Comments:
In this study, Kapitza and colleagues compared the PK and PD characteristics of a biosimilar pre mixed insulin SAR341402 Mix 70/30 (premixed formulation with 70% protamine crystallized insulin aspart and 30% soluble insulin aspart) with two commercially available preparations of protaminated aspart/soluble aspart premixes for pharmakometric equivalence and SAR341402 Mix 70/30 with insulin aspart solution (SAR-Asp) to show pharmakometric difference in subjects with type 1 diabetes .

The study is well designed and quality of the clamps appropriate.

I just have a few comments I would like the authors to address

1. Line 36, p 6 the authors mentioning excluding patients positive for “anti- insulin” antibodies.

a. Since these were all type 1 diabetes patients, they would all be expected to be positive for anti-insulin antibodies. What type of “anti- insulin antibodies” were tested for?

b. Why were patients positive for antibodies excluded?

1. Line 21, p 7: Please clarify how patients were treated during the washout period since they all had Type 1 diabetes and according to the study design could have been off of their own insulin for up to 72 hours.

2. Figure S2 is confusing (i) Top Panel A shows pump data but legend says 'no pump" (ii) vertical hashed lines I am presuming are representing 24 hour periods - might want to consider labeling them.