GU Advisory Panel Meeting

1. GU Advisory Panel Meeting Nocturnal Home Hemodialysis Carolyn Y. Neuland, Ph.D. Chief, Gastroenterology and Renal Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health June 8, 2005

2. Overview • Introduction • Panel Update • Regulation of Hemodialysis Devices • Guidance Documents for Hemodialysis • Definition of Nocturnal Home Hemodialysis • Meeting Objectives

3. Linda CarrConsumer Safety Technician Jeffrey Cooper, D.V.M.Veterinarian / Panel Exec. Sec. Linda Dart, M.S.Biochemist Gema Gonzalez, M.S.Biomedical Engineer Irada Isayeva, Ph.D. Polymer Chemist Kristina Lauritsen, Ph.D. Tumor Biologist Barbara McCool, M.S.R.N.Nurse Consultant Joshua Nipper, M.E. Biomedical Engineer Kathleen Olvey Biologist Claudia Ruiz-Zacharek, M.D.Nephrologist Rebecca StephensonChemical Engineer Kellie Straughn Clerk Typist Richard Williams Mechanical Engineer

4. Panel Update

5. P020006 - Enteryx Procedure KitBoston Scientific Corporation • Description/Indication – solution injected into the LES for the treatment of GERD in patients who are responsive to pharmacologic therapy • Panel Meeting Date – January 17, 2003 • GU Panel Recommendation – Approval with Conditions • Modified physician labeling • Modified patient labeling • Post market study with 36 months follow-up from the last injection

6. P020006 - Enteryx Procedure KitBoston Scientific Corporation • Current Status – PMA approved April 22, 2003 • Post-approval Study • 3 year post-implantation follow-up • Medical Device Reporting (MDR)

7. Nocturnal Home Hemodialysis

8. Regulation of Hemodialysis Devices • Class II Medical Devices • Risk Based classification • Moderate level of risk • Requirement for General Controls and Special Controls to ensure safety and effectiveness • 510(k) - Premarket Notification • There are currently no devices cleared by FDA for Nocturnal Home Hemodialysis

9. Regulation of Hemodialysis Devices • Establishes substantial equivalence(SE) to a legally marketed predicate device • As safe and as effective as predicate device • Performance data: • Bench studies • Clinical studies (especially for Home Systems)

10. Dialysis Devices • Most are regulated as Class II devices • Primary classification regulations used: • §876.5820 – Hemodialysis systems and accessories • Conventional Dialyzers • Reuse of Conventional Dialyzers • Dialysis Delivery Systems and Tubing Sets • Hemodialysates • §876.5860 – High permeability hemodialysis systems • High Flux Dialyzers • Reuse of High Flux Dialyzers • Dialysis Systems with Ultrafiltration Controller

11. Dialysis Devices • §876. 5600 - Sorbent regenerated dialysate delivery system for hemodialysis • §876. 5665 - Water purification system for hemodialysis • §876. 5540 - Blood access device and accessories • Class III for implanted catheters • §876.5630 - Peritoneal dialysis system and accessories

12. Guidance Documents for Hemodialysis Devices • Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers – 1998 • Guidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems – 1998 • Guidance for Hemodialyzer Reuse Labeling – 1995 • Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis – 1997

13. Guidance Document “Guidance documents are documents prepared for FDA staff, applicants/sponsors, and the public that describe the agency’s interpretation of or policy on a regulatory issue” 21 CFR §10.115

14. Definition of Nocturnal Home Hemodialysis • Nocturnal Home Hemodialysis (NHD) is a type of hemodialysis performed in the home by the patient, while the patient is asleep (typically at night), over a 6-10 hour period, using slower flow rates for blood and dialysate, and a treatment frequency of 5 to 7 days per week.

