Elcam Medical New Generation Flexi-Q Auto-Injectors

Elcam MedicalNew GenerationFlexi-Q Auto-InjectorsThe Flexi-Q DV / P-DVR –a Unique DisposableAutoinjector for LyophilizedDrugs in VialsDr. Menachem Zucker, VP, I3DGuy Keenan, Design & Testing, I3DLyophilization for Biologicals conferenceBrussels, 24-25 January 2011

Elcam Medical• Elcam Medical is a leading worldwide OEMsupplier of Fluid Management, Drug Delivery andVital Signs Monitoring systems and devices• Our Quality System is in full accordance with theFDA QSR, European Medical Devices Directiveand is ISO 9001, ISO 13485 certified2

Elcam’s Manufacturing Facilities• 27,000 sq. ft. of class 100,000 clean rooms at Kibbutz BarAm• 10,000 sq. ft. of class 100,000 clean rooms at Dalton• Manufacturing in the US via acquisition of Injectech• Manufacturing in the EU via acquisition of Lucomed• Precision injection molding processes, including 2C (TwoComponents) and LSR (Liquid Silicon Rubber)• Fully automated production floor utilizing custom madeassembly machines3

Product Lines• Stopcocks & Manifolds• Needle-less• Valves• Disposable Pressure Transducer• Injectable Drug Delivery Devices (I3D)4

5Elcam’s Major Customers

Overview:Flexi-Q Auto-injector Platform

Novel, Commercially AvailableFlexi-Q PFSDisposableAuto-InjectorforPre-filled SyringesMAF(DeviceMaster File)submitted• Safe & Simple• Reduced Pain Perception• Injection starts only afterfull needle penetration• Easy & safe drugreconstitution andaspiration from vials• Single or multiple vials• Drug viscosity range• Unique LCM toolsFlexi-Q DVDisposableAuto-InjectorforDrugs in Vials510(k)submitted7

Flexi-Q DV Design Characteristics –Pharmaceutical Customer AdvantagesDifferentiation:• Unique auto-injector for drugs in vials – no needto change drug container• Compatible with drugs with differentadministration volumes• Allows reconstitution of multiple vials forincreased drug dosing / mixing• Provides flexibility – the diluents may becontained in either vials or pre-filled* in the injectorto minimize the number of user operation steps* Further submission8

Flexi-Q DV Design Characteristics –Patient Advantages – Ease Of UseBetter patient compliance:• Quiet injection - reducing anxiety andperceived pain• Enables a fully automatic injection process• Prevents needle-phobia – by hiding the needlethrough all the reconstitution and injectionprocesses• Easy titration and expelling of air bubblesusing the long observation window9

Flexi-Q DV Design Characteristics -Patient Advantages – Safety• Prevents needle-stick injuries – needle isprotected throughout the process of reconstitutionand injection• Reduced local skin reactions – Injection startsonly after full needle penetration and into the correctdepth (SC)• Clear visual and audible confirmation of theinjection progress from beginning to end• Prevents expensive drug spillage duringreconstitution and injection – proprietary featurelocks plunger while not reconstituting orautomatically injecting• Prevents false trigger activation during all steps10

Vial Adaptor Options• Standard Vial Adaptor is designed for 13 mm neckvials:‣ most common for self-injectable drugs‣ all relevant sizes• Additional options available:1. For vials with 20 mm neck2. A vented Vial Adaptor11

E N G L I S HFlexi-QAuto-injectorP-DVR Model Instructions for Usefor 1.0 mL pre-filled diluent volume

Yellow RodRed INJECTButtonGrip AreaDosageWindowGrayConnectorSafetyCoverVial

1. Remove plastic cap from the Vial.2. Clean the top of the Vial with an alcohol swab.3. Place the Vial on a hard surface.4. Insert the Vial into the Gray Connector byholding the Vial in one hand and pressing theGray Connector over the top of the Vial withthe other hand until it snaps into place.See fig. A.Fig. A

1. Remove the Safety Cover of theAuto-injector by pulling it down.See fig. B.Fig. B

1. Hold the Auto-injector at the Grip Area withthe Red INJECT Button in front of you and theYellow Rod at the top. See fig. C.2. Hold the Gray Connector with the other hand.3. Insert the Auto-injector into the GrayConnector until it’s all the way in.See fig. C.Fig. CMake sure theGray Connector cannot bepressed in any further.

41. Gently Push the Yellow Rodall the way in. See fig. D.Fig. DPush the YellowRod very slowly to avoid foaming.

51. Mix the drug by gently rotating the Autoinjectorin a swirl motion. See fig. E.avoid foaming.DO NOT shake toFig. E2. Wait until the drug has dissolvedaccording to the instructions providedwith the drug.Make sure all theparticles have been completelydissolved and most of the foaminghas disappeared.If the solution is opaque or containsparticles – the Auto-injector mustbe discarded!(See Discarding instructions below).

