Federal Food, Drug & Cosmetics Act Kefauver's-Harris Amendments ABDUL MUHEEM M.PHARMA 2 ND SEM. (PHARMACEUTICS) JAMIA HAMADARD [email protected]
Transcript
Federal Food, Drug & Cosmetics ActKefauvers-Harris
Amendments ABDUL MUHEEM M.PHARMA 2ND SEM. (PHARMACEUTICS) JAMIA
HAMADARD [email protected]
OBJECTIVES OF FFDCAIn United States Federal Food, Drug, and
CosmeticAct (FFDCA, FDCA, or FD&C), is a set of laws passed by
Congress in 1938 givingauthority to the U.S. Food and Drug
Administration (FDA) to oversee the safetyof food, drugs, and
cosmetics. It replaced the earlier Pure Food and Drug Act of 1906
due to Elixir Sulphanilamide disaster. 1938 Act continued the
information provision requirements of the 1906 Act. The
classification misbranded was expanded example, and now included
any drug whose label failed to identify and quantify the precise
ingredients, to list effects and possible side effects, and to give
directions and cautionary information. 1938 Act also expanded the
FDAs powers over medical devices .
Reason for implemented new act 1937 sulfanilamide crisis
November 16, 1937: A Senate resolution directs the U.S. Department
of Agriculture to give a full accounting of the "Elixir
Sulfanilamide" tragedy. The drug, containing a poisonous
solvent(ethylene glycol / propylene glycol mix-up), was not safety
tested and has killed 107 persons, many of them children. The
incident made Congress to pass the Federal Food, Drug, and Cosmetic
Act, which includes stronger drug safety requirements
OTHER TRAGEDIESKoremlu CreamContained Thallium acetateSerious
hazardous side effects due to thalliumRadiothor"Radium containing
waterConsumers died of radiation exposureLabel true and no
therapeutic claims
Lack of standards for food products Developments in Science and
technology Canning / Chemical analysis Expansion of cosmetics
industry
GOALS OF FDCA(1938) The FDCA mandates the safety, purity, and
in some cases the "effectiveness" of the products within its scope.
FDA ensures safety through inspections of products already on the
market, controls the manufacturing practices of companies, and
possesses recall and seizure authority. The FDCAs Goal is to
disclose information- requires truthfulness and completeness in
product labeling and other marketing communications. The act
forbids "misbranding," and provides a range of civil and criminal
enforcement mechanisms against inaccurate product labeling. Section
contains both civil law and criminal law clauses. The FDCA in 1958
with the Food Additives Amendment (also called the "Delaney Clause"
after its House sponsor), precluding FDA approval of any food
additive found to cause cancer in humans or animals.
Food & drug act Prohibited the sales of adulterated
&misbranded drugs. Drug could be marketed as long as the label
did not present false information regarding the strength &
purity. no requirement to disclose ingredients. A largely
unregulated industry was causing numerous public health
problems.
CHAPTER WISE DESCRIPTION:Chapter I. Short TitlesChapter II
Definitions. 201(f) is the definition for a food, which explicitly
includes chewing gum 201(g) is the definition for a drug 201(h) is
the definition for a medical device 201(s) is the definition of a
food additive 201(ff) is the definition of a dietary
supplement
CHAPTER III. Prohibited Acts and Penalties 301. Prohibited Acts
302. Injunction proceedings 303. Penalties 304. Seizures 305.
Hearing before report of criminal violation 306. Report of minor
violations 307. Proceedings in name of United States; provision as
to subpoenas .
CHAPTER IV. Food 401. Definitions and standards for food 402.
Adulterated food 403. Misbranded food 404. Emergency permit control
405. Regulations making exemptions 406. Tolerances for poisonous
ingredients in food 407. Oleomargarine or margarine 408. Tolerances
for pesticide chemicals in or on raw agricultural commodities 409.
Food additives 410. Bottled drinking water 411. Vitamins and
minerals 412. Requirements for Infant Formulas .
CHAPTER V. Drugs and Devices 505 is the description of the drug
approval process 510(k) is the section that allows for clearance of
medical devices 515 is the description of the device approval
process.
DRUG AND DEVICESSections in FDCA gives following information-
505 is the description of the drug approval process 510(k) is the
section that allows for clearance of class II medical devices 515
is the description of the (class III) device approval
process.Section 510(k) of the Federal Food, Drug, and Cosmetic Act
requires those device manufacturers who must register to notify
FDA, at least 90 days in advance, of their intent to market a
medical device. This is known as Premarket Notification.Class I:
Devices that do not require premarket approval or clearance but
must follow general controls. Dental floss is a class I
device.Class II: Devices that are cleared using the 510(k) process.