15. Nocturnal Home HemodialysisObjectives of Meeting • To discuss and provide recommendations on the clinical and scientific issues associated with hemodialysis device design, labeling, and training for Nocturnal Home Hemodialysis • To discuss and provide recommendations on clinical trial design to study Nocturnal Home Hemodialysis • To obtain scientific feedback which can be used to help in device evaluation decisions and may lead to the future development of a guidance document for Nocturnal Home Hemodialysis

16. Nocturnal Home Hemodialysis Overview of Conventional Hemodialysis System Joshua Nipper – Biomedical Engineer Gastroenterology and Renal Devices Branch

17. Overview of Conventional Hemodialysis Delivery Devices Joshua C. Nipper, M.E. Biomedical Engineer Gastroenterology and Renal Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health June 8, 2005

18. Overview • Conventional Hemodialysis (HD) Systems • A “standard” device • Monitored parameters • Alarms • Accessory Devices • Water treatment systems • Hemodialysis blood tubing • Remote monitoring systems • Blood access devices

19. Disclaimer • Any examples in this presentation are not intended as an endorsement or criticism of any specific technology, device or company • No devices are currently cleared for nocturnal home hemodialysis

20. Hemodialysis Delivery Systems • Classified under two different sections of the Code of Federal Regulations (CFR): • 21 CFR §876.5820 for a low permeability system • 21 CFR §876.5860 for a high permeability system (ultrafiltration controller) • Suggestions for the content of a 510(k) submission found in the FDA guidance document: “Guidance for the Content of Premarket Notifications for Hemodialysis Delivery System”

21. A “Standard” HD Delivery System Informational Display Saline PT = Pressure Transducer Anticoagulant PT Blood from Patient Dialysate / UF Out (green / yellow) Blood Leak Detector Conductivity Meter PT Mixing System Pre-mixed or sorbent regenerated dialysate Dialysate In Water, Acid Concentrate, Bicarbonate Concentrate In PT Venous clamp Drip Chamber Air Detector Blood return to Patient

22. Solute Transfer & Ultrafiltration C blood > C Dialysate P blood ≈ P Dialysate C blood > C Dialysate P blood > P Dialysate Blood Dialysate

23. Monitored HD Parameters • Blood and dialysate flow rates (pump speed) • Pressure • Arterial • Venous • Dialysate • Waste / Dialysate Out • Transmembrane Pressure (TMP) • Patient fluid removed (UF) • Temperature

24. HD Alarms Typically come in two varieties: CAUTION WARNING

25. Temperature Blood leak Flow rates Pressure Arterial Venous Transmembrane Pressure (TMP) Dialysate Waste / Dialysate Out Excessive UF Air embolism Conductivity / pH Water quality System alarms Vascular access disconnection – venous pressure? Standard HD Alarms

26. Accessory Devices • Water Treatment Systems • HD Blood Tubing • Remote Monitoring Systems • Blood Access Devices

27. Water Treatment Systems • Classified under 21 CFR §876.5665 • Guidance for The Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis • Converts potable water to purified water meeting the requirements of the Association for the Advancement for Medical Instrumentation (AAMI) RD:62 standard • Can be designed for multiple patients, or can be single patient

28. Water Treatment Systems Water In Water Out Deionization Reverse Osmosis Pre-treatment Carbon Filters Worker / Polisher Ultrafilter Data Out

29. Blood Tubing • Serves as basic conduit for blood • Contains a “blood pump” segment • Can have multiple connection points • Patient access (arterial & venous) • Pressure transducers with transducer protectors • Air detectors • Roller / peristaltic blood pump

30. Blood Tubing • Can be “cassette” based, which limits the number of user connections needed • Kinked tubing can cause hemolysis, which can lead to death

31. Remote Monitoring Systems • Can be used for data transmission • Connect HD machine to Internet via modem or broadband connection • Can transmit real time alarms, and/or completed treatment data • FDA labels current systems are contraindicated as the sole method of monitoring a patient during hemodialysis

32. Blood Access Devices • Long-term, cuffed HD Catheters • Single or double lumen • Contain luer locks meeting ISO standards for connection to blood tubing • Arterio-Venous (AV) Grafts • Implanted prosthesis designed to bypass sections of native vessels • AV Fistulas • Surgical procedure, not a device regulated by FDA • Fistula needles are medical devices, and contain the same luer locks as catheters

33. Nocturnal Home Hemodialysis Michael Mendelson, D.D.S., M.S. Biomedical Engineer, Director Health Promotion Officer Human Factors Science and Engineering Branch

34. Human Factors and Nocturnal Home Hemodialysis • Michael Mendelson, D.D.S., M.S. • Biomedical Engineer, Director Health Promotion Officer • Human Factors Science and Engineering Branch • Division of Device User Programs • Office of Communication, Education, and Radiation Control • Center for Devices and Radiological Health • June 8, 2005

