TY - JOUR T1 - Use of a Predictive Regression Model for estimating Hold-Up Volume for Biologic Drug Product Presentations JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2019.010728 SP - pdajpst.2019.010728 AU - Shyam Mehta AU - Srishty Subramanian AU - Rebecca Brown AU - Rowena DMello AU - Charlene Brisbane AU - Shouvik Roy Y1 - 2019/01/01 UR - http://journal.pda.org/content/early/2019/11/15/pdajpst.2019.010728.abstract N2 - A drug delivery system is designed to administer a therapeutic dose according to its label claim. Upon delivery of a parenteral drug product, the volume remaining inside the container which cannot be extracted at the end of drug administration is called the hold-up volume (HUV) and is primarily considered product wastage. In order to meet the label claim every drug product container is filled with a slight excess volume to meet the label claim. For early stage products in clinical phase, where material availability is often a limitation, excess volume in drug product containers has to be determined experimentally using several grams of product. In such scenarios, established models which can predict HUV in primary drug product containers would be valuable for product development. The objective of this study was to determine HUV with 95% confidence intervals across various container closures and drug delivery systems by using aqueous PEG400 solution mimicking the viscosity of biologic drug products. ISO 2R, 6R and 10R vials and single-use hypodermic syringe attached to luer lock needle (25G, 1½″) were used to mimic parenteral drug product container and delivery systems for determination of HUV. Glass PFS in 1mL and 2.25 mL configurations were also used to determine HUV with 95% confidence intervals. A linear regression model was developed for determination of HUV as a function of viscosity and as a function of container closure and needle based delivery system. This model predicting HUV was confirmed by using mAbs of varying formulations and viscosities for container closure and delivery systems tested in this study. The model provided here can be used to determine HUV for a particular container closure for a drug solution with known viscosity which can subsequently be used to evaluate fill volume specifications and label claim for a dosage form. ER -