Supplementary Material to:

Measuring tissue back-pressure

- in vivo injection forces during subcutaneous injection

Andrea Allmendingera,b, Robert Muellera, Edward Schwarbc, Mark Chipperfieldc, Joerg Huwylerb, Hanns-Christian Mahlera, Stefan Fischera,*

a Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland

b Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland

c Device Development, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland

*Corresponding author:

Stefan Fischer

Phone: + 41 61 68 79118

The supporting information contains one table Table S-1 and two figures Figure S-1 and S-2.

Table S-1: Temperature correction factor for sc back-pressure related injection force to account for local temperature effect in the needle/at the injection site of the minipig. The correction factor is presented in this table as an example for a temperature increase from 20 - 39°C (minipig) and additionally from 20 - 37°C (humans) between in vivo and control measurement (injection into tempered water bath) dependent on viscosity and injection rate. As outlined in the Method’s section, the temperature correction factor was calculated individually for each in vivo injection according to the Arrhenius equation based on temperature monitoring.

Temperature correction factor [N] for 20-39°C / 20-37°C / 0.025 mL/s / 0.1 mL/s / 0.2 mL/s
1 mPas / 0.0 /0.0 / -0.2 /-0.1 / 0.0 /0.0
10 mPas / 0.3 /0.2 / 1.0 /0.7 / 1.4 /0.9
20 mPas / 1.4 /0.9 / 2.8 /1.9 / 4.2 /2.8
100 mPas / 6.2 /4.2 / - / -

Figure S-1: Instrumental set-up of control measurements (in vitro, 39°C) for correction of local temperature effect at the body surface of the minipig/at the injection site. Injections were performed with only the needle inserted into the water bath to simulate in vivo conditions. The water was tempered to 39°C which is the body temperature of minipigs.

Figure S-2: Number of injection sites showing blister formation after injection per number of total injections as a function of body weight of the minipigs.