Diagnostic tests, cardiac catheters, and amalgam alloys used to
fill cavities are all class II devices.Class III: Devices that are
approved by the Premarket Approval (PMA) process, analogous to a
New Drug Application. These tend to be devices that are permanently
implanted into a human body or may be necessary to sustain
life
CHAPTER VII :GENERAL ADMINISTRATIVE PROVISIONS 701. Regulations
and hearings 702. Examinations and investigations 702a. Seafood
inspection 703. Records of interstate shipment 704. Factory
inspection 705. Publicity 706. Listing and certification of color
additives for foods, drugs, and cosmetics.
CHAPTER VIII : 801.Imports And Exports 8CHAPTER IX : 901.
Miscellaneous
LIMITATIONS OF 1938,FOOD DRUGAND COSMETIC ACT INCLUDES It did
not included drugs which were previously marketed. Drugs had to be
proven safe but not proven effective. The federal govt. had little
authority to enact penalties, if the information on the labels was
not written clearly. Drugs manufacturer were given the
responsibility for determining whether a drug would be sold as a
prescription or over the counter drug. Drug manufacturers conducted
their own test to determine drugs effectiveness.
Introduction The Food and Drug Administration (FDA),
established in 1938 as a part of the US Department of Health and
Human Services (HHS), regulates products accounting for roughly 25%
of the US gross national product. Major concerns arose with the
scandal of birth defects in European nations caused by Thalidomide,
a drug to be introduced into the US. The drug was already in use by
the pregnant women in Africa and Europe from 1956-1962 and caused
an estimated 10,000 children born with congenital
deformitiesPhocomelia.).
IMPORTANT ACT &AMENDMENTS
News & Implementation Of AmendmentsWeek In FDA History -
July 15,1962Thalidomide, a newly developedsleeping pill, is found
to havecaused birth defects inthousands of babies born inWestern
Europe. News reportson the role of FDA medicalofficer Dr. Frances
O. Kelsey inkeeping the drug off theAmerican market arouse
publicsupport for stronger drugregulation
Week In FDA History - Oct. 10,1962 October 10, 1962: The
Kefauver-Harris Drug Amendments are passed, prompted in part by
public concern over birth defects caused by the drug thalidomide.
Among the new requirements: proof of drug effectiveness as well as
safety, controls over clinical trials, and better quality assurance
practices in drug manufacturing
Dr. Francis Kathleen Oldham Kelsey, working for the US FDA did
not want to approve thalidomide into the American drug market
because it was not properly tested as a result of what was going on
in those years. The KEFAUVER HARRIS AMENDMENT was a response to the
thalidomide tragedy. It was signed by President John F. Kennedy on
October 10, 1962. US senator Estes Kefauver of the state of
Tennessee and Arkansas state representative Oren Harris required
the American drug manufacturers to present proof of the safety and
effectiveness of their drugs before any endorsements. Hence, this
amendment is also referred to as the DRUG EFFICACY AMENDMENT.
KEFAUVER HARRISAMENDMENTINT Concerne ControlsR over clinicalO d
with trials andD proof of Passed in better QAU drug 1962 practices
inC effectiven drugT ess and manufacturiI safety ngON
Objectives Of Amendments Efficacy was to be established for all
drugs since 1938. Required FDA to assess the efficacy as well as
safety for all drugs products. First time manufactures were
required to prove effectiveness of drug products prior to
marketing. Gave FDA stricter control over clinical drug trials. Set
GMP to be followed by drug industry. Regulated advertising.
Kefauver-Harris imposed the efficacy requirement prior to NDA
approval by FDA.
APPROVAL OF NEW DRUGS AFTERIMPLEMENTED OF AMENDMENTS New drug:
1) safe and effective. 2) approved under NDA procedure a/c to act
at section 505. IND: for filing IND, form FD-1571,FD- 1572 and
FD-1573 are filled. NDA: Form FD-356.
DRUG EFFICACY STUDyIMPLEMENTATION (DESI) COLLABORATION WITH
NATIONAL ESTABLISHME ACADEMY OF NT OF THE SCIENCE- DESI NATIONAL
PROGRAM IN RESEARCH 1968 COUNCIL (NAS- NRC) It was a retrospective
efficacy assessment of drugs approved prior to 1962.
