pharmacist receiving rx’s for drug
• Established relationship between PharmD and MD
• Pharmacy holds no more than 30-day supply of drug
product to fill prescriptions
• The 30-day supply is based on number of valid rx’s for
legitimate patients in a 30-day period, over the past year
Compounding 503A - Review
• The drug compounded is for an identified individual patient
based on the receipt of a valid prescription order, or a
notation, approved by the prescribing practitioner, on the
prescription order that a compounded product is necessary
for the identified patient, and
• The compounding of the drug is performed by a licensed
pharmacist in a state licensed pharmacy or a federal facility,
or by a licensed physician or other licensed practitioner
authorized under state law to prescribe drugs or by a
licensed pharmacist or licensed physician in limited
quantities before the receipt of a valid prescription based
upon the past history and established relationship
between the pharmacist, physician and patient
503A: https://www.fda.gov/media/98973/download
503B: https://www.fda.gov/media/98964/download
Insanitary conditions: https://www.fda.gov/media/124948/download
Compounding FDCA 503B – Sterile
Allows compounders to become an “outsourcing facility”
• Registration
• Compliance with GMP’s
• FDA inspections
• Report adverse events
• No FDA preapproval process, or labeling for adequate
directions for use
• If they do not become an outsourcing facility, they will
be considered manufacturers if they compound outside
of normal business
USP 800 – Hazardous Drugs
• Effective December 1, 2019
• Intended to protect healthcare workers, environment, and
• NIOSH defines hazardous drug list
• Three categories:
• Antineoplastics
• Non-antineoplastics
• Reproductive effects
• Assess risk for each product
NIOSH [2016]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. By Connor TH, MacKenzie BA, DeBord DG, Trout
DB, O’Callaghan JP. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for
Occupational Safety and Health, DHHS (NIOSH) Publication Number 2016-161 (Supersedes 2014-138). https://www.cdc.gov/niosh/docs/2016161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB2016161
Risk Assessment: http://www.hoparx.org/images/hopa/resource-library/professional-tools/USP800_Assessment_of_Risk_Form.pdf
Pharmacy Compounding vs Manufacturing
• Pharmacies are exempt from registering as manufacturers if they do not
manufacturer, prepare, propagate, compound, or process drugs or
devices for sale other than in the regular course of their business of
dispensing or selling drugs or devices at retail
• Generally state law determines whether a pharmacy falls within this
definition. A pharmacy that compounds only in response to legitimate
prescriptions issued by authorized prescribers would not need to
register as a manufacturer
• A pharmacy may not advertise or promote a particular drug that it
compounds, but it may advertise and promote the compounding service
• A pharmacy that repackages OTC products or in any way changes the
container, wrapper, labeling of these products for resale must register as
a manufacturer
• A pharmacy that is in the business of repackaging prescription drug
products for sale to other health care providers must register as a
Current Good Manufacturing Practices
• GMP is a set of regulations that specify the
minimum standards required to manufacturer
pharmaceutical products in the United States
• A manufacturer must be registered with the FDA
and must describe is manufacturing and production
processes as part of the NDA process
Off-Label Uses of Approved Drugs
• Once a drug has been approved by the FDA and introduced into market,
health professional may find new therapeutic uses of the drug that have
not been approved by the FDA and are not included in the drug’s
product insert
• An authorized prescriber may legally prescribe off-label uses of the FDAapproved drugs, and a pharmacist may legally dispense them, subject to
their professional judgment
• Before dispensing a drug for an off-label use, a pharmacist should use
professional judgment in determining the risk to the patient, including:
• If there is no unreasonable risk to the patient, the pharmacist should dispense
• If there is an unreasonable risk of harm to the patient, the pharmacist should
confirm with the prescriber that the prescription is the proper drug and dosage
• If there is significant risk of harm to the patient, the pharmacist may ask the
prescriber to justify the prescription
• Manufacturers cannot advertise off-label uses of an approved drug to
consumers. However, manufacturers may distribute peer-reviewed
research papers that describe off-label uses of their drug
Drugs and International Commerce
• Exportation: Shipment of drug products to a foreign
• Acceptable/legal if done by manufacturer/licensed
• Importation: A drug product is being brought into the
U.S. for distribution
• Illegal unless manufacturer approved by FDA
• Personal Use Exception (Canada, controlled substances)
• Re-Importation: Drug product manufactured in U.S.
with FDA-approved labeling, shipped to a foreign
country, and then imported back into the U.S.
