Class II Special Controls Guidance Document: Root-form Endosseous Dental Implants and Abutments; Draft Guidance for Industry and FDA

Transcription

1 Cass II Specia Contros Guidance Document: Root-form Endosseous Denta Impants and Abutments; Draft Guidance for Industry and FDA Draft Guidance - Not for Impementation This guidance document is being distributed for comment purposes ony Draft reeased for comment on [reease date as stated in FR Notice] When fina this document wi supersede: Overview of Information Necessary for Premarket Notification Submissions for Endosseous Impants; Fina, 04/2 / 999 Information Necessary for Premarket Notification Submissions For Screw-Type Endosseous Impants, 12/09/ 996 Guidance For the Arrangement and Content of a Premarket Approva (PMA) Appication for An Endosseous Impant For Prosthetic Attachment, 5/16/89 (parts of) Cacium Phosphate(Ca-P) Coating Draft Guidance for Preparation of FDA Submissions for Orthopedic and Denta Endosseous Impants, 2/2 /97 US Department of Heath and Human Services Food and Drug Administration Center for Devices and Radioogica Heath Denta Device Branch Division of Denta, Infection Contro, and Genera Hospita Devices Office of Device Evauation

2 Draft - Not for Impementation Tabe of Contents BACKGROUND ~ 1 SCOPE 2 RISKS TO HEALTH 3 CONTROLS 3 ABBREVIATED 510(K) CONTENT 4 MATERIAL COMPOSITION 8 MECHANICAL PROPERTIES 8 FIXTURE TO ABUTMENT COMPATIBILITY 8 FATIGUE TESTING IN COMPRESSION AND SHEAR 8 CORROSION TESTING 9 MODIFIED SURFACES INFORMATION 10 ANIMAL AND CLINICAL STUDIES 12 CLINICAL PROTOCOL 12 CLINICAL RESULTS LABELING 16

3 Draft - Not for Impementation Preface Pubic Comment For 90 days foowing the date of pubication in the Federa Register of the notice announcing the avaiabiity of this guidance, comments and suggestions regarding this document shoud be submitted to the Docket No assigned to that notice, Dockets Management Branch, Division of Management Systems and Poicy, Office of Human Resources and Management Services, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockvie, MD Additiona Copies Additiona copies are avaiabe from the Internet at: address], or CDRH Facts-On-Demand In order to receive this document via your fax machine, ca the CDRH Facts-On-Demand system at or from a touch-tone teephone Press 1 to enter the system At the second voice prompt, press 1 to order a document Enter the document number (13 89) foowed by the pound sign (#) Foow the remaining voice prompts to compete your request

4 Draft - Not for Impementation Cass II Specia Contros Guidance Document: Root-form Endosseous Denta Impants and Abutments; Draft Guidance for Industry and FDA This document is intended to provide guidance It represents the Agency s current thinking on this topic It does not create or confer any rights for or on any person and does not operate to bind the Food and Drug Administration (FDA) or the pubic An aternative approach may be used if such approach satisfies the requirements of the appicabe statute and reguations 1 Background This guidance document was deveoped as a specia contro guidance to support the recassification of the root-form endosseous denta impant device into cass II and the recassification of the endosseous denta impant abutment device into cass II The root-form endosseous denta impant device refers to the endosseous denta impant fixture It is intended to be surgicay paced in the bone of the upper or ower jaws to provide support for prosthetic devices, such as artificia teeth, in order to restore the patient s chewing function The endosseous denta impant abutment device is intended to be used with the denta impant fixture to aid in prosthetic rehabiitation Some endosseous denta impants may incude an integra transgingiva component These impants do not require the concurrent use of a denta impant abutment FDA wi issue this guidance in conjunction with a Federa Register notice announcing the proposa to recassify these devices This guidance is for comment purposes ony If the fina rue does not recassify these devices, this guidance document wi not be issued as a specia contro FDA beieves that these specia contros, when combined with the genera contros, wi be sufficient to provide reasonabe assurance of the safety and effectiveness of the root-form endosseous denta impant device and the endosseous denta impant abutment device If these devices are recassified, a manufacturer who intends to market a device of either generic type must (1) conform with the genera contros of the Food, Drug & Cosmetic Act, incuding the 5 1 O(k) requirements described in 2 1 CFR 807 Subpart E, (2) address the specific risks to heath associated with the device described in the specia contro guidance, and (3) receive a substantia equivaence determination from FDA prior to marketing the device This specia contro guidance document identifies the cassification, product code, and cassification definition for the root-form endosseous denta impant device and the endosseous denta impant abutment device In addition, it identifies the risks to heath FDA beieves that the contros described in this guidance, when foowed and combined with the genera contros, 1

