Comprehensive FD&C Act and Drug Regulation Principles for Pharmacists

Today, what is the FD&C Act designed to ensure for drugs?

That drugs are safe, effective, and properly labeled; refills only as authorized; specific labeling for Rx and OTC; adherence to CGMP; and Rx-only dispensing.

Which federal agency primarily enforces the FD&C Act?

The Food and Drug Administration (FDA).

What does the FD&C Act require of manufacturers and repackagers regarding registration?

They must register with the FDA.

What is the 1938 Act's 'grandfather clause'?

It exempted certain pre-1938 drugs from the new approval process; few remain unapproved today.

What is the application required for approval of a new drug for interstate marketing?

A New Drug Application (NDA).

What is the Durham-Humphrey Amendment (1951) best known for?

It defined 'legend' (prescription) drugs, restricted them to prescription, and authorized refills.

What major change did the Kefauver-Harris Amendment (1962) introduce?

It required substantial evidence of effectiveness before marketing and strengthened safety scrutiny and CGMP.

Which federal agency regulates prescription drug advertising vs. OTC advertising?

FDA regulates prescription drug advertising; FTC regulates OTC advertising.

Under the Medical Device Amendments (1976), which devices require premarket approval?

Class III devices (life-supporting or sustaining), e.g., pacemakers, heart valves.

What did the Drug Price Competition and Patent Term Restoration Act of 1984 do for generics?

Created ANDA pathway—bioequivalence instead of full trials—and allowed patent extensions.

How long is a typical U.S. patent term and what's the cap on restored life under Hatch-Waxman?

Patent term is 20 years from filing; total post-approval life cannot exceed 14 years after FDA approval.

What did the Prescription Drug Marketing Act (PDMA) of 1987 prohibit regarding samples?

It banned the sale of prescription drug samples and curbed diversion.

What is the goal of the Drug Efficacy Study Implementation (DESI) program?

To assess effectiveness of drugs approved between 1938-1962.

Which event catalyzed the Drug Quality and Security Act (DQSA) of 2013?

The 2012 fungal meningitis outbreak linked to contaminated NECC compounded products.

What are the two major parts of DQSA?

Drug Supply Chain Security Act (product tracing) and Compounding Quality Act (503A and 503B).

Under 503A, when can traditional compounding pharmacies compound?

Only with a valid, patient-specific prescription; not for office use; must meet USP standards; not copies of available drugs.

Under 503B, what is an 'outsourcing facility'?

A facility supervised by a pharmacist that compounds sterile drugs without patient-specific prescriptions, follows FDA CGMP, and may compound for office use.

Define 'drug' under the FD&C Act.

Articles recognized in USP/NF; intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; or to affect body structure or function.

What does 'intended use' mean for FDA jurisdiction?

FDA reviews labeling, websites, and promotions to determine if an item is regulated as a drug.

What labeling must bulk prescription containers of legend drugs include (name 5 items)?

Manufacturer, drug name, ingredients, route, quantity/strength, net quantity, dosage info, 'Rx only', lot number, expiration, and directions.

Define 'new drug' per the FD&C Act.

Any drug not generally recognized by experts as safe and effective for labeled uses.

What are the core criteria for an OTC drug to be appropriate for self-use?

Adequate labeling for self-diagnosis/treatment; safe without supervision; favorable risk-benefit; low misuse potential.

List the standardized OTC 'Drug Facts' headings.

Active ingredients, Purpose, Uses, Warnings, Directions, Other information, Inactive ingredients.

What pregnancy/lactation warning is required on OTCs intended for systemic absorption?

"If pregnant or breast-feeding, ask a health professional before use."

When must OTC labels list sodium, calcium, magnesium, or potassium content per dose?

Sodium ≥5 mg; Calcium ≥20 mg; Magnesium ≥8 mg; Potassium ≥5 mg in one maximum dose.

Give two examples of drug adulteration.

Prepared or held under unsanitary conditions; strength/quality differs from compendial standards; contains unsafe additive; container leaches substance.

Give two examples of misbranding.

Label false or misleading; missing 'Rx only'; not packaged correctly; imitation; lacks required warnings or directions.

What is the general beyond-use date (BUD) rule for non-sterile solids/liquids repackaged into unit dose?

One year or less from repackaging, unless stability data shows otherwise.

What is the default BUD for a typical prescription vial?

No later than manufacturer's expiration or one year from dispensing, whichever is earlier.

Define 'dietary supplement' under DSHEA.