• Illegal, unless by original manufacturer or for emergency use
Importation for Personal Use
FDA has allowed personal importation of small amount of drugs if:
• Product is not for treatment of a serious condition and there is no
known significant health risk (Over the Counter)
• Product is for the treatment of a serious condition (Rx product)
• The product is for a serious condition for which effective
treatment may not be available domestically either through
commercial or clinical means
• There is no known commercialization or promotion of the
product to persons residing in the U.S
• The product does not represent an unreasonable risk
• The consumer affirms in writing that the product is for personal
• The quantity is not more than a three month supply and either:
• Provides the name and address of the doctor licensed in the U.S.
responsible for treatment with the product, or
• Provides evidence that the product is for the continuation of a
treatment begun in a foreign country
Canadian Personal Use Exemption
• Applies to individuals transporting drugs obtained
in Canada into the US
• FDA-approved prescription drugs
• On their person
• In a quantity not to exceed a 90- day supply
• That is not a controlled substance or a biological
Personal Use Exemption – Controlled
Any individual who has in his/her possession a controlled substance listed
in Schedules II, III, IV or V, which he/she has lawfully obtained for his/her
personal medical use, or for administration to an animal accompanying
him/her, may enter or depart the US with such substance providing the
following conditions are met:
• The controlled substance is in its original container in which it was
dispensed and the individual declares it in Customs and Border
Protection stating:
• It is for personal use (or for an animal accompanying him/her) and
• The trade or chemical name and symbol designating the Schedule
appears on the label, or if the name does not appear on the label, the
name and address of the pharmacy or practitioner who dispensed the
• The prescription number
• Does not exceed total 50 units
• A US resident may import into the US no more than 50 dosage units
combined for all such controlled substances in the individual’s
possession that were obtained abroad for personal medical use
Prescription Drug Samples
• A drug sample is not intended to be sold. It is usually
intended to acquaint a prescriber with a drug product by
providing several doses for a short-term or initial therapy. It
is illegal for a retail pharmacy to obtain, possess, or
distribute drug samples.
• Institutional pharmacy practice sites may possess drug
samples under specific conditions. Manufacturer
representatives can distribute drug samples to license
practitioners or to a hospital if:
• Manufacturer must receive from the practitioner a written request
signed by the practitioner before delivery of the sample
• Manufacturer must verify with the state that the practitioner is
licensed under state law to prescribe the drug product
• A receipt must be signed by the recipient when the drug is
• The receipt must be returned to the manufacturer
• Required inventories must be kept
• Alcohol = 95% ethyl alcohol
• Proof = two times the % of ethyl alcohol
• Rubbing alcohol = 70% denatured ethyl alcohol
• Isopropyl rubbing alcohol = normally sold in
pharmacies, and indicate % concentration
Use of Alcohol in Pharmacy Practice
• Tax-paid alcohol
Used in compounding in community pharmacies
Used in any beverage purpose
Laboratory testing for private outpatients of physicians
Obtainable from outlets that sell liquor at retail
• Tax-free alcohol (190 proof ethyl alcohol)
• Available to hospitals for medicinal, mechanical, and scientific
purposes and in treatment of patients. May be used only for
• Educational institutions for scientific/mechanical purposes
• Laboratories for scientific research
• Non-profit/Charity clinics may use for outpatients if they do
not charge.
Product Recalls
• FDAAA established FDA authority to order drug recalls
for certain products but not drugs.
