pharm law and ethics

1914 Harrison Narcotic Act

1. This act established a record keeping requirement for the receipt and

dispensing of opium or coca leaf products.

2. A tax was also assessed on the dispensing of these products.

3. Physicians could prescribe these products for legitimate treatment of patients

other than drug addicts.

4. The possession of narcotics without a prescription became illegal.

Federal Food, Drug, and Cosmetic Act of 1938

A. Scope and Purpose

1. The FDA has the primary responsibility of enforcing the FD&C Act

2. The Sulfanilamide Disaster led to the Act’s passage people sick from the order

3. Originally, only required:

a. Drugs to be proven safe not efficacious

b. Directions for Use

c. Adequate Warnings

4. Today, designed to Protect the Public Health by requiring:

a. Safe, effective, and properly labeled drugs

b. Safe and properly labeled food and cosmetic preparations

c. Current Good Manufacturing Practices (CGMP) for certain entities

like manufacturers and 503(b) outsourcing compounding pharmacies

d. Prescription drugs dispensed to an individual only pursuant to a

prescription or administered directly by a physician or other

authorized prescriber

e. Drug prescriptions be refilled only as authorized

f. Specific labeling for both prescription and nonprescription drugs

g. Dispensing a drug for distribution in violation of the Act’s labeling

requirements is misbranding

h. Drugs containing filthy, putrid, and decomposed substances and drugs

packed and held under unsanitary conditions be deemed adulterated

i. The FDA is authorized to perform limited inspections of pharmacies

in certain circumstances

j. Manufacturers or repackagers of drugs must register with the FDA

The FD&C Act began the approval process for new drugs

a. The process requires a New Drug Application (NDA)

b. The 1938 Act provided a “grandfather clause” exempting certain

drugs on the market prior to the act.

(1) Few exist on the market today

(2) The majority of those that do exist have obtained approval via

an NDA or an Abbreviated New Drug Application (ANDA)

1951 Durham-Humphrey Amendment

SAFTEY

1. Defined Prescription Drugs “Legend Drugs” to distinguish from OTCs authorization

2. Restricted the sale of such drugs to prescription by a licensed practitioner

3. Authorized refills on prescriptions

1962 Kefauver-Harris Amendment

SAFTEY AND EFFICACY

1. Triggered by the Thalidomide Disaster

2. Increase scrutiny on safety

3. First to require evidence of effectiveness before marketing

4. Defines Current Good Manufacturing Practices (CGMP)

a. Minimum requirements for the methods, facilities or controls used in

manufacture, processing, packaging, or holding of a drug product.

b. Apply to Manufactures and only certain pharmacies engaged in:

(1) 503(b) Outsourcing Compounding Pharmacy

(2) Hospital Repackaging

(3) Pharmacy Chain Distribution Center that Repackages

5. Added informed consent requirement

6. Prescription drug advertising is regulated by the FDA. Nonprescription

(OTC) advertising is regulated by the Federal Trade Commission (FTC).

1976 Medical Device Ammendment

Definition of Device

(1) Device is defined as an instrument, apparatus, implant, etc.

(2) No Chemical Action

b. Three Classes

(1) Class I – Least Regulation

(a) Needles,

(b) Scissors,

(c) Stethoscopes, and

(d) Toothbrushes

(2) Class II – Must meet performance standards

(a) Insulin Syringes

(b) Electric Heating Pads

(c) Thermometers

(3) Class III – Must have Premarket Approval because they are

life supporting or life sustaining

(a) Pacemakers;

(b) Replacement Heart Valves

1984 The Drug Price Competition and Patent Term Restoration Act

a. Extended the ANDA to generics, thereby making generic approval

easier by:

(1) Not requiring proof of safety and efficacy through clinical

trials

(2) Only need to show the drug is bioavailable and bioequivalent

to the innovator drug

b. Extended Patent Life for Brand Drugs

(1) A patent is the grant of a property right to the inventor issued

by the Patent and Trademark Office of the United States.

(2) The life of the patent is 20 years from the date of first filing of

the patent application.

(3) Because manufacturers usually file for patent protection prior

to product marketing, the effective term of the patent is less

than 20 years.

(4) The Drug Price Competition and Patent Term Restoration Act

of 1984 (P.L. 98-417) provides manufacturers with an

opportunity to extend the life of the patent for an additional 5

years.

