2About Myraqa, Inc. Myraqa is the leading IVD consulting firm Headquarters in Silicon ValleyClients include IVD manufacturers, pharma, clinical labs, investors and other industry stakeholders
3About Myraqa, Inc. Team-Driven Success We employ leading experts in IVD Regulatory, Quality, Clinical, Biostatistics, Development and MarketingTeam approach best combines diverse expertiseTeam members are employees, not contractorsAll senior staff have at least 15 years of relevant experience, most have considerably more
4What is a 510(k)? Premarket Notification Section 510(k) of Federal Food, Drug, & Cosmetic Act21 CFR 807 Subpart EMarketing Clearance ApplicationAllows FDA to Determine Substantial Equivalence (SE)Classification process for a device
5What a 510(k) Is Not A Form Establishment Registration Device Listing Premarket Approval (PMA)
6What is a Predicate?An identification of the legally marketed device to which the submitter claims equivalence. A legally marketed device to which a new device may be compared for a determination regarding substantial equivalence is:a device that was legally marketed prior to May 28, 1976,or a device which has been reclassified from class III to class II or I (the predicate),or a device which has been found to be substantially equivalent through the 510(k) process;
7Regulatory Classes for Devices Three Regulatory Classes (level of control based on risk):Class I – General ControlsClass II – General Controls, Special Controls and Premarket NotificationClass III – General Controls and Premarket ApprovalNotes: Most Class II and some Class I are subject to 510k premarket notification
8General ControlsClass I devices are subject to the least regulatory control and are subject to “General Controls”General controls include:Establishment Registration of companies which are required to register under 21 CFR , such as manufacturers, distributers, repackages and relabelersMedical Device Listing with FDA of devices to be marketedManufacturing devices in accordance with current Good Manufacturing Practices (Quality System Regulation in 21 CFR 820)Labeling devices in accordance with labeling regulations in 21 CFR 801 or 908Submission of a premarket notification [510(k)] before marketing a device
9Special ControlsMay include special labeling requirements, mandatory performance standards and post-market surveillance
10510(k) Submission Required When? Introducing a device to the U.S. market for the first timeChange in indications for use for a previously cleared deviceMaking significant modification to a previously cleared device
11Who Must Submit a 510(k)? Device Manufacturers Specifications DevelopersRepackagers who change device or its labelingRelabelers who change the labeling- e.g., instructions for useAnyone who both manufactures & distributesA company that distributes devices but does not perform any of the other functions above is not required to submit a 510(k)Who is Not Required to Submit a 510(k)?Private Label Distributor who ONLY adds company name & wording such as:“Distributed by ___________” or “Manufactured for _________”Repackager who does not alter labelingDistributor or Importer who furthers marketing of the legally marketed device and does not alter labeling or change device
12Intended Use Statement FDA generally regulates devices according to the intended use – not the technology used to generate the informationIntended use statementincludes a general description of diseases or conditions that the device will diagnose, treat, prevent, cure, or mitigate including a description, where appropriate of the patient population for which the device intended (21 CFR Part 812.2)
13Systems ApproachFDA takes a ‘systems approach’ to the regulation of devices and IVDsReagents, instruments, software – everything that is needed to produce a diagnostic result must be includedCan utilize a partnership approach with parallel submissionsExamplesAffymetrix/RocheCDC/Applied Biosystems
14Device Classifications There are three classifications of devicesClass I: Low RiskOften 510(k) ExemptGeneral ControlsExamples: General purpose reagents, Mass spectrometersClass II: Moderate RiskRequire 510(k) clearance before commercializationGeneral Controls + Special Controls (e.g., clinical testing)Class III: High RiskRequire Premarket Approval (PMA)PMA inspectionSpecial Controls are typically documented in an FDA Guidance document.
15Contents of a 510(k) Medical Device User Fee Cover Sheet CDRH Premarket Review Submission Cover SheetCover LetterIntended Use / Indications for Use510(k) SummaryTruthful and Accurate StatementFinancial Certification or Disclosure StatementsExecutive SummaryNote the 510K summary is publicly available once your device is cleared so only provide what’s required in this section and avoid anything considered proprietary.Prior to submitting 510(k) need to submit the User Fee. Fiscal year 2012 $4049 and $2024 for companies that qualify for small business exemption. New fees will be in effect Oct. 1st. Change $4960 and$ 2480.
16Contents of a 510(k) (Cont) Device DescriptionInclude all reagents and instruments usedThis is where we give FDA the details on how our product worksProposed LabelingWill include Package Insert or Operator’s Manual (Instructions for Use)Kit and component labelingStabilityStudies conducted and results (Real-Time)SoftwareRequirements outlined in Software Guidance document
17Contents of a 510(k) (Cont) Performance TestingAnalytical/bench testing – Often multiple studiesAnimal testing (if required)Clinical testing –external clinical sites (typically 3 site minimum)Approximately 10% of all 510(k)sImportant difference with the predicate device, e.g., new indication for use or new technologyMust be collected under Investigational Device Exemption Regulations (21 CFR Part 812)
18FDA 510(k) ReviewFDA recently published Refuse to Accept Policy for 510(k)s, which also includes administrative checklists for Traditional, Abbreviated and Special 510(k)s.Administrative ReviewAdministrative review will be completed within 15 days of receipt of 510(k)Assessment of completeness of 510(k) not the quality of informationThe submitter will be notified in writing if the 510(k) was found administratively complete or incomplete.If incomplete submitter has 30 days to respond to the RTA lettereither provide the missing information orrequest an extension request for up to 180 days from the date of the RTA letter.If complete FDA staff can begin the substantivePurpose of revised guidance is to improve efficiency of reviews. In past FDA has accepted inadequate submissions for review and FDA staff invests significant time in constructing extensive letters requesting additional information to conduct a substantive review. Goal of new guidance is to clarify content needed to allow FDA to conduct a substantive review , hopefully improving the quality of 510k submissions and overall review time.Extensions are granted.
19FDA 510(k) Review Substantive Review Review of content and quality of information submittedFDA may request additional information/performance data to determine substantial equivalence to the predicateReviewer requests by telephone, or formal letter (from Doc Center)Clock stops by letter onlySubmit additional information to Document Mail Center30 days to submitMay request an extension within 30 days of the request for additional informationThe request for extension should state the reason and time neededThe 510(k) may be deleted from the 510(k) tracking system if there is no response to the request for additional information within 30 days of FDA’s request letter
20Substantial Equivalence (SE) Device is Substantially Equivalent to predicate if:Has the same intended use, andHas the same technological characteristics as the predicate device,OrHas different technological characteristics and the information in the 510(k):Does not raise new questions of safety and effectiveness, andDemonstrates new device at least as safe and effective as the predicate
21Not Substantially Equivalent (NSE) There is no predicate deviceHas a NEW intended useHas different technological characteristics compared to the predicate device and raises a new questions regarding safety and effectivenessThe NSE determination did not include data review and will require PMA or De Novo
22Not Substantially Equivalent (NSE) (Cont) Does not demonstrate device is at least as safe and effective as the predicateThe NSE determination included data review and is eligible for a new 510(k) with new dataApproximately 3% are found NSEData is looked at last in the 510(k) regulatory review processFDA usually asks for additional information at least once prior to determining the device is NSE for lack of data
23Key Take-AwaysReview relevant FDA guidance documents and search the releasable 510(k) database510(k) summaries and decision summaries for similar productsUse new RTA ChecklistConfirm regulatory pathway with FDAPre-IDE or Pre-Submission MeetingsLorry will cover pre-Submission meetings in more detail