Case Studies on Changes and Proposed Process Development Approaches reflecting applicability of PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management.

被引量：- 发表：1970

Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results.

被引量：- 发表：1970

A Holistic Approach for Fill volume Variability Evaluation and Control with Statistical Tool.

被引量：- 发表：1970

Challenges and solutions to manufacturing of low viscosity, ultra-high concentration IgG1 drug products: From late downstream process to final fill finish processing.

Challenges in manufacturing of high concentration antibody formulations have seldom been discussed. These are observed mainly form late downstream operations where antibody gets concentrated to its final strength, to final fill finish processing and containerization of the product. Present paper summarizes challenges typically observed in manufacturing and processing of high concentration antibody products and provides turnkey solutions to these typical challenges in order to have their consistent and robust manufacturing process. IgG1 has been used as model protein for studying the challenges and providing solutions to them. The late downstream challenges like increased viscosity limiting further concentration can be resolved by used of viscosity modifying agents in the formulation. Replacement of conventionally used 'A' screen membranes with 'D' screen or using single pass TFF can further provide advantage in targeting higher concentrations for same protein with lesser shear and aggregation. Using 0.5μm/0.2μm asymmetric or bilayered membrane instead of conventional 0.2μm membrane resulted in better flux while filtration of high concentration IgG1 formulation. In process holding time during filling operation was optimized to be <60min based on the nozzle drying time for high concentration IgG1 formulation. Appropriate control strategy of replacing filling nozzles and performing periodic fill weight check was proposed for fill finish process of high concentration IgG1 formulation.

被引量：- 发表：1970

Characterizing Extractables and Leachables Chemical Space to Support In Silico Toxicological Hazard Assessments.

This article describes the development of a representative dataset of extractables and leachables (E&L) from the combined Extractables and Leachables Safety Information Exchange (ELSIE) Consortium and the Product Quality Research Institute (PQRI) published datasets, representing a total of 783 chemicals. A chemical structure-based clustering of the combined dataset identified 142 distinct chemical classes with two or more chemicals across the combined dataset. The majority of these classes (105 chemical classes out of 142) contained chemicals from both datasets, whereas 8 classes contained only chemicals from the ELSIE dataset and 29 classes contain only chemicals from the PQRI dataset. This evaluation also identified classes containing chemicals that were flagged as potentially mutagenic as well as potent (strong or extreme) dermal sensitizers by in silico tools. The prevalence of alerting structures in the E&L datasets was approximately 9% (69 examples) for mutagens and 3% (25 examples) for potent sensitizers. This analysis showed that most (80%; 20 of 25) E&L predicted to be strong or extreme dermal sensitizers were also flagged as potential mutagens. Only two chemical classes, each containing three chemicals (alkyl bromides and isothiocyanates), were uniquely identified in the PQRI dataset and contained chemicals predicted to be potential mutagens and/or potent dermal sensitizers.

被引量：- 发表：1970