Current Perspectives on Stability of Protein Drug Products during Formulation, Fill and Finish Operations

Biotechnology Progress - Tập 24 Số 3 - Trang 504-514 - 2008
Nitin Rathore1, Rahul S. Rajan2
1Drug Product & Device Development, Amgen Inc. Thousand Oaks, California 91320
2Process and Product Development, Amgen Inc., Thousand Oaks, California 91320

Tóm tắt

Abstract

Commercialization of protein‐based therapeutics is a challenging task in part due to the difficulties in maintaining protein solutions safe and efficacious throughout the drug product development process, storage, transportation and patient administration. Bulk drug substance goes through a series of formulation, fill and finish operations to provide the final dosage form in the desired formulation and container or delivery device. Different process parameters during each of these operations can affect the purity, activity and efficacy of the final product. Common protein degradation pathways and the various physical and chemical factors that can induce such reactions have been extensively studied for years. This review presents an overview of the various formulation‐fill‐finish operations with a focus on processing steps and conditions that can impact product quality. Various manufacturing operations including bulk freeze‐thaw, formulation, filtration, filling, lyophilization, inspection, labeling, packaging, storage, transport and delivery have been reviewed. The article highlights our present day understanding of protein instability issues during biopharmaceutical manufacturing and provides guidance on process considerations that can help alleviate these concerns.

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