5 Draft - Not for Impementation wi generay address the risks associated with these generic device types and faciitate 51 O(k) review and cearance For the specific content requirements of a 51 O(k) submission, you shoud refer to 21 CFR and other agency documents on this topic, such as the 510(k) Manua - Premarket Notification: 510(k) - Reguatory Requirements for Medica Devices, 1 Okprt htm Device manufacturers may submit an Abbreviated 51 O(k) when: (1) a guidance documents exists, (2) a specia contro has been estabished, or (3) FDA has recognized a reevant consensus standard FDA beieves an Abbreviated 51 O(k) is the east burdensome means of demonstrating substantia equivaence once a Cass II Specia Contros Guidance Document has been issued See aso The New 510(k) Paradigm - Aternate Approaches to Demonstrating Substantia Equivaence in Premarket Notifications; Fina Guidance, 1 Ohtm An Abbreviated 5 1 O(k) submission must incude the required eements identified in 2 1 CFR 80787, incuding a description of the device, the intended use of the device, and the proposed abeing for the device An Abbreviated 5 1 O(k) shoud aso incude a summary report In an Abbreviated 5 1 O(k), FDA may consider the contents of a summary report to be appropriate supporting data within the meaning of 21 CFR 80787(f) or (g) The summary report shoud briefy describe the methods or tests used and the acceptance criteria appied to address the risks identified in this guidance document as we as any additiona risks specific to your device When a suggested test method is foowed, a simpe reference to the method wi be an acceptabe description If there are any deviations from a suggested test method, you shoud provide more detaied information in the summary report to characterize the particuar deviation The summary report shoud aso either (1) briefy present the data resuting from each test x (2) describe the acceptance criteria to be appied to the test resuts (See aso 21 CFR Subpart C Design Contros for the Quaity System Reguation) 2 Scope FDA identifies the generic root-form endosseous denta impant device as a Denta Devices Pane device cassified under 21 CFR , product code DZE A root-form endosseous denta impant device is intended to be surgicay paced in the bone of the upper or ower arches to provide support for prosthetic devices, such as artificia teeth, in order to restore the patient s chewing function FDA identifies the generic and the endosseous denta impant abutment device as a Denta Devices Pane device cassified under 21 CFR , product code NHA An endosseous denta impant abutment device is intended to be used in conjunction with an endosseous denta impant fixture to aid in prosthetic rehabiitation 2