(5) With the 5-year extension, the total patent life of the drug

patent cannot exceed 14 years from the approval date of the

drug produc

1987 The Prescription Drug Marketing Act (PDMA)

a. Bans the Sale of Drug Samples

b. Works to reduce health risks from Diversion of Prescription Drugs

c. States License Wholesale Distribution

Orphan drug act

a. Encourages development of products used for rare diseases or

conditions

Drug efficacy study implementation program DESI

a. Tests the effectiveness of drugs approved from 1938-1962

The Drug Quality and Security Act of 2013 (DQSA) why passed

In 2012, a number of patients died or became ill from fungal

meningitis. Investigation revealed they were caused by contaminated

compounded products prepared by New England Compounding

Center. This focused attention on some pharmacies that were

engaging in large-scale, non-patient-specific preparation of sterile

products.

DQSA contains two parts:

The Drug Supply Chain Security Act, which helps track

products throughout distribution using a database

(2) The Compounding Quality Act, which describes the

conditions under which certain compounded human drug

products are entitled to exemptions from the Food, Drug and

Cosmetic Act (FDCA), including exemptions from:

(a) Compliance with CGMP;

(b) FDA required labeling; and

(c) FDA approval prior to marketing.

The Compounding Quality Act identifies two types of compounders,

who do not need to register as manufactures:

(1) 503A Traditional Compounding Pharmacies

(2) 503B Outsourcing Facilities

The following describes the conditions for a traditional compounding

pharmacy (Section 503A) to avoid being construed as a manufacturer

for purposes of FDA registration and for the compounded product to

remain exempt from the FDA’s CGMP, Labeling, and Approval

requirements:

(1) Compounding (sterile and nonsterile) can occur subsequent to

a prescription order only. Pharmacies:

(a) Cannot compound large quantities in advance

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e. (b) Cannot compound drugs that were withdrawn from

market due to safety issues (e.g. Vioxx)

(c) Cannot sell compounded products to anyone other than

the patient. Cannot compound for “office use”

(d) Cannot compound copies of commercially available

drugs

(e) To be considered a compounding activity, a proper

PATIENT – PRESCRIBER – PHARMACIST

relationship must exist

(f) Must comply with United States Pharmacopeia

standards

(g) A licensed practitioner must complete the

compoundin

A 503B outsourcing facility must comply with the FDA’s CGMP, but

its products may remain exempt from the FDA’s Labeling and

Approval requirements.

503B Outsourcing Facilities:

(a) Will be inspected by FDA according to a risk-based

schedule, and

(b) Must meet certain other conditions, such as reporting

adverse events and providing FDA with certain

information about the products they compound.

(c) No prescription is required and “office use” of

compounded products is allowed.

(d) A pharmacist must supervise the compounding.

(e) No limits are placed on the amounts that can be

compounded, but distribution to a wholesaler is

prohibited

(f) May choose to register with the FDA

Definition of a Drug

1. The FD&C defines drUg as

A.Articles recognized in the official United States Pharmacopeia or

other listed reference;

b. Articles intended for use in the diagnosis, cure, mitigation, treatment,

or prevention of disease, in man or other animals (this is also known

as the therapeutic or disease claim);

c. Articles (other than food) intended to affect the structure of any

function of the body of man or other animals;

Intended use

The FDA looks at various documentation from the manufacturer to

determine whether it will regulate a product as a drug:

(2) Labeling for the product, websites, promotional pamphlets,

and other marketing materials.

The intent of the manufacturer or distributor is key to

determining whether a particular item is a drug.

Legend Drugs

Defined as a drug intended for use by man which because of its

toxicity or other potential harmful effect, or other method of use, is

not safe for use except under the supervision of a practitioner licensed

by law to administer such drug.

Bulk prescription containers must include

(1) The name and address of the manufacturer, packer, or distributor

(2) The established name of the drug product

(3) Ingredient Information

(4) If for other than oral use, the names of all inactive ingredients

and route of administration

(5) The quantity in terms of weight or measure

(6) The net quantity of the container

(7) A statement of the recommended or usual dosage, or reference to the package insert

(8) “Rx only” or “Caution, federal law prohibits dispensing without a prescription”

(9) Identifying Lot or Control number

(10) Directions for the pharmacist regarding container usage

(11) The expiration date

(12) Adequate information for use

New drug

Defined as any drug that has not received general recognition by medical experts as being both safe and effective for the intended use.

