FDA Regulations
FDA budget
$3.8 billion FY 2012 $4.4 billion FY 2013
American Chamber of Horrors "Lash-Lure"
eyelash dye that was toxic and caused blindness
5 priorities of FDA 2014-2018
1Advance regulatory science and innovation New ways to assess safety, efficacy, quality, public health impact of FDA regulated products 2 Globalization FDA regulated products (food and medicine) comprise substantial component of global economy), come from over 200 countries, engage with O/S agencies to ensure safety and quality of products before they get to the US 3 Safety and quality Practices used to make products, integrity of the supply chain before they get to consumers 4 Smart regulation Protecting public health while encouraging innovation through most appropriate regulation that minimizes unnecessary burden 5 Stewartship -maximizing public health value per federal $ spent (efficiency)
compounding reform of FDAMA background
Background ----Manufacturing versus compounding
desrice major reforms of FDAMA (4)
Compounding PDUFA Dissemination of Off-label use HCEI
problem with Sherley Amendment
Difficult to enforce Must prove defendant had fraudulent intent Protected by claiming ignorance (they can say oh i thought it worked) Safety?
1962 Harris-Kefauver Amendment
Drug Efficacy and Safety Implementation (DESI) ---Required drugs marketed 1938-1962 to prove efficacy in addition to safety -Required manufacturers of generic drugs marketed after 1938 to complete abbreviated new drug application (ANDA) - requires bioequivalency data
FDA 4 core mission goals and objectives are..
Enhance oversight of FDA regulated products Improve and safeguard access to FDA regulated products to benefit health Promote better informed decisions about the use of FDA regulated products Strengthen organizational excellence and accountability
provisions of 1983 Orphan Drug Act
For years recognized that NDA process was too expensive to warrant innovation of Rx for rare disease Before the passage of the ODA the FDA did not have any mission to promote drug therapy for rare diseases Enabled FDA to promote R&D of drugs (orphan drugs) treating "rare diseases and conditions" 25 million Americans with 1 of 7,000 'rare diseases'
1951 Durham-Humphrey Amendment guidelines
Guidelines for Prescription Drugs Hypnotic or habit forming Drug not safe for self medication because of toxicity or potentially harmful effects A new drug that has not been shown to be safe for use in self-medication
4. Promotion of Health Care Economic Information (HCEI) caveats
HC information must relate to approved use Dissemination is limited -Formulary committees -MCO -Large scale buyers of HC information -not individual MDs or patients
1951 Durham-Humphrey Amendment aka did what
Prescription drug amendment established prescription and OTC drugs as two classes
Financial incentives for 1983 Orphan drug act
Tax and exclusive licensing incentives for manufacturers PDUFA waived Require IND submission
PDUFA 1992
(pronounced Pah DEW fah) Enacted 1992, then renewed every 5 years (FDAMA) Authorized FDA to collect user fees for certain applications for approval of human drugs and biological products (Rx drugs) User fees - augment FDA's resources devoted to review of human drug applications Aim to eliminate back logs of drug applications http://www.fda.gov/oc/pdufa/
FDAMA objective (5)
1 Maximize availability and clarity of information about Agency application and submission review process for consumers and patients 2 Post-marketing monitoring provisions 3 Access to scientific expertise 4 Establish mechanisms for meeting specified review periods of applications and submissions 5 Eliminate back logs in review of applications
drug considered FDA approved generic (6 req.)
1 Same active ingredients as innovator drug ***Inactive ingredients may vary 2 Identical in strength, dosage form, route of administration 3 Same use indications 4 Bioequivalent 5 Meet same batch requirements for identity, strength, purity, quality 6 Manufactured under same strict standards of FDA's GMP regs required for innovator drugs
1st legislative Act regarding food and drugs 1st consumer protection Act passed in the US
1906 Pure Food & Drug Act Problems with adulterated foods and "cure all" claims in medicines Agricultural to Industrial Economy POISON SQUAD Dr Wiley raised interest in preservative use
1912 Sherley Amendment
1911 US v Johnson Manufacturer claimed cancer cure --"Johnson's mild combination treatment for cancer" Supreme court rules 1906 Act did not consider false therapeutic claims but only false and misleading statements about ingredients --i.e. legal to make false therapeutic claims 1912 Sherley Amendment Congress disagreed, passed amendment
1st act to address safety
1938 The Federal Food Drug and Cosmetic (FDC) Act sulfanilamide disaster
1st Act instituted on purely economic basis
1984 Waxman-Hatch Act Drug Price Competition and Patent Term Restoration Act of 1984
provisions of 1962 Harris-Kefauver Amendment
1st time manufacturer had to show __safety___and _efficacy____ for intended use Allowed for factory inspections and required animal manufacturer registration Established GMP* good manufacturing practice Grandfathered drugs marketed 1938 to 1962 Transferred Rx drug ads (FTC) to FDA
Federal Drug Administration Modernization Act 1997 (FDAMA 1997) stakeholders (everyone who had an interest in what happened)
Appropriate scientific and academic experts Health care professionals Representatives of patient and consumer advocacy groups Regulatory industry
more rules for dissemination of off label information
Drug legally marketed State information is for a un-approved FDA use Information not derived from another manufacturer's research (without approval) Information must be balanced and scientifically sound Canceled due to violation of 1st amendment --Need to submit to FDA copy of information - 60 days in advance prior to dissemination ---File supplemental NDA within 6 months (new use)
4. Promotion of Health Care Economic Information (HCEI)
Economic studies use mathematical models. FDAMA softened Agency's previous ban on use of such models FDA adopted FTC standard of "competent and reliable evidence" -Data collected outside of clinical trial -Still related to labelled indication -Epidemiological sttudies- real life data cw CT
1984 Waxman-Hatch Act Drug Price Competition and Patent Term Restoration Act of 1984 two parts
Expedites availability of less costly generic drugs to consumers (ANDA) - KH Amendment Extension of patent life up to 5years (incentive to develop new Rx)
oldest consumer protection agency in US
FDA
1938 The Federal Food Drug and Cosmetic (FDC) Act
FFDCA 1938 with amendments forms the nucleus for today's law All the amendments and laws are amendments to this act.