6 Draft - Not for Impementation 3 Risks to Heath FDA has identified the risks to heath generay associated with the use of the root-form endosseous denta impant device in the tabe beow You shoud aso conduct a risk anaysis, before submitting your 5 10(k), to identify any other risks specific to your device The premarket notification shoud describe the risk anaysis method The measures recommended to mitigate the identified risks are given in this guidance document, as shown in the tabe beow (If a manufacturer eects to use an aternative approach to address a particuar risk, or has identified risks additiona to those in the guidance, you shoud provide sufficient detai to support the aternative approach) Identified risk Recommended mitigation measures oca soft tissue degeneration I 9, hyperpasia 11,12 progressive bone resorption 9, exfoiation 9, damage to existing dentition 779 impant mobiity 7,9,11 infection 11,12 PP1 paresthesia I 12,15 perforation of the maxiary sinus I 12,15 perforation of the abia and ingua aveoar pates 12,15 bacteria endocarditis 11,12 oss of impant integrity 7,9,11 I I I I I The risks to heath that are generay associated with the use of endosseous denta impant abutment devices are isted in the tabe beow Identified risk oca soft tissue degeneration Recommended mitigation 9, measures damage to existing dentition 779 oss of abutment integrity I 7,8,12 I 4 Contros FDA beieves that the contros in the foowing sections of this guidance, when combined with 3

7 Draft - Not for Impementation genera contros, wi address the identi fied risks to heath associated with the use of the rootform endosseous denta impant device and the endosseous denta impant abutment devices You shoud demonstrate that your device compies with either the specific recommendations of this guidance or an aternate means to address the above identified risks, in order to provide reasonabe assurance of the safety and effectiveness of the device If you have identified any additiona risks, specific to your device, your 5 1 O(k) shoud identify those risks, as we as the methods or tests used and the acceptance criteria appied to address them 5 Abbreviated 510(k) Content An Abbreviated 5 1 O(k) that reies on a Cass II Specia Contros Guidance Document shoud contain the foowing Coversheet The coversheet shoud prominenty identify the submission as an Abbreviated 510(k) and cite the tite of the specific Cass II Specia Contros Guidance Document Items Required Under 21 CFR The items required under 21 CFR are: Description of the device You shoud incude a compete discussion of the performance specifications and, when appropriate, detaied, abeed drawings of the device You shoud aso incude a description of device features, with dimensions and toerances Exampes of features incude anti-rotationa features, such as interna or externa hexagona features, fat axia surface features on fixtures, fins, threads, or vertica anti-rotation sots Engineering drawings of a components You shoud incude drawings showing a dimensions and toerances A drawing abes shoud be ceary egibe and in Engish Intended use of the device You shoud incude a description of compatibe abutments, incuding surfaces that mate with impant fixtures List or give exampes of compatibe fixture types made by other manufacturers You shoud aso submit an indications for use encosure See for the recommended format Proposed abeing

8 Summary Report Draft - Not for Impementation A summary report shoud describe how the Cass II Specia Contros Guidance Document was used to address the risks associated with the particuar device type In an Abbreviated 5 1 O(k), FDA may consider the contents of a summary report to be appropriate supporting data within the meaning of 21 CFR 80787(f) or (8) The summary report shoud contain: Risk anaysis Description of device performance requirements Discussion of the features and functions provided to address the risks identified in this Cass II Specia Contros Guidance Document, as we as any additiona risks identified in your risk anaysis For each performance aspect identified in sections 6 through 10 of this Cass II Specia Contros Guidance document, you shoud briefy discuss each test method and your acceptance criteria When a suggested test method is foowed, a simpe reference to the method wi be an acceptabe description If there are any deviations from a suggested test method, you shoud provide more detaied information in the summary report to characterize the particuar deviation The summary report shoud aso either (1) briefy present the data resuting from each test in tabuar form or (2) describe the acceptance criteria to be appied to the test resuts If the device, as manufactured, does not meet your acceptance criteria, you may not market it Instead, vow must submit a new 51 O(k) with revised acceptance criteria which must be ceared by FDA before you market the device If any part of the device design or testing reies on a recognized standard, the summary report shoud incude: (1) a statement that testing wi be conducted and meet specified acceptance criteria before the product is marketed, or (2) a decaration of conformity to the standard Testing must be competed before submitting a decaration of conformity to a recognized standard (2 1 USC 5WCPP))~ F or more information, see FDA guidance, Use of Standards in Substantia Equivaence Determinations; Fina Guidance for Industry and FDA, 1 htm If FDA recommends a cinica study for your device (see section 12), your summary report shoud state that you foowed the cinica protoco described in section 13 If you have deviated from this protoco, you shoud describe the deviations and expain how your protoco addressed the risks Your summary report shoud incude the information described in section 14 If you have omitted any of the information described in section 14, you shoud expain how substantia equivaence can be determined without this information If it is not cear how you have addressed the risks identified by FDA or by your risk anaysis, we may request additiona information about aspects of the device s performance characteristics 5

