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Considerations for the Terminal Sterilisation of Oligonucleotide Drug Products

Lindenberg, Christian, Abarrou, Nounja, DeCollibus, Daniel, Searcy, Justin, Tivesten, Anna, Akhtar, Nadim, Pradhan, Sujana, Fiandaca, Maggie, Franklin, Jenny, Govindan, Geetha, Hung-Yi, Liu, Royle, David, Lim Soo, Patrick and Storch, Kirsten (2023) Considerations for the Terminal Sterilisation of Oligonucleotide Drug Products. Nucleic Acid Therapeutics. ISSN 2159-33372159-3345


A primary function of the parenteral drug product manufacturing process is to ensure sterility of the final product. The two most common methods for sterilizing parenteral drug products are terminal sterilisation (TS), whereby the drug product is sterilized in the final container following filling and finish, and membrane sterilisation, whereby the product stream is sterilized by membrane filtration and filled into pre-sterilized containers in an aseptic processing environment. Though TS provides greater sterility assurance than membrane sterilisation and aseptic processing, not all drug products are amenable to TS processes, which typically employ heat treatment or exposure to ionizing radiation.
Oligonucleotides represent an emerging class of therapeutics that have great potential to treat a broad range of indications, including previously undruggable targets. Due to their size, structural complexity, and relative lack of governing regulations, there are several challenges in drug development that are unique for oligonucleotides. This exceptionality justifies a focused assessment of traditional chemistry, manufacturing, and control strategies prior to their adoption. In this article, we review the current state of sterile oligonucleotide drug product processing, highlight key aspects to consider when assessing options for product sterilisation, and provide recommendations to aid in the successful evaluation and development of TS processes. We also explore the current regulatory expectations and provide our interpretation as it pertains to oligonucleotide drug product.

Item Type: Article
Date Deposited: 01 Mar 2023 00:45
Last Modified: 01 Mar 2023 00:45