OTC Drug

a. Defined as safe and effective for the general public

b. When considering OTC approval, the FDA expects the drug will

generally have these characteristics:

(1) It can be adequately labeled so the consumer can self-

diagnose, self-treat, and self-manage the condition being

treated;

(2) No healthcare practitioner is needed for the safe and effective

us of the product;

(3) The safety margin adequately ensures that the benefits of OTC

availability outweigh its risks;

(4) The drug has a low potential for misuse and abuse.

OTC labeling req

(1) Active Ingredients

(2) Purpose

(3) Use(s), Indications

(4) Warnings

(5) Directions

(6) Other Information

(7) Inactive Ingredients

d. Pregnancy and nursing labeling (21 CFR §210.63)

(1) All products intended for OTC systemic absorption, unlessexempt, shall contain in the Warning section the warning, “If pregnant or breast-feeding, ask a health professional before use.”

e. Over-the-counter labeling of sodium content (21 CFR §201.64)

(1) The labeling of OTC products intended for oral ingestion shall contain the sodium content per dosage unit if the sodium content of a single maximum recommended dose of the product is 5 mg or more.

f. Calcium labeling (21 CFR §201.70)

(1) The labeling of OTC products intended for oral ingestion shall contain the calcium content per dosage unit if the calcium content of a single maximum recommended dose of the product is 20 mg or more.

g. Magnesium labeling (21 CFR §201.71)

(1) The labeling of OTC products intended for oral ingestion shall contain the magnesium content per dosage unit if the magnesium content of a single maximum recommended dose of the product is 8 mg or more.

h. Potassium labeling (21 CFR §201.71)

(1) The labeling of OTC products intended for oral ingestion shall contain the potassium content per dosage unit if the potassium content of a single maximum recommended dose of the product is 5 mg or more.

a. A drug is adulterated if:

(1) It consists in whole or in part of any filthy, putrid, or

decomposed substance;

(2) It has been prepared, packed, or held under unsanitary

conditions;

(3) It is manufactured contrary to Good Manufacturing Practice

standards

(4) The container is made of poisonous or deleterious substances

that may leech into the contents

(5) It contains an unsafe color additive

(6) Its strength, purity, or quality varies from that which it purports

to be or is listed in the official compendial – May also be

misbranding

(7) It is a drug and any substance has been added to it to reduce its

quality or strength.

(8) PA includes the following:

(a) Exposure to fire, water, or extreme temperatures

A drug is misbranded if:

(1) Sold, dispensed, or distributed in violation of the labeling

requirements of the FD&C

(2) Its label is false or misleading

(3) It’s not labeled and packed according to compendial standards

(4) The package or drug is misleading in the way it is filled or

formed or is imitative of another drug

(5) The drug is subject to deterioration and the label does not bear

such a warning

(6) The drug/device is health-endangering if used in the manner

suggested by the labeling;

(7) It is not packaged in accordance with the Poison Prevention

Packaging Act (PPPA) of 1970

(8) Drugs dispensed via prescription if at any time prior to

dispensing the label of the drug failed to state at a minimum,

“Rx only”

(9) If a pharmacist sells a drug without a prescription or refills

without authorization.

Expiration dates

a.For non-sterile solid and liquid pharmaceutical products repackaged into unit-dose or single-unit containers, pharmacists must: affix a “beyond-use date” that is “one year or less”

2) unless stability data or the manufacturer’s labeling indicates

otherwise

b. For ordinary prescription vials the beyond-use date is not later than:

(1) The expiration date on the manufacturer’s container; or

(2) One year from the date the drug is dispensed, whichever is

earlier.

Dietary supplements

1. 2. 3. A product intended to supplement the diet, which contains any of the

following:

a. Vitamin;

b. Amino Acid

c. Mineral;

d. Herb;

e. Dietary Substance for use by man to supplement the diet by

increasing the dietary intake;

f. Concentrate, metabolite, constituent, extract or combination the

above.

The following structure/function claims are permissible for use with dietary

supplements:

a. Description of the role of the dietary supplement in affecting the

structure or function of the body. That is, “calcium supplement with

vitamin D for strong bones; helps maintain a healthy heart.”

b. Identification of the mechanism utilized by the dietary supplement to

maintain structure and function. That is, “fiber maintains bowel

regularity.”

c. Description of the benefit from consumption of the supplement. That

is, “helps body adapt and promote physical performance.”

d. Description of a benefit of a classic nutrient deficiency disease as long

as the prevalence of the disease in the United States is stated in the

claim.

