Food & Drug Administration A focus on safety

Food and Drug Administration JenGee, Westy, Marco polo, Kmoe October 22nd, 2012

An Overview of the FDARegulates more than $1 trillion worth consumer goods.25 cents of every dollar spent by AmericansRegulates cosmetics, food, blood supply, medicines, biological, medical devices, radiation-emitting products, and feed & drugs for animalsPerforms surveillance of regulated productsMakes sure products are labeled truthfullyEmploys 9,000 employeescost is $3 / person/yr95,000 FDA-regulated businesses

An Overview of the FDA (cont)Visits to 15,000 facilities/yrcollect 80,000 domestic & imported product samplesViolations of FDA laws & regulationsencourage firm to voluntarily correct the problemrecall a faulty product from the marketabout 3,000 products recalled/yrFDA can go to court to force a company to stop selling a product, can seize and destroy productsAlso criminal penalties against manufacturers and distributorsExample of Product RecallKelloggs Mini-Wheats Bite Size CerealOn October 8, 2012, Kelloggs issued a voluntary recall of certain lots of this cereal due to the possible presence of fragments of flexible metal mesh from a faulty manufacturing part.The company is recalling approximately 3 million packages of Mini-Wheats.Kelloggs is a Fortune 500 ranking company.

Now that's a cereal that stays crunchy in milk.http://blogs.laweekly.com/squidink/2012/10/mini-wheats_recalled_due_to_co.php Major Centers at FDAFDA is an agency of the Public Health Service which is part of the Department of Health and Human ServicesCenter for Biologics Evaluation & Researchregulates biologically produced products such as blood, vaccines, biological therapeuticsCenter for Drug Evaluation and Researchregulates the safe and effective use of drugsCenter for Devices and Radiological Healthregulates the safe and effective use of medical devices and eliminates unnecessary exposure to man-made radiation from medical, occupational, and consumer productsLatest Major Medical Device LawThe Medical Device User Fee and Stabilization Act (MDUFSA) of 2005.The MDUFSA amends the user-fee system created by the original Medical Device User Fee and Modernization Act of 2002, which allows the FDA to charge a fee for medical device product reviews.The History of the FDA

History of the FDA Oldest comprehensive consumer protection agency in the U. S. federal governmentAppointment of Lewis Caleb Beck to the US Patent Office in 1848Job of carrying out chemical analysis of agricultural products1906 Pure Food and Drugs Act (The Jungle)Began as Division of Chemistry, then the Bureau of Chemistry, then the Food, Drug, and Insecticide Administration (1927), then the FDA (1930)History of the FDA

Federal Food, Drug, and Cosmetic Act (FD&C Act) 1938Following the death of the 1906 actTennessee wonder sulfa drugUS Congress for the first time addressed issues related to medical devices and drugs Radiation Control & Health Safety Act of 1968Both medical and nonmedical applicationsPerformance standards for x-ray systems, computed tomography, laser-based devices, and ultrasonic diagnostic and therapeutic productsCooper Committee Report 1970Requires premarket clearance of risky devicesBased on 10,000 device-related injuries over a 10 yr periodClassified medical devices into 3 groups: Class I, Class II, Class IIINumerous deaths from a popular consumer medicine (elixir of sulfanilamide) in the 1930s led Congress to enact the FDCA in 1938. The FDCA significantly expanded federal regulatory authority, most notably by requiring premarket safety approval for new drugs, adding cosmetics to the statutory scheme, and providing express authority for factory inspections.