9 Draft - Not for Impementation We may aso request additiona information, if we need it to assess the adequacy of your acceptance criteria As an aternative to submitting an Abbreviated 5 1 O(k), you can submit a traditiona 5 1 O(k) that provides a of the information and data described in this guidance A traditiona 5 1 O(k) shoud incude a of your methods, data, acceptance criteria, and concusions For a testing, your summary report shoud incude: standard deviation anaysis reference to the test method or summary of your test protoco methods for sampe preparation drawing of your test set up 0 faiure report magnified photographs of the faiure regions acceptance criteria for each test, uness specification incuded in the recognized standard You may use the FDA guidance documents and recognized consensus standards isted beow to estabish the performance characteristics of your device FDA Guidance Documents 51 O(k) Steriity Review Guidance 2/ 2/90 (K90-1) htm Use of Internationa Standard ISO , Bioogica Evauation of Medica Devices Part 1: Evauation and Testing 1 htm Consensus Standards ASTM F67-95 Standard Specifications for Unaoyed Titanium for Surgica Impant Appications ASTM F86-91 Standard Practice for Surface Preparation and Marking of Metaic Surgica Impants ASTM F136-98e Standard Specification for Wrought Titanium-6 Auminum-4 Vanadium ELI (Extra Low Interstitia) Aoy (R56401) for Surgica Impant Appications ASTM F Practice for Retrieva and Anaysis of Impanted Medica Devices, and Associated Tissues 6

10 Draft - Not for Impementation ASTM F Standard Practice for Fuorescent Penetrant Inspection of Metaic Surgica Impants ASTM F Standard Specification for Titanium-6 Auminum-4 Aoy Forgings for Surgica Impants (UNS R56401) Vanadium ELI ASTM F746-87(1994) Standard Test Method for Pitting or Crevice Corrosion of Metaic Surgica Impant Materias ASTM FO44-95 Standard Test Method for Shear Testing of Porous Meta Coatings ASTM F Standard Specification for Titanium-6 Auminum-4 Aoy Castings for Surgica Impants (UNS R56406) Vanadium ASTM F Standard Test method for Tension Testing of Cacium Phosphate and Meta Coatings ASTM F Standard Test Method for Shear and Bending Fatigue Testing of Cacium Phosphate and Metaic Medica Coatings ASTM F (1993)e Standard Specification for Composition of Ceramic Hydroxyapatite for Surgica Impants ASTM F Standard Specification for Wrought Ti-6A-4V Impant Appications Aoy for Surgica ASTM F Standard Test Method for Tension Testing of Cacium Phosphate Coatings ASTM F Standard Specification for Titanium and Titanium-6% Auminum- 4% Vanadium Aoy Powders for Coating Surgica Impants ASTM F Standard Specification for Cacium Phosphate Coatings for Impantabe Materias ASTM F Standard Test Method for Shear Testing of Cacium Phosphate ASTM F Standard Test Method for Bending and Shear Testing of Cacium Phosphate Coatings on Soid Metaic Substrates ASTM F Standard Practice for Corrosion Fatigue Testing of Metaic Impant Materias IS : 1993 Impants for Surgery - Metaic Materias - Part 2: Unaoyed Titanium

