Upstream Development

PAT Tools for Accelerated Process Development and Improvement

Broadley-James Corporation, Emerson Process Management, and the University of Texas at Austin are working together to examine and quantify the potential for faster optimization of batch operating points, process design, and cycle times. We’re also looking for more reproducible and predictable batch endpoints. The objective of this effort is to show that the impact of PAT can be maximized through the integration of dynamic simulation and multivariate analytics in a laboratory-optimized control system during product development. Data from bench-top and…

A New Era for Bioprocess Design and Control, Part 2

The level or intensity of product and process understanding that can or should be achieved beyond the acceptable minimum level promises to be the scope of a continuing debate among biotech industry and its regulators. In practice, the path of increased understanding may follow a series of incremental steps toward the desired state (Figure 1) after a product launch. Realistically that is expected to occur when the level of product and process understanding has reached or slightly exceeded the minimum…

A New Era for Bioprocess Design and Control, Part 1

Elements of the biopharmaceutical industry’s new operating paradigm have inevitably created an immediate need to condense, interpret, and relate their implications to existing regulatory and industry practices. This also provides us with an opportunity to look at them in a broader context and in relationship to one another. Such a perspective may open up new directions in discussion on how design and control aspects of biopharmaceutical manufacturing are likely to evolve. These are exciting times for scientists, engineers, statisticians, quality…

Carbohydrates and Their Analysis, Part One

A mammalian cell exists, interacts, reproduces, and dies as a result of intricate biochemical and biophysical mechanisms — many of which remain unknown or not fully understood even today. Technological advances have allowed us to investigate the details of organelles and cell membranes, of the types of molecules synthesized within cells, and their distribution and trafficking and the effects they have in their environment. Among the main macromolecules that make up a living cell, DNA and protein structures were studied…

Integrated Strategies for Clone and Media Formulation Selection

Clone selection techniques used for development of stable, high-expressing recombinant cell lines suitable for robust fed-batch cell culture processes are critical for biopharmaceutical manufacturing. Basal media screening, feed development and addition strategies, and fed-batch bioreactor performance are all intimately tied to overall performance of the clones during scale-up. Serious issues can arise if a high-quality clone is not established, such as low or unstable protein yield and ineffective use of costly resources. PRODUCT FOCUS: Recombinant proteinsPROCESS FOCUS: ProductionWHO SHOULD READ:…

Proteomics Technology Applied to Upstream and Downstream Process Development of a