Training module 1 – Introduction and Preparation Dialysis System SW 8.09.13 Training module 1 – Introduction and Preparation Ref: Operator’s Manual SW 8.09.13 Chapter 1 – General Description Chapter 3 – Machine Dressing and Priming Chapter 4 – HD-DN Treatment

Introduction and Preparation 2017-11-27 Introduction and Preparation Important Notice: This presentation does not relieve any user of the Artis Dialysis System from his or her duty to carefully read the full text of the Operator’s Manual before using the system. Important: Please note that the SW change to 8.09.13 of this presentation does not change the training of the Artis Dialysis System for the users. Introduction and Preparation Ref: Operator’s Manual SW 8.08, Service code 6998397 Chapter 1 – General Description Chapter 3 – Machine Dressing and Priming Chapter 4 – HD-DN Treatment

Making life in the clinic easier for everyone 2017-11-27 Making life in the clinic easier for everyone Usability and design Graphical User Interface ArtiSet Blood Tubing System Serviceability Modular construction Adapting therapies to every individual Making life in the clinic easier for everyone Artis is an advanced Hemodialysis System that makes everyone's life easier in the dialysis clinic. Artis Dialysis System is built upon four cornerstones to meet the needs of : The operator – usability and design - graphical user interface – blood cassette system Bioprotective blood module – ArtiSet blood tubing system The technician – serviceability of the ADS is an important criteria and has been an integral part of the design work. The patient – bio-controlled therapies / bio-protective blood module Ref: Artis Concept Brochure HCEN53602© 2010.09. Gambro Lundia AB Artis Product Brochure HCEN5346© 2010.09. Gambro Lundia AB

2017-11-27 Usability and design The user interface is easy to read and displays step by step instructions in the operator message area one flow setup – one touch priming Usability and design USERnomics is a Gambro trademark expression, describing Artis Dialysis System usability and design.

Appealing Design Clear, pure-line, ‘human touch’ Design for function 2017-11-27 Appealing Design Clear, pure-line, ‘human touch’ Pleasant – Convenient – Neat Helps create an appealing and serene environment for patients and staff Design for function All components at your fingertips Large and visible touch screen Design for emotion It has an appealing design The technology is inside Possible comment: The size of the machine  NOTE: Artis is still not the biggest machine on the market – 5008 is higher Design for function – Ergonomics Components accessible at the right height Large and visible screen

Design for function The critical part needing surveillance 2017-11-27 Design for function The critical part needing surveillance Status lights: decoupled from the screen – on the side, for high visibility 15’’ color touch screen Hard Key Panel: for all key actions that can be required at any time: pump speed, alarm management and events Blood pumps: highly visible and accessible, yet compact and protected Sensor bar: all in one – used as a guide for patient lines with clamps Trainers “don’t forget”: You do not have to show the slide, but should remember to demonstrate on the machine Let’s start with the functional design review with the critical part requiring blood modules. All components requiring surveillance gathered in the central part of the monitor; all others are elsewhere. Several sensors inside the sensor bar – blood, air, Hemoscan, lines All actions are done at same height, i.e. no work above shoulders level or below the knees.

Design for function Infusion pole Top Tray EvaClean 2017-11-27 Design for function Dialysis Fluid Module All related components found in the same area Top Tray Removable, used as disposable holder Bottom Tray Plenty of space for concentrate canisters Infusion pole Easily adjustable EvaClean Waste handling device Trainers “don’t forget”: You do not have to show the slide, but should remember to demonstrate on the machine

Design for function Move-ability Clean-ability 2017-11-27 Design for function Move-ability Front and back handles for easy transportation Clean-ability Smooth surfaces Cabinet validated for various cleaning agents Trainers “don’t forget”: You do not have to show the slide, but should remember to demonstrate on the machine A particular attention has been given to the clean-ability of the device: Smooth surfaces have been given the priority and sharp edges have been avoided as much as possible. The material used for the structure and the quality of the paintings have also made it possible to validate the use of various cleaning agents. 360°Swiveling wheels with front brakes

