PMID- 37244516 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20231122 IS - 1520-6017 (Electronic) IS - 0022-3549 (Linking) VI - 112 IP - 8 DP - 2023 Aug TI - Variables Impacting Silicone Oil Migration and Biologics in Prefilled Syringes. PG - 2203-2211 LID - S0022-3549(23)00204-6 [pii] LID - 10.1016/j.xphs.2023.05.017 [doi] AB - Prefilled syringes (PFS) as a primary container for parenteral drug products offer significant advantages, such as fast delivery time, ease of self-administration and fewer dosing errors. Despite the benefits that PFS can provide to patients, the silicone oil pre-coated on the glass barrels has shown migration into the drug product, which can impact particle formation and syringe functionality. Health authorities have urged product developers to better understand the susceptibility of drug products to particle formation in PFS due to silicone oil. In the market, there are multiple syringe sources provided by various PFS suppliers. Due to current supply chain shortages and procurement preferences for commercial products, the PFS source may change in the middle of development. Additionally, health authorities require establishing source duality. Therefore, it is crucial to understand how different syringe sources and formulation compositions impact the drug product quality. Here, several design of experiments (DOE) are executed that focus on the risk of silicone oil migration induced by syringe sources, surfactants, protein types, stress, etc. We utilized Resonant Mass Measurement (RMM) and Micro Flow Imaging (MFI) to characterize silicone oil and proteinaceous particle distribution in both micron and submicron size ranges, as well as ICP-MS to quantify silicon content. The protein aggregation and PFS functionality were also monitored in the stability study. The results show that silicone oil migration is impacted more by syringe source, siliconization process and surfactant (type & concentration). The break loose force and extrusion force across all syringe sources increase significantly as protein concentration and storage temperature increase. Protein stability is found to be impacted by its molecular properties and is less impacted by the presence of silicone oil, which is the same inference drawn in other literatures. A detailed evaluation described in this paper enables a thorough and optimal selection of primary container closure and de-risks the impact of silicone oil on drug product stability. CI - Copyright (c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. FAU - Gentile, Kayla AU - Gentile K AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Huang, Chengbin AU - Huang C AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Liu, Xiaoyang AU - Liu X AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Whitty-Leveille, Laurence AU - Whitty-Leveille L AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Hamzaoui, Hassen AU - Hamzaoui H AD - Device Development, Pharmaceutical Sciences & Clinical Supply Merck & Co., Inc., 126 E Lincoln Ave, Rahway, NJ,07065, USA. FAU - Cristofolli, Eduardo AU - Cristofolli E AD - Device Development, Pharmaceutical Sciences & Clinical Supply Merck & Co., Inc., 126 E Lincoln Ave, Rahway, NJ,07065, USA. FAU - Rayfield, William AU - Rayfield W AD - Bioprocess Downstream Platform Development, Bioprocess Research & Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Afanador, Nelson Lee AU - Afanador NL AD - Biostatistics, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA, 19486, USA. FAU - Mittal, Sarita AU - Mittal S AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Krishnamachari, Yogita AU - Krishnamachari Y AD - Sterile and Specialty Products, Pharmaceutical Sciences & Clinical Supply, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Xi, Hanmi AU - Xi H AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. FAU - Zhao, Xi AU - Zhao X AD - Analytical Enabling Capabilities, Analytical Research and Development, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA; Sterile and Specialty Products, Pharmaceutical Sciences & Clinical Supply, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ, 07033, USA. Electronic address: xi.zhao1@merck.com. LA - eng PT - Journal Article DEP - 20230525 PL - United States TA - J Pharm Sci JT - Journal of pharmaceutical sciences JID - 2985195R RN - 0 (Silicone Oils) RN - 0 (Biological Products) RN - 0 (Pharmaceutical Preparations) RN - 0 (Proteins) SB - IM MH - Humans MH - *Silicone Oils MH - *Biological Products MH - Syringes MH - Pharmaceutical Preparations MH - Proteins OTO - NOTNLM OT - ICP-MS OT - MFI OT - Prefilled syringes (PFS) OT - Protein formulation OT - RMM OT - Silicone oil migration OT - Siliconization process OT - Surfactants OT - Syringe functionality OT - Syringe manufacturer COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/05/28 01:07 MHDA- 2023/07/17 06:42 CRDT- 2023/05/27 19:26 PHST- 2023/03/10 00:00 [received] PHST- 2023/05/20 00:00 [revised] PHST- 2023/05/21 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/05/28 01:07 [pubmed] PHST- 2023/05/27 19:26 [entrez] AID - S0022-3549(23)00204-6 [pii] AID - 10.1016/j.xphs.2023.05.017 [doi] PST - ppublish SO - J Pharm Sci. 2023 Aug;112(8):2203-2211. doi: 10.1016/j.xphs.2023.05.017. Epub 2023 May 25.