Product to supplement diet with vitamin, mineral, herb, amino acid, or similar substance.

What disclaimer must accompany dietary supplement structure/function claims?

"This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease."

How far in advance must a manufacturer notify FDA before marketing a new dietary supplement with claims?

At least 75 days prior, with safety basis.

When is a cosmetic also a 'drug-cosmetic' product?

When intended to treat or prevent disease or affect structure/function (based on claims).

Define 'homeopathic drug product.'

Any drug labeled as homeopathic and listed in the Homeopathic Pharmacopeia of the United States.

Differentiate pharmaceutical equivalence vs. therapeutic equivalence.

Pharmaceutical equivalence: same active, dosage form, route, strength. Therapeutic equivalence: plus bioequivalence and same effect.

Which Orange Book codes indicate products that are substitutable in PA?

AA or AB; B codes are not; NTI drugs often excluded.

What is a Reference Listed Drug (RLD)?

The innovator drug to which generics are compared for bioequivalence.

How are biological products regulated differently from small-molecule drugs?

Require biologics licensure (CBER); biosimilars must be highly similar with no meaningful differences.

What premarket step begins human testing for a new drug?

Filing an Investigational New Drug (IND) application with preclinical data and protocols.

Summarize clinical trial phases I-IV.

Phase I: PK/safety (20-80 healthy); Phase II: efficacy (100-300 patients); Phase III: large-scale (1,000-3,000); Phase IV: postmarketing.

When is 'expedited approval' available?

For drugs treating serious/life-threatening illnesses offering meaningful therapeutic advantage.

Define FDA recall Classes I-III.

Class I: serious/death risk; Class II: temporary/reversible harm; Class III: not likely harmful.

What is a 'market withdrawal'?

Removal for minor violation not subject to legal action (e.g., labeling fix).

What must an FDA inspection be?

At a reasonable time, in a reasonable manner, and reasonably limited.

May practitioners prescribe FDA-approved drugs for unlabeled uses?

Yes, off-label prescribing is permitted using professional judgment.

When may unapproved devices be used without prior approval?

In life-threatening situations with no alternatives and insufficient time; report to FDA afterward.

What conditions allow investigational drugs to be used outside trials?

Serious disease; no alternatives; IND in effect; sponsor pursuing approval; treatment protocol submitted.

What is 'tamper-evident' packaging and to what does it apply?

OTC products must show visible barrier to entry (e.g., sealed two-piece capsules).

Who can request non-child-resistant packaging under PPPA?

The prescriber or the patient (or head of household), verbally or in writing.

List three Rx products exempt from child-resistant packaging.

SL nitroglycerin, isosorbide dinitrate ≤10 mg, oral contraceptives in mnemonic packs, certain steroids, pancrelipase.

Name two OTC categories that must comply with PPPA.

Loperamide, diphenhydramine, acetaminophen, mouthwashes, naproxen (specific products).

Where may tax-free alcohol be used and not used?

Used for scientific, medicinal, or mechanical purposes; not for beverages or foods.

What are the ipecac syrup OTC sale conditions?

Max 30 mL; labeled with use directions, warnings, and usual dose (15 mL for >1 year old).

Define USP storage conditions: 'Cold', 'Refrigerator', 'Freezer'.

Cold ≤8°C; Refrigerator 2-8°C; Freezer −20° to −10°C.

What is 'controlled room temperature' per USP?

15-30°C (59-86°F).

USP <795> applies to what?

Nonsterile compounding—process, facilities, documentation, BUD guidance.

USP <797> addresses what?

Preventing microbial contamination in sterile compounding.

Give two examples of USP <797> CSPs.

Injections, ophthalmics, irrigations, inhalations.

What is the USP <800> stance on exposure to hazardous drugs?

No acceptable exposure; requires engineering controls, PPE, and training.

Under USP <800>, may HDs be handled in positive pressure rooms?

No; HDs cannot be stored or compounded in positive pressure areas.

What cleaning sequence does USP <800> recommend?

Deactivation/disinfection → cleaning → disinfection (sterile alcohol last).

What are closed-system drug-transfer devices (CSTDs) used for?

Used in compounding and required for HD administration.

What does USP <825> cover?

Standards for compounding/dispensing radiopharmaceuticals.

What did the EPA 2019 pharmaceutical waste rule ban?

Disposal of hazardous waste pharmaceuticals down the drain.

Name two examples of products affected by EPA ban.

Insulin, nasal sprays, scopolamine, silver nitrate, witch hazel, flexible collodion.

Which nicotine products were exempted under EPA 2019 rule?

