measurement and optimization of injection force · 2021. 1. 26. · 3. case study 2 – force...
TRANSCRIPT
Measurement andoptimization ofinjection force:
Two case studies on material selection and
user perception
Jakob Lange, Ulm, October 17, 2018
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Outline
1. Introduction to Ypsomed and devices for self injection2. Case study 1: Modelling, measurement and material selection3. Case study 2: Force measurement versus perception4. Conclusions
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1. Ypsomed – Key facts
Turnover CHF ~466 M R&D-Investment CHF ~41 M Listed at SWX, majority shareholder
and founder family owning ~75% > 1‘450 employees
- ~990 in Switzerland - ~460 in Sales Affiliates
Manufacturing & assembly- Reusable devices > 1 million units- Disposable devices
> 80 million units- Pen needles > 600 million units
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1. Devices for self-injection – Introduction
Syringe and vial
Pre-filled syringe
Cartridge
Autoinjector
Pen Injector
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1. Devices for self-injection – Drivers
Ease of use
Improved convenience
Higher dose accuracy
Increased safety
Increased compliance
Differentiation / marketing
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1. Devices for self-injection – Markets
Diabetes hormones:Insulins, GLP-1s
PCSK-9s
Other hormones:hGH, infertility, osteoporosis
Emergency drugs: Anaphylactic shock,
migraine, military
MABs: Autoimmune diseases, MS, RA,
psoriasis, IBD, asthma Cancer, hep C
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8 millionreusable pens
1000 milliondisposable pens 80+ million
disposableautoinjectors
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1. Devices for self-injection – Disposable pens
Single use, come with the cartridge already inside Simple dial and dose or pull-push operation Range of devices for different applications
– Variable dose – Fix-dose
Insulin and diabetes largest market Efficient gearing mechanisms for
optimized user handling forces
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1. Injection force – Overview
Everybody agrees injection force isimportant, is touted as the single mostimportant performance parameter
Lots of studies on mechanical injectionforce measurement have beenconducted and published in theliterature
No systematic method comparison oragreement on how to best measureinjection force – tensile tester is usedbut test setup / method not standardized
Few people have studied how usersactually inject or what they perceive
F
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2. Case study 1 – The problem
How can injection force be minimized? Optimize the efficiency of the pen mechanism through material selection!
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75% of the frictional resistance comes from
this interface
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2. Case study 1 – The method
Zwick Roell Z 2.5 universal test machine with custom fittings
Measurement of force and torque over 450 degrees rotation 15 times back and forth at 90 degrees/s
Force and torque converted to CoFthrough a simple analytical model
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νax
νcirc
ν
α
y
x
νcirc
νax
ν
2Rπ
Pitch
Dose sleeve
Threaded sleeve
J Lange, L Urbanek, S Burren; Development of devices for self-injection: using tribological analysis to optimize injection force, Medical Devices: Evidence and Research 2016:9 93–103
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2. Case study 1 – Data evaluation
Calculation of the average coefficient of friction for each individual pair of up and down runs, gives 15 data points per tested sample. 10 samples were tested for each material combination
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Angle [degrees]
CoF
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2. Case study 1 – The tests
Testing was performed on a range of materials and combinations with different additives and lubricants:
J Lange, L Urbanek, S Burren; Development of devices for self-injection: using tribological analysis to optimize injection force, Medical Devices: Evidence and Research 2016:9 93–103
12 Ypsomed | Injection force optimization
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2. Case study 1 – The results 1
J Lange, L Urbanek, S Burren; Development of devices for self-injection: using tribological analysis to optimize injection force, Medical Devices: Evidence and Research 2016:9 93–103
1614121086420
0.200
0.175
0.150
0.125
0.100
0.075
0.050
Cycle no
CoF
Combination 1
1614121086420Cycle no
Combination 3
1614121086420Cycle no
Combination 7
1614121086420Cycle no
Combination 11
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2. Case study 1 – The results 2
J Lange, L Urbanek, S Burren; Development of devices for self-injection: using tribological analysis to optimize injection force, Medical Devices: Evidence and Research 2016:9 93–103
Combin
ation
3
Combin
ation
2
Combination 1
0.90.8
0.70.60.5
0.40.30.2
0.10.0
Syst
em fo
rce
effic
ienc
y
Polymers
0.28
0.38
0.12 0.12
-0.01
0.21
0.48
0.60
0.34
Combin
ation
11
Combination 10
Combin
ation
9
Combin
ation
8
External lubrication
0.39
0.48
0.23
0.61
0.68
0.46
0.820.85
0.770.81
0.84
0.77
Combina
tion 7
Combin
ation 6
Combin
ation
5
Combin
ation
4
Internal lubrication
0.550.59
0.48
0.12
0.24
0.02
0.15
0.27
0.00
0.690.73
0.65
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3. Case study 2 – Force measurement versus perception
Questions to be adressed:– Which is the best way to measure injection force?– Under what test conditions can / should pens be compared?– How do users actually perceive pens with different
measured forces?
