1. Accelerating Product Development June 25, 2015 IMDMC REG 101 Pathways To Market

2. Classification of Devices 510(k) Requirements PMA Requirements

3. Device Classification Class I - low risk, manual toothbrush Class II – moderate risk, blood pressure monitor Class III – high risk, heart valve

4. Classification Tips Don't think of buckets Think of ski slopes ◦Light in Class vs Heavy Class I can require clinical data Class II may not require clinical data Test to consensus standards Check with FDA if not sure

5. FDA Request for designation 513(g) process Costs money Part of CDRH presubmission process Follow FDA guidance Usually takes a couple of months

6. Class I Low risk Subject to General Controls Some may be exempted Check regulations Must register with FDA Recall and reporting system Usually no submission is required

7. Class II Medium Risk Subject to General and Special Controls ◦Performance standards ◦Postmarket surveillance ◦Patient registries ◦Special labeling requirements ◦Premarket data requirements ◦Guidelines Some may be exempted 510(k) clearance required

8. Class III Highest risk OR very novel Subject to general and special controls Pre-Market approval required FDA inspection required Clinical data required Check regulations and guidance Talk to FDA

9. How to Classify Your Product Define indication for use Pick a predicate FDA.gov ◦Classification Database ◦Device panel Revisit IFU Look at competitors Confirm with FDA

10. Example Transcutaneous Electrical Nerve Stimulator (TENS) device Indications for use: Depression and Pain http://www.accessdata.fda.gov/scripts/cd rh/cfdocs/cfpcd/classification.cfm http://www.accessdata.fda.gov/scripts/cd rh/cfdocs/cfpcd/classification.cfm

11. Device Panel http://www.fda.gov/MedicalDevices/Devic eRegulationandGuidance/Overview/Classif yYourDevice/ucm051530.htm http://www.fda.gov/MedicalDevices/Devic eRegulationandGuidance/Overview/Classif yYourDevice/ucm051530.htm

12. Panel Listing 73Anesthesiology Part 868 74Cardiovascular Part 870 75Chemistry Part 862 76Dental Part 872 77Ear, Nose, and Throat Part 874 78Gastroenterology and Urology Part 876 79General and Plastic Surgery Part 878 80General Hospital Part 880 81Hematology Part 864 82Immunology Part 866 83Microbiology Part 866 84Neurology Part 882 85Obstetrical and Gynecological Part 884 86Ophthalmic Part 886 87Orthopedic Part 888 88Pathology Part 864 89Physical Medicine Part 890 90Radiology Part 892 91Toxicology Part 862

13. Product Classification

14. Regulation TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER H--MEDICAL DEVICESPART 882 -- NEUROLOGICAL DEVICES Subpart F--Neurological Therapeutic Devices Sec. 882.5890 Transcutaneous electrical nerve stimulator for pain relief. (a) Identification. A transcutaneous electrical nerve stimulator for pain relief is a device used to apply an electrical current to electrodes on a patient's skin to treat pain. (b) Classification. Class II (performance standards).

15. TENS Device Class II Check guidance http://www.fda.gov/downloads/medicalde vices/deviceregulationandguidance/guidan cedocuments/ucm207059.pdf http://www.fda.gov/downloads/medicalde vices/deviceregulationandguidance/guidan cedocuments/ucm207059.pdf Guidance applies to specific product codes, not all 6 possible codes

17. Intended use Wanted: Indications for use of Depression and Pain Found: A transcutaneous electrical nerve stimulator for pain relief How to get a depression claim? ◦Talk to FDA ◦Probably run a clinical endpoint ◦Is it worth it?

18. Summary Multiple classes of devices based on risk, novelty, patient population, intended use, indication for use First understand market and user requirements Check FDA resources Can pay FDA to tell you (Be careful what you with for!)