61. Hold the Auto-injector vertically withthe Vial on top! See fig. F.2. Push the Yellow Rod very slowly allthe way in. See fig. F.Fig. FPush the YellowRod very slowly to avoid foaming.

71. Withdraw all the solution back bypulling down the Yellow Rod veryslowly all the way out. See fig. G.Fig. G

81. Tap near Dosage Window to movelarge air bubbles to the top.See fig. H.2. Push the Yellow Rod slightly onlyuntil all the air is removed (NOT allthe way).Fig. H

91. If there is air left in the syringe(see fig. I), repeat steps 7 and 8.It is OK if it takes a coupleof times.Fig. I

101. Remove the Gray Connector bypressing the Gray Connectorhandles and pulling it out.See fig. J.Fig. JDO NOT TOUCHthe Yellow Rod from this stage on.

111. Select one of the following injectionsites according to your medicalpractitioner’s instructions. See fig. K:• Upper thighs.• Lower abdomen, except for thearea two inches around your navel.• Back of your arms, only if theinjection is performed by someoneelse.2. Prepare the skin on the injection siteas recommended by the drug label(e.g. clean the injection site withan alcohol swab).Fig. KFrontBack

121. Hold the Auto-injector at the Grip Areawith the Red INJECT Button in front of youand the Yellow Rod at the top.Fig. LDO NOT TOUCH the Yellow Rod!2. Press the Auto-injector firmly against yourskin until you hear a click (the green tipfolds into the Auto-injector).h3. Maintain the Auto-injector pressed againstyour skin and press the Red INJECT Button(the Yellow Rod will automatically movedown). See fig. L.The injection is completed when theYellow Rod stops moving. This usuallytakes around 10 seconds, after which theDosage Window will turn yellow.

131. Lift the Auto-injector away from yourskin while holding it tightly. Thegreen tip will cover the needle forsafe disposal. See fig. M.2. In case of bleeding, gently place acotton ball or gauze over the injectionsite for 10-15 seconds.Fig. M

• Discard the device according to your local laws andregulations, or instructions provided by your medical practitioner.• The Auto-injector SHOULD NOT be reused.IFU Flexi-Q P-DVR 1.0 mL (English), DRAFT 06, December 23, 2010

Flexi-Q DV Auto-injectorCase Studies:1. Simulated Clinical Use Study2. Needle Tip StudyFlexi –Q DV

Device Validation• Simulated Clinical Use Study• Performed based on the FDA CDRH Guidance:“Medical Devices With Sharps Injury PreventionFeatures”29

Study Methodology - Brief1. Devices tested:500 units of Flexi-Q DV auto-injectors2. 30 total naive participants recruited:○○5 participants being mild to moderate RA/MS patientsMale and female aged 18-70 years old; recruited fromeach of the following age groups:• 18-36 years of age (17 evaluators)• 37-53 years of age (5 evaluators)• 54-70 years of age (8 evaluators)3. Each participant operated 15-17 Flexi-Q DV’s:○Injecting into foam-pad positioned:on her/his thigh (~½);on her/his abdomen (~½);30

Study Results1. All users successfully operated the Flexi-Q DV2. No drug spillage has occurred (due to theproprietary plunger-lock)(0/500 operations)31

32Flexi-Q DV use by MS Patient:video clip

33Flexi-Q P-DVR use by RA Patient:video clip

Flexi-Q DV Auto-injectorCase Studies:1. Simulated Clinical Use Study2. Needle Tip StudyFlexi –Q DV

Background• Flexi-Q DV is assembled with 1 mL long glasssyringe with ½” staked-in needle covered withNS/RNS• Allows a configuration of a pre-filled diluentsyringe for reconstitution (Flexi-Q P-DVR)• Usage of Vial Adaptor (VA) for drug aspirationand reconstitution35

Background (cont.)• Needle penetrates two elastomers’:ooNS/RNS (assembled by syringe manufacturer)VA Septum (during usage)Septum(TPE)VialAdaptorNS / RNSStandardVial36

Background (cont.)• In many cases people use the same needle fordrug aspiration / reconstitution and for drugadministration (e.g., Epoetin alfa (EPO), insulin):37

General• Identified Hazard: Compromised needleproperties (e.g., needle dulling) due to a singleadditional penetration into the VA septum• Mitigation:○○Performing a study with the following objectives:• Examine whether the needle properties arecompromised• Selection of septum material (TPE or a onecommonly used for NS)Performing the study with the most experienced,external objective laboratory for testing needle quality(Melab GmbH, Germany)38

Method• Glass syringe, 3-bevel 27G staked-in needle, RNS• Penetration force test – DIN 13097 (09/2002)○○commonly used world-wide to examine needles quality0.4 mm thick Polyurethane (PU) foilPenetration load-measuring equipment(a) glass syringe with staked-in needle , (b) testingfoil, (c) foil support, (d) transferring unit, (e) loaddetector, (f) amplifier, (g) recording unitTypical graphF 0 – tip resistance (piercing)F 1 – cutting resistanceF 2 – dilatation resistanceF R – friction of the shaft39

Method (cont.)• Compare needle quality before and after penetrationinto the vial adaptor septum:○○Group A*: simulation of real use (N=32)tested once following removal of the RNS, and thenafter a single penetration into the Vial Adaptor Septum (TPE)Group B: excessive number of septum penetrations (N=3)tested after 12 septum’s penetrations, and after re-coatingwith silicone oil (explore wiped away silicone effect)• Needle tip investigation for damages by usingx30 magnifying microscope40* Note: another group (N=32) was used for the 2 nd option ofSeptum material (as material not selected – these results are notshown).

