Measurement and optimization of injection force · – Injection of 20 units (small dose) with 31G...

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

2 Ypsomed | Zwick Seminar Ulm October 17, 2018

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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

Ypsomed | Zwick Seminar Ulm October 17, 20184

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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


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!


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

Ypsomed | Zwick Seminar Ulm June 13, 201810

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

Ypsomed | Zwick Seminar Ulm June 13, 201811

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:


12 Ypsomed | Injection force optimization

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2. Case study 1 – The results 1


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


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)


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)


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)


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) !


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) !


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!


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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Measurement and optimization of injection force · – Injection of 20 units (small dose) with 31G...

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