11 Draft - Not for Impementation IS : 1996 Impants for Surgery - Metaic Materias - Part 3: Wrought Titanium 6-Auminum 4-Vanadium Aoy IS : 1997 Dentistry - Precinica Evauation of Biocompatibiity of Medica Devices Used in Dentistry - Test Methods for Denta Materias 6 Materia Composition Your summary report shoud incude the foowing information for a components: the materia identity the compete chemica composition, uness decaring conformance to a materias standard 7 Mechanica Properties Your summary report shoud incude the foowing information for the finished device: a description of mechanica properties the methodoogy for determining the mechanica properties, if a testing standard was not used 8 Fixture To Abutment Compatibiity You shoud describe the performance testing conducted to determine fixture-to-abutment compatibiity 9 Fatigue Testing in Compression and Shear You shoud conduct mechanica testing for devices that: consist of anged abutments; are impant or abutment designs that are significanty different from predicate devices; or have design features or technoogica characteristics that have not been previousy ceared for market You shoud test the finished device or components that have undergone the same manufacturing processes as a finished device You shoud expain how the properties of the new device show adequate device performance

12 Draft - Not for Impementation Some impants do not use a separate abutment component However, for those that do, you shoud test the assembed impant/abutment system If the impant or abutment is marketed by another manufacturer, you shoud foow the assemby instructions that manufacturer provides You shoud set up testing to ensure that the impant or impant/abutment system is subjected to both compressive and shear (atera) forces No atera constraint shoud occur Testing conditions shoud mimic actua intraora use as much as possibe You shoud perform testing of anged abutments at the greatest anguation intended (ie, the worst case scenario) Abutment anguation greater than 30 shoud be supported by cinica data The test setup shoud camp the impant so that the impant s ong axis makes a 30 ange with the oading direction of the testing machine, uness you are testing an anged abutment of greater than 20 For anged abutments, the test setup shoud eave at east 10 of the anguation uncorrected (ie, a 30 abutment shoud be tested with the impants ong axis at 40 and a 25 abutment shoud be tested with the impants ong axis at 35 ) The impant shoud be supported 3mm beow the anticipated cresta bone eve, simuating 3mm of bone resorption You shoud perform fatigue testing in a simuated physioogica soution at 37 C, at 2 Hz frequency You shoud determine the maximum oad (endurance imit) your device can withstand for 2 x 1 O6 cyces without faiure Aternativey, if the materias used are not subject to corrosion fatigue and there are no pastic components, you may perform the test in air at 20 C, at 3-15Hz frequency for 5 x 1 O6 cyces You shoud begin testing at a oad above the static faiure oad of your device system (this oad shoud be determined using a test setup ike that used for the fatigue testing, but without the cycic oading) and decrease the oad unti the endurance imit is reached You shoud test three specimens to faiure at each oad, incuding the endurance imit You shoud test a minimum of 4 oads for a tota of 12 specimens You shoud identify the critica faiure point and the ocation of faiure initiation on the device component that fais Faiure is defined as materia yieding, deformation, or fracture You shoud compare testing resuts observed for the caimed predicate device(s) You shoud incude a graph of the oad versus number of cyces curve aong with testing resuts and data presented in tabuar form An aternate approach to the oad versus number of cyces curve is acceptabe This may aow the use of fewer sampes One approach is to seect a oad that is 10% beow the static faiure oad of the device system Test at east 5 sampes at the seected oad A sampes shoud withstand 5 miion cyces If any sampes fai, you shoud test 5 additiona sampes at a sighty ower oad Using this aternate approach, testing shoud be performed in a simuated physioogica soution as described above uness the materias are not subject to corrosion fatigue and there are no pastic components 10 Corrosion Testing