• Three classes of recalls:
• Class I: reasonable probability that the product will cause
serious adverse events/death
• Class II: may cause temporary or medically reversible adverse
health consequences, but probability is low for serious events
• Class III: apply to products that are not likely to cause adverse
health consequences
• Manufacturers responsible for notifying seller and
seller for notifying consumers if necessary
• Pharmacists responsible for knowing of product recalls
• “URGENT: DRUG RECALL” notification from wholesalers
OBRA ‘90: Overview
• First federal law directly regulating pharmacy
practice standards
• Primary goal to save money
• Adopts the “pharmaceutical care” or “pharmacist
care” model that pharmacy developed for itself
• Only applies to new Medicaid prescriptions, but the
states adopted it for all prescriptions
OBRA ‘90: Basic Framework
• Rebates
• Requires manufacturers to provide drug products to the Medicaid
program at their “best price”
• “Best price” is the lowest price at which they sell the product to any
• Accomplished by requiring manufacturer to rebate to the state the
difference between the average manufacturer’s price and the “best
• Demonstration projects
• OBRA funded demonstration projects to evaluate whether the DUR
requirements would result in improved patient care and decreased
• Establishes two types of drug utilization review (DUR)
• Retrospective review
• Prospective DUR
Retrospective DUR
• Each state must establish a DUR board composed
of physicians and pharmacists to oversee
retrospective DUR
• Board reviews medication use data and compares
to target criteria
• Board has authority to recommend and establish
educational programs for providers who are not
meeting target criteria
Prospective DUR
• Provides opportunity to evaluate the prescribed
drug therapy before the Rx is dispensed
• This occurs in the pharmacy when the pharmacist is
evaluating the patient’s drug therapy and reviewing
all information the pharmacist has about the
• Patient counseling by the pharmacist
• DUR board can examine data generated from proDUR to determine if drug use problems are being
resolved or continuing
Components of Pro-DUR
• Patient profile
• Requires pharmacy to obtain, record, and maintain a
record of specified information about the patient
• Review of the patient profile prior to dispensing is
critical to effective screening and counseling
• Screening
• Pharmacists must detect potential drug use problems
before Rx is dispensed
• OBRA lists seven general categories of potential
problems which should be screened
• Computer software does not replace the professional
judgment of a pharmacist
Components of Pro-DUR
The state plan shall provide for review of drug therapy
before each prescription is filled or delivered to an
individual receiving benefits under this subchapter,
typically at the point-of-sale or point of distribution. The
review shall include the screening for potential drug
therapy problems due to therapeutic duplication, drugdisease contraindications, drug-drug interactions
(including serious interactions with nonprescription or
over-the-counter drugs), incorrect drug dosage or
duration of treatment, drug-allergy interactions and
clinical abuse/misuse.
42 U.S.C §1396r-8(g)(2)(A)(i)
Components of Pro-DUR
• Counseling
• Requires an “offer to counsel” patient or caregiver
• Lists several points of information counseling could include,
but allows pharmacist to determine the content of the
counseling based on professional judgment
• Meaning of phrase “common severe side effect” generally
believed to mean common or severe
• Offer to counsel may be made by ancillary personnel or
other means in some states, while some states require
• Patient has the right to waive counseling
Health Information Portability and
Accountability Act (HIPAA)
• HIPAA protects a patient’s private health information, defined as
protected health information (PHI), and imposes penalties on
covered entities that make unauthorized disclosures of PHI.
Covered entities include health plans, health care clearing houses,
and health care providers that conduct financial or administrative
transactions electronically
• A pharmacy is subject to HIPPA. Privacy rules protect a patient’s
rights to access their health records, maintain confidentiality of
PHI, and authorize its disclosure. The privacy rules also control
how, when, and to whom PHI may be disclosed without patient
authorization. The security rules protect the confidentiality,
integrity, and availability of electronic health information.
• The privacy rules cover prescriptions, patient record systems,
patient prescription profiles, recorded pharmacist comments
relevant to the patient therapy, and payment records.
