HMGT 3310 - Chapter 5: Regulation of Drugs and Health Care Products
competition arrives when patent expires
"Generic" versions Clinical trials/FDA approval can take 10-15 years so only leaves short period for patent protection while drug on market 1938 law + 1962 amendments did not clarify whether generic drugs considered new drugs that have to go thru all phases of testing and get FDA approval -Additional decade or so if new approval needed
Food, Drug, and Cosmetic Act drugs definition
"articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals"
most significant expansion of FDA authority
-1976: Medical Devices Amendments→ devices must be registered w/ agency and required some receive premarket approval --Process for testing an approval of devices -Congress reduced FDA authority over vitamins, minerals, and food supplements→ Vitamin Amendments: exempted products from agencies review
2 FDA directives in 1999 + 2001 set rules under which DTC advertisements on TV considered acceptable -Form of guidance i/o actual regulations -Help them avoid FDA investigation & prosecution
-1st directive: advised companies to reference in ads 4 sources where consumers can get more info on drug, including --toll-free phone # --web site --Print ad --Encouragement to consult HC professional -2nd directive: permitted companies to use wording in FDA-approved labeling to summarize drugs uses & risks in print ads, as long as full labeling reprinted in another accessible printed form w/ discussion of risks
Important challenges market-based pricing of drugs in US
-Brings foreign price controls into American market -Could make American pricing structure meaningless -Concern over long-term effects on manufacturers profits→ safety concerns bc drugs not subject to FDA oversight
1958 Food Additives Amendment
-Delaney clause: prohibited the addition of any substance to human food shown to cause cancer in any animal at any dose
FDA agency structure
-FDA headed by commissioner appointed by president, senate confirmation
US only industrialized country that does not directly regulate drug prices
-Result: prices in the US for brand-name drugs higher than other places -w/ lower costs abroad: Americans buy outside of the country→ "Reimport" meds -Through Canada (Easiest way)→ inc # Americans go to Canadian pharmacies
2003: Medicare Prescription Drug, Improvement, and Modernization Act (MMA)→
-added benefit for outpatient prescription drugs to Medicare --Drugs admin to hospital inpatients and in physicians' offices previously covered but not those obtained by patients directly from pharmacists --MMA coverage limitations: substantial copayments and deductibles --Makes drugs more accessible for elderly patients
Drug Enforcement Administration (DEA)→
-component of Department of Justice -Physicians must register w/ DEA to prescribe controlled substances
Wheeler-Lea Act
1938, Made unfair and deceptive advertising practices illegal and put FTC over food and drug promotion authorized Federal Trade Commission (FTC) to regulate advertising of products subject to FDA oversight other than prescription drugs Central Element of law--> authority that it grants to FDA to eval new drugs for safety/efficacy: -To convince FDA that drug is safe: manufacturers must conduct clinical trials -Institutional review boards (IRBs)
3 phases of clinical trials
1st phase: test for safety in small group of healthy volunteers 2nd phase: patients who suffer from target condition 3rd phase: drug given to large sample of subjects
Investigational New Drug (IND)
A drug not yet approved for marketing by the FDA but available for use in experiments to determine its safety and efficacy
Another transportation of pharma marketing→
Ability of manufacturers to advertise prescription products directly to consumers: "direct-to-consumer" (DTC) advertising -Patients who request specific products can actively influence physician decisions
PDUFA implemented for 5-year period, reauthorized as part of Food and Drug Administration Modernization Act (FDAMA)
Accelerated review of medical devices Changes to oversight of pharma marketing Softened food regulation (replaced premarket approval w/ premarket notification requirement for packaging) Drug marketing provisions: greatest effect + may lead to fundamental realignments in relationship bw manufacturers, physicians, and patients
1938 Food, Drug, and Cosmetic Act
Act required a warning on all package labeling of habit-forming drugs Procedures for review of safety of drugs Extension of FDA scope of authority to include cosmetics and therapeutic devices Elimination of requirements that govt prove fraud to prosecute false claims New authority for FDA to inspect factories & obtain court injunctions against distribution of unsafe/unadulterated products Expansion of FDA standard-setting authority for quality & packaging of food