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3. Case study 2 – Force measurements
1. Three pens tested– Disposable pen (UnoPenTM)– Reusable pen with the same gearing ratio (4:1)– Prototype disposable pen with different gearing ratio (3:1)
2. Injection force evaluated in different ways– Constant mechanical rate [mm/s]– Constant volumetric flow rate [U/s]
3. Tests with controlled rate– 2 different needle gauges (31G and 29G)– 25 measurements per pen type / condition
(provides a resolution of at least ~1N)
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Andreas E. Schneider & Jakob Lange (2018) Pen devices for self-injection: contrasting measured injection force with users’ perceived ease of injection, Expert Opinion on Drug Delivery, 15:2, 115-125, DOI: 10.1080/17425247.2018.1415884
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3. Case study 2 – Force raw data
Force profiles aresimilar between pens
Force level is differentbetween pens
Force increaseswith rate
Plateau values canbe used to comparebetweenmeasurements
Force increases withneedle gauge (thinnerneedle, data not shown)
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12
6
0
12
6
0
3020100
12
6
03020100
Reusable 5 IU/s / 2.75 mm/s
Travel [mm]
Forc
e [N
]
Reusable 15 IU/s / 8.25 mm/s
Disp. 1 5 IU/s / 2.75 mm/s Disp. 1 15 IU/s / 8.25 mm/s
Disp. 2 5 IU/s / 2.065 mm/s Disp. 2 15 IU/s / 6.20 mm/s
Injection force 29G needle
Andreas E. Schneider & Jakob Lange (2018) Pen devices for self-injection: contrasting measured injection force with users’ perceived ease of injection, Expert Opinion on Drug Delivery, 15:2, 115-125, DOI: 10.1080/17425247.2018.1415884
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3. Case study 2 – Force results 1
The two ways of comparing pens are not equivalent! Constant flow rate is considered the most appropriate (closest to user behaviour)
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987654321
35
30
25
20
15
10
5
0
Injection rate [mm/s]
Forc
e [N
]
Reusable 29GDisposable 1 29GDisposable 2 29GReusable 31GDisposable 1 31GDisposable 2 31G
Constant push-button rate
161412108642
25
20
15
10
5
Injection rate [IU/s]
Forc
e [N
]
Reusable 29GDisposable 1 29GDisposable 2 29GReusable 31GDisposable 1 31GDisposable 2 31G
Constant flow rate
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3. Case study 2 – Force results 2
Larger differences between needle gauges (for a given pen and rate) than between pens (at a given rate and needle gauge) !
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10 IU/s 31G10 IU/s 29G5 IU/s 31G5 IU/s 29G
16
14
12
10
8
6
4
2
0
Forc
e [N
]
ReusableDisposable 1Disposable 2
Comparison between pen types
Flow rate / needle gauge
Disposable 2Disposable 1Reusable
16
14
12
10
8
6
4
2
0
Forc
e [N
]
5 IU/s 29G5 IU/s 31G10 IU/s 29G10 IU/s 31G
Comparison between needle gauges / flow rates
Pen type
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3. Case study 2 – Patient perception study
Simulated injections into an injection pad– All three pens tested, reusable pen included twice– Injection of 20 units (small dose) with 31G needle and 60 units (large / max dose) with
29G needle– Each participant performed every injection 2 times, in random order
Participant rating of injection experience directly after each injection on a five-level Likert-Scale (1= strongly disagree; 5=strongly agree):– “How would you rate the handling comfort during the injection?” – “Please respond to the following statement: I had a pleasant feeling when performing an
injection with this pen.” Participants
– 39 participants, 19 female and 20 male– Age distribution 11-60 years– All injection naïve
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3. Case study injection force – Perception results
Smaller differences between needle gauges (for a given pen) than between pens (at a given needle gauge) !
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0
0
0
0
0
0
2
2
1
1
1
1
1
2
1
2
4
5
6
3
7
7
11
9
20
18
15
21
18
17
14
21
14
15
17
14
13
12
11
5
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Reusable A 29G
Reusable A 31G
Reusable B 29G
Reusable B 31G
Disposable 1 29G
Disposable 1 31G
Disposable 2 29G
Disposable 2 31G
Handling / comfort score (n=39*)
Score 1 Score 2 Score 3 Score 4 Score 5
*n=38 for Disposable 1 31G
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3. Case study 2 – Force versus perception
Very little correlation is observed, other factors than measurable injection force must be at play!
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1614121086420
5.0
4.5
4.0
3.5
3.0
2.5
2.0
Force [N]
Mea
n sc
ore
Force 5 IU/s, R squared 25.3%Force 10 IU/s, R squared 27.5%
Handling / comfort vs injection force
1614121086420
5.0
4.5
4.0
3.5
3.0
2.5
2.0
Force [N]
Mea
n sc
ore
Force 5 IU/s, R squared 17.0%Force 10 IU/s, R squared 27.0%
Feeling / convenience vs injection force
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4. Conclusions
Self-injection devices is an important and growing market Everybody agrees injection force is important but
– There is no agreed standard for how to measure– Nobody has studied how users actually inject and what they prefer!
Injection force is heavily influenced by the materials used in the pen– Frictional testing combined with modelling is a useful development tool– There are large differences between different materials– Additives / lubricants have as much influence on performance as the material itself
Force measurement and perceptions– Measured forces / outcome depend strongly on the needle gauge, rate of injection and
how pens are compared (constant push-button or flow rate)– Patients do perceive differences, but perception is only indirectly related to measured
forces
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