• Any healthcare provider that submits electronic
claims must follow
• Four components of healthcare info
• Uniform electronic transaction/code sets
• Increases efficiency in billing
• Enforced by Centers for Medicare and Medicaid Services (CMS)
• National Provider identified numbers (NPI):
• Standardization of national ID numbers for all providers
• Security: confidentiality, availability, integrity of patient’s
• Privacy: protects patient’s private health information
• Privacy of patient’s health information: Protected
Health Information (PHI)
• Enforced by the Office of Civil Rights in HHS
• Includes any health information that could be
identified with a particular patient
• May only disclose PHI for treatment, payment, or
health care operations (TPO) relationship
• Must disclose to the patient if the patient requests
• Pharmacies must develop policies and procedures
for implementing HIPAA privacy standards
• Must provide a patient with one Notice of Privacy
• How the pharmacy uses the patient’s information/legal
• The statement must include the patient’s rights,
name/telephone # of the person who the patient may
• Pharmacies must train employees on HIPAA
requirements and document the training
Conscientious Objection
• Refers to whether a pharmacist has a right to refuse
to dispense prescriptions when a moral or religious
objection exists
• States have passed laws or regulations addressing this
• Courts have held that a pharmacist cannot obstruct a
patient’s legal right to receive medications, but that
state regulations requiring pharmacists to dispense
violate first amendment rights
• https://www.cnn.com/2018/06/25/health/arizonaprescription-walgreens-miscarriage/index.html
Adulteration vs. Misbranding
• Composition of a
product or facility
where the product is
• Labeling or label of a
• Adulteration provisions focus on both the facility
and the product. A pure drug may be considered
adulterated on the basis of the facility
• How can a pharmacist adulterate a drug?
A product is adulterated if it contains:
• Any filthy, putrid, or decomposed substance
• Prepared, packaged, or held under unsanitary conditions where it may have
been contaminated
• Manufactured under conditions that do not meet GMP standards
• Contains an unapproved color additive
• Contains a drug recognized in official compendia, but its strength, purity, or
quality is below the official standards, unless plainly stated on the label
• Container is composed of a poisonous or deleterious substance that may leach
into the product contents
• Contains a drug not recognized in official compendia, but its strength, quality, or
purity is lower than listed on the label
• Contains any ingredient as a substitute for the active drug
• Failure to manufacture a product in a tamper-resistant container when required
by law is adulteration, and also misbranding
• Focuses on representations made by the manufacturer
on the label/labeling
• FDA has to approve the exact wording on a
label/labeling as a part of the premarket approval
• Must include name or location of manufacturer
• Must contain a precautionary statement for a drug that
is subject to deterioration
• Must have accurate statement of the quantity of the
contents in terms of weight, measure, or numerical
• Must include all advertisements and other descriptive
material required for prescription drugs (information
for use, typically in the form of package insert)
• Labeling must not be false or misleading
• Labeling must include a listing of active ingredients and
quantity and listing of inactive ingredients in alpha order.
• Labeling must contain “adequate directions for use” and
“adequate warnings against use” by children and others for
whom use might be dangerous.
• If drug cannot be labeled with “adequate directions for use,”
it must contain “adequate information for use.”
• It is misbranding if a drug imitates another drug (sale of one
drug under the name of a different drug)
• Must contain “Rx only” if the drug is available only by
prescription or legend (“Caution: Federal law prohibits
dispensing without prescription”)
Misbranded if:
• The container is misleading
• Manufactured, prepared, compounded not duly
• Not manufactured using tamper-resistant or
tamper-evident packaging (OTC only)
• A pharmacy dispenses a prescription-only drug
without a legal prescription or an unauthorized
Misbranded or Adulterated?
• Claims to be a drug that
which is not packed and
labeled as in the
• The drug/container is
made to be misleading
• Imitation of another drug
• Offered for sale under a
different name
• The drug has been mixed
or packed with a drug so
to reduce its
• Substituted wholly or in
part for another drug
Regulation of Advertising
• FDA regulates advertising of prescription drug
• FTC regulates advertising of non-prescription drug
• FDA is in charge of the approval process for drug
development, whether it be OTC or prescription
Email me if you have any questions studying!
[email protected]