DRUG EFFICACY STUDIES Early developmentIn 1966, FDA
commissioner approached NAS-NRC to reviewalready marketed drugs
under NDAs approved from 1938-1962.There were about 300 different
medicinal agents. This was carried out by establishing review
committees and a Policy Advisory Committee whose members were well
acquainted with medical, legal and industrial problems of drugs.27
and more panels were developed concerning with drugs usedin
allergy, anti histaminics, dermatology, anti neoplastics,
etc.Guidelines were established by the advisory committee to
reviewwork of the panels.By October 1969, the review program was
formerly organized andin operation. The types of products reviewed
included single drugentities or products with two or more
entities.
DRUG EFFICACY STUDIES Early developmentThe panels sought
evidence of drug efficacyfrom four main sources: 1) Briefs
submitted by the sponsor of the drug 2)Additional evidence directly
solicited from the sponsor 3)The files of the FDA 4)Pertinent
medical literature brought in by the panelists.
DRUG EFFICACY STUDIESEffectivenesscategories EFFECTIVE
Substantial evidence of efficacy INEFFECTI VE Insufficient data
supporting efficacy PROBABLY POSSIBLY EFFECTIVE EFFECTIVE Needed
Research extra info, needed, max max time 12 time 6 months
months
DRUG EFFICACY STUDIESThe conclusions IMMEDIATE REMOVAL OF
PRODUCTS CURRENTLY MARKETED RECOGNITION OF CLINICAL STUDIES TO
VERIFY OR ESTABLISH EFFECTIVENESS UNDER THE NEW LAW RECOGNITION
THAT DIRECTION OR LABELLING OF CERTAIN PRODUCTS WERE POORLY
ORGANIZED, OUTDATED AND ORIENTED TO PROMOTION OF PRODUCT PACKAGE
INSERTS NEEDED TO BE BROUGHT UP TO MODERN STANDARDS OF ACCURATE AND
OBJECTIVE DRUG INFORMATION.
DRUG EFFICACY STUDY RECORDSThe records of the Drug Efficacy
Study contains: Correspondence reports meeting minutes press
clippings other records documenting the activities of the DES.
DRUG EFFICACY STUDIES abbreviated new drug applications One of
the early effects of DESI study was the development of ANDA. An
Abbreviated New Drug Application (ANDA) is an application for a
U.S. generic drug approval for an existing licensed medication or
approved drug. The ANDA is submitted to FDAs Center for Drug
Evaluation and Research, Office of Generic Drugs, which provides
for the review and ultimate approval of a generic drug product.
Once approved, an applicant may manufacture and market the generic
drug product to provide a safe, effective, low cost alternative to
the American public. A generic drug product is one that is
comparable to an innovator drug product in dosage form, strength,
route of administration, quality, performance characteristics and
intended use. All approved products, both innovator and generic,
are listed in FDAs Approved Drug Products with Therapeutic
Equivalence Evaluations.
DRUG EFFICACY STUDIES abbreviated new drug applications Generic
drug applications are termed "abbreviated" because they are
generally not required to include preclinical (animal) and clinical
(human) data to establish safety and effectiveness. Instead,
generic applicants must scientifically demonstrate that their
product is bioequivalent (i.e., performs in the same manner as the
innovator drug). The generic version must deliver the same amount
of active ingredients into a patients bloodstream in the same
amount of time as the innovator drug. Using bioequivalence as the
basis for approving generic copies of drug products was established
by the Drug Price Competition and Patent Term Restoration Act of
1984, also known as the HATCH-WAXMAN ACT. This Act expedites the
availability of less costly generic drugs by permitting FDA to
approve applications to market generic versions of brand-name drugs
without conducting costly and duplicative clinical trials.
FLUOROQU INOLONE THE BLACK BOXTendonitis (8 july, REGULATION
2008) On 12 Feb. 1972 FDA promulgated this regulation which
required that the less than effective products should be AVANDIA
notified to the practitioners by including a statement (anti
prominently in the labeling & surrounding it with an diabetic)
appropriate border.Heart attack 14Nov, 2007 It is a type of warning
that appears on the package insert DEPO for prescription drugs that
may cause serious adverse PROVERA effects. It is so named for the
black border that usuallyLoss of bone surrounds the text of the
warning. density 17 Nov, 2004 It is the strongest warning that the
FDA requires.CELEBREX(celecoxib) CV & GI risk 2002
THE BLACK BOXREGULATION
Other FDA REASSESSMENTPROJECTS The GRAS List Review of 1969
(review of the safety of all the food ingredients that had been
included on the Generally Recognized As Safe List of the late
1950s); The OTC Drug Review of 1972 (review of the safety and
efficacy of all OTC drugs; and The Biologics Review of 1972 (review
the safety and efficacy of all biologicals)
Other relatedlegislations The Medical Device Amendments of 1976
followed a U.S. Senate finding that faulty medical devices had
caused 10,000 injuries, including 731 deaths. The law applied
safety and effectiveness safeguards to new devices.