If a dietary supplement label contains one of the permissible claims, the label

must include the following statement, “This statement has not been evaluated by the Food and Drug Administration. This product is not

intended to diagnose, treat, cure, or prevent any disease.”

4. Manufacturers must notify the FDA at least 75 days prior to marketing and

include in the notification the manufacturer’s basis for concluding that the

dietary supplement “will reasonably be expected to be safe.”

Cosmetics

1. The Food, Drug, and Cosmetic Act defines cosmetics as articles intending for

cleansing, beautifying, promoting attractiveness, or altering the appearance

without affecting the body’s structure or function.

2. Cosmetics that are drug products

a. Cosmetics that are intended to treat or prevent disease or alter a body

function are considered drug products.

b. The key in determining whether a product is a cosmetic or a drug-

cosmetic product is the products claim. Does the label claim that the

product will treat or prevent disease?

Homeopathic drug products and herbal products

1. Defined as “any drug labeled as being homeopathic which is listed in the

Homeopathic Pharmacopeia of the United States, an addendum to it, or its

supplements.”

2. Homeopathy is the practice of treating the syndromes and conditions which

constitute disease with remedies that have produced similar syndromes and

conditions in healthy subjects.

3. Homeopathic medicine stimulates the person’s natural defense system, helps

heal illness, and raises the general level of healt

Generics orange book

1. Single source products are drug products that are the only product approved

by the FDA for that active ingredient, dosage form, route of administration,

and strength.

2. Multisource drug products are drug products that are manufactured by several

manufacturers.

3. Pharmaceutical equivalence refers to drug products with the same active

ingredients, same dosage form, same route of administration, and identical in

strength or concentration. These products must meet the same compendia

standards for purity, quality, strength, and labeling.

COPYRIGHT ©2026 BY Robert A. Gallagher.

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333347710v12026

4. 5. 6. 7. 8. 9. Therapeutic equivalents are those products that are pharmaceutical

equivalents and bioequivalent. The FDA utilizes the following criteria to

determine if a drug product is a therapeutic equivalent:

a. Approved for safety and effectiveness

b. Pharmaceutical equivalent

c. Bioequivalent

d. Adequate labeling

e. Manufactured in compliance with Good Manufacturing Practices.

Bioavailability is the rate that the active ingredient of the drug product is

absorbed from the product and made available to the site of action.

Bioequivalent drug products are products that are pharmaceutically

equivalent that provide the same results of drug delivery with the same

pharmacokinetic properties.

Reference Listed Drug (RLD) is the standard against which all generic drug

products are compared. The RLD has filed a New Drug Application that has

been approved by the FDA. Upon expiration of the RLD patent, generic

manufacturers can file an Abbreviated New Drug Application for approval of

their generic product. All bioavailability is measured against the information

for the RLD product. The generic drug product must demonstrate that the

drug product provides the same results as the RLD product through

bioavailability studies.

Pharmaceutical Alternatives are drug products that contain the same

therapeutic moiety, but are different salts, esters, or complexes of that moiety,

or are different dosage forms or strengths. Orange Book – Approved drug

products with therapeutic equivalence evaluations

Multisource Drug Products equivalence Codes

a. A – products are considered to be therapeutically equivalent to other

pharmaceutically equivalent products. These products utilize the

designation of:

(1) AA – products in conventional dosage forms not presenting

bioequivalence problems

(2) AB – products with actual or potential bioequivalence problems that have been resolved in vivo or in vitro

b. B – products are not therapeutically equivalent. The problem usually is with the dosage forms not the active ingredients in the drug products.

c. See PA Generic Substitution Law, infra:

(1) AA and AB – Drug Products considered equivalent –Can Substitute in PA, unless it has a narrow therapeutic range – Coumadin and Lanoxin (NTI Drugs)

(2) B – Drug Products not substitutable.

Biological Product

a. Vaccines, Various Toxoids, skin test substances, blood and blood

products for transfusion

b. A manufacturer license issued by CBER (Center for Biologics

Evaluation and Research)

c. Biosimilars – Unique biological drugs from living organisms using

recombinant technology. Highly similar to the reference product.

