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20 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 P h a r mTe c h . c o m Analytics B iopharmaceutical products are becoming the driving force of the pharmaceutical industry. The primary route of administration for biopharmaceutical products is by injection, and the commonly used container/closure systems use glass vials with rubber stop- pers and prefilled syringes. Silicone oil has been widely used to coat the components of container/ closure systems for biopharmaceutical products, including syringe barrels and plungers for prefilled syringes and stoppers for glass vials (1). The drug product formulations typically are in direct contact with the silicone oil coat- ing over long periods of time; there is a general concern that the silicone oil may leach into the drug product formulations, which may affect the drug product's purity and efficacy (2, 3, 4). Unlike small-molecule pharmaceutical products, leachable silicone oil may affect the conformation of the large-molecule APIs of biopharmaceuti- cal products, which can cause protein denaturation and, in the long term, can lead to protein aggregation (3). Protein aggregates can result in a loss of protein biological activity and may induce immunogenic effects (4) when injected into the human body. Therefore, it is important to evaluate leach- able silicone oil for biopharmaceutical products. There are different methods for analyzing silicone oil that, in general, fall into two categories: one is based on the polymeric nature of silicone oil, using a gel permeation chromatography column to separate silicone oil from the drug product ingredients. Silicone oil molecules typically do not contain a chromophore, so the commonly used ultraviolet detector is not suitable. The detectors typically used for silicone oil analysis are refractive index detector, evaporative light scattering detector, charged aerosol detector, etc. The second category of methods is based on silica-specific techniques, such as atomic absorption spectroscopy, inductively coupled plasma–atomic emission spectroscopy , also referred to as inductively coupled plasma–opti- A Study of Leachable Silicone Oil in Simulated Biopharmaceutical Formulations Xiaochun Yu, PhD, is senior principal scientist; Nicholas Keyes is scientist; Neal Andrist is scientist; Ashley Hellenbrand is senior scientist; Jeffrey Nordin is senior group leader; and Roxanne Aide is senior project manager; all at PPD Laboratories GMP lab, Middleton, WI. SVETL ANA ANIKINA- STOCK.ADOBE.COM Xiaochun Yu, Nicholas Keyes, Neal Andrist, Ashley Hellenbrand, Jeffrey Nordin, and Roxanne Aide Leachable silicone oil may have an effect on large-molecule APIs, making it important to establish a robust analytical method to detect and quantify the substance.