ArtiSet blood tubing system 2017-11-27 ArtiSet blood tubing system Compact design, optimized ergonomics Non invasive pressure monitoring Bio-materials and radio-sterilization Bioprotective Blood Module - ArtiSetTM blood tubing system Ref: Brochure HCEN54641© 2010.09 Gambro Lundia AB ArtiSet blood tubing system is a cassette system with a compact design and reduced complexity minimizing the risk of errors, both at the level of manufacturing and clinical use (less components, less gluing points). It facilitates a non invasive pressure monitoring and improved hemodynamics*. The various ArtiSets comply with the latest European best Practice Guidelines: Plastics, sterilization, user safety and connector blood contact (see below) Phtalates-free plasticizer used in the PVC formulation (”Bioline” reducing migration into blood) EtO free sterilization (Beta rays) Injection site validated for safe needles (plastic) Dialyzer connectors avoiding blood contact with tinted components * = Flow dynamic softwares have been used to analyze and improve the ArtiSets hemodynamics. The velocity of blood is carefully controlled, avoiding dead zones with no flow as well as turbulences creating foaming. Also, the chambers bottom entry - bottom exit of blood helps reducing splashing effects. The specially shaped deflectors, ensuring laminar flow even at high blood flow rates, the venous filter (surface coated) with an asymmetrical window design (smaller at the bottom, bigger at the top) are ensuring a performant removal of micro-bubbles and particles. Combined, these features also contribute to improving the thrombogenicity of the system, which is investigated in a recent study using a reduced heparinization protocol. Both the TAT levels observed in the blood samples taken at regular intervals and the final residual blood volume were significantly reduced

ArtiSet blood tubing system 2017-11-27 ArtiSet blood tubing system Reduced extra-corporeal blood volumes compared to previous Gambro HD machines1 125 mL in DN / 145 mL in HDF / ~ 225 mL in SN Reduced blood air-interface and contact surface 7 cm2 (50% less than standard lines - compared to previous Gambro bloodlines2) Compact design, chambers in a single unit Non-invasive pressure monitoring No handling of transducer protectors No risk of blood getting inside the machine Non invasive and accurate pressure monitoring system 1-2: Refer to specific Operator Manuals for different bloodline volumes Bio-protective blood module Ref: ??? The total extra-corporeal blood volume is considerably reduced compared to conventional blood line sets and by that also the contact surface between blood and foreign materials. The compact design of the arterial and venous chambers, which are cast in a single unit, the blood-air interface is down to 7cm2 (no expansion chamber and smaller chambers). This is approximately half the blood-air interface of conventional sets The non-invasive pressure monitoring system is made out of a silicone diaphragm, enclosed in a mould POD. It is the position of the diaphragms inside the POD that gives the pressure signal to the monitor. The POD is impermeable, thus, the risk of blood leakage into the machine is eliminated

Adapting therapies to every individual 2017-11-27 Adapting therapies to every individual Easier approach to on-line HDF Automatically achieve convective volumes >20 L3 with on-line HDF Reduce the number of TMP alarms, manual checks and interventions Automated profiling of UF rate and [NA+] level (Biofeedback system) Manage fluid removal as per patient’s physiological response – vascular refill capacity Recommended by the European Best Practice Guidelines (EBPG 3.1.2a) Adapting Therapies to Every Individual - Bio-controlled therapies Bio-controlled therapies Bio-controlled therapies benefits: Enable more patients to benefit from yet efficient and comfortable treatments Treatments self-adapt to patient physiological status Bio-controlled therapies reduce the need for repeated adjustment of the treatment settings 3 : Maduell et al, High Efficiency Post dilution Online Hemodiafiltration reduces All-Cause Mortality in Hemodialysis patients; JASN 24, p. 6, 2013

Artis in Practice Touch screen Intuitive user interface BiCart Select 2017-11-27 Artis in Practice Touch screen Intuitive user interface BiCart Select Self-loading blood tubing systems EvaClean One touch priming Alarm status and support Artis in Practice Our first hands-on session will include and deal with the above

Intuitive User Interface 2017-11-27 Intuitive User Interface The NavPad Prescription Before treatment During treatment Blood Treatment overview Fluid Report After treatment Intuitive User Interface Operator’s Manual, section 1.4.1 The Artis Treatment Overview screen with the navigation tool – The NavPad – in its lower right corner, which allows the operator to move between the 5 Main screens. The NavPad is available on all the Main screens in the lower right corner.. The slide is animated in 4 steps to explain the NavPad: 1. The 5 color coded NavPad buttons give access to the 5 Main screens: 2. Prescription button - Light blue Blood button - Red Treatment overview button - Dark blue Fluid button - Green Report button - Yellow 3. Before and after treatment – specifically emphasize the use of the Prescription button to set treatment parameters before treatment start while the Report button gives access to all the treatment parameters automatically monitored by the system during the session but also after the treatment is ended 4. During treatment buttons - Blood, Treatment Overview and Fluid buttons are used for checking/adjusting detailed treatment parameters and activated functions All five buttons may of course be used at all times during the dialysis process.

