Determination of time to onset and rate of action of insulin products: importance and new approaches.

One important aspect of insulin drug development is to ascertain that short-acting insulins mimic the normal mealtime insulin release in healthy subjects. Therefore, it is important to identify metrics that allow identification of unique characteristics of insulin products based on pharmacokinetic (PK) (time-concentration) or glucodynamic (time course of action) profiles. Current development programs use metrics such as "onset of action" to characterize insulin products, in addition to peak and area under the curve parameters for PK and glucodynamic profiles. However, in current practice, onset of action parameter is often interchangeably used with rate of action for insulin products, which points to existence of confusion about their definitions and methods of determination. In this paper, we discuss these two parameters with an underlying objective to prompt discussion on development of a quantitative standard for insulin products based on the onset and/or rate of action. This paper presents euglycemic clamp and meal challenge study data using a hypothetical insulin product and attempts to clear confusion by emphasizing on the distinct properties of these parameters.