provisions of 1938 The Federal Food Drug and Cosmetic (FDC) Act
False claims could be stopped without proving intend to defraud (Eliminated Sherley Amendment) ***adequate directions for use and warning safety testing prior to marketing applies to cosmetics and medical devices
dissemination of off label information
Industry permitted to distribute peer reviewed journal articles and reprints from text books describing un-approved product uses to qualified recipients: --MDs --PBM --Health Plan Administratorshealth insurance companies/health plans --State Agency Officials NOT PATIENTS
define misbranded
Misbranded: providing false or misleading label statements about a food or drug (labeling) i.e., purity, strength, & quality
Federal Drug Administration Modernization Act 1997 (FDAMA 1997 Background congress affirmed
Mission for FDA FDA's role as virtual protector and promoter of public health Endorsed many actions of FDA Responsibilities are vast Agency stakeholders' play an important role Most demanding challenge in 92 yr history
1938 The Federal Food Drug and Cosmetic (FDC) Act
More stringent laws needed -1933 Bill defeated -1937 Sulphanilamide Disaster ----Sulphanilamide Elixir (antibiotic) -----contained solvent - diethylene glycol -----Company not charged with unsafe product ----107 killed, mostly children ----Established need for drug safety prior to marketing -----Charge: MISBRANDED vs Safety?(not) bc they called elixir but it didnt contain alcohol
compounding reform of FDAMA not allowed
Not allowed ---Soliciting business (promoting, advertising) to compound specific drug product classes or therapeutic classes ---Compounding regularly or inordinate amounts of drug products that are already available in the marketplace (generic copies) ---Using commercial scale manufacturing equipment for compounding
provision/goal of 1912 Sherley Amendment
Prohibited false and misleading claims for drug products
provisions of 1906 Pure Food and Drug Act
Prohibited interstate commerce of adulterated and misbranded food and drugs Adulterated: mixing foreign or inferior substances in food and drugs (manufacturing) eg. unsafe drug color, contaminated Misbranded: providing false or misleading label statements about a food or drug (labeling) i.e., purity, strength, & quality USP and NF official compendia Drug can be simultaneously misbranded and adulterated
As part of the Dept of Health and Human Services (DHHS) the FDA is:
Public Health Agency charged with promoting and protecting American Consumers by enforcing FFD&C Act Oldest consumer protection agency in US FDA decisions affect virtually every American every day Regulates >$2 trillion worth of products or > 20 % of all consumer expenditures
1962 Harris-Kefauver Amendment aka Drug efficacy amendment
Thalidomide Tragedy --Tranquillizer available in Germany (3 yrs) w/o Rx --Considered very safe --Teratogenic - phocomelia ------1000s of babies affected in Europe --Aroused public support for stronger drug regulation --"Drug Efficacy Amendment"
mission of the FDA
To promote public health by the timely review of applications for new products, and to protect public health by ensuring that regulated products are safe, effective, and properly labeled (FDAMA, 1997).
Orphan drugs:
Treat rare diseases which affect <200,000 persons in US Treat rare diseases which affect >200,000 persons in US but for which there is no reasonable expectation that the cost of development and making drug available in US will be recovered from US drug sales
1951 Durham-Humphrey Amendment requirements
all Rx must say "Caution: Federal Law Prohibits Dispensing without a Prescription" refills must be auth. by physician legend drugs to be dispensed only by written or oral prescription
compounding reform of FDAMA allowed
allowed Compounding for an individual patient based on the unsolicited receipt of a valid prescription order..if the compounding is by a licensed pharmacist. Anticipatory compounding based on patient-physician-pharmacist relationship
Fee schedule for PDUFA V
application fee establishment fee/yr product fee/yr
The Pure Food and Drug Act 1906 did not (5)
did not give government authority to set standards of purity or ban unsafe drugs did not extend to cosmetics or devices did not consider false therapeutic or efficacy claims about a drug as misbranding Newspaper ads "cancer cure" did not require manufacturers to label: list ingredients, directions, warnings
KH amendment-
don't have to do ANDA anymore get to market faster so patients can get cheaper meds faster
What does FDA regulate
foods, dietary supplements, human drugs, vaccines, blood products, other biologics, medical devices, electronic products, cosmetics, vet products
graph for Harris Kefauver amendment
generics also had to do NDA makes them more expensive bc all those studies had to be done again
define adulterated
mixing foreign or inferior substances in food and drugs (manufacturing) eg. unsafe drug color, contaminated
FDA is responsible for
protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation (e.g. TSA full body security scanners, microwave ovens, cell phones). advancing public health by helping to speed innovations that make medicines and foods more effective, safer, and affordable; helping the public get the accurate, science-based information they need to use medicines and foods to improve their health. for regulating the manufacturing, marketing and distribution of tobacco products