Veterinary Products

1. Must gain approval by New Animal Drug Application (NADA)

2. If used in food producing animals then all edible products must be free of

unsafe residues

3. Flea Control Products

a. Topical – EPA regulation

b. Oral – FDA regulation

Before a new drug can be marketed, federal law requires submission and

approval and this process begins with:

A sponsor submitting information on an Investigation New Drug (IND)

approval which includes:

a. Name of drug

b. Composition

c. Methods of manufacturing

d. Quality Control

e. Preclinical nonhuman studies

f. Pharmacological, Pharmacokenetic, and toxicology studies

g. Outline of clinical studies proposed

no men

2. If the FDA does not reject the IND within 30 days of submission, clinical testing on humans may begin with:

a. Phase I – Small number of healthy individuals (20-80), to determine the pharmacology of the drug and its toxicology – Not Efficacy

b. Phase II – Limited number of people (100-300) who actually have the disease to determine efficacy

c. Phase III – Lager Scale of affected individuals (1000-3000)

(1) If results are favorable the company then submits an New

Drug Approval (NDA)

Post market

d. Phase IV – Performed after drug has been granted FDA approval to

monitor any reported serious side effects.

Expedited approval

. For Drugs used to treat serious life-threatening illnesses and that also provide

a meaningful therapeutic advantage over existing treatments.

Drug Recalls

A. Three Classes

Class I – Reasonable possibility that the use of or exposure to a product will

cause either serious adverse effects on health or death.

2. Class II – Use of or exposure to product may cause temporary or medically

reversible adverse effects on health or where the probability of serious adverse

effects on health is remote.

3. Class III – use of or exposure to product is not likely to cause adverse health

consequences.

Market withdrawal

1. Product removed from the market due to a minor violation is not subject to

FDA legal action

FDA Inspections

1. The inspection must:

a. Be conducted at a reasonable time

b. In a reasonable manner; and

c. Be reasonably limited.

2. The inspector needs to present

a. Credentials; and

b. Notice of Inspection

Approved Drugs may be used for unlabeled Indications

1. Unapproved medical devices may be used by a physician in Life Threatening

Situations, where:

a. no alternative is available, and

b. sufficient time to seek approval is not possible, but

c. must substantiate use at a later time.

2. Although discouraged by the FDA, prescribers may prescribe the drug for

these unofficial indications and pharmacies, using their professional

discretion, may dispense such prescriptions.

Investigational drugs

May be used in the general population provided that:

a. b. c. d. Treatment Protocol is submitted to the FDA

Serious or immediately life-threatening disease

No comparable or satisfactory alternative

The drug must be an approved investigational new drug being used in

a controlled clinical trial and the sponsor of the clinical trial is seeking

approval.

Tamper Evident Packaging

OTC’s must be packaged in a tamper evident container

a. One or more indicators or barriers to entry must exist to provide

evidence of tampering

b. The Packaging should be difficult to duplicate

c. Two-Piece hard gelatin capsules must be sealed with tamper-evident

technology

Child Resistant Packaging

1. Poison Prevention Packaging Act requires Child resistant caps on all legend

drugs

a. 80% under 5 years of age cannot open and 90% of adults can open

2. Physician or Patient (or head of household) may request non-child resistant

packaging

a. Request may be in writing or made orally

b. Several drug products are exempted from child-resistant packaging:

(1) Products in aerosol containers intended for inhalation therapy.

(8) Sublingual nitroglycerin tablets.

(9) Oral contraceptives cyclically administered in a manufacturer’s mnemonic (memory-aid) packages (e.g. Dial pak).

(13) Methylprednisolone tablets containing not more than 84 mg per package.

Some OTC products must comply with the PPPA’s child resistant

packaging:

(1) Loperamide

(2) Diphenhydramine

(3) Acetaminophen

(4) Mouthwashes

(5) NaproxeN

Tax-Free Alcohol

1. May be used for:

2. a. Scientific;

b. Medicinal and Mechanical Purposes; and

c. In the treatment of patients

May not be used for:

a. Beverages; or

b. Foods

Ipecac Syrup

1. Available for sale without a prescription provided that:

a. It is packaged in a quantity of 30 milliliters; and

b. Its label bears:

(1) A statement in red letters, “For Emergency use to cause

vomiting in poisoning. Before using, call physician, the

Poison Control Center, or hospital emergency room

immediately for advice.”

(2) A warning – “Warning – Keep out of reach of Children. Do

not use in unconscious persons. Ordinarily this drug should

not be used if strychnine, corrosives such as alkalies (lye) and

strong acids, or petroleum distillates such as kerosene,

gasoline, coal oil, fuel oil, paint thinner, or cleaning fluid have

been ingested.”