Results & DiscussionTPE SeptumF 1 – cutting resistancerepresents tip qualityF R – friction of the shaftassociated with siliconization layerNeedle conditionNew. Only RNS piercingAfter single septum penetrationAfter 12 septum penetrationsF 1– max load [N]Avg. ± SD0.84 ± 0.030.94 ± 0.040.96 ± 0.04F R[N]Avg. ± SD0.16 ± 0.020.18 ± 0.020.33 ± 0.01ControlgroupDevicenormaluseAfter re-coating0.88 ± 0.030.11 ± 0.0141• Slight increase in the max force (F 1 ) after septumpenetration (single or multiple)• Decreased after re-coating with silicone-oil• No change in Friction Force (F R ) after singleseptum penetration• Friction Force is doubled after 12 penetrations anddecreased back after re-coating

Results & Discussion (cont.)TPE Septum• No visible changes on the bevels even after12 penetrations (x30 magnification)42

ConclusionsUsing the TPE Septum material:• The slight increase of force is attributed to partialremoval of the silicone layer from the needle• Furthermore, “the tested samples are of standardmarket quality even after the 12 septumpenetrations: These changes in penetration forcesare covered by the standard deviations of thesevalues as measured in market batches of the sametype of needles”**Ref.: Citation of Dr. Kinast, based on Melab GmbH quality testsfor marketed syringes43

Summary: Needle Tip Quality Confirmed The needle quality is NOT compromisedwhen using the Flexi-Q DV and P-DVRauto-injectors It was proved that the same needle canbe used both for drug aspiration /reconstitution and for injectionAcknowledgement: Melab GmbH, Leonberg, Germany44

Testimonials – from recent work withpharma companiesYear /Company* Description Testimonials452010One of top10 pharmaTechnical duediligenceperformedby a US third-partyon behalf of apharma customerfor the use of theFlexi-Q PFSautoinjector for aPhase III drug(auto-immuneindication)"The assembly steps as outlined here look relativelyeasy to manage and tool for scale up activities...""One thing that jumps out of the design review is that ingeneral, clever and novel design approaches areevident throughout the product...“"The product uses the minimum number ofcomponents to achieve the desired functionality,without undue component complexity... “"… we consider the device to be below average riskfor dose repeatability, and generalized functionalperformance.“"… our assessment of the “robustness” of thedesign, its perceived fault tolerance, and ability tofunction reliably and repeatably in a wide variety ofmanufacturing and environmental conditions isfavorable.“J.C., CEO, founder, major US-based engineering firm performingtechnical due-diligence* Due to confidentiality agreements, no disclosure of company names are possible

Testimonials – from recent work withpharma companies (cont.)Year /Company* Description Testimonials2010Smallmediumsize biotech2009One of top10 pharmaStage I: Few conceptdesigns and draftinga patent applicationfor the sameFeasibility project forthe use of one of theFlexi-Q PFSautoinjector for aPhase III drug“Very much satisfied from the work done; Well done!Awaiting for the next stage of feasibility”;R.L. , PhD, Patent Attorney, Director of Intellectual Property“The engineering analysis David provided wasexcellent. I would rate it on par with work we havecontracted in the past with ENGINEERING companieswho have ONLY THAT FOCUS AS THEIR BUSINESSSERVICE. “J.J., Senior Program Manager462008One of top10 biopharmacompaniesFeasibility project forthe use of one of theFlexi-Q DVautoinjector for aPhase II drug“… Regarding the new prototype of the Flexi-Qdevice, all of the people I have shown the device tohave been really pleased with the outcome.”“As always, you have provided an exceptionalamount of quality with your work. Thank you for allof your efforts.”C.B., PhD, Senior Biologic Project Manager, R&D* Due to confidentiality agreements, no disclosure of company names are possible

Summary: Elcam Medical• Elcam has a broad line of innovative solutions for easyto-useself-administration of drugs - all are customizableto meet your specific needs• Elcam has a long history being a reliable partner providinghigh quality and excellent service in the single-usedisposable fluid control products• Experience working with some major US pharma companiesin the fields of anemia, RA, MS, microspheres/high viscosity• Elcam is well positioned to provide you with its uniqueFlexi-Q line for current and future needs and assist in lifecyclemanagement47