4th phase: postmarket surveillance is controversial
Agency critics: phase of oversight too lax and many drugs remain on market longer than they should Agency lacks clear authority to directly require clinical testing for safety after drug has been approved
1962 Kefauver-Harris Amendment
All drugs made from 1938 forward must be proven SAFE & EFFECTIVE Also the FTC now handles drug advertisement. Stricter requirements for drug approval. Manufacturers must now register annually, be inspected ever 2 years, and report adverse effects of drugs limits on extent of patent protection
implications of Hatch-Waxman beyond effects on drug costs
Alters scope of FDA responsibility -intellectual property disputes -Keeper of drug patents that Orange Book contains -Oversees bureaucratic mechanism that resolves disputes -Merged regulatory function of safety assurance and economic oversight
1902: first national law to regulate a pharmaceutical product:
Biologics Control Act Established licensing procedures for manufacturer and distribution of vaccines + permitted govt officials to inspect labs and factories
movement to today's regulatory scheme for food/drugs began w/ founding of
Bureau of Chemistry in US Dept of Agriculture (USDA) Investigate safety of foods/dogs/animal feed on national level First call for national food & drug law
Blood supply, vaccines and transplant tissues→
Center for Biologics Evaluation and Research
Labeling of food under
Center for Food Safety and Applied Nutrition
FDA's bureaucratic home
Department of Health & Human Services (DHHS)
1999: restrictions loosened further under Washington Legal Foundation v. Shalala
Drug manufacturers can promote off-label uses as long as promotions say off-label use not approved by FDA
1951 Durham-Humphrey Amendment
Established more specific guidelines for prescription drugs: habit forming, safety, and evaluation of new drugs which drugs safe to be sold OTC and which need prescriptions 3 criteria for when drugs need medical oversight: -Habit forming -Potential toxicity is excessive -Initial approval was limited to use only under guidance of physician prohibited refills w/o authorization of prescribing practitioner
No laws explicitly prevent manufacturers from advertising products to consumers
FDA has authority to punch companies for false/misleading ads Can impose sanctions for "overly aggressive" DTC promotions By early 1990s DTC ads widespread -Potential consumer confusion + possibility of harm from misleading ads increased
1906 Pure Food and Drug Act
First to regulate the manufacture or sale of adulterated or misbranded drugs in interstate commerce Prohibited labels for food + drugs that were false/misleading and required drugs be manufactured in accordance w/ standard set by US Pharmacopoeia
Provisions for children by FDAMA
Gave manufacturers additional 6 months of marketing exclusivity beyond patent expiration Pediatric exclusivity provision→ voluntary mechanism
Hatch-Waxman benefit to pioneer manufacturers
Gave manufacturers extension of patent terms up additional 5 years to account for lost time in FDA approval process
1983 U.S. v Generix Drug Corporation
Generic drugs are new drugs, subject to full regulatory review process Active ingredient same but released @ diff time or extent bc "excipients" and changes it "bioavailability"
FDAMA directed NIH to establish public registry of trials (federally funded and privately finance)
Goal: inc access to clinical trials to those who can benefit most Listing of private trials preceded @ slower pace
infringement of patent list in orange book
If Pioneer Manufacturer wins: gets automatic extension of exclusive right to market drug Generic manufacturer can challenge patent and if they win: -additional 180 days of marketing for product and another generic brand can compete
New Drug Application (NDA)
If there is sufficient data to demonstrate that a drug is safe and effective, the company submits an NDA as a formal request that the FDA approve it for marketing Review data, recommendations Indications for use Contraindications
congress enacted 1st broad based ban on food & drug adulteration:
Import Drugs Act of 1848: Congress set limits on foreign drugs Provided for inspection of drugs @ ports & for destruction/detention/exportation of drugs that did not meet standards of US Pharmacopeia: compendium of all recognized medications Law largely ineffective
1960 Color Additive Law
