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FEDERAL REGULATORY ISSUES: US Food and Drug Administration Medical Device Amendments
M. Spect Spector, Ph.D.

2.782 FDA REPORT

10% of grade Total length: 8 pages
Includes text, all images and all references

Line spacing: 1.5 Minimum font: 12

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GOVERNMENT REGULATION OF MEDICAL DEVICES US Canada Mexico Europe China India FDA Health Canada Health Ministry (uses US FDA) European Union CE Mark Chinese FDA None

INDIA
India does not regulate the sale of medical medica devices. India accepts non-U.S. Food & Drug Administration-approved as well as nonCE-marked medical devices
however, in accordance with U.S. FDA requirements, U.S. manufacturers may only export to India and to other countries medical devices that have been approved either by the US FDA
www.ita.doc. gov/td/mdequip/indiar quip/indiare egs.html ita.doc.gov/td/mde s.html

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US FDA ORGANIZATION
Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH) Center for Drug Evaluation and Research (CDER) Center for Food Safety and Applied Nutrition (CFSAN) Center for Veterinary Medicine (CVM) National Center for Toxicological Research (NCTR) Office of the Commissioner (OC) Office of Regulatory Affairs (ORA)
Which center to review review your application?

FDA
Center for Devices and Radiologi cal Radiologic al Health http://www.fda.gov/cdr h/index.html

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FDA APPROVAL PROCESS

Classification of Product as I, II, or III
TE products

I. General Controls

II. Special Controls

III. Premarket Approval (PMA)

Good Manuf. nuf. Practice GMP GMP

FDA APPROVAL PROCESS

Classification of Product as I, II, or III
TE products

I. General Controls
No approval of FDA prior to selling the product.
Good Manuf. nuf. Practice GMP GMP

II. Special Controls

III. Premarket Approval (PMA)

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FDA APPROVAL PROCESS

Classification of Product as I, II, or III
TE products

I. General Controls

II. Special Controls

III. Premarket Approval (PMA)

No approval of Equival ent to Market ed Equivalent Marketed FDA prior to Device?; Device?; selling the Premar Premarket Notification product.

510 (k)

Good Manuf. nuf. Practice GMP GMP

FDA APPROVAL PROCESS

Classification of Product as I, II, or III
TE products

I. General Controls

II. Special Controls

III. Premarket Approval (PMA)

No approval of Equival ent to Market ed Equivalent Marketed FDA prior to Device?; Device?; selling the Premar Premarket Notification product.

510 (k)

Good Manuf. nuf. Practice GMP GMP

Analysis of composition and properties, and in vitro and in vivo studies

Good Lab Pract. Pract.

GLP

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FDA APPROVAL PROCESS

Classification of Product as I, II, or III
TE products

I. General Controls

II. Special Controls

III. Premarket Approval (PMA)

Human Trial Investigational Device Exemption IDE

No approval of Equival ent to Market ed Equivalent Marketed FDA prior to Device?; Device?; selling the Premar Premarket Notification product.

510 (k)

Good Manuf. nuf. Practice GMP GMP

Analysis of composition and properties, and in vitro and in vivo studies

PMA
Good Lab Pract. Pract. GLP

FDA History http://www.fda.gov/oc/opacom/fda101/sld017.html

In 1906, 906, Pres President Theodore Theodore Roosev Roosevelt elt signed signed into la law the Food and and Drugs Drugs Act. round in Am Act. The 1906 law's law's relevant relevant backg backgr America star starts with col colonial nial food statut statutes concer concerned with brea bread and and meat. meat. The firs first na national law ca came in in 1848 1848 during an War. tatio ,a during the Mexic Mexica War. It bann banned the impor import ation of adulterated adulterated drugs drugs, chronic public health proble m. problem. In 1937, a public th disa er federal public heal health disaster demo demonstrated trated the need for a strong ronge ral law. Sulfani lamide, the firs ve Sulfanilamide, first "wonder drug drug" and and a popular pular and effecti fectiv trea rrhea, , was ulat ate ed into an treatment for diseases diseases like strep throat and gono gonorrhea was form formul Elixir eted d for use in Elixir of Sulfanilamide and mark markete in chil children dren. But the the liquid formulat ion cont aine ed a pois on, the same chemica eeze, e, and it rmulati contain poiso chemical used in antifr antifreez killed 107 107 people, most of them chil children. The earlier earlier la law did not not require the drug's on for safety drug's manufact manufacturer to test test the form formulati ulatio safety before it was was sold. sold. Congress s co o rrected ected this weakness in the la a w in 1938 38 when en it pass sse e d t he Congres c rr l 19 wh pa Federal Food, Drug Drug, and Cosmet Cosmetic Act Act. This la law, for the the firs first time, time, required required compan ies to prove the safety companies fety of new drug drugs before before putting putting them on on the the market. The new act also also added the the re regul gulation tion of cosmeti metics and therapeutic herapeuti devices, ion n. devices, and generally generally updated the law to improve improve consumer consumer protect protectio 1976 Medica Medical Devices Devices Amendment Cong ress continues Congress continues to give FDA new responsibilities. responsibilities.

