Flexi-Q DV Auto-injector - DALI Medical Devices

Elcam Medical
New Generation
Flexi-Q Auto-Injectors
The Use of Pre-Filled Syringes
in Auto-Injector with
Reconstitution Capabilities
Dr. Menachem Zucker, VP, I3D
David Daily, Director of R&D, I3D
Management Forum, Pre-Filled Syringes and Advanced
Injection Technologies Conference
London, 7-8 May 2009

Contents
1. Elcam Medical - Overview
2. Flexi-Q Disposable Auto-Injector Platform:
• Flexi-Q PFS Auto-Injector for Pre-Filled
Syringes
• Flexi-Q DV Auto-Injector for Drugs in Vials
3. Two Risk-Related Case Studies Regarding the
Use of Pre-Filled Syringes in Disposable Auto-
Injector for Drugs in Vials:
• Potential Usability Issue
• Potential Design Issue
2

Elcam Medical
• Elcam Medical is a leading worldwide OEM
supplier of Fluid Management, Drug Delivery and
Vital Signs Monitoring systems and devices
3
• Our Quality System is in full accordance with the
FDA QSR, European Medical Devices Directive
and is ISO 9001, ISO 13485 compliant

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, opened
in December 2007
• Precision injection molding processes, including 2C (Two
Components) and LSR (Liquid Silicon Rubber)
• Fully automated production floor utilizing custom made
assembly machines
4

Product Lines
• Stopcocks & Manifolds
• Needle-less
• Valves
• Disposable Pressure Transducer
• Injectable Drug Delivery Devices (I3D)
5

Elcam’s Major Customers
• Covidien/Tyco
• Hospira
• ICU Medical
• Edwards Lifesciences
• Teleflex/Arrow International
• Baxter
• Medtronic
• B.Braun
• BD
• Cardinal
• Abbott
• J&J
6

Overview:
Flexi-Q Auto-injector Platform

Elcam Flexi-Q PFS Auto-injector
• The Flexi-Q PFS is a
Fully-Disposable Auto-
Injector for self
administration of drugs
in Pre-Filled Syringes
Inject Button
• It is a 2 step, singleuse,
passive needle
shielding, automatic
injection device
Drug
Pre-Filled
Syringe
Long
Observation
Window
Skin Sensor
8

Flexi-Q PFS Design Characteristics –
Pharmaceutical Customer Advantages
• Flexible delivery volumes of 0.3 – 1.0 mL
• Delivery of entire dose
• Reduced skin reactions
• Large windows for visual inspection of syringe
contents
Wide range of customization options
e.g.: use with high-viscosity drugs
9

Flexi-Q PFS Design Characteristics –
Major Patient Advantages
• Quiet injection - reducing anxiety and perceived
pain
• Side positioned trigger button – easily activated
by one or two hands
• Clear visual and audible confirmation of the
injection progress from beginning to end
• Prevents false activation - allows activation only
after pressing the injector against patient’s skin
• Suitable for use by RA and MS patients
10

Elcam Flexi-Q DV Auto-injector
• The Flexi-Q DV is the only
Disposable Auto-Injector for
reconstitution and self
administration of drugs in vials
(in both lyophilized and liquid
forms)
• It provides life cycle
management opportunities for
new and existing drugs, along
with patient compatibility and
safety in self injection
Syringe
Plunger
INJECT
Button
Long
Observation
Window
Standard
glass
syringe
Skin
Sensor
Vial
Adaptor
11

Flexi-Q DV Design Characteristics –
Pharmaceutical Customer Advantages
Differentiation:
• Unique auto-injector for drugs in vials – no need
to change drug container
• Compatible with drugs with different
administration volumes
• Allows reconstitution of multiple vials for
increased drug dosing / mixing
• Provides flexibility – the diluents may be
contained in either vials or pre-filled* in the injector
to minimize the number of user operation steps
* Further submission
12

Flexi-Q DV Design Characteristics –
Patient Advantages – Ease Of Use
Better patient compliance:
• Quiet injection - reducing anxiety and
perceived pain
• Enables a fully automatic injection process
• Prevents needle-phobia – by hiding the needle
through all the reconstitution and injection
processes
• Easy titration and expelling of air bubbles
using the long observation window
13