Sub screens 2017-11-27 Treatment Type Patient Card Distribution Volume BP Monitoring A/V Limits Hemoscan Heparin Fluid Settings Diascan Isolated UF Hemocontrol Special Procedures Disinfection Treatment Type Patient Card Distribution Volume Time Reminder BlackBox Screen Cleaning System Data Service Sub screens By pressing the different NavPad buttons the respective Main screen appears (Prescription, Blood, Overview, Fluid and Report) from which many related sub-screens can be reached. The slide shows some examples of sub-screens.

2017-11-27 Treatment Overview Screen Operator’s Manual, section 1.4.3 Describe the Treatment Overview Screen in detail Specifically explain: The different values for set blood pump speed and arterial pressure compensated blood flow The button bar next process button (the Center button) is ONLY displayed in the Treatment Overview Screen – it is recommended to always return to this screen Click = Arrow down on computer key board Click – finger appears on NavPad Prescription button Click on Prescription button to move to next slide

2017-11-27 Prescription Screen Operator’s Manual, section 1.4.4 and 1.4.2.1 Describe the Prescription Screen in detail Treatment time range is 10 minutes to 8 hours UF Volume range in HD is 0 – 24L (UFR max. 3L/h) This slide is animated as follows: Click – finger appears on the select pad UF Volume button  the key pad opens Click – finger moves to key pad confirm button  key pad disappears and exclamation mark on the UF Volume select pad button disappears Click – finger appears on NavPad Prescription button Click to move to next slide

2017-11-27 Prescription Screen Operator’s Manual, section 1.4.4 Explain the Activated Function Select Pad Click – finger appears on the select pad BPM button Click to move to next slide BPM settings screen is animated as follows:

2017-11-27 Prescription Screen Operator’s Manual, section 1.4.4 and 9.4 BPM settings screen is animated as follows: Click – finger appears on the BPM activation button  activation bar turns green, heart + clock icon appears showing the function is activated Click – finger appears on Close button  BPM sub screen disappears and the select pad activation bar on the prescription screen turns green Click – finger appears on NavPad Blood Screen button Click to move to next slide (Blood Screen Screen)

2017-11-27 Blood Screen Operator’s Manual, section 1.4.5 Describe the Blood Screen in detail Specifically explain the buttons in the button bar – they are all related to blood and there is no Center button This slide is animated as follows: Click – finger appears on NavPad Fluid button Click to move to next slide (Fluid screen)

2017-11-27 Fluid Screen Operator’s Manual, section 1.4.6 Describe the Fluid Screen in detail Note that the UF Volume is already set via the Prescription Screen while the Treatment Time exclamation mark is still in place as this was not set earlier Specifically explain: Real treatment time, which is equal with elapsed diffusion time Remaining treatment time is displayed on the Treatment Overview Screen Non-diffusion time must be calculated by the Operator This slide is animated as follows: Click – finger appears on Fluid Settings button Click to move to next slide

© YEAR, Legal owner 2017-11-27 Fluid Screen Operator’s Manual, section 1.4.6 and 3.3 Fluid Settings Sub-screen appears – explain the Fluid Settings Sub-screen This slide is animated as follows: Click – finger appears on Close button  Fluid Settings sub screen disappears Click – finger appears on NavPad Report button Click to move to next slide (Report screen) © YEAR, Legal owner

2017-11-27 Report Screen Operator’s Manual, section 1.4.7 Only describe very briefly as the Report Screen is presented in detail in Module 9 ADS continuously stores treatment data according to a set time interval This slide is animated as follows: Click – finger appears on NavPad Overview button Click to move to next slide (Overview Screen)

