regulation of drug development, marketing, and prescription in the US

lecture given 3/12/2026

what was the first US regulation of drug marketing?

labeling of ingredients

food and drug act- drugs shipped in interstate commerce must be labeled properly according to ingredients

amendments- prohibition of false advertisting claims

food, drug, and cosmetic act- proof of safety

sulfanilamide disaster of 1936-7: an elixer of sulanilamide formulated in diethylene glycol (antifreeze) that resulted in over 100 fatalities

drugs shipped in interstate commerce must be proven experimentally to be safe- experimental data on safety must be submitted to FDA for marketing approval

durham-humphrey amendment

distinction between the two categories of prescription and over the counter (OTC)

standards of labeling and safety apply to both

certain criteria of safety must be satisfied to permit OTC status

note that insurers only cover prescription drugs

thaliodomide distaster

thalidomide for morning sickness in pregnancy foound to cause major limb malformation in babies born in europe

FDA denied approval

climate set for reforms

kefauver-harris amendments- proof of efficacy

efficacy for indication must be proven experimentally

label and advertisement must list all ingredients and side effects

subjects in clinical trials must give informed consent

what are the safeguards for subjects in clinical trials?

approval of trials by IRB

are subjects rights and welfare protected?

are risks to subject outweighed by benefit or importance of new knowledge?

has subject given informed consent without coercion

what product types are currently regulated by the FDA?

drugs- new molecular entities, new drug combinations, new dosage forms or strengths, diagnostics (CDER)

vaccines, blood, and cell products (CBER)

dental and medical devices and radiation emitting products (CDRH)

tobacco products, including e-cigarettes (CTP)

how are dietary supplements regulated by the FDA?

no premarket approval needed, only adulteration or false advertisting with claims of efficacy

tldr us drug discovery and development process

years 0-2: in vitro studies

years 2-4: animal testing for efficacy, selectivity, and mechanism

year 5ish: phase 1- is it safe, pharmacokinetics, 20-100 subjects

year 6ish: phase 2- does it work in patients, 100-200 patients

year 7-8ish: phase 3- does it work, double blind, 1000-6000 patients

year 8-9: apply for new drug application

year 9 to indef: phase 4: postmarketing surveillance

patient expires after 20 years, and generics can become available

new drug application (NDA) and biologics license application (BLA)

data from all studies submitted to FDA

FDA may require additional studies prior to approval, or as a condition of approval, for indication tested in phase 3 trials

data used to prepare the drug label (aka package insert, full prescribing information)

prescription drug label

approved by FDA as part of NDA or BLA process

available from FDA, dailymed, and PDR

contai

what is the impact of label indication?

illegal to ship interstate or advertise for other than label indication

prescriber may use product for off-label indication in individual patient

IND must be obtained for clinical trail for new indication, even of approved drug

label indications change, as new data on efficacy are obtained and approved

what is a success rate of phase 1 clinical phases?

about 20% of tested drugs are approved

what is a success rate of phase 2 clinical phases?

about 30% of tested drugs are approved

what is a success rate of phase 3 clinical phases?

about 30% of tested drugs are approved

what is a success rate of phase 3 clinical phases?

about 70% of tested drugs are approved

overall, what percentage of drugs that enter clinical testing are approved, and what is the cost?

14%, estimated 1.1 billion for each new drug

phase 4 studies

post market surveillance for detection of low incidence side effects (<1 in 10,000), based on reports to FDA from manufacturers/prescribers/hospitals

may result in black box warning on label or drug recall

why do drug patents expire 20 years after filing?

filing typically occurs early in development, effective patent life lasts less than 12-16 years

approve process implemented to decrease development cost of generics and price to consumer

what is the approval process for generic small MW drugs?

generic manufacturer must prove bioequivalence of generic formulation to the patented drug product

same amount of active ingredient

similar bioavailability measured in about 20 healthy human subjects

data submitted to FDA as an abbreviated NDA

low research expenditure, so generic typically much less costly than patented version

what is the approval process for biosimilar protein therapeutics?

more complex studies required as manufacturing in cell culture can lead to subtle differences in composition and structure

may require costly studies of clinical efficacy and safety, not just bioavailability so cost are not markedly less than patented verion

how are approved biosimilar protein therapeutics marketed?

with the official name followed by 4 lower case letters

treatment IND

promising investigational drugs in late phase 2 or 3 can be available to patients with life-threatening chronic conditions

orphan drug act

incentives for development of drugs for conditions affecting fewer than 200,000 in US

has lead to over 500 new drugs, typically very costly

emergency use authorization

promising drug can be available in pandemic prior to formal review for the indication (covid vax)

food and drug administration modernization act

access to informationon clinical trials for serious illness

incentives and requirements for clinical trials in children

inclusion of underrepresented groups in clinical trials

improved post-marketing drug safety surveillance with increased use of real world evidence

removal of requirement for animal testing

cost effective analysis not required in US unlike other countries

explain direct to consumer ads of prescription drugs

pharmaceutical companies spent over 10 billion since 1997

effective marketing strategies increase consumer awareness of new drugs, consumer requests for heavily promoted drugs, physicians prescribing new expensive drugs in response to patient requests

increasing with digital media

fed tried to require inclusion of a list price in TV ads- was blocked by big pharma lawsuit

explain advertisting of prescription drugs to healthcare professionals

substantial percentage of total marketing budget- much more than direct to consumer

includes free samples

physician payment sunshine act requires manufacturers to report to DHHS all transfers of value (gifts) to individual dentists and physicians

who regulates prescriptions?

regulatory authority- state boards authorized by state legislation

prescribers: dentists, physicians, osteopaths, in some states with restrictions pharmacists, nurse practitioners, PAs, optometrists

e-prescribing required by many health plants, insurers, and hospitals

what drug choices does a pharmacist have?

if prescription is written as generic- give generic

if prescription is written by proprietary name- pharmacist may dispense bioequivalent generic

if prescription is written as “proprietary name, dispense as written”- cannot substitute

harrison narcotic act

regulated production and use of opioids, cocaine, and later marijuana

enforced by federal bureau of narcotics in treasury dept

taxation of prescriber

controlled substances act

purpose of decreasing availability of drugs to potential misusers, component of war on drugs in early 70s

enforced by DEA within the DOJ- issues permits to dentists to prescribe controlled substances for a fee

what are chemicals categorized into schedules based on?

misuse potential, pattern and significance of misuse, risk of dependence

what does the schedule of a drug affect?

registration of handlers, record-keeping, storage security, limits on dispensing, penalties for illegal trafficking

what are prescription requirements for controlled substances?

prescriber’s DEA registration number

prescriber must alo register within rate and enroll in prescription monitoring program

e-prescribing allowed by DEA as of 2010

prescription monitoring programs

in MA and other states, data on prescribing of schedule II-V substances are posted online

patient prescription history must be reviewed before prescribing schedule II and III drugs and benzos

limits on amount of prescribed opioids in MA

7 day dosing limit was imposed on new opioid prescriptions, along with other measures to reduce opioid deaths

schedule I controlled substances

research use only

heroin, marijuana (in conflict with laws of many states)

schedule II controlled substances

no prescription refills

morphine, hydrocodone combinations

schedule III controlled substances

limit to refils

codeine

schedule IV controlled substances

limit to refils

benzos

schedule V controlled substances

OTC with some limits

antitussives with low codeine

where can you find current federal drug regulations?

FDA website

where can you find current state drug regulations?

state websites like mass.gov

where can you find current CDC drug regulations?

public health law program, publications on federal and state regulations