(3) Usual Dosage: 1 tablespoon (15 milliliters) in persons over 1

year of age.

United States Pharmacopeia Storage Temperature Guidelines

A. Temperature Ranges

1. Cold – not exceeding 8ºC (46ºF)

2. Cool –between 8 and 15ºC (46-59ºF)

3. Room temperature – temperature prevailing in work area

4. Controlled room temperature – maintained between 15 and 30ºC (58-86ºF)

5. Warm – between 30 and 40ºC (86-104ºF)

6. Excessive heat – above 40ºC (104ºF)

7. Refrigerator – maintained between 2 and 8ºC (36-46ºF)

8. Freezer – maintained between -20 and -10ºC (-4 and 14ºF)

9. Expired products should be removed from the operating stock in the

pharmacy to prevent dispensing of expired products.

USP 795: Nonsterile Compounding

1. Provides standards for compounding quality nonsterile preparations.

2. The chapter describes requirements for the compounding process, facilities,

equipment, components, documentation, quality controls and training.

3. General Chapter <795> also provides general guidelines for assigning

beyond-use dates to nonsterile preparations.

USP 797: Sterile Compounding

1. A national standard for the process, testing and verification of any

compounded sterile preparations.

2. It provides guidance on preventing microbial contamination and other

variances in compounded sterile products regardless of setting (for example,

hospitals, community pharmacies) and who is performing the compounding

(pharmacists, nurses, pharmacy technicians, or others).

3. USP Chapter <797> sets forth criteria for compounding the following sterile

products:

a. Preparations prepared according to the manufacturer’s labeled

instructions where the original contents may be exposed to

contamination.

b. Preparations containing nonsterile ingredients or nonsterile

components and devices that must be sterilized before administration.

c. Biologics, diagnostics, drugs, nutrients, and radiopharmaceuticals that

possess either of the above two characteristics and which may include

baths and soaks for live organs or tissue, implants, inhalations,

injections, powders for injection, irrigations, metered sprays, and

ophthalmic and otic preparations.

C. USP 800: Hazardous Drugs

. According to the National Institute for Occupational Safety and Health

(NIOSH), a hazardous drug exhibits one or more of the following six

characteristics in humans or animals:

a. Carcinogenicity

b. Teratogenicity or other developmental toxicity

c. Reproductive toxicity

d. Organ toxicity at low doses

e. Genotoxicity

2. Structure and toxicity profiles of new drugs that mimic existing drugs

determined hazardous by the above criteria

3. The standard applies to all healthcare personnel (i.e., physicians, nurses,

veterinarians, pharmacists and technicians) and all healthcare facilities where

hazardous drugs are handled or manipulated, including their storage and

distribution— with a goal of preventing and/or limiting exposure.

4. USP 800 is designed to complement both USP 795 (Nonsterile Preparations)

and USP 797 (Sterile Preparations).

5. There is no acceptable level of personnel exposure to Hazardous Drugs.

USP 800: Hazardous Drugs Personnel

a. Each entity must have a designated person who is qualified and

trained to be responsible for

(1) developing and implementing appropriate procedures;

(2) overseeing entity compliance with this chapter and other

applicable laws, regulations, and standards;

(3) ensuring competency of personnel; and

4) ensuring environmental control of the storage and

compounding areas.

b. All personnel who handle HDs are responsible for understanding the

fundamental practices and precautions and for continually evaluating

these procedures and the quality of final HDs to prevent harm to

patients, minimize exposure to personnel, and minimize

contamination of the work and patient-care environment.

Hazard drugs Facility design – No Positive Pressure Areas

a. Hazardous drugs shall not be stored, unpacked, compounded or

otherwise manipulated in an area that is positive pressure relative to

the surrounding areas, so hazardous drugs must be stored in negative

or normal/neutral pressure,

b. A laminar air flow workbench (LAFW) or compounding aseptic

isolator (CAI) shall not be used for the compounding of a hazardous

drugs.

c. All hazardous drug compounding shall be done in a separate area

designated for hazardous drug compounding.

Hazard drugs garb cleaning administering

8. Garb

a. b. Details for personal protective equipment are based on the function

being performed

Gloves, gowns, head, hair and sleeve covers, eye and face protection,

respiratory protection.