Operator Message guidance 2017-11-27 Operator Message guidance Operator Message Guidance Operator’s Manual, section 1.3.1 Emphasize the importance of reading and following the messages appearing in this area and in the specific windows appearing (e.g. Confirmation Required windows) on the screen

BiCart Select System Both concentrates are prepared on-line 2017-11-27 BiCart Select System Both concentrates are prepared on-line during treatment from the: BiCart (bicarbonate powder) SelectCart (sodium chloride pearls) SelectBag One (small electrolytes and glucose) BiCart Select offers: Closed System for Concentrates Possible options for individualization Simplified handling and storage * Consult the respective product monographs of BiCart, SelectCart and SelectBag One for contraindications, warnings, precautions, adverse reactions, interactions, dosing and conditions of clinical use. Product monographs are also available by contacting us at www.Baxter.com BiCart Select Operator’s Manual, section 3.3 Sodium and bicarbonate settings do not influence the level of minor electrolytes (K+, Ca2+, Mg2+) A range of ready-to-use SelectBag One compositions allows for easy tailoring of the prescription On-line preparation in a closed system, eliminating contamination risks The label clearly identifies both K+ and Ca2+ levels 80% weight reduction Required storage space reduced by 80% Improved flexibility: The clinic can keep the necessary variety

Concentrate Combinations 2017-11-27 Concentrate Combinations At concentrate connection ensure the correct combination is set (presetable) BiCart Select BiCart, SelectCart and SelectBag One BiCart + A-concentrate Canister Central distribution Concentrate Combinations Operator’s Manual, section 3.3 To avoid alarms, the correct concentrate combination needs to be set before attaching the concentrates The dialysis fluid preparation phase starts as soon as the concentrates are connected By preset the dialysis fluid preparation phase can be delayed 15 minutes (no alarm appearing during this time) Highlight After the preparation phase is started, it is no longer possible to change concentrate combination Note: It is still possible to change acid alternative (e.g. C205 to C295) After Preparation phase is started, it is no longer possible to change Concentrate Combination

Fluid circuit - treatment 2017-11-27 Fluid circuit - treatment Fluid circuit - Treatment EvaClean – waste handling connects directly to drain (used priming fluid goes from EvaClean directly to the drain) Single pass fluid system Ultrafilters after water inlet and dialysis fluid mixing A third Ultrafilter included in the ArtiSet Ultra for on line treatments Clearance measurement after the dialyzer

ArtiSet Blood Tubing System 2017-11-27 ArtiSet Blood Tubing System ArtiSetTM Blood Tubing System Operator’s Manual, section 3.5 “Link Slide”

ArtiSet HD-DN HC Venous Infusion line Dialyzer Arterial line 2017-11-27 ArtiSet HD-DN HC Venous Infusion line Dialyzer Arterial line Priming line Arterial Infusion lines Heparin line Dialyzer Venous line Back valve Venous Injection port Arterial Chamber Venous Chamber Hemoscan cuvette Venous Infusion line Artiset HD-DN HC Operator’s Manual, section 3.5 Demonstrate the ArtiSet HD-DN HC with its different components Arterial Injection port Venous Patient line Arterial Patient line

ArtiSet - Venous and Arterial pathways 2017-11-27 ArtiSet - Venous and Arterial pathways Post-pump Pre-pump Artiset - arterial and venous pathways Operator’s Manual, section 3.5 Specifically emphasize what lines are pre and post the blood pump

Auto-loading Blood Tubing Sets 2017-11-27 Auto-loading Blood Tubing Sets Follow operator’s message for: Auto-loading of the ArtiSet Disposable set up / connections Auto-loading Blood Tubing Sets Operator’s Manual, section 3.5 When loading the ArtiSet specifically notice: After the cassette is set on the hooks place the heparin line in its line guides. Close the blood pump cover Identify the Dialyzer A/V lines and place those in their respective line guides (above and below the venous pump) Let the A/V Patient lines hang down with the paper strips still in place until they are set in the EvaClean; the weight of the lined bundle will help the lines to “fall” in place in the sensor bar slots Place the A/V Patient lines in the automatic clamps with the paper strips still in place Wait for the next Operator’s message to appear and continue Highlight All disposables connected in one single series of action Dressing and preparing ADS takes only a few minutes All disposables are connected in one single series of action