Flexi-Q DV Design Characteristics -
Patient Advantages – Safety
14
• Prevents needle-stick injuries – needle is
protected throughout the process of reconstitution
and injection
• Reduced local skin reactions – Injection starts
only after full needle penetration and into the correct
depth (SC)
• Clear visual and audible confirmation of the
injection progress from beginning to end
• Prevents expensive drug spillage during
reconstitution and injection – proprietary feature
locks plunger while not reconstituting or
automatically injecting
• Prevents false trigger activation during all steps
Live Demonstration

Regulatory Path
• Flexi-Q DV:
○ 510(k), CE Mark (2009)
• Flexi-Q PFS:
○ Device Master File (submitted)
No change in administration route (SC)
No change in drug container (PFS or Vials)
15
Flexi –Q PFS
Flexi –Q DV

Flexi-Q DV Auto-injector
Two Risk-Related Case Studies Regarding
the Use of Pre-Filled Syringes in Disposable
Auto-Injector for Drugs in Vials:
1. Potential Usability Issue
2. Potential Design Issue
Flexi –Q DV

Risk Management Approach
1. Done according to ISO 14971:2007.
We use the FMEA method
2. Systematic listing of hazards related to features /
components / subassemblies / final-assy / use:
Hazard, Cause, Effect RPN = severity X prob.
X detect. Mitigation Activity
3. QA Engineer responsibility for Risk Management
process activities
4. Starting at the beginning of the project;
○
○
being updated at every important phase
and at every important design change
17

Flexi-Q DV Auto-injector
Two Risk-Related Case Studies Regarding
the Use of Pre-Filled Syringes in Disposable
Auto-Injector for Drugs in Vials:
1. Potential Usability Issue
2. Potential Design Issue
Flexi –Q DV

Background
• Developed with a major pharmaceutical company
• Drug in vial (expensive)
• Generally elderly patient population (50-75 years)
• Frequent or infrequent injections
• Market transition from injection by healthcare
providers to self-injection at home
• Design Concept: a Plunger Rod is used to fill the
drug from the vial into the injector
19

Background (cont.)
HAZARD: Drug spillage due to press on the Plunger
instead of pressing the Trigger Button
Device as used in early Usability Study (2006):
• Note Plunger tip design: 1 st Mitigation
20
• Note no Device Labeling was used

The Problem
• In a usability study performed in the US with 28
participants, occasionally, some people pushed on
the Plunger Rod instead of pressing the Inject
Button for activation (while not looking at the
instructions for use)
• Result: Spillage of expensive drug
• Conclusion of our Pharma partner: Our 1 st
mitigation isn’t effective enough…
Oops… What do
we do now???
21

The Way to Solution
• About 40 solutions were screened…
• From which 4 reached the “finals”….
○
Parameters Considered:
Usability, Manufacturability, COGS, Timeline
22

Chosen Solution
1. Implementing a Design Change:
○
○
Adding a proprietary feature* – Plunger Locker
Allows manual Plunger Rod manipulation for durg
reconstitution and aspiration
○ Prevents expensive drug spillage during injection -
Locks plunger while not reconstituting or automatically
injecting
2. Adding Device Labeling:
○
“INJECT” print on the Trigger Button
* International patent applications filed
23

Device and Changes Validation
• Simulated Clinical Use Study
• Performed based on the FDA CDRH Guidance:
“Medical Devices With Sharps Injury Prevention
Features”
24

Study Methodology - Brief
1. Devices tested:
500 units of Flexi-Q DV auto-injectors
2. 30 total naive participants recruited:
○
○
5 participants being mild to moderate RA/MS patients
Male and female aged 18-70 years old; recruited from
each 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);
25

Results
1. No drug spillage has occurred
(0/500 operations)
2. Solution unrelated to labeling – no matter if
reading IFU…!
Video Example….MS Patient
26

Lessons Learned
• Whatever you think users will do – they would find
a way to make it even worse…
• Device labels can make the difference
• Minimize reliance on labeling
• Perform as many usability trials as possible, and
start as early as possible
• There is always a better way / easy way to do it –
it’s just a matter of time and money
27

Flexi-Q DV Auto-injector
Two Risk-Related Case Studies Regarding
the Use of Pre-Filled Syringes in Disposable
Auto-Injector for Drugs in Vials:
1. Potential Usability Issue
2. Potential Design Issue
Flexi –Q DV