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FDA STAFFING
To carry out its mission, FDA employs some 9,000 staff who work in locations around the country. The network of 167 field offices is generally the first point of contact for the public and regulated manufacturers. The employees in these offices focus on inspection and surveillance, laboratory work, and public and industry education. The FDA staff who work in the greater Washington, D.C., area focus on product review revie and regulatory policy.

CDRH Advisory Committees

The Center for Devices and Radiological Radiological Heal Health has established advisory committees committees to provide independent, professional professional expertise and and technical technical assist assistance on the development, safety and ess, and regulation of and effectiven effectiveness, medical devices and electronic products that produce radiation. Each committee consists of experts wi with recogniz ed expertise and recognized and judgment in a specific field. The committees are advisory nd advisory -- they provide their expertise a and recommendations recommendations -- but final decisions are made by FDA. The Center has four advisory committees, including a Medical Devices Advisory Committee which consists of 18 panels that cover the medical medical specialty specialty areas. areas. These advisory committee committee meet meetings are open to the public, and and time is provided for public comment on the topic under consideration.

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CDRH Advisory Committees

Medical Devices Advisory Committee
Consists of 18 Panels

Devices Good Manufacturing Practice (GMP) Advisory Committee National Mammography Quality Assurance Advisory Committee Technical Electronic Product Radiation Safety Standards Committee

FDA ADVISORY PANELS

Anesthesiology and Respiratory Therapy Devices Circulatory System Devices Clinical Chemistry and Clinical Toxicology Devices Dental Products Ear, Nose, and Throat Devices Gastroenterology and Urology Devices General and Plastic Surgery Devices General Hospital and Personal Use Devices Hematology and Pathology Devices

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FDA ADVISORY PANELS

Immunology Devices Medical Devices Dispute Resolution Microbiology Devices Molecular and Clinical Genetics Neurological Devices Obstetrics and Gynecology Devices Ophthalmic Devices Orthopaedic and Rehabilitation Devices Radiological Devices

FDA ADVISORY PANELS Current Role in the Regulatory Process

Each Panel is made up of experts in the field including physicians, surgeons, scientists and engineers, a consumer representative, and an industry representative (non-voting member) FDA staff requests that the Panel review certain submissions to FDA and make a recommendation to FDA regarding the acceptance or rejection of the documentation with respect to sufficient evidence to support safety and efficacy; the Panel takes a vote to determine the recommendation At the Panel meeting, the company makes a presentation to the Panel to support its documentation FDA may choose to accept or reject the Panel recommendation

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FDA ADVISORY PANELS Initial Role in the Regulatory Process Each Panel reviewed every medical device in i its specialty to determine of the classification of the device should be I, II, or II. The Panels currently make recommendations about the down-classification of devices; e.g., hip replacement prostheses were downclassified from II to II.

CDRH Overview of Regulations

The CDRH is responsible for regulating firms who manufacture, repackage, relabel, and/or import medical devices sold in the United States. Medical devices are classified into Class I, II, and III. A description of device classification and a link to the Product Classification Database can be found at: ttp://www.fda.gov/cdrh/devadvice/313.html. Regulatory control increases from Class I to Class III. The device classification regulation defines the regulatory requirements for a general device type.
Most Class I devices are exempt from Premarket Premarke Notification 510(k) Most Class II devices require Premarket Notifi cation on Notificati 510(k); 510(k); Most Class III devices require Premarket Premarket Approval. Approval.

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CDRH Overview of Regulations

The basic regulatory requirements that manufacturers of medical devices distributed in the U.S. must comply with are:
Premar Premarket Notification 510(k), unless exempt, or Premar Premarket Approval (PMA), Establishment ration on form Establishment regist registr form FDAFDA-2891, Medical Device Listing on form FD FDA-2892, Quality System (QS) regulation, Labeling requirements, and Medical Device Reporting (MDR)

Is My Product Regulated by FDA's Center for Devices and Radiological Health?