13 Draft - Not for Impementation You shoud conduct corrosion testing when the impant system incudes components fabricated from dissimiar metas You shoud perform this testing in a simuated physioogica soution at 37 C Passivated (ie, finished device condition) and nonpassivated meta surfaces shoud be evauated This testing shoud assess: corrosion potentia of each meta or aoy; coupe potentia for the assembed dissimiar meta impant system; and corrosion rate for the assembed dissimiar meta impant system 11 Modified Surfaces Information You shoud describe the impant surface characteristics, if the surface is modified or has properties caimed to faciitate bone deposition You shoud incude information on the nature of, and processes by which surfaces are modified such as coatings, basted surfaces, etched surfaces, or other surface treatments that are appied Ceramic Coating Information Your summary report shoud incude the information isted beow for an impant coated with a ceramic coating such as hydroxyapatite or cacium phosphate partice size and partice size distribution of the powder used for the coating average porosity size overa pore voume identity of the area of the impant to be coated scanning eectron microscopy pictures at 100X of the coated impant surfaces and of a cross-sectioned area of the device showing the coating interface measurements of coating thickness and toerances chemica anaysis of the powder before and after coating, incuding Ca/P ratios in atomic percent and eementa anaysis tota percentage of a crystaine phases in the coating and tota percentage of crystaine hydroxyapatite in the coating static tensie and shear bonding strengths between the coating and the impant surface with testing from at east 5 sampes incuded in the averages type of deposition process used and the post-deposition treatment 10

14 Draft - Not for Impementation x-ray diffraction pattern of the powder and the coating in terms of reative intensity versus diffraction ange surface roughness of the coating abrasion characteristics of the coating, incuding the abrasion testing methodoogy Metaic Coating Information Your summary report shoud incude the information isted beow for an impant coated with a metaic coating: compete chemica composition of the coating coating thickness and porosity mean voume percent of voids surface roughness of the coating identity of the area of the impant to be coated scanning eectron microscopy pictures at 100X of the coated impant surfaces and of a cross-sectioned area of the device showing the coating interface static tensie and shear bonding strengths of the coating to the impant with resuts from at east 5 sampes incuded in the averages abrasion characteristics of the coating, incuding the abrasion testing methodoogy Basted Surfaces Information Your summary report shoud incude the information isted beow for an impant with a basted surface: identity of any surface treatments that bast the impant composition of the partices identity of any treatments to remove partices from impant fixture surfaces identity of agents used in partice remova chemica anaysis of the surface to verify that any chemicas used to remove partices have been washed from the surface photomicrographs of basted surfaces to show whether or not there are partices remaining behind on the surface 11

15 Draft - Not for Impementation 12 Anima and Cinica Studies FDA recommends anima and/or cinica studies for denta impants with the foowing features: designs dissimiar from designs previousy ceared under a 51 O(k) engths ess than 7 mm and/or fixture diameters ess than 325 mm an anguation of the accompanying or recommended fixture abutment greater than 30 If you beieve cinica studies are not warranted, you shoud submit a justification evauate this justification on its scientific merit FDA wi Cinica investigation ordinariy shoud incude a randomized, we-controed cinica tria designed to demonstrate the substantia equivaence of the device when used as described in the Indications for Use statement For statistica purposes, the study shoud demonstrate the device is substantiay equivaent to, or not inferior to the performance of devices with estabished designs Each study arm shoud have a statisticay vaid number of patients Consutation with a statistician famiiar with medica device research statistics is highy recommended You shoud conduct cinica evauation of impants and abutments for a minimum of three years with the impant under oaded conditions Data to be evauated shoud incude such information as impant mobiity, infections, broken fixtures or abutments, adverse events, and incude a detaied expanation for a patients ost to foow-up Data derived from these investigations shoud meet the definition of vaid scientific data as defined in 21 CFR 8607 The studies shoud be conducted by quaified investigators experienced in impant dentistry, cinica research design, and data anaysis If a cinica study is needed to demonstrate substantia equivaence, ie, conducted prior to obtaining 5 1 O(k) cearance of the device, the study must be conducted under the IDE reguation (2 1 CFR 8 12) FDA has determined this device is a significant risk device as defined in 2 1 CFR 8 123(m)(4) and, therefore, studies invoving these devices do not quaify for the abbreviated IDE requirements of 21 CFR 8122(b) In addition to the requirement of having an FDAapproved IDE, sponsors of such trias must compy with the reguations governing institutiona review boards (21 CFR 56) and informed consent (21 CFR 50) 13 Cinica Protoco Study Popuation and Incusion Criteria You shoud ceary define the incusion/excusion criteria You shoud describe and justify any deviations from your incusion/excusion criteria You shoud describe the study popuation in terms of the distribution of the variabes, if reevant to study outcome, isted beow: intended use of the device number of patients in experimenta and contro groups 12