EvaClean Priming fluid draining device i.e. no waste bag is needed 2017-11-27 EvaClean Priming fluid draining device i.e. no waste bag is needed Design to draw fluid through the blood tubing system – where the A/V patient blood lines are connected Anti-backflow safety system embedded Automatically disinfected during the regular disinfection processes EvaClean Operator’s Manual, section 1.2.1 and 3.5.1

Heparin syringe installation 2017-11-27 Heparin syringe installation Heparin Syringe Installation Operator’s Manual, section 3.5.5 When loading the heparin syringe specifically notice: That the syringe plunger base must have firm contact with the heparin syringe holder (see photo) That the syringe plunger is placed in the two slots; one in the syringe holder (rear) and one as the white plunger lock (front)

Heparin administration 2017-11-27 Heparin administration The heparin line is automatically primed if the heparin administration function is activated before Auto-Prime starts Artis performs a few “kicks” to open the one-way-valve and prime the line If heparin administration function is not activated before Auto-Prime starts, the heparin line can be primed manually using the heparin ▲ position key During heparin administration the light indicator on the pump panel is green lit The Initial Dose is administered when blood enters the arterial dialyzer line (30 ml processed) Heparin Administration Operator’s Manual, section 3.7 The heparin volume needed to prime the heparin line is 0.6 ml. Neither this volume nor the volume needed for each “kick” (0.3 ml) are added to the Accumulated heparin volume displayed on the heparin settings sub-screen and the Reports screen.

Heparin Administration 2017-11-27 Heparin Administration 30cc syringe (option) Administration types available: Linear: range 1.5 to 10 mL/h Intermittent: dose range 0.5-12mL Manual: range 0.5 to 12mL 10 cc syringe kit (standard) Administration type available: Linear: range 0.5 to 4 mL/h Intermittent: dose range 0.5-4mL Manual: range 0.5 to 4 mL/h Heparin Administration Operator’s Manual, section 3.7 Highlight Extra Bolus button becomes available after Start Treatment Administered upon Operator’s Confirmation – Displayed in the Report Screen Event list Options available: Initial Dose Automatic bolus is administered upon the Operator’s confirmation (Extra Bolus) Extra Bolus button becomes available after Start Treatment

Auto-Prime Preparation 2017-11-27 Auto-Prime Preparation Follow operator’s message for auto-prime preparations Close the lower venous infusion line and the two arterial pre-pump infusion lines Check that the venous infusion line and the saline line clamps are open Auto-Prime Preparation Operator’s Manual, section 3.6 Highlight Saline should be connected to the Venous Infusion line Contradictory to other systems where saline is connected to the arterial line - During Auto-Prime the ADS blood pump runs clockwise (in opposite direction) Saline line is connected to the Venous Infusion line

Auto-Prime - One touch priming 2017-11-27 Auto-Prime - One touch priming Press the Auto-Prime button for “booking” automatic start of the priming process - the button indicator bar turns yellow When the function check is completed, the automatic priming process starts - the button indicator bar turns green The dialyzer is primed and deairated from bottom to top - no need of rotating the dialyzer during the Auto-Prime process Dialysis fluid sampling should be performed before Auto-Prime; do not book Auto-Prime when sampling is planned Auto-Prime - One Touch Priming Operator’s Manual, section 3.6.1 Specifically notice that if dialysis fluid sampling should be performed, Auto-Prime should not be booked. The Sampling button will not be displayed if Auto-Prime is booked/running/completed. Highlight True auto-priming; simply dress, press and leave Even the dialysis fluid tubes are connected from the beginning (before the dialysis fluid is prepared) True auto-priming; simply dress, press and leave

2017-11-27 Auto-Prime Settings Auto-Prime Settings Operator’s Manual., section 3.6.2. Specifically notice that after Auto-Prime is completed, Auto-Prime can be reset in this Autopriming Settings sub-screen (repetition of the full Auto-Prime process) Also an Extra Prime process can be performed by pressing the Extra Prime button available in the Treatment Overview screen button bar when Auto-Prime is completed. If using an Evodial 2.2 dialyzer, the following Priming Volume should be set: • High Volume: 2000 mL of Priming Volume • Low Volume: 1750 mL of Priming Volume Priming volumes are calculated and presetable in accordance with the respective dialyzer instruction for use + a minimum of 250 ml