The FDA regulates medical devices to assure their safety and effectiveness. The CDRH is the component within the FDA that is responsible for this program. To fulfill the provisions of the FD&C Act that apply to medical devices and radiation-emitting products, the FDA develops, publishes and implements regulations. These regulations are initially published in the Federal Register (FR) for public comment. The FR is a compilation of the daily government activities including proposed and final regulations. Final regulations are subsequently placed or codified into the Code of Federal Regulations (CFR) on an annual basis. One of the most important aspects of getting a medical device to market is to know where to begin. The starting point is determining whether the product you plan to market is a medical device, as defined in section 201(h) of the FD&C Act. If your product meets the definitions, it will be subject to the provisions of the FD&C Act, that is, there are FDA regulatory requirements that must be met before a product can be marketed in the U.S. The purpose of Device Advice is to help you decide whether your product is subject to FDA regulations, and if so, to identify what these regulatory requirements are and help you comply with them.

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Medical Device Definition

Medica Medical device devices range from simple simple tongue depress depressors and and bedp bedpans to complex program mable pacemakers ogy and la programm pacemakers with micro-c micro-chip technol technolo laser se surgical devic es. If a produc t is oted or used device product is labeled, beled, prom promoted used in a man manner th that meets the following on in section 201(h) of the Federal Food Drug & following definiti definition Cosm ated by the FDA as a medic medical dev device Cosmetic (FD& (FD&C) Act Act it it will be regul regula and is subjec t to prem ng and rketing ry cont rols. ls. subject premarketi arketing and postma postmar eting regulato latory contro A device an instru ement, ma device is:" is:"a instrument, appara apparatus, impl implement, machine, contrivance, contrivance, implan t, in vit ent, t, or other cle, incl plant, vitro reag reagen other similar similar or related related arti article, including uding a componen ory y which is component part, or access accessor is:
recogniz ed in the recognized the offici official Nation National Formul Formulary, or the the United United States Pharmac opoei armaco poeia, or any any supplem supplement to them them, intende d for use in the diagnosis of disease or other conditions , intended conditions, or in the the cure cure, mitigation, treatment, treatment, or prevention prevention of disease, in man or or other animals, or inten ded to affect re or any intend affect the the st structu ructur any function of the body of man or other animals, and which s which does does not achieve achieve any any of it's it's primary intended purpose purposes through chemical acti action within or on the body of man or other animals animals and which nt upon be ed for the achie vement of any ich is not depende dependent being metaboliz metabolize achiev any of its primary d purpose s." " primary intende intended purposes.

Medical Device Definition

The definition provides a clear di distinction between between a medical medical device and other FDA regulated products products such as drugs. If the primary intended use of of the product is achieved through chemical action or by being metabolize metabolized by th the body, the product is usually a drug. Human drugs are regulated by FDA's Center for Drug Evaluation and Research (CDER). Biological pr products wh which include include blood and blood products, and blood banking equipment are regulated by FDA's Center for Biologics Evaluation and Research (CBER). FDA's Center for for Veterinary Medicine (CVM) regulat regulates products used used wi with animals. If your product is not a medical device but regulated by another Center in the FDA, each component of the FDA has an office to assist wi with questions about the products they re regulate. late. In cases wh where it is not clear wh whether a product is a medical device there are proc procedures in place place to use DSMICA Staff Directory to assist you in making a determination.

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FDA DEVICE CLASSIFICATION

The FDA has established classifications for approximately approximately 1,700 different ge generic types of devices and grouped them into 16 medical specialties specialties referred to as panels. Each of these gene generic ri types of devices is assigned to one of three regu regulatory classes classes based on the level of control control necess necessary to assure assure the safety safety and an effectivenes s of the device: effectiveness
Class Class I Genera General Cont Controls Class ral Cont Class II Gene General Controls and Sp Special Contro Controls Class t Approv al Class III General General Cont Controls and Premarke Premarket pproval

The class to which your device is assigned determines, among other things tion things, the type of of premarketing submission/applica submission/applicat required for for FDA clearance to market. market.
If your your devi device is cla classified sified as Class II a 510k will be required required for fo marketin marketing. For Clas s III devices, ion (PMA) will be Class devices, a prem premarke arket approval approval applicat applicati required.

