Synchromed II programmable implantable drug pump Medtronic Neuromodulation

Learning Objectives • Describe the N’Vision® Clinician Programmer • Describe the Synchromed II programming strategy • Demonstrate programmer functions • Exercises – Practice using clinician programmer functions 2 | MDT Confidential

Intrathecal Therapy • Why? – Drug dose intrathecally 1/300 th oral – Minimise side effects and reduce systemic dose and oral meds – Programmable pump allows varied infusion rates/regimens to reflect pain pattern – Cost-effective Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis. Kumar K, Hunter G, Demeria DD. J Neurosurg. 2002 Oct; 97(4): 803 -10 3

Intrathecal Therapy Synchromed II Pump Indications • Chronic infusion of Lioresal™ Intrathecal (baclofen injection) for the management of severe spasticity of spinal or cerebral origin • Chronic intrathecal or epidural infusion of sterile, preservative-free morphine sulfate for chronic, intractable pain of malignant and/or non-malignant origin • Chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain Medtronic Synchromed II Infusion System: Information for Prescribers. http: //professional. medtronic. com/pt/neuro/itb/prod/synchromed-ii/features-specifications/index. htm 4 | MDT Confidential 4

Intrathecal Therapy – In reality…. • Multiple-drug combinations for pain are common • Baclofen is used in multiple dilutions – 500, 1000, 1500, 2000, 3000 mcg/ml 5 | MDT Confidential Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, Caraway D, Cousins M, De Andrés J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs MS, Kim P, Kumar K, Leong M, Liem L, Mc. Dowell GC 2 nd, Panchal S, Rauck R, Saulino M, Sitzman BT, Staats P, Stanton-Hicks M, Stearns L, Wallace M, Willis KD, Witt W, Yaksh T, Mekhail N. Neuromodulation. 2012 Sep-Oct; 15(5): 436 -64; discussion 464 -6. doi: 10. 1111/j. 15251403. 2012. 00476. x. Epub 2012 Jul 2. 5

Synchromed II Overview • System Components: – Programmable pump • 20 and 40 ml reservoirs – Catheter • One or two piece – Physician Programmer

The Pump Catheter Access Port (CAP) 2 D barcode (tracking) Test hole (used to test top shield weld integrity) Refill Port Suture Loops 7 | MDT Confidential

Inside Synchromed II… Internal tubing Peristaltic pump Motor Battery Refill Port Hybrid Reservoir

Ascenda Catheter Design: Summary of Benefits Polyurethane Outer Layer Silicone Inner Layer • Resistance to leaks and breaks • Drug compatible Thermoplastic PET Braid • Six times stronger than our previous silicone catheters • Offers improved resistance to kinking and occlusions 9 | MDT Confidential – INTERNAL USE ONLY

Implantable components Synchro. Med® II infusion pump • • Stores and precisely delivers baclofen at rate tailored to each individual patient Wide range of programmable parameters and modes Prescriptions can be programmed for combinations of bolus and continuous infusion doses Battery-powered: – Longevity up to 7 years at 0. 9 ml/day • Two reservoir sizes: – 20 and 40 ml • Thin profile with contoured shape for comfort: – Width 20 vs. 40 ml pump: 19. 5 mm vs. 26 mm • Contains alarm to indicate need for refill or pump replacement

Implantable components How Synchro. Med® II infusion pump works • • Bellows design allows reservoir to expand/contract according to drug volume At normal body temperatures: – Pressurized gas in space below reservoir expands and exerts constant pressure on reservoir – Drug advances into pump tubing • Battery-powered electronics and motor cause roller arm in peristaltic pump to rotate – Precisely pushes programmed dose through catheter port and into catheter • • Valve protects pump reservoir from being over-filled or overpressurized CAP allows direct access to catheter and CSF and may be used for diagnostic tests – Catheter Access Port (CAP) has funneled design that only allows 24 -gauge or smaller needle to pass through – Safety feature that helps prevent inadvertent access during pump refill procedures (uses 22 -gauge needle) • Equipped with suture loops to secure pump in pocket site