General Electrics 1967 recall of 90,000 television sets believed to emit dangerouslevels of radiation. Congress soon proposed a federal radiation control bill.9History of the FDA (cont)

Bureau of Medical Devices (BMD) 1974Began classifying medical devicesCreated Office of Small Manufacturers Assistance to help manufacturers understand the lawMedical Device Amendments 1976Made into law the tripartite medical device classification schemeManufacturers had to notify FDA prior to marketing any device, unless the device was exemptIntroduced concept of substantial equivalence to pre-amendment devicesCertain products previously classified as drugs were reclassified as class III devices Required registration of medical device establishmentsAuthorized what became Good Manufacturing Practices (GMP)Expanded FDA enforcement authorityMedical Device Amendments 1976- Very similar to copper committee report although it includes more enforcement authority of FDA. It classifies the medical devices into the three classes. Class III are required to contact the FDA prior to marketing device.

Any device that is equivalent to devices prior to 1976 can market immediately. 10

History of the FDA (cont)Good Manufacturing Practices Regulation (GMP) 1978Comprehensive set of requirements onFacilitiesMethodsControls for manufacturing, packaging, and storage of medical devicesMedical Device Reporting Regulation (MDR rule) 1984Requires manufacturer to submit a report to FDA whenever a device they marketed might have caused an adverse event resulting in death or serious injuryMust file a report whenever 1 device was known to have failed and a repeat occurrence would be likely to lead to death or serious injury

Good Manufacturing Practice (GMP) regulations also were authorized at that time. These are a set of procedures to ensure that devices are manufactured to be safe and effective through quality design, manufacture, labeling, testing, storage, and distribution.

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History of the FDA (cont)FDA Plan of Action (first) 1985Response to criticism of FDAs implementation of the 1976 amendmentsMaintain regulatory control without putting up roadblocks to innovationProvided guidelines for functional substantial equivalence rather than technological equivalenceAllowed premarket notifications (PMN or 510 (k) s) rather than premarket approvals (PMA)FDA Plan of Action (second) 1987FDA would focus on risk assessment for informed judgments on device safetyEmphasize post-market surveillance of devicesFDA focus on user educationA 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to PMA.

device is substantially equivalent if, in comparison to a predicate it:has the same intended use as the predicate; and has the same technological characteristics as the predicate; or has the same intended use as the predicate; and has different technological characteristics and the information submitted to FDA; does not raise new questions of safety and effectiveness; and demonstrates that the device is at least as safe and effective as the legally marketed device.

12History of the FDA (cont)FDA reviewer Guidance for Computer-controlled Medical Devices undergoing 510(k) review 1991Applies to medical products having software as part of the deviceEnsures uniform review of such devicesFDA Regulatory Procedures Manual Revision 1991Replaced older enforcement system of notices of adverse findings and regulatory lettersNow a single type of FDA communication - warning letterMedical Device Amendments of 1992Refined medical device tracking regulationsMade noncompliance with postmarket surveillance a civil or criminal penaltyFDA can require repair, replacement, or refund for devices not designed or made properly

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14History of the FDA (cont)Temple Report 1993Found deficiencies in the design, conduct, and analysis of clinical trials in support of PMAs and 510(k)sExpressed a need for better scientific rigor, called for controlled, randomized, and masked trials when feasibleMedical Device Reporting regulation for Manufacturers 1995Requires device manufacturers to provide FDA with more information about adverse events with substantially more specificityRevised GMP Regulation 1996FDA rules for GMP now include preproduction quality control

History of the FDA (cont)FDA Modernization Act of 1997Device industrys efforts to reform FDAtheir view, FDA is inefficient, unfair, needs reformBecame effective February 19, 1998

What is a Medical Device?Medical Device (section 201 of Federal Food, Drug, & Cosmetic Act)Instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article including any component, part, or accessory which is:recognized in the official National Formulary, or the United States Pharmacopeia (USP), or any supplement to them;intended for the use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or animals; orintended to affect the structure of any function of the body of man or other animals; and which does not achieve its primary intended purposes through chemical action within or on the body of man and which is not dependent upon being metabolized for the achievement of its primary purposes (i.e. not a drug).

