510k Submission Overview Myraqa, Inc. August 22, 2012

About Myraqa, Inc. Myraqa is the leading IVD consulting firm Headquarters in Silicon Valley Clients include IVD manufacturers, pharma, clinical labs, investors and other industry stakeholders

About Myraqa, Inc. Team-Driven Success We employ leading experts in IVD Regulatory, Quality, Clinical, Biostatistics, Development and Marketing Team approach best combines diverse expertise Team members are employees, not contractors All senior staff have at least 15 years of relevant experience, most have considerably more

What is a 510(k)? Premarket Notification Section 510(k) of Federal Food, Drug, & Cosmetic Act 21 CFR 807 Subpart E Marketing Clearance Application Allows FDA to Determine Substantial Equivalence (SE) Classification process for a device

What a 510(k) Is Not A Form Establishment Registration Device Listing Premarket Approval (PMA)

What 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;

Regulatory Classes for Devices Three Regulatory Classes (level of control based on risk): Class I – General Controls Class II – General Controls, Special Controls and Premarket Notification Class III – General Controls and Premarket Approval Notes: Most Class II and some Class I are subject to 510k premarket notification

General Controls Class 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 807.20, such as manufacturers, distributers, repackages and relabelers Medical Device Listing with FDA of devices to be marketed Manufacturing 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 908 Submission of a premarket notification [510(k)] before marketing a device

Special Controls May include special labeling requirements, mandatory performance standards and post-market surveillance

510(k) Submission Required When? Introducing a device to the U.S. market for the first time Change in indications for use for a previously cleared device Making significant modification to a previously cleared device

Who Must Submit a 510(k)? Device Manufacturers Specifications Developers Repackagers who change device or its labeling Relabelers who change the labeling- e.g., instructions for use Anyone who both manufactures & distributes A 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 labeling Distributor or Importer who furthers marketing of the legally marketed device and does not alter labeling or change device

Intended Use Statement FDA generally regulates devices according to the intended use – not the technology used to generate the information Intended use statement includes 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)

Systems Approach FDA takes a ‘systems approach’ to the regulation of devices and IVDs Reagents, instruments, software – everything that is needed to produce a diagnostic result must be included Can utilize a partnership approach with parallel submissions Examples Affymetrix/Roche CDC/Applied Biosystems

Device Classifications There are three classifications of devices Class I: Low Risk Often 510(k) Exempt General Controls Examples: General purpose reagents, Mass spectrometers Class II: Moderate Risk Require 510(k) clearance before commercialization General Controls + Special Controls (e.g., clinical testing) Class III: High Risk Require Premarket Approval (PMA) PMA inspection Special Controls are typically documented in an FDA Guidance document.

Contents of a 510(k) Medical Device User Fee Cover Sheet CDRH Premarket Review Submission Cover Sheet Cover Letter Intended Use / Indications for Use 510(k) Summary Truthful and Accurate Statement Financial Certification or Disclosure Statements Executive Summary Note 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.

Contents of a 510(k) (Cont) Device Description Include all reagents and instruments used This is where we give FDA the details on how our product works Proposed Labeling Will include Package Insert or Operator’s Manual (Instructions for Use) Kit and component labeling Stability Studies conducted and results (Real-Time) Software Requirements outlined in Software Guidance document

Contents of a 510(k) (Cont) Performance Testing Analytical/bench testing – Often multiple studies Animal testing (if required) Clinical testing –external clinical sites (typically 3 site minimum) Approximately 10% of all 510(k)s Important difference with the predicate device, e.g., new indication for use or new technology Must be collected under Investigational Device Exemption Regulations (21 CFR Part 812)

FDA 510(k) Review FDA recently published Refuse to Accept Policy for 510(k)s, which also includes administrative checklists for Traditional, Abbreviated and Special 510(k)s. Administrative Review Administrative review will be completed within 15 days of receipt of 510(k) Assessment of completeness of 510(k) not the quality of information The 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 letter either provide the missing information or request an extension request for up to 180 days from the date of the RTA letter. If complete FDA staff can begin the substantive Purpose 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.

FDA 510(k) Review Substantive Review Review of content and quality of information submitted FDA may request additional information/performance data to determine substantial equivalence to the predicate Reviewer requests by telephone, email or formal letter (from Doc Center) Clock stops by letter only Submit additional information to Document Mail Center 30 days to submit May request an extension within 30 days of the request for additional information The request for extension should state the reason and time needed The 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

Substantial Equivalence (SE) Device is Substantially Equivalent to predicate if: Has the same intended use, and Has the same technological characteristics as the predicate device, Or Has different technological characteristics and the information in the 510(k): Does not raise new questions of safety and effectiveness, and Demonstrates new device at least as safe and effective as the predicate

Not Substantially Equivalent (NSE) There is no predicate device Has a NEW intended use Has different technological characteristics compared to the predicate device and raises a new questions regarding safety and effectiveness The NSE determination did not include data review and will require PMA or De Novo

Not Substantially Equivalent (NSE) (Cont) Does not demonstrate device is at least as safe and effective as the predicate The NSE determination included data review and is eligible for a new 510(k) with new data Approximately 3% are found NSE Data is looked at last in the 510(k) regulatory review process FDA usually asks for additional information at least once prior to determining the device is NSE for lack of data

Key Take-Aways Review relevant FDA guidance documents and search the releasable 510(k) database 510(k) summaries and decision summaries for similar products Use new RTA Checklist Confirm regulatory pathway with FDA Pre-IDE or Pre-Submission Meetings Lorry will cover pre-Submission meetings in more detail

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