Implantable components Catheter • Thin, elastic and flexible tube – Delivers baclofen from pump to intrathecal space • Made of durable radiopaque silicone rubber – Trimmable at pump end of placed catheter • Sutureless pump connector – Facilitates connection to pump • • • Spinal end of catheters has closed tip and side holes for drug delivery Marked at 1 -cm increments to aid catheter placement Guide wire in lumen: – Provides additional stiffness and catheter tip control during placement

Synchromed II – in detail (2) Programming options Simple continuous, flexible dosing, patient activated bolus, minimum infusion rate Pump data log Patient demographics, drug details, catheter information, time stamped event log MRI Compatibility Up to 3 Tesla Alarm functions Critical alarm: end of service, empty reservoir, stalled pump, critical memory error, stopped pump duration exceeded Non-critical alarm: low reservoir, elective replacement indicator (90 days pre-EOS)

Programming options Simple Continuous mode Single bolus continuous Flex mode

External component N’Vision® programmer • • • Handheld portable device Allows physicians to program pump and tailor therapy to patient Weighs 680 g Uses AA batteries Contains: – Touch screen display with iconbased navigation for data entry – Telemetry module for device programming – Integrated calculator – Infrared port through which communications can be established with compatible printers • Single programming platform

N’Vision® Programmer • N’Vision clinician programmer communicates with pump via telemetry – Radio-frequency (RF) communication ® • Synchro. Med EL pump requires Model 8529 magnet – Attaches to programming head 20 | MDT Confidential

N’Vision® Programmer • The pump is programmed during: – System implant (initial pump fill) – Patient management • Optimize therapy • Pump refill with same drug and drug concentration • Change drug or drug concentration – Troubleshooting 21 | MDT Confidential

Programming Features Synchro. Med® II Pump > Full patient information • Includes name and address > Pump serial and model numbers > Catheter information • • Model number Catheter volume > Drug information • • > > Name (25 characters) Concentration Infusion prescription Calibration constant Notes Event logs Synchro. Med® EL Pump > Patient ID (3 characters) > > Pump model number Catheter information • • > Model number Catheter volume Drug Information • Name (5 characters) • Concentration > Infusion prescription > Calibration constant Note: Telemetry takes 30 -90 seconds because of the amount of information transmitted 22 | MDT Confidential

Programming Features • Alarms—Pump sounds an alarm when certain events occur: Synchro. Med II® Pump > Critical alarm— 3 -second, 2 -tone • • • Empty reservoir End of Service (EOS) Motor stall Stopped pump exceeds 48 hours Critical pump memory error Synchro. Med® EL Pump > 1 -tone alarm • • Low reservoir volume reached Low battery > 2 -tone alarm • Pump memory error > Non-critical alarm— 1 -second, single-tone • • • Low reservoir volume reached Elective Replacement Indicator (ERI) Non-critical pump memory error 23 | MDT Confidential

Calibration Constant • Number of electrical pulses required for specific pump to dispense one mc. L (µL) of fluid • Specific value for each pump determined during manufacturing • Displayed on Pump Status screen of N’Vision® clinician programmer – Verify before implant • Match calibration constant printed on pump package – Troubleshoot pump • Match calibration constant written in patient record or printed on patient ID card 24 | MDT Confidential

Prepare for Programming Session 1. Ensure software application card is inserted 2. Turn the programmer on 3. Check programmer battery status – Install batteries if needed 4. Select the Pump Application button 25 | MDT Confidential

Prepare for Programming Session 2. Select Synchromed II demo 3. Select Interrogate 26 | MDT Confidential

Overview Screen • This screen shows: – Pump in shelf state (for a new pump), serial number, model number and calibration constant. • Minimise screen using small cross 27 | MDT Confidential

Questions? 28 | MDT Confidential