Analytical Method Development and Validation at PT Kalbio Global Medika: pH and Subvisible Particle Relationship Study of Ezelin (Insulin Glargine)

Abstract

PT Kalbio Global Medika (KGM) is a subsidiary company of PT Kalbe Farma Tbk. which is a pioneer biopharmaceutical-manufacturing company in the country. The analytical method development (AnDev) team in the research and development (RnD) department of KGM is responsible for verifications of the analytical methods used throughout the manufacturing process in KGM and for analytical studies in the case of an issue in the product manufacturing. The analytical study discussed in this report is regarding the relationship between pH and subvisible particles of Ezelin (Insulin Glargine), one of the products currently manufactured by KGM. Particulate matter in biotherapeutic products could occur due to aggregations in which based on the source could be categorized into inherent, intrinsic, and extrinsic aggregates. Formation of these aggregates are influenced by several factors, of which changes in pH level is included. The study was conducted by dividing Ezelin samples into different treatment groups where each group is adjusted to a certain level of pH using – solutions. Subvisible particle analysis was conducted using the light obscuration method using the Lighthouse LS-20v.1 Liquid Sampler. The result of the study showed that the subvisible particle count of Ezeline was neither directly nor inversely proportional to the decrease or increase of pH. It is suggested that the varying value of subvisible particle count was caused by a factor other than pH, such as contamination from personnels, the difference of pH adjustments to different treatment groups, and formation of air bubbles during mixing of the samples which may affect the light obscuration test results.