FDA DEVICE CLASSIFICATION

Device classification depends on th the intended intended us use of the device and also upon indicatio ns for use. For exampl indication example, a scalpel's intended use is to cut tissue. A su subset of intend intended use arises when when a more specia lized ed indication is added in the device's labeling specializ such as, "for making incisions incisions in the the cornea." Indications for use use can be found in the device's labeling, labeling, but may also be conv conveyed orally during sale of the product. In addition, classification is risk risk based, that is, the risk the the device poses to the patient and/or the user user is a major factor in the class class it is assigned. Class I includes devices wi with the lowe lowest risk and and Class III includes those wi with the greatest risk. As indicated above all classes of devices as subject to General Controls. General General Controls are are the baseline requirements of the Food, Drug and Cosmetic (FD&C) Act that apply to all medical devices, Class Class I, II, and III.

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How to Determine Classification

To find the classification of your device you need to find the regulation number that is the classification regulation for your device. There are two methods for accomplishing this: go directly to the classification database and search for a part of the device name, or, if you know the device panel (medical specialty) to which your device belongs, go directly to the listing for that panel and identify your device and the corresponding regulation. If you already know the appropriate panel you can go directly to the CFR and find the classification for your device by reading through the list of classified devices, or if you're not sure, you can use the keyword directory in the PRODUCT CODE CLASSIFICATION DATABASE. In most cases this database will identify the classification regulation in the CFR. You can also check the classification regulations below and the Precedent Correspondenc for information on various products and how they are regulated by CDRH. Once you have identified the correct classification regulation go to What are the Classification Panels below and click on the correct classification regulation or go to the CFR Search page. Some Class I devices are exempt from the premarket notification and/or parts of the good manufacturing practices regulations. Approximately 572 or 74% of the Class I devices are exempt from the premarket notification process. These exemptions are listed in the classification regulations of 21 CFR and also has been collected together in the Medical Device Exemptions document.

DEVICE CLASSES

Class I - General Controls Controls Class II - Special Controls Class III - Premarket Approval

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DEVICE CLASSES Class I - General Controls

Class I devices are subject to the the least regulat regulatory control. control. They They present minimal potential for harm to the user and are often simpler in design than Class II or Class III devices. devices. Class I devices devices are subject to "General Controls" as are Class II and Class III devices. Genera l controls General controls incl include:
Establis hmen nt Regis on of co ter Establishme Registrati ration companies mpanies which are required required to regis regist kages under 21 CFR Part 20, su such as ma manufact nufacturers, urers, dis distributors butors, repac repack Part 807. 807.2 and relabeler s. relabelers ) wi Medical Form 2892 2892) with FDA of devices devices to be cal De Device List Listing ing (use FDA Form marketed marketed. Manufac turing s in accordance tice ces Manufact uring device devices accordance with with Good Ma Manuf nufacturin uring Prac Practi (GMP (GMP). Labeling Labeling devices devices in acco accordance with labeli labeling regulatio regulations. Submiss ion of a prem icatio n [510 (k)] before Submissi premarket arket notif notifi cation [510(k)] before ma market rketing a device.

Examples of Class I devices include include elastic bandages, examination examination gloves, and handhand-held surgical surgical instruments. instruments.

DEVICE CLASSES Class II - Special Controls

Class II devices are those for which general controls alone are insufficient to assure safety and effectiveness, and existing methods are available to provide such assurances. In addition to complying with general controls, Class II devices are also subject to special controls. Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance. Examples of Class II devices include powered were wheelchairs, infusion pumps, and surgical drapes.

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DEVICE CLASSES Class III - Premarket Approval

Class nt regulatory category s III Class III is the the mo most stringe ringen category for devices. devices. Clas Class III devices devices are those for which insufficient insufficient informat information exists exists to assu ssure safe safety and effect effectiveness sole solely through general general or special special contro controls. ls. Clas s III devi ces are usually those t or sust ain hum , are Class devices those that suppor support susta human life life, of subs tantia al importance in preve nting im substanti preven impairment of human human health, health, or which present a potentia potential, unreaso unreasonable nable risk risk of illness illness or injury. injury. Premarket approval ss of scientif approval is the re required proce process scientific review review to ensure ensur the safety s II . Not all Class ces fety and effect effectiveness eness of Clas Class III devices devices. Class III devi devices require an approved premarket on to be market premarket approval approval applicati applicatio rketed. ed. Class ces which are equivalent y market Class III devi devices equivalent to devices devices legall legally marketed before May 28, 1976 may be market fica ation rketed through the prem premarket arket noti notific [510(k)] proce ss until FDA has publishe d a requirement turers process published requirement for manufac nufacturers of that c ty that generi generic type of devic device to subm submit PMA dat data. Class ces which require t approval Class III devi devices require an approved approved premarke premarket pproval applicati on to be ma applicatio market rketed are those:
regulated as new drugs prior tional devices. prior to to May May 28, 28, 1976, 1976, also called called transi transitional devic es found not substantially equivalen device quivalent to device devices mark marketed prior to May May 28, 28, 1976. Class III preamend es which, on in 21 CFR, require a reamendment ent devic device ich, by by regulati regulation premarke remarket appr approval application. application.