In which act did the FDA establish additional conditions for the safe use of color additives in food, drugs, & cosmetics. Mfg were required to perform scientific investigations to establish safety for intended use. extended prohibition of food colorings
provisions of Kefauver-Harris Amendments
Law abolished 60 day time limit for FDA new drug reviews Permitted FDA to order a drug off market if evidence of danger/false labeling Prohibited drug testing on humans b4 animal testing Required all ads have labeling on possible side effects Required drug companies register manufacturing facilities w/ FDA and be inspected yearly Record maintained for inspection Reports of adverse drug effects transmitted to FDA Informed consent from patients in clinical trials Altered foundation of FDA oversight -Effectiveness + safety of new drugs be demonstrated to gain FDA approval
FDAMA + court decisions bring new freedom to manufacturers in drug marketing
Loosened FDA restrictions on advertising + enabled more info to flow from prescribers and patients Alter relationship bw patients, provider, and manufacturers
Requirement that manufacturers show drug efficacy as part of approval process placed significant new burden on FDA
New criterion to eval NDAs, required review drugs previously approved for efficacy Massive Drug Efficacy Study Implementation (DESI) review
Physicians can prescribe a drug for any application for any patient→ "off-label"
No direct regulatory limit on physician prescribing decisions -Use drug to treat closely related condition -Prescribe drugs to different age-group -Prescribe drugs for conditions that are entirely unrelated
Traditionally, physicians assessed + filtered data on prescription drugs
Now patients have gained increasing access to info that enables the to act as equal partners in deciding treatments
FDA office for regulation of drugs→ Center for Drug Evaluation and Research (CDER)
Oversees all aspects of drug development & production (manufacturing, testing, research & advertising)
apply for patent with federal
Patent and Trademark Office (PTO)
Manufacturers won't invest in drugs w/o protection of patents→ exclusive marketing rights
Patent prohibits anyone other than patent holder from buying/selling product for 20 years -Govt regulation that forbids market competition on temp basis
Orange Book
Published by the FDA, the "Approved Drug Products With Therapeutic Equivalence Evaluations" is available as a resource to help healthcare professionals in choosing drugs for generic substitution
Oversight of medical products reflects process of balancing
Regulatory scheme must weigh risk of harm from medicines against lost benefits of therapeutic breakthroughs that are delayed
1990: Safe Medical Devices Act
Required institutions (hospitals & nursing homes) report problems to FDA Gave FDA authority to order recalls Manufacturers required to conduct postmarket surveillance + establish systems to locate patients
Before 1997: FDA prohibited manufacturers from promoting drugs for off-label uses
Research evaluating off-label claims frequently published in reputable scientific journals
1987 Prescription Drug Marketing Act
Restricts distribution of prescription drugs to legitimate commercial channels; requires drug wholesalers to be licensed by the states. Banned diversion of prescription drugs from legit channels Prohibited sale of manufacturer samples Restricted reimportation of American drugs back from foreign countries
Prescribing of drugs by physicians regulated by states
States grant licenses for clinical practice, include authority to write prescriptions Dentists, NPs and PAs in some , psychologists in 2 states (prescribing power) Authority to write/fill prescriptions limited to state that issued license
1992 Prescription Drug User Fee Act (PDUFA)
The FDA received authority to collect application fees from drug companies to provide additional resources to shorten the drug-approval process Speed FDA approval process @ manufacturers expense Time limits on FDA to complete reviews of NDAs Hire more reviewers w/ funds from user fees levied on applicants Concerns that reviews too speedy and failed to adequate assess all risks
The Orphan Drug Act
This act gives incentives to companies to create drugs for rare diseases - must still submit an NDA "orphan drugs" -grants -tax credits -market exclusivity for drugs for rare diseases
Federal Trade Commission (FTC)→
advertising of HC products + prescription drugs and devices
Hatch-Waxman Act
aka Drug Price Competition and Patent Term Restoration Act of 1984. Considered the most significant drug-related legislation affecting pharma and healthcare. H-W made it easier to bring generics to the marker by requiring FDA to only look at bioavailability studies in order to approve. Also gave protection to the research based manufacturer's by providing a 30 months automatic cooling off period allowed FDA to approve generic versions of brand-named drugs