Auto-Prime – 4 phases process 2017-11-27 Auto-Prime – 4 phases process The venous line and chamber The EvaClean applies a negative pressure and sucks saline into the venous chamber and line. The arterial line and chamber and dialyzer blood side The arterial blood pump starts at a rate of 50 ml/min filling up the arterial line and chamber from the bottom-up, running pump clockwise The dialyzer fluid side Continues until Artis no longer sense air in the dialysis fluid compartment Removal of air from the extracorporeal circuit The arterial blood pump restarts running at a rate of 250 ml/min. Intermittently the blood pump speeds up in order to purge air. Auto-Prime – 4 phases Process Priming of venous blood line. Saline line and venous infusion line clamps open. EvaClean applies a negative pressure to the venous blood line i.e. the EvaClean sucks saline into the venous chamber and line (from the saline infusion bag). Priming of the dialyzer blood side, arterial chamber and blood line. Arterial blood pump starts, running in reverse, at 50 ml/min. This phase lasts 2.5 minutes, or until the system delivers 125 ml of saline, which is to the top of the dialyzer. Specifically notice that it is NOT possible to change the BP speed during this phase. Priming of dialyzer dialysis fluid side. Automatically the Artis primes the dialysis fluid side, hydraulically. This is complete when the Artis no longer sees air in the dialysis fluid compartment. Removal of air. Arterial blood pump restarts, running in reverse, at 250 ml/min, to complete the removal of air. Intermittently the blood pump will speed up in order to purge air. This continues until 1100 ml (default) of saline is delivered. Blood pump stops. Specifically notice that it is possible to change the BP speed (preset 10 to 350mL/min) during this phase. Highlight During Auto-Prime the blood pump runs in clockwise direction facilitating an improved deairation as the dialyzer is primed from bottom-up No need to turn or tap the dialyzer during the Auto-Prime process Operator’s Manual: At the end of the priming procedure internal functional checks will be performed. If one of these checks fail, perform an Extra Prime procedure. During Auto-Prime, the blood pump runs in clockwise direction facilitating an improved deaeration as the dialyzer is primed from the bottom-up

Alarm status and support 2017-11-27 Alarm status and support 3 alarm priorities: = sound = lamp flashing 2 info messages: Alarm messages appearance Alarm Status and Support Operator’s Manual, section 16.2 Only describe this slide very briefly as the Alarm handling is presented in detail in Module 5

2017-11-27 Nice to Know ! T1 Test - whenever Artis is switched on, a serial of function checks are performed. If any of these checks fails a resetable alarm is generated. In case a General Safe State alarm appears the protective system has identified an error prohibiting the use of the machine – try to switch Artis OFF and then ON again. Dialysis fluid sampling - should be performed before priming; do not book Auto-Prime when sampling is planned Automatic priming of the heparin line – Artis performs a serial of kicks to open the back valve and prime the line. The volume used is not added to the accumulated heparin volume displayed on the heparin settings screen The Evodial dialyzer - special attention is needed in regards to the Auto-Prime procedure and priming volumes, see Op. Man. Section 3.6.1. and 3.6.2 Nice to Know

Hands on Module 1 Attach concentrates Attach dialyzer 2017-11-27 Hands on Module 1 Attach concentrates Attach dialyzer Load the Artiset and connect lines Attach heparin syringe Set heparin prescription Linear 1.0mL/h, Initial Dose 2.0mL, Stop Time15 min) Connect saline Clamp status Ready for priming? Book Auto-prime Demonstration & Hands on The Trainer’s Check List should be used and ticked off during the hands-on training By following the different hands-on prescriptions all function will have been practiced at the end of the course Highlight Ready for priming? The Trainer should check that the clamp status is correct and that Auto-Prime is booked.

References Maduell et al, High Efficiency Post dilution Online Hemodiafiltration reduces All-Cause Mortality in Hemodialysis patients; JASN 24, p. 6, 2013

For safe and proper use of the devices referenced within, refer to Warnings, Precautions and the complete Instructions for Use or the appropriate manual available by contacting customer support. ArtiSet, BiCart, SelectCart and SelectBag One are trademarks of Gambro AB. Gambro is an indirect subsidiary of Baxter International.