16 Draft - Not for Impementation age and gender distribution of the patients in the experimenta and contro groups status of dentition (dentate vs edentuous, minimum number of teeth and maxiomandibuar jaw reationships) occusa scheme (ie, cross bites, tited teeth, teeth in buccoversion/abioversion) minima ridge dimensions and quaity of bone (Type I-IV ), if part of the protoco appicabe prosthetic variabes, such as restorative materias, permissibe abutment anguation, and ength of span for impant supported bridges Pre-impantation Assessment The pre-impant assessment described in your study protoco shoud incude the foowing information: description of the genera heath of the patient, identifying any medica conditions that may affect the outcome of the study description of the patient s denta status that may affect the outcome of the study ocation of the intended site(s) for impantation description of specia conditions for which the impant is to be used (eg, Type IV bone, for maxiary sinus areas), pathoogica conditions (eg, infection, beeding, infammation), and the condition of the opposing teeth and type of occusion identification of patients who brux or cench standardized radiographs to quantify the ridge height and width of the supporting bone and ocate major anatomica features These radiographs shoud be standardized so that each subsequent radiograph can be directy compared to the origina preoperative radiographs You shoud aso use this procedure in the post-impant assessments Exampes of appropriate radiographs are isted beow: q q periapica or panoramic radiographs extraora radiographs 0 cephaometric radiographs q Computed Axia Tomography (CAT) Scans ora hygiene regimen to be used around the impant based on abeing caims or instructions density of bone at the impant site (ie, Type I to Type IV bone) Misch, CE Contemporary Impant Dentistry St Louis, Missouri: Mosby, 1999 ~~

17 Draft - Not for Impementation Post-impant Assessment The post-impant assessment described in your study protoco shoud incude the foowing information: You shoud define how frequenty cinica and radiographic assessment wi occur Postsurgica intervas that have been reported in the denta iterature are acceptabe These intervas are weeky for the first month, three months, 6 months, 12 months, 2 years, and 3 years Minor deviations from this sequence do not raise new questions of safety or effectiveness Abbreviated evauation intervas or significant deviations from these parameters shoud be justified on the basis of wound heaing parameters You shoud specify the time interva between each stage of the impantation (ie, the time between fixture pacement and uncovering for abutment pacement and time between fixture pacement and occusa oading) The 3-year foow-up period shoud be measured from the time the impant is subject to occusa forces You shoud describe the occusa oading parameters and variations permissibe within the protoco You shoud identify any medications and the amounts taken during the cinica tria that might affect study outcomes Medications such as antibiotics, anagesics, and topica rinses are exampes of medications that you shoud record Use of antibiotics, anagesics, and topica rinses shoud be standardized as much as possibe You shoud obtain radiographs as described in the study protoco Radiographs may not be required at each post-impant assessment You shoud quantify the amount of aveoar ridge resorption based on radiographs You shoud aso document any radiographic evidence of periapica radioucency You shoud record the foowing cinica parameters and observations during each evauation Gingiva Heath You shoud specify the gingiva and infammatory indices used Tooth and Impant Mobiity You shoud specify method of evauation and type of cassification used Pocket Probing Depth You shoud use the same type of probe and probing technique at each evauation The cinician s technique shoud be caibrated with respect to force used as we as probe anguation The use of stents, wherever practica, may improve intra- as we as interexaminer reiabiity Cinica Attachment Leve 14

