Federal Food, Drug & Cosmetics ActKefauvers-Harris Amendments ABDUL MUHEEM M.PHARMA 2ND SEM. (PHARMACEUTICS) JAMIA HAMADARD firstname.lastname@example.org
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 FDA’s 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 water“Consumers 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.).
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 practitioner’s 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
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 it’s efficacy. A similar article was also published in the AACR, in the same year.
SAFETY AND EFFICACY MONITORING Current scenario FDA’s 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 Council’s 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