Which Class is my Device?Depends mainly on intended use and indications for use

Classification of Medical DevicesClass I Medical Devices General ControlNot life sustaining, no risk to lifeLeast risk of injury to either the operator or the patientOnly general controls such as adulteration/misbranding, registration and listing, repair, replacement, refund, and banned products are needed to ensure safety and effectivenessSome class I devices can be exempt from PMN (Pre-Market Notification) and/or GMP (Good Manufacturing Practice)Examples: manual stethoscopes, surgical scalpels, forceps, wheelchairs, elastic bandages, exam gloves, hand-held surgical instruments

Class II Medical Devices General and Special ControlNot life sustaining, no risk of lifeNeed additional controls such as performance standards, post market surveillance, special labeling, patient registries, guidelines, recommendationsUsually exempt from proving safety and efficacy, however FDA may require additional laboratory or clinical studiesNever exempt from PMN or GMPExamples: endoscopes for viewing body cavities, surgical lasers, powered wheelchairs, infusion pumps, surgical drapes, physiological monitoring

Classification of Medical Devices

Classification of Medical Devices

Class III Medical Devices General and Premarket ApprovalGeneral and special controls not sufficient to establish safety and efficacyUsed to support or sustain life or present a potential unreasonable risk of injury or illnessGenerally requires an approved premarket approval (PMA) application (PMAA), unless: equivalent to devices marketed before 5/28/76 in which case you follow premarket notification (PMN or 510(k)) process unless FDA has already made that type of device follow the PMA processPMA can take several yearsFailure mode analysis, animal tests, toxicology, human clinical trials (IDE and IRB) are requiredExamples: indwelling gas analyzers, implanted cardiac pacemakers, balloon catheters, stents, cardiac arrhythmia alarms, heart valves, breast implants

Types of Class III DevicesPreamendment DeviceDevice that was in commercial distribution before May 28, 1976, the date the Medical Device Amendments were signed into law. Require a PMA only after FDA publishes a regulation calling for PMA submissions.Postamendment DevicesDevice that was first distributed commercially on or after May 28, 1976. Subject to same requirements as equivalent preamendment devices.Transitional DevicesDevice that was regulated as a new drug before May 28, 1976. Any Class III device that was approved by a New Drug Application (NDA) is now governed by the PMA regulations.Some of the transitional devices were down-classified to Class II.

Types of DevicesIn Vitro Diagnostics (IVD)Medical devices that test for diseases, conditions, or infections. Can be used in a laboratory setting, a professional healthcare setting, or even for at home use.Includes reagents, instruments, kits, or systems used to examine body specimens such as blood or tissue. Examples:Common tests include blood tests for glucose, liver enzymes, levels of electrolytes such as calcium, sodium, and potassium, and tests for drugs.Specimen receptacles - devices specifically intended by their manufacturers for the primary containment and preservation of specimens derived from the human body for the purpose of in vitro diagnostic examination. Exempt: General lab equipment not specifically intended for in vitro diagnostic examination.

Types of DevicesCombination DevicesA product that is a combination of a drug, device, and/or biologic.Includes products that are physically or chemically combined, products that are packaged together as one unit, and any other products that are intended for use specifically with another product. Office of Combination Products (OCP) assigns which center has the primary responsibility for these types of devices.Examples:Device coated withdrug or biologicDrug delivery system

Types of DevicesCustom DevicesDevices ordered by a physician or dentist for his or her own use or for a specific patient and that are not generally available.These devices cannot be labeled or advertised for commercial distribution.Currently being scrutinized by the FDA since a complete DHF and FDA submission is not required.Doctors must sign waivers saying that they release the company from all liabilities.

FDA Approval ProcessRegistrationMedical device manufacturers, US importers, distributors, repackers, and relabelers must register with the FDA.

Exempt from registration:Licensed practitioners such as physicians, dentists, and optometrists who manufacture or alter devices solely for their own use or practice.

Retail outlets, research manufacturers with no commercial products, warehouse operators provided they do not alter the devices, delivery people, people who dispense such as audiologists, optometrists, etc.