DEVICE CLASSES Class III - Premarket Approval

Examples of of Class III devices wh which require a premarket premarke approval include include replacement heart valves, silicone gelgel-filled breast implants, and implanted cerebella stimulators. Class III devices devices which can be marketed wi with a premarket notification 510(k) are those:
post nt (i.e., oduced uced to the U. postamendme amendmen (i.e., intr introd U.S. ma market rket after after May 28, 28, 197 1976) Class ces which are substan tially nt Class III devi devices substant lly equivalent quivalent to preamendme preamendmen (i.e., ed to the U.S. market bef (i.e., introduc introduced before May May 28, 28, 1976) 1976) Class III devices ation ca t approval devices and for which the regul regula calling lling for the premarke premarket pproval applicati on has no d in 21 CFR. applicatio not been been publishe published

Examples of of Class III devices wh which currently require a premarket notification include implantable implantable pa pacemak cemaker pulse generators generators and endoss endosseous implan implants.

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What is Premarket Notification [510(k)]

Each person who wants to market Class I, II and some III devices intended for human use in the U.S. must submit a 510(k) to FDA at least 90 days before marketing unless the device is exempt from 510(k) requirements. A 510(k) is a premarketing submission made to FDA to demonstrate that the device to be marketed is as safe and effective, that is, substantially equivalent (SE), to a legally marketed device that is not subject to premarket premarke approval (PMA). Applicants must compare their 510(k) 510(k device to one or more similar devices currently on the U.S. market and make and support their substantial equivalency claims.

What is Premarket Notification [510(k)]

A legally marketed device is
a device that wa was legally marketed prior to May 28, 1976 (preamendments device), or a device which has been reclassified from Class III to Class II or I, a device which has been found to be substantially substantially equivalent to such a device through the 510(k) process.

The legally marketed device(s) to which equivalence is drawn is known as the "predicate" device(s).

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What is Premarket Notification [510(k)] Applicants must submit descriptive data and, when necessary, performance data to establish that their device is SE to a predicate device. Again, the data in a 510(k) is to show comparability, that is, substantial equivalency (SE) of a new device to a predicate device.

What is Substantial Equivalence

Unlike PMA, which requires demonstration of reasonable safety and effectiveness, 510(k) requires demonstration of substantial equivalence. SE means that the new device is as safe and effective as the predicate device(s). A device is SE if, in comparison to a predicate device it:
has the same intended use as the predicate device; and has the same technological characteristics characteristics as the predicate device; or has different technological characteristics, characteristics, that that do not raise new question eness, and the sponsor questions of safety and effectiv effectiveness, demonstrates that the device device is as safe and effective as the legally marketed device.

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IDE Overview
An in ce exemp tio on (IDE) invest vestigati ational devi device exempti (IDE) all allows the in invest vestigational onal devic device to be used in a clinical tiveness clinical study in order to collect safety safety and effec effect eness data required to suppor t a Premar al (PMA ) appli support emarket Approv pproval (PMA) application or a Premarket Notification cation [510(k)] 510(k)] submission to FDA FDA. Clinical ort t a PM Clinical studies studies are are mo most often conducted conducted to supp suppor PMA. Only ort t the Only a small small percentage of 510(k) 510(k)s re require quire clinical clinical data to supp suppor applicati on. applicatio All clini ationa l devices, unless exempt, inical eva evaluat uations of inve investig stiga ional pt, must have hav an appro ved IDE before the stu study is ini initiated. approv Cli ces that Clinical evalu aluation of devi devic that have not been cle cleared red fo for market rketing requires: requires:
an IDE approve d by an institut approved institutional ional review board board (IRB). If th the study study involve involves a significant risk device, the IDE must also be appr oved d by FDA; approve FDA; informed informed cons consent from from all patients; labeling for for inve investigational use only monitori monitoring of the study and; requ s and . required record records and reports reports.