Other relatedlegislations 2005 Formation of the Drug Safety
Board consisting of FDA staff and representatives from the National
Institutes of Health and the Veterans Administration. The Board
will advise the Director, Center for Drug Evaluation and Research,
FDA, on drug safety issues.
Contd DRUG SAFETY AND DRUG EFFICACY: TWO SIDES OF THE SAME COIN
In 2007, a committee of academic scientists, research advocates and
representatives of patient community was convened to recommend ways
in which the Congress and the FDA could further strengthen product
evaluation for its efficacy. A similar article was also published
in the AACR, in the same year.
SAFETY AND EFFICACY MONITORING Current scenario FDAs MedWatch
program can Serious & also be unexpected approached side
effects for thisNDA sponsors should write to purpose.submit reports
the FDA withinquarterly for 15 days offirst 3 yrs and receipt of
info.annuallyafterwards.
Impacts of Kefauver HarrisAmendment(1962) The Kefauver Harris
Amendment strengthened the U.S. Food and Drug Administrations
control of experimentation on humans. It changed the way new drugs
are approved and regulated. It introduced a "proof-of-efficacy"
requirement, that was not present before. The Amendment required
drug advertising to disclose accurate information about side
effects and efficacy of treatments. Cheap generic drugs could no
longer be marketed as expensive drugs under new trade names as new
"breakthrough" medications, as they were prior to the
amendment
DRUG EFFICACY STUDY IMPLEMENTATIONThe amendment made onerous to
evaluate eachproduct, also to evaluate the active ingredients inthe
products. The active ingredients were placedinto one of the three
categories.Category I drugs: those determined to be safe
,effective, and properly labeled.Category II drugs: those not
generallyrecognized as safe and effective, or recognized
asmislabeled; must be removed from medicationswithin 6 months after
the FDA issues its finalregulations.Category III drugs: those for
which data isinsufficient to determine general recognition ofsafety
and effectiveness.
CONCLUSIONToday, the FDA regulates $1 trillion worthof products
a year. It ensures the safety ofall food except for meat, poultry
and someegg products; ensures the safety andeffectiveness of all
drugs, biologicalproducts (including blood, vaccines andtissues for
transplantation), medicaldevices, and animal drugs and feed;
andmakes sure that cosmetics and medicaland consumer products that
emit radiationdo no harm.
ConClusions By 1984, final action had been completed on
3,443products; - 2,225 were found to be effective, 1,051were found
not effective, and 167 were pending.
References
http://www.absoluteastronomy.com/discussion/Drug_Efficacy_Stu
dy_Implementation
http://en.wikipedia.org/wiki/Talk:Drug_Efficacy_Study_Implement
ation http://www.ssa.gov/OP_Home/comp2/B-CFR-42.html
http://www.nationalacademies.org/ The Drug Efficacy Study of the
National Research Councils Division of Medical Sciences, 1966-
1969, W.M. WARDELL, The US Drug Efficacy Study and its Implication
(DESI), Associate Professor, Pharmacology and Toxicology,
University of Rochester, and Director, Center for the Study of Drug
Development, USA
http://edocket.access.gpo.gov/cfr_2008/aprqtr/pdf/21cfr207.20.p df
W.E. GILBERTSON, The OCT Drug Review - FDAs Viewpoint, Director
Division of OTC Drug Evaluation, Food and Drug Administration,
Rockville, Maryland, USA Julie B. Esmay, B.S., and Albert I.
Wertheimer, Ph.D., A REVIEW OF OVER-THE-COUNTER DRUG THERAPY,
Journal of Community Health Vol. 5, No. 1, Fall 1979,
References Http://www.Personalcarecouncil.Org/
Http://www.Fda.Gov/drugs/informationondrugs/default.Htm
Http://www.Fda.Gov/drugs/guidancecomplianceregulatoryin
formation/drugregistrationandlisting/default.Htm Center for
veterinary medicine program policy and procedures manual, guide
1240.3560, General review and enforcement policies, responsible
office: hfv-210, registration of producers of drugs and listing of
drugs in commercial distribution. Guidance for industry , providing
regulatory submissions in electronic format drug establishment
registration and drug listing Alan h. Kaplan, esq., Fifty years of
drug amendments revisited: in easy-to-swallow capsule form