18 Draft - Not for Impementation You shoud use a standardized technique as we as examiner caibration for this measuring the eve cinica attachment You shoud record any postoperative compications encountered, and the times at which they occurred These incude, but are not imited to the post-operative compications isted beow: C anesthesia or paresthesia, temporary or permanent 0 mandibuar fracture 0 significant oss of aveoar ridge height, as specified in the protoco 0 oteomyeitis, ora-antra, or ora-nasa fistua 0 adjacent teeth adversey affected by impant pacement C abnorma or proonged pain after insertion as described in protoco 0 infection reated to impant pacement q faiure to maintain adequate ora hygiene 14 Cinica Resuts Adverse reactions and compications Your summary report shoud report each adverse reaction and compication the events isted beow: These incude infection impant oss prior to oading impant breakage oss of oaded impants pain atered sensation temporomandibuar joint probems Your summary report shoud provide the number of patients discontinued, the rationae for discontinuation, and the time of discontinuation Under Adverse Events, you shoud provide a detaied and compete faiure anaysis report for each device faiure Data Tabuation 15

19 Draft - Not for Impementation Your summary report shoud contain a tabuation of data from a individua subject report forms You shoud incude copies of subject report forms for each subject who did not compete the investigation, if possibe You shoud aso incude a summary tabe showing the duration of foow-up for each subject in the investigation Statistica Anayses Your summary report shoud contain the resuts of statistica anayses of the cinica investigations These resuts shoud incude statistica methodoogy and rationae for each statistica test You shoud cite references or submit formuas for each methodoogy, as we as an expanation of any deviations from the methodoogy Anaysis of statistica data shoud show the rate of success, faiure, and compications The time-specific cumuative faiure rate and compication rate shoud be cacuated by statistica surviva anaysis You shoud incude a ifetabe anaysis Additiona Cinica Study Information You shoud incude artices pubished in peer reviewed journas, containing information on the device in the 5 1 O(k) reevant to the cinica study (ie, for the same indication, or uses of the impant in a cinica study) Your cinica study protoco shoud incude a statement regarding study progress at the time you submit your 5 1 O(k), stating whether the study is competed, presenty in ong term foow-up, or enroing patients You shoud aso incude a statement about how cearance of the 5 1 O(k) wi change the status of the study You shoud incude in the cinica protoco, any methods not previousy mentioned, that are used to eiminate bias on the part of the subjects or investigators 15 Labeing The premarket notification must incude abeing in sufficient detai to satisfy the requirements of 21 CFR 80787(e) A root-form endosseous denta impant and endosseous denta impant abutment devices are prescription medica devices Fina abeing for medica devices must compy with the requirements of 2 1 CFR and fina abeing for prescription medica devices must compy with 2 1 CFR before being introduced into interstate commerce, however, fina abeing is not required for 510(k) cearance The foowing information is aimed at assisting manufacturers in compying with Prescription Legend In accordance with 2 1 CFR , root-form endosseous denta impant and endosseous denta impant abutment devices must bear the foowing caution statement: Caution: Federa aw restricts this device to sae by or on the order of a physician 16

20 Draft - Not for Impementation Professiona Labeing You provide users with a surgica manua aong with the instructions for use Professiona abeing shoud contain detaied instructions, particuary for those sections of the surgica or restoration procedures where the device differs from other endosseous denta impant systems You shoud provide a the precautions and warnings in the professiona abeing If there are any precautions or warnings which reate to unpackaging or steriity, these shoud be repeated on the package abes Steriization Instructions If any parts are provided non-sterie that must be steriized before use, you shoud provide steriization instructions Patient Labeing If patient abeing is appropriate, it shoud be consistent with Guidance on Medica Device Patient Labeing; Fina Guidance for Industry and FDA Reviewers, 17