Premarket Approval (PMA)

PMA is s of scientif y review uate the is the FDA proces process scientific and regulator regulatory review to eval evalu the safety cal devices. safety and effectiv ffectiveness eness of Class Class III medi medical devices.
Class III devic es are device are those that support support or sustain sustain human life, are are of substantia substantial impo g impa ent ta importance rtance in preventin reventing impairment ment of human health, health, or which ich pres presen potential, potential, unre unreasonable risk of illness illness or injury injury. Due to the level es, FDA has determine level of risk associ associated ated with Class III devic device termined that that general general and and special cont controls rols alone alone ar are ins insufficient fficient to ass assure the safety safety and and effec es. ffectiven iveness of class III devic device Therefore , thes e de t approval (PMA) application Therefore, these devices vices require a prem premarke arket under section rance. section 515 of the the FD&C Act in order to obtain marketing clea clear ance.

PMA is the most most stringe ringent typ type of device device marketin marketing applicatio application required required by FDA. Th ve FDA val of its PM The appl applicant ant must must recei receive FDA appro approv PMA appl applicatio ation prior to marketin g the devi ce. PMA approval ina ation marketing device. approval is based on a determ determin io by FDA that icient va that the PMA co contains suff sufficient valid scientif scientific evi evidence ence to assure assure tha ved that the devi device is safe safe and ef effective fective for its its intended intended use( use(s). An appro approv PMA is, tin ng the appl icant is, in effec effect, a priva ivate lic license gran granti appli ant (o (or owner) permiss rize permission to market the device. device. The PMA owner, howe however, can autho authorize use of its data by another. another.

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PMA Data Requirements

A PMA applicat atory docume application is is a scie scientif ntific, ic, regul regula documentation to FDA FDA to t demonstr ate the safety and effect demonstrate effectiven iveness ess of the class III III device. device. Good science and scientific val of PMA appli scientific writing is a key to the appro approv pplicati ation. If a PMA PM applicati on lacks valid clinic on and scientif pplicatio clinical informati formatio scientific analysis ysis on so sound und scientif ew and al. . PMA scientific reas reasoning, ing, it will delay FDA FDAs revi review and approv approval PMA applications te, , inc al ions tha that are inc incompl mplete, inaccura curate inconsist istent, om omit critic critica informati on, and po ed have informatio poorly organiz organize have result resulted in delays delays in ap approval roval or denial of PMA applic ations. . Manu urers rol l applications Manufact factu ers sho should perform a qu quality cont contro audit ation before sendin audit of a PM PMA applic application sending it to FDA to assure assure tha that it is scient y sound ed form scientificall ically und and presented presented in a well organiz organize format. g data and Technical Sect technical sect sections cont containin aining and in inform formatio ation Sections: ns: The technical should allo mine whet allow FDA to deter determ whether to approve approve or disa disapprove pprove the the applicatio n. Thes e sections lly divi clinical la tor ry ication. These ections are usua usually divided into non non-clinical labora borato studies and cl tigatio clinical inves invest gations. ns. ratory ies Non-clin ical Labo ratory ry Stud ies Sect Non-clini inical labo labor tory stud studi Non-clinical Laborato Studies Section: Non-c sectio on on microbiology, gy, section includes includes informati informatio microbiology, to toxicol cology, gy, immunolo immunolog biocom patibil bili ity, st biocompati stress, ress, wear, shelf shelf life, life, and other laboratory boratory or anim animal tes tests. Non-cli nical st on must nce Non-clin studies for safety safety ev evaluati aluation must be co conducted nducted in complia compliance ratory with Laboratory tory Practice actice for Nonclinical Nonclinical Labo Labor with 21C 21CFR Part Part 58 (Good Labora Stud Studies) ies).

PMA Data Requirements

Clinical Inve Investigat stigations ions Section: Clinical investigations investigations section includes study protocols, safety and effectiveness effectiveness data, adverse advers reactions and complications, device failures failures and and replacements, patient information, laints, tabulations of data information, patient comp complaints, from all individual subjects, results results of statistical analyses, and and any other information from the clinical investigations. Any investigation conducted under an Investigational Device Exemption (IDE) must be identified identified as such. Like ot other sc scientific reports, FDA has observed problems wi with study designs, study conduct, conduct, data analyses, presentations, and conclusions. Investigators should always always consult consult all applicable FDA guidance documents (http://www.accessdata.fda.gov/scripts/cdrh /cfdocs/cfGGP/Sear http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfGGP/Sea ch.cfm). ch.cfm).

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