FDA Approval ProcessDevice ListingAfter being cleared for commercial distribution, the owner/operator must list the device with the FDA.Identifies the owner/operator and all others involved in the manufacturing, repacking, relabeling, specification development, distribution, or importation of the device.Responsibility of the device is now listed

FDA Approval ProcessDevice LabelingFDA requires following information on a label:Common name of device and accurate statement of its principal intended actions.Adequate directions for use:Indications, dose, frequency of administration, duration of administration, time of administration, route of administration, preparation for useDeclaration of its net quantity of contents.Name and address of the manufacturer, packer, or distributor.

FDA Approval ProcessPremarket Approval (PMA)PMA is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices.PMAs must contain sufficient scientific evidence to ensure it is safe and effective for its intended use.FDA regulations provide 180 days to review the PMA and must decide that the device is safe and effective for PMA approval which may use advisory committeesIf there is not an effective date listed for the PMA then a Class III 510(k) should be submitted.

FDA Approval ProcessPremarket notification (PMN or 510(k) )Any Class I, II or III device intended for human use that does not require a PMA must submit a 510(k) unless:the device is exempt from PMNwas marketed before May 28, 1976requires premarket approval (PMA)This is a premarket submission to the FDA that demonstrates that the device is as safe and effective as a legally marketed device which is not subject to PMA (aka equal).The legally marketed device to which equivalence is drawn is known as the predicate device.This allows the FDA to decide whether the device is substantially equivalent to a legally marketed Class I or Class II device, or to a predicate Class III device not requiring a PMA

FDA Approval ProcessPremarket notification (PMN or 510(k) ) (cont)To say the device is substantially equivalent means it need to be AT LEAST as safe and effective as the predicate device therefore it:Has the same intended use as the predicate and as the same technological characteristics as the predicate ORHas the same intended use as the predicate and has different technological characteristics and information submitted to the FDAA device may not be marketed until the device is declared substantially equivalent. If it is not then the submitter mayResubmit a 510(k) with new dataSubmit a PMAOr reclassify the device

FDA Approval ProcessGood Manufacturing Practices (GMP)Part of a quality system covering the manufacture and testing of pharmaceuticals, food and medical devices. Includes clearly defined and controlled processes to validate a process for consistent testing and results.Must provide assurance that the device is manufactured under regulated conditions and controls that ensure it is safe and effective for the intended use.6oNeeds a quality assurance program (QA)Refers to a program with systematic monitoring and evaluation to ensure the quality of the system/product is met.Quality Departments

FDA Approval ProcessInvestigational Device Exemptions (IDE)Section 520 of the FD&C Act provides manufacturers the authority to ship devices solely for investigational use if they obtain approval for an IDE as part of a Pre Market Approvalget the clinical data needed for the PMAUnless exempt, all clinical evaluations of investigational devices must have an approved IDE before starting the study.If evaluation is not cleared for marketing requires: An IDE approved by an institutional review board (IRB) and if there is a risk with the device then FDA approval is also needed.Consent from patientsLabeling for investigational use onlyMonitoring of the study as well as records and reports.

FDA Approval ProcessInvestigational Device Exemptions (IDE) (cont)the IDE application must includedevice descriptionprior investigationsinvestigational planfacility where the device was madeinvestigator agreementsinstitutions where the study will be conductedproposed labelingdescription of clinical evaluation and IRB supervisioninformed consent from human subjectsExample In Industry (Pharmaceuticals)

Example in Industry (Medical Devices)New Development Product (i.e. at US Endoscopy)

Production Level Device is ReadyIn Vitro Testing on Animal PartsDesign Limited Market Release (Clinical Testing on Patients)Bench Testing (Age, Output Verification, etc.)Full Market ReleaseTesting acceptableTesting acceptableTesting acceptableredesignFormal Application to the FDA90 or 180 days