19. Resources Product Classification Database http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cf m 510(k) Database http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm Premarket Approval Database http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm Class I and Class II Devices Exempt from 510(k) Requirements http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm Device Guidance Documents http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guida nceDocuments/default.htm

20. Let’s Try it Together!

21. 510k Requirements Some class I and most class II Demonstrates that the new device is “substantially equivalent” to a predicate device in terms of intended use, technological characteristics, and performance testing, as needed Follow 21CFR807 Use FDA presubmission checklist

22. Substantial Equivalence Has the same intended use as the predicate; and has the same technological characteristics as the predicate; or Has the same intended use as the predicate; and has different technological characteristics and the information submitted to FDA; ◦does not raise new questions of safety and effectiveness; and ◦demonstrates that the device is at least as safe and effective as the legally marketed device

23. FDA Pre-submission Checklist Acceptance Checklist for 510(k)s The Guidance for Industry and Food and Drug Administration Staff: Refuse to Accept Policy for 510(k)s describes the criteria FDA intends to use in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for substantive reviewGuidance for Industry and Food and Drug Administration Staff: Refuse to Accept Policy for 510(k)s The guidance includes acceptance checklists for each type of 510(k) submission: Traditional 510(k) Checklist Abbreviated 510(k) Checklist Special 510(k) Checklist

24. Types of 510k Submissions Abbreviated – No Brainer Special – Change that doesn’t alter risk Traditional – All others

25. Abbreviated 510K A guidance documents exist Special controls are established Recognized standards exist Summary report ◦Information regarding the efforts to conform with the guidance document/special control(s) & outline any deviations

26. Not a Special 510k Modifications that have the potential to alter the fundamental scientific technology of the device, operating principle(s), mechanism of actionbe submitted as Examples: ◦surgical instrument that uses a sharpened metal blade to one that cuts with at a laser ◦in vitro diagnostic (IVD) device that uses immunoassay technology to one that uses nucleic acid ◦Incorporation of a sensing mechanism in a device to allow the device to function "on demand" rather than continuously

27. Special 510k examples Energy type Environmental specifications Performance specifications Ergonomics of the patient-user interface Dimensional specifications Software or firmware Packaging or expiration dating Sterilization Contact FDA if conducting clinicals

28. FDA Pre-submission Checklist Checklist for CDRH reviewers Use as a guide for your benefit Good war story

29. Pre-Market Application (PMA) Require FDA approval Probably not in the classification database Supports or sustains human life, is of substantial importance in preventing impairment of human health, or presents a potential, unreasonable risk of illness or injury Check for Guidance Documents

30. Types of PMAs Traditional PMA ◦It’s traditional Modular PMA ◦Submitted in pre-defined components ◦Project specific Streamlined PMA ◦FDA guidance document or other published methods for review which have been evaluated ◦FDA review history dealing with like products (2+) ◦Must be available for the Interactive review process

31. CBER Devices Medical devices associated with the blood collection and processing procedures Medical devices associated with cellular therapies InVitro Diagnostics involved with blood testing Device regulations apply Check CBER device list Follow CBER guidance documents

32. PMA Data requirements Non-clinical data ◦microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal tests Clinical data ◦study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations

33. Companion Diagnostics Any InVitro Diagnostic developed to choose patients for therapy with a specific therapeutic Must be co-developed with the therapeutic Starts as a lab developed test and then progresses to an IDE and PMA PMA and NDA or BLA approved on the same day

34. FDA Pre-submission Checklist Acceptance and Filing Reviews for Premarket Approval Applications (PMAs) Guidance Document Have a third party review Talk with FDA about Advisory Committee Meeting Multiple FDA meetings

35. AM Manufacturing What class is the Powered wheelchair with built in monitors? What questions should you ask about the change in the polymer for the HOA product? How would you report a change in the data transfer system for the wheelchair

36. CONTACT US Diana Caldwell, President & CEO ◦dcaldwell@pearlpathways.com Gretchen Bowker, Chief Operating Officer ◦gbowker@pearlpathways.com Contact us at 317.899.9341 Websites: www.pearlpathways.com and www.pearlirb.comwww.pearlpathways.com www.pearlirb.com