Premarket Processes & Pathways to Market Pre-amendment, Exempt, 510(k), and 513(g)

1. Premarket Processes & Pathways to MarketPre-amendment, Exempt, 510(k), and 513(g) Chris Kilander – Cook Pharmica, LLC 15 May 2014

2. Medical Device Risk Classes

3. Medical Device Risk Classes • General Controls (all classes): • Establishment Registration & Device Listing (21 CFR 807, Subpart B) • Quality System Regulation (21 CFR 820) • Most Class I devices exempt from Design Control (21 CFR 820.30) • PostmarketMedical Device Reporting (21 CFR 803) • Premarket Notification (21 CFR 807 , Subpart E) • Most Class I devices exempt from premarket notification • Labeling (21 CFR 801) • Special Controls (Class II & III): • Product-specific FDA guidance documents and/or recognized standards • Premarket clinical studies • Postmarket clinical studies/registries

4. Classification Framework • Classification based upon Intended Use • Purpose for which the device is to be used • Objective intent of the persons marketing the device • vs. Indications for Use • By default, medical devices are Class III, however: • FDA may issue classification regulations • Regulations indicate class and exempt or premarket notification status, if appropriate • Regulations establish special controls, when appropriate • ~1,700 device types covering 16 different medical specialties

5. Classification Framework • 21 CFR 860 – Medical Device Classification Procedures • 21 CFR 862 – Clinical Chemistry & Clinical Toxicology • 21 CFR 864 – Hematology & Pathology • 21 CFR 866 – Immunology & Microbiology • 21 CFR 868 – Anesthesiology • 21 CFR 870 – Cardiology • 21 CFR 872 – Dental • 21 CFR 874 – Ear, Nose & Throat • 21 CFR 876 – Gastroenterology-urology

6. Classification Framework • 21 CFR 878 – General & Plastic surgery • 21 CFR 880 – General Hospital & Personal Use • 21 CFR 882 – Neurological • 21 CFR 884 – Obstetrical & Gynecological • 21 CFR 886 – Ophthalmic • 21 CFR 888 – Orthopedic • 21 CFR 890 – Physical Medicine • 21 CFR 892 – Radiology

7. Classification Framework

8. Classification Framework • FDA Product Codes • No established legislative or regulatory authority • Define specific device types within a classification regulation

9. Exempt from Premarket Notification • Most Class I devices and some Class II devices are exempt from premarket notification requirements (i.e., 510(k)) • As established by classification regulations • “.9 exceptions” • Each classification regulation includes a general requirement that a device is exempt from premarket notification regulations only if there is already a similar device on the market with the same intended use and fundamental scientific technology • Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act • If not, manufacturer must still submit a 510(k) for the device

10. Request for Classification – 513(g) • If there is uncertainty regarding the classification of a medical device, manufacturers can submit a Request for Classification under 513(g) • Subject to user fees ($3,490 for FY2014) • Contents: • Cover letter • Description of the device • Description of what device is to be used for • Proposed labeling (yours and similar, legally marketed device) • Guidance: FDA and Industry Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act (2012)

11. Premarket Notification – 510(k) • Comparison to predicate device to determine if they are substantially equivalent • 510(k) is “cleared” rather “approved” • Substantial equivalence: • Same intended use as predicate device • Either same technological characteristics as predicate or different technological characteristics but not raise new questions of safety or effectiveness • Predicate device: • Legally marketed Class I or Class II device • Class III device for which FDA has not yet required premarket approval (PMA)

12. Premarket Notification – 510(k) • If FDA determines not substantially equivalent (NSE): • Resubmit 510(k) with new data • Request Class I or Class II designation via de novo pathway • File reclassification petition • Submit a premarket approval (PMA) application

13. Identification of a Predicate Device • Product Lifecycle database: • Cleared 510(k)s (or PMAs) • Adverse events • Recalls

14. Identification of a Predicate Device • Published 510(k) summaries

15. Identification of a Predicate Device • Competitor marketing materials

16. Types of 510(k)s • FDA Guidance: The New 510(k) Paradigm: Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications (1998) • Types of 510(k)s not defined within law or regulation

17. Contents of a Traditional 510(k) • Cover letter & 510(k) cover sheet (Form FDA 3514) • Device name, classification & description • Applicant’s identification & FDA registration number • Substantial equivalence comparison with predicate device(s) • Standards (see Form FDA 3654) • Performance data to demonstrate as safe and effective as predicate • Labeling • Class III Certification & Summary, if applicable • 510(k) summary or statement • Truthful and Accuracy Statement

18. Contents of a Traditional 510(k) • If applicable: • Software validation • Biocompatibility data • Sterilization and packaging data

19. Substantial Equivalence Comparison

20. Special 510(k)s • Modification to manufacturer’s own device • Not applicable for: • Changes to intended use or indications for use • Change to fundamental scientific technology • FDA can and does convert to traditional • Focuses on the changes to your device • Risk management & design control

21. Special 510(k)s • Contents: • 510(k) coversheet (Form FDA 3514) • Name & 510(k) number for legally cleared device • Description of modified device • Proposed labeling • Concise summary of design control activities • Risk analysis • Verification & Validation activities • Declaration of Conformity with Design Control requirements

22. Abbreviated 510(k)s • Focus on conformance to an established Special Control • Product-specific FDA guidance document • FDA-recognized product standard • Contents: • 510(k) coversheet (Form FDA 3514) • Description of device • Proposed labeling • Summary report that shows how standard/guidance applied • Specifically how risks were addressed • Justification for deviations from the standard • Declaration of conformity to the standard

23. Refuse to Accept Process • FDA Guidance: Refuse to Accept Policy for 510(k)s Guidance for Industry and Food and Drug Administration Staff (2012) • Within 15 calendar days, FDA will preview submission for inclusion of appropriate content • Combination device? • Submitted to appropriate Center? • 510(k) eligible? • Organization? • Include appropriate elements?

24. Standards

25. Pre-amendment Devices • On the market prior to May 28, 1976 • Documentable evidence • Catalogs/datasheets • Shipping records/invoices • Employee affidavit • Pre-amendment Determination Request – guidance on FDA website

26. Current Developments in 510(k) • Draft Guidance: The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] (2011) • Modifications to 510(k) devices: • Report to Congress: Report on FDA’s Policy to be Proposed Regarding Premarket Notification Requirements for Modifications to Legally Marketed Devices (January 2014)

27. 510(k) Tips • More than just gathering engineering and marketing information • Tell the “story” • Work with engineering and marketing • How do you want to market the device? • Clearly state intended use and indications • Address differences between your device and predicate • Implement thorough QC process • RTA checklist

28. Additional Resources • Guidance for Industry: General/Specific Intended Use, 1998 • K97-1: Deciding When to Submit a 510(k) for a Change to an Existing Device, 1997 • K95-1: 510(k) Requirements During Firm-Initiated Recalls, 1995

29. Exercise • For the pedicle bone screw, what is the classification? • Classification • Regulation • Product Code • Identify two applicable predicates • Identify applicable standards