Background
• Flexi-Q DV is assembled with 1 mL long glass
syringe with ½” staked-in needle covered with
NS/RNS
• Allows a configuration of a pre-filled diluent
syringe for reconstitution
• Usage of Vial Adaptor (VA) for drug aspiration
and reconstitution
29

Background (cont.)
• Two elastomers’ penetrations:
o
o
NS/RNS
VA Septum
Septum
(TPE)
Vial
Adaptor
NS / RNS
Standard
Vial
30

Background (cont.)
• In many cases people use the same needle for
drug aspiration / reconstitution and for drug
administration (e.g., Epoetin alfa (EPO), insulin):
31

General
• Identified Hazard: Compromised needle
properties (e.g., needle dulling) due to a single
additional penetration into the VA septum
• Mitigation:
○
○
Performing a study with the following objectives:
• Examine whether the needle properties are
compromised
• Selection of septum material (TPE or a one
commonly used for NS)
Performing the study with the most experienced,
objective, known in the industry, external laboratory
(Melab GmbH, Germany)
32

Method
• Glass syringe, 3-bevel 27G staked-in needle, RNS
• Penetration force test – DIN 13097 (09/2002)
○
○
commonly used world-wide to examine needles quality
0.4 mm thick Polyurethane (PU) foil
Penetration load-measuring equipment
(a) glass syringe with staked-in needle , (b) testing
foil, (c) foil support, (d) transferring unit, (e) load
detector, (f) amplifier, (g) recording unit
Typical graph
F0 – tip resistance (piercing)
F1 – cutting resistance
F2 – dilatation resistance
FR – friction of the shaft
33

Method (cont.)
• Compare needle quality before and after penetration
into the vial adaptor septum:
○
○
Group A*: simulation of real use (N=32)
tested once following removal of the RNS, and then
after 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-coating
with silicone oil (explore wiped away silicone effect)
• Needle tip investigation for damages by using
x30 magnifying microscope
* Note: another group (N=32) was used for the 2 nd option of septum
material (as material not selected – these results are not shown).
34

Results & Discussion
Needle condition
F 0
[N]
Avg.
F 1
– max load [N]
Avg. ± SD
F 2
[N]
Avg.
F R
[N]
Avg. ± SD
New. Only RNS piercing
0.77
0.84 ± 0.03
0.52
0.16 ± 0.02
After single septum penetration
0.83
0.94 ± 0.04
0.61
0.18 ± 0.02
After 12 septum penetrations
0.86
0.96 ± 0.04
0.66
0.33 ± 0.01
After re-coating
0.85
0.88 ± 0.03
0.51
0.11 ± 0.01
• Slight increase in the max force (F 1 ) after septum
penetration (single or multiple)
• Decreased after re-coating with silicone-oil
• Friction force (F R ) is doubled after 12 penetrations and
decreased back after re-coating
• No visible changes on
the bevels even after
12 penetrations (x30)
35
F0 – tip resistance (piercing)
F1 – cutting resistance
F2 – dilatation resistance
FR – friction of the shaft

Conclusions
• The slight increase of force is attributed to partial
removal of the silicone layer from the needle
• Furthermore, “the tested samples are of
standard market quality even after the 12
septum penetrations: These changes in
penetration forces are covered by the standard
deviations of these values as measured in market
batches of the same type of needles”*
*Ref.: Citation from Dr. Kinast, based on Melab GmbH internal
tests data
36

Summary
• The needle quality is not compromised when using
the Flexi-Q DV auto-injector
• It was proved that the same needle can be used
both for drug aspiration / reconstitution and for
injection
Acknowledgement: Melab GmbH, Leonberg, Germany
(Melab’s full report available)
37

Summary
• Development of an A-I is not a simple task
• Need to consider many things
• Close collaboration with different stake
holders
• Always takes longer than expected
• Manage many risks associated
• The unique Flexi-Q product line is validated
38

Summary: Elcam Medical
• Elcam has a broad line of innovative solutions for
easy-to-use self-administration of drugs - all are
customizable to meet your specific needs
• Elcam has a long history being a reliable partner
providing high quality and excellent service in the
single-use disposable fluid control products
• Experience working with some major US pharma
companies in the fields of anemia, RA, MS,
microspheres/high viscosity
• Elcam is well positioned to provide you with its
unique Flexi-Q line for current and future needs
and assist in life-cycle management
39