RESUMO
Measurement and characterization of subvisible particles (including proteinaceous and non-proteinaceous particulate matter) is an important aspect of the pharmaceutical development process for biotherapeutics. Health authorities have increased expectations for subvisible particle data beyond criteria specified in the pharmacopeia and covering a wider size range. In addition, subvisible particle data is being requested for samples exposed to various stress conditions and to support process/product changes. Consequently, subvisible particle analysis has expanded beyond routine testing of finished dosage forms using traditional compendial methods. Over the past decade, advances have been made in the detection and understanding of subvisible particle formation. This article presents industry case studies to illustrate the implementation of strategies for subvisible particle analysis as a characterization tool to assess the nature of the particulate matter and applications in drug product development, stability studies and post-marketing changes.
Assuntos
Nefelometria e Turbidimetria/métodos , Material Particulado/análise , Preparações Farmacêuticas/análise , Ar , Anticorpos Monoclonais/análise , Terapia Biológica , Composição de Medicamentos , Contaminação de Medicamentos , Embalagem de Medicamentos , Liofilização , Microbolhas , Técnicas Analíticas Microfluídicas , Tamanho da Partícula , Proteínas Recombinantes/análise , Espalhamento de Radiação , Óleos de Silicone , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Measurement and characterization of subvisible particles (defined here as those ranging in size from 2 to 100 µm), including proteinaceous and nonproteinaceous particles, is an important part of every stage of protein therapeutic development. The tools used and the ways in which the information generated is applied depends on the particular product development stage, the amount of material, and the time available for the analysis. In order to compare results across laboratories and products, it is important to harmonize nomenclature, experimental protocols, data analysis, and interpretation. In this manuscript on perspectives on subvisible particles in protein therapeutic drug products, we focus on the tools available for detection, characterization, and quantification of these species and the strategy around their application.