9. Cleaning

a. Deactivation and disinfection with an oxidizer, cleaning with a

germicidal detergent, and disinfection with sterile alcohol.

10. Administering

a. Closed-system drug-transfer devices should be used when

compounding and shall be used when administering.

USP 825 – Radiopharmaceuticals

USP 825 outlines the minimum standards for preparing,

compounding, dispensing, and repackaging sterile and nonsterile

radiopharmaceuticals for humans and animals.

EPA 2019 Disposal Rule

Impacts all pharmacies and healthcare facilities including those authorized to

distribute, sell, or dispense drugs:

a. Bans intentional disposal of hazardous waste pharmaceuticals via

toilets, sinks, drains

(1) E.g., flexible collodion, insulin, nasal sprays, scopolamine,

silver nitrate, witch hazel

(2) Exempts OTC nicotine gums, patches, and lozenges from

hazardous waste list

b. Creates two categories of pharmaceutical waste:

(1) potentially creditable waste (unused or un-administered and

unexpired less than 1 year past expiration date)

(2) non-creditable waste (removed from original container,

returned after pharmacy has received payment, more than 1

year past expiration, refused by patient after attempt to

administer, free samples, unused investigational drugs)

Bar code rule (21 CFR 201.25)

Requires bar coding, consisting of, at a minimum, the National Drug Code

(NDC) number, on certain products administered to patient in hospitals in an

effort to reduce medication errors. This rule applies to manufacturers,

repackers, relablers, and private label distributors of the following products:

a. Prescription drugs, except physician drug samples, allergenic extracts,

intrauterine devices, medical gases, radiopharmaceuticals, low density

form fill, and seal containers that are not packaged with an over wrap.

b. Biological products.

c. Over-the-counter products dispensed pursuant to an order and that are

commonly used in hospitals.

National Drug Code (NDC)

1. The NDC is a numbering system that aids in identifying a drug product.

Third party payers also employ NDC numbers to identify products for

reimbursement.

2. The NDC of a specific drug product contains ten or eleven digits. For

example, a number may be:

1 0 7 4 manufacturer

0 1 2 8 ID Of specific drug

0 4 ID of package

3. All prescription drugs marketed in the United States must have NDC

numbers.

4. The NDC number does not have to appear on individual dosage units nor is

there any federal law requiring that NDC numbers appear on prescription

labels.

Unit Dose Packaging and Labeling

The FDA has issued guidelines as to what information should be on each

unit-dose package. This information includes:

a. Generic name and trade name, if appropriate.

b. Quantity of active drug or drugs present (and the number of dosage

units, if more than one).

c. Name of the manufacturer, packer, or distributer.

d. The repackager’s lot number.

e. The expiration date.

f. Any other appropriate information concerning the specific drug (e.g.

special storage requirements).

Risk Evaluation and Mitigation Strategy (REMS)

A. REMS

1. A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program

that the FDA can require for certain medications with serious safety concerns

to help ensure the benefits of the medication outweigh its risks.

2. REMS are designed to reinforce medication use behaviors and actions that

support the safe use of that medication.

B. Mifepristone

1. FDA approved a REMS program for mifepristone. The REMS includes the

definition and requirements for a “certified” pharmacy.

2. Mifepristone (Mifeprex and one generic) and misoprostol (Cytotec) were approved by the FDA in 2000 to be used together for pregnancy termination. Now that the certification process has been approved, pharmacies can achieve certification by agreeing to a number of requirement

3. Mifepristone will become available at some FDA-certified retail pharmacies,

subject to state laws and regulations.

Pregnancy and Lactation Labeling

A. Pregnancy (including labor and delivery)

1. The FDA requires the removal of all pregnancy categories A, B, C, D, and X

from all drug product labeling.

2. If the drug has a scientifically acceptable pregnancy exposure registry for the

drug, the labeling must contain a specified statement about the registry.

3. Label must contain a summary of the drug’s risks during pregnancy.

4. If the drug is systemically absorbed the summary should include relevant

information to help health care providers and counsel women, including:

a. disease-associated maternal and/or embryo/fetal risk

b. dose adjustments during pregnancy and the postpartum period,

c. maternal adverse reactions,

d. fetal/neonatal adverse reactions, and/or

e. the effect of the drug on labor or delivery

B. Lactation

1. Label must contain a summary of the drug’s risks during lactation

2. If the drug is systemically absorbed the summary must include:

a. relevant information on the presence of the drug in human milk

b. effects of the drug on the breast-fed child,

c. effects of the drug on milk production

d. ways to minimize drug exposure in the breast-fed child

e. available interventions for monitoring or mitigating the adverse

reactions

f. pertinent information about the data that are the basis for the labeling.

g. a risk and benefit statement, unless breastfeeding is contraindicated

during drug therapy.