35. Topics • Introduction to human factors (HF) • Magnitude of medical error-caused adverse incidents • HF methods • Nocturnal Home Hemodialysis (NHD) challenges and observations • Human Factors Branch recommendations for premarket submissions

36. General Definition of Human Factors Human Factors discovers and applies information about human behavior, abilities, limitations, and other characteristics to the design of tools, machines, systems, tasks, jobs and environments for productive, safe, comfortable, and effective human use. * -- Alphonse Chapanis, 1985 • *Sanders & McCormick, Human Factors in Engineering • and Design., McGraw-Hill, Inc., 1987; p 5

37. General Definition of Error Human error is an inappropriate or undesirable human decision or behavior that reduces, or has the potential for reducing, effectiveness, safety, or system performance.* • *Sanders & McCormick, Human Factors in Engineering • and Design., McGraw-Hill, Inc., 1987; p 607

38. Magnitude of the Problem of Medical Error Errors during hospital treatment result in 120,000 deaths each year – roughly equivalent to a jumbo jet’s crashing each day. (Leape, Harvard School of Public Health) At least 44,000 people,and perhaps as many as 98,000 people,die in hospitals each year as a result of medical errors that could have been prevented…(To Err is Human: Building a Safer Health System; Institute of Medicine / National Academy of Sciences, 1999) Photo courtesy of Boeing

39. Design of Hemodialysis Systems Requires Human Factors Engineering Process The Quality System Regulation: HF implied in Design Controls Section (21 CFR 820.30) Manufacturer • Must address the intended use • Must address the needs of the user and patient • Shall include testing under actual or simulated use conditions • HF required at Input phase (design needs), Output phase (compare user needs <===> device design), and Validation Phase (realistic “use” study)

40. Human Factors Considerations Use • Use Environment • Light, Noise • Distraction • Motion/Vibration Safe & effective Device Use • Device User • Knowledge • Abilities • Expectations • Limitations Unsafe or ineffective(Use Error) • Device • Operational requirements, procedures • Device complexity • Specific user interface characteristics

41. Increased Patient Safety through USABILITY of the Use Interface • Intuitive operation • Clear displays • Safe and simple-to-use controls • Positive and safe connections • Effective alarms • Clear and effective labeling • Safe and simple installation, repair, maintenance, and disposal

42. Two Key Human Factors Messages • A poorly designed device use interface can needlessly permit and even induce error • Warnings and instructions in the operating manual (and even on the device) may help but they can not OVERCOME a flawed design

43. Important Principles of Good Design* • Make things visible • Communicate clearly • Provide correct and natural mappings • Don’t be arbitrary, be consistent • Simplify tasks • Use appropriate constraints • Design for error *modified from The Design of Everyday Things, Donald Norman

44. Make Things Visible: This PCA pump fails. Obradovich and Woods (1996)

45. Obradovich and Woods (1996)

46. Important Principles of Good Design* • Make things visible • Communicate clearly: e.g., mode / system status • Provide correct and natural mappings • Don’t be arbitrary, be consistent • Simplify tasks • Use appropriate constraints • Design for error *modified from The Design of Everyday Things, Donald Norman

47. Important Principles of Good Design* • Make things visible • Communicate clearly • Provide correct and natural mappings: “What is this switch for?” • Don’t be arbitrary, be consistent • Simplify tasks • Use appropriate constraints • Design for error *modified from The Design of Everyday Things, Donald Norman

48. Important Principles of Good Design* • Make things visible • Communicate clearly • Provide correct and natural mappings • Don’t be arbitrary, be consistent: e.g., valve conventions • Simplify tasks • Use appropriate constraints • Design for error *modified from The Design of Everyday Things, Donald Norman

49. Important Principles of Good Design* • Make things visible • Communicate clearly • Provide correct and natural mappings • Don’t be arbitrary, be consistent • Simplify tasks: e.g., reduce programming steps • Use appropriate constraints • Design for error *modified from The Design of Everyday Things, Donald Norman

50. Protected Pins SAFE Lead Wires with Protected Pins and Correct Connections Power Cord Protected Pins Monitor Electrode Lead Wires Patient Cable Use only lead wires that have protected pins. Protected pins can not accidentally be plugged into power cords or electrical outlets. UNSAFE Lead Wires with Unprotected Pins and Incorrect Connections From Patient From Patient Power Cord or Extension Cord Unprotected Pins Unprotected Pins Use Appropriate Constraints FDA, Dec. 28, 1993