OTC nicotine gums, patches, and lozenges.

Differentiate 'potentially creditable' vs. 'non-creditable' pharmaceutical waste.

Potentially creditable: unopened/unused <1 year expired; Non-creditable: opened, >1 year expired, samples, investigational drugs.

What does the Bar Code Rule (21 CFR 201.25) require?

Linear bar code with NDC on hospital-used Rx drugs and biologics.

What is an NDC and must it appear on the Rx label?

10-11 digit identifier (labeler-product-package); not required on patient label federally.

What six items must appear on unit-dose packages?

Drug name, quantity/strength, manufacturer, lot, expiration, special info.

What is a REMS program?

Risk Evaluation and Mitigation Strategy to ensure benefits outweigh risks.

Which drug has a pharmacy certification REMS for abortion?

Mifepristone (Mifeprex/generic) under REMS with pharmacy certification.

What change did PLLR make to pregnancy labeling?

Replaced A/B/C/D/X with narrative sections: pregnancy, lactation, reproductive potential.

What federal law first comprehensively regulated addicting drugs in the U.S.?

The Controlled Substances Act (CSA) of 1970.

Which department houses the DEA and what does it administer?

Department of Justice; DEA enforces CSA and 21 CFR 1300+.

What entities must register under the CSA?

Manufacturers, distributors, dispensers (prescribers/pharmacies), importers, exporters.

Do pharmacists themselves register with DEA?

No; pharmacies register, not individual pharmacists.

What defines a Schedule I substance?

High abuse, no accepted medical use, unsafe (e.g., heroin, LSD).

What defines a Schedule II substance?

Accepted medical use, high abuse potential, severe dependence risk (e.g., morphine, oxycodone, methylphenidate).

What defines a Schedule III substance?

Accepted use; abuse less than CII; moderate/low physical dependence or high psychological dependence (e.g., buprenorphine, anabolic steroids).

What defines a Schedule IV substance?

Accepted use; low abuse potential relative to CIII; limited dependence (e.g., benzodiazepines, zolpidem, tramadol).

What defines a Schedule V substance?

Accepted use; low abuse potential vs. CIV; limited dependence (e.g., codeine cough syrups, certain antidiarrheals).

At what codeine strength does a product typically become Schedule II?

>90 mg/dosage unit or >18 mg/mL; ≤2 mg/mL is typical cutoff for CV combos.

Who ultimately determines scheduling decisions under the CSA?

U.S. Attorney General via DEA, with binding scientific input from HHS.

How are controlled substance analogs treated under the CSA?

As Schedule I or II if structurally/effectively similar or intended for similar use.

What unique rule applies to suppository dosage forms for certain controls?

Some Schedule II drugs in suppository form may be treated as Schedule III.

What DEA form is used by a new pharmacy to register?

DEA Form 224 (renew via 224a every 3 years).

Where must the pharmacy's DEA Certificate of Registration be kept?

At the registered location and available for inspection.

How often must manufacturers/distributors renew vs. pharmacies?

Annually for manufacturers/distributors; every 3 years for pharmacies.

Which practitioners can use a hospital's DEA registration?

Interns, residents, or foreign physicians acting within scope and assigned a hospital code suffix.

Name one circumstance exempt from DEA registration.

Officials of the Armed Services, PHS, Bureau of Prisons, or law enforcement while on duty.

What are import rules for U.S. residents carrying controlled substances?

In original container; declare to customs; ≤50 dosage units.

What did DATA 2000 (as modified) allow?

Qualified practitioners may prescribe buprenorphine for OUD; X-waiver no longer required (2023 update).

Are pharmacies required to register separately to dispense buprenorphine?

No; they may dispense under existing DEA registration for valid prescriptions.

What DEA actions can trigger revocation of registration?

False application, felony drug conviction, acts against public interest, exclusion from Medicare/Medicaid.

What must occur when a pharmacy transfers ownership?

Notify DEA ≥14 days before, complete inventory day of transfer, transfer all records.

What is considered a 'significant loss' under CSA?

Any notable loss or theft of controlled substances; must report promptly to DEA and complete required forms.

How are in-transit losses handled?

Responsible entity (shipper/receiver) reports loss and notifies DEA per rules.

What must be done for breakage/spillage of controlled substances?

Document and, if destroyed, use DEA Form 41; not a "loss" if recovered and recorded.

What is the pharmacist's 'corresponding responsibility'?

To ensure a controlled Rx is for a legitimate medical purpose within usual course of practice.