Sulfanilamide
antibiotic for children not tested for toxicity 107 deaths
1984: Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act)
balance bw interest of generic and pioneer drug firms to facilitate vibrant role for both Fostering as widespread mechanism for generic competition as possible
1996 Food Quality Protection Act
eliminated application of the Delaney Clause to pesticides
1994 Dietary Supplement Health and Education Act (DSHEA)
expanded the definition of dietary supplements and restricted the FDA's regulatory authority over them Created regulatory structure for products more stringent than for foods but less stringent than that for drugs Manufacturing practice regulations Review safety & efficacy No requirement for premarket testing & approval -Not req to record, investigate, report to FDA info on adverse events
significant benefit of Hatch-Waxman Act
gave generic manufacturers streamlined review process, eliminated dilemma posed by Generix decision
FDA rules for drug promotion + advertising
indication contraindications side effects
1914: Harrison Narcotics Tax Act→
mandated prescriptions for narcotics Inc record-keeping requirements for physicians that prescribe them & pharmacists that dispense them
after drug device is approved
manufacturer must convince payers of its worth added ayer of regulatory pressure emerging to address economics of medical products
FDAMA offered compromise:
manufacturers permitted to disseminate peer-reviewed scholarly articles that eval off-label uses of products, IF company commits that it will file application w/ FDA for permission to promote use Companies also permitted to provide info on econ factors related to use for products to institutional purchasers s/a MCOs
Narcotics→
outside of FDA jurisdiction
1977 Saccharine Study and Labeling Act
overturned ban on saccharin as long as warning label included on packaging Congress repealed warning requirement in 1996
2000: Medicine Equity and Drug Safety Act→
permit reimportation on wider scale -FDA make regulations to permit wholesalers to reimport drugs from foreign countries for resale if safety ensured
1999 Pediatric Rule
permits agency to affirmatively require pediatric testing of new drugs & of biologic products Induced more pediatric drug studies than FDAMA
twist in regulatory framework
permits physicians to prescribe approved drug for any use even one not covered by FDAs approval
⅓ Americans covered by private health insurance don't have
prescription benefit
1914 Harrison Narcotics Tax Act
regulated the legal supply of certain drugs required prescription b4 patients could obtain products w/ more than minimal amount of narcotic substances mandated that physicians & pharmacists maintain records of prescriptions issued/dispensed
1953 Factory Inspection Amendment
required FDA to provide manufacturer's/ written reports of results of inspections
Between 1962-1984 FDA resolved issue in favor of manufacturers of pioneer drugs:
required generic companies submit original clinical data on safety/efficacy
4th phase of clinical trials:
requires that manufacturers collect data on adverse reactions Continuing surveillance of new drugs effects
overall: Hatch-Waxman did what?
reshaped market for generic drugs Enhanced competition in brand-name industry, encouraged companies to fill pipelines w/ new drugs that face impeding generic threats Generic drugs= integral part of many HC cost control strategies
1988: Prescription Drug Marketing Act→
restricted Americans ability to reimport prescription drugs -Rarely enforced against individual purchasers of meds
1954 Miller Pesticide Amendment
test procedures for setting limits for pesticide residue on raw agricultural products
1990 Nutrition Labeling and Education Act
this act covers food items and their labeling; vitamins, minerals, or other nutrients are on the label and in some cases are highlighted required all food packages inclined nutrition info standardized use of labeling terms w/ health implications "low fat"
central challenge for regulation of drugs
to determine whether the products are safe & effective: drugs/devices had little/no regulatory review until beg of 20th century as HC costs have inc: payers of care have played larger role in policing $$ use large health maintenance orgs (HMOs) + fed pymt programs (Medicare & Medicaid)
Absolutist regulatory schemes reduce chance that interest groups can dilute a public safety initiative
w/ no regulatory discretion, agency has novice but to act as prescribed by Congress