C. Females and males of Reproductive Potential

1. Labeling must include relevant information when:

a. pregnancy testing or contraception is required or recommended

before, during or after drug therapy; or

b. there are human or animal data that suggest drug-associated fertility

effects.

Background of the Controlled Substances Act

1. The Federal law that regulates controlled substances is the Controlled

Substance Act (CSA) of 1970.

2. The CSA was the first Federal legislation to control addicting drugs.

3. Congress Enacted the CSA under its authority to regulate commerce

4. The Courts have the final say in interpreting the CSA

Controlled substances

The CSA regulates all aspects of drugs which are subject to or have potential

for abuse or physical or psychological dependence.

2. CSA includes not only narcotic drugs but also non-narcotic stimulants,

depressants, and hallucinogenic drugs.

Drug Enforcement Administration (DEA)

1. Part of the U.S. Department of Justice and Federal Agency responsible for

administration and enforcement of CSA.

2. Implements regulations regarding controlled substances and regulated

chemicals (Title 21, Code of Federal Regulations (“CFR”) Part 1300 to end).

Method of Control Under the CSA

1. The DEA does not routinely inspect pharmacies for controlled substances

violations (state agencies do so).

2. Control is obtained through Registration of all persons in chain of possession.

a. Manufacturers

b. Distributors

c. Dispensers

(1) Prescribers

(2) Pharmacies

d. Importers

e. Exporters

Schedule I

Currently Accepted Medical use - none

Abuse potential - high

Severity of physical/psychological dependence - lack saftey

Examples: Heroin, Marijuana, LSD, Methaqualone, Gamma Hydroxybutyric Acid (GHB), Methcathinone, MDMA

Not Available for prescribing.
Investigational drugs.
*DEA does allow for research involving Schedule I substances. This Requires a separate registration as research facility.

Schedule II

Currently Accepted Medical use - yes

Abuse potential - high

Severity of physical/psychological dependence - severe

Examples: Hydrocodone (effective October 6, 2014), Morphine, Codeine, Cocaine, Oxycodone, Opium, Fentanyl, Methylphenidate, Methamphetamine

*Substances containing more than 90 milligrams/dosage unit or 18 mg/ml of Codeine are CII’s.

Schedule III

Currently Accepted Medical use - yes

Abuse potential - moderate

Severity of physical/psychological dependence - Low/Moderate (Physical) High (Psychological)

Examples: Anabolic Steroids, Tylenol w/Codeine, Butalbital, Chlorphentermine

Buprenorphine (Subutex) and Buprenorphine/Naloxone (Suboxone) previously dispensed in Special Treatment Centers only, but now any pharmacy may fill Prescriptions for these. Dronabinol (Marinol) is now a CIII in PA.
*Xyrem (the GHB-containing pharmaceutical product is a Schedule III.

Schedule IV

Currently Accepted Medical use - yes

Abuse potential - low

Severity of physical/psychological dependence - limited

Examples: Alprazolam, Chloral Hydrate, Diazepam, Lorazepam, Phentermine, Temazepam, Zolpidem; Carisoprodol (Soma); Tramadol (Ultram)

Schedule V

Currently Accepted Medical use - yes

Abuse potential - low

Severity of physical/psychological dependence - limited

Examples: Lomotil, Codeine Preparations (Anti-Tussive), Opium Preparations, etc. * 2mg/ml of Codeine is the cutoff for CV (Title 21, under Part 1308) (www.usdoj.gov/dea/pubs/scheduling.html)

Scheduling Issues

To avoid and “imminent hazard to public safety” the AG may place a drug into schedule I without consulting the Secretary of the HHS.

1. The DEA through the Attorney General Determines Classifications based on binding input regarding scientific matters from the Department of Health and Human Services.

2. Controlled Substance Analogs are treated as C-I’s or C-II’s and are similar to a controlled substance:

   1. In Chemical Structure;

   2. In CNS Effect; or

   3. In a person’s representation or intention of such effect.

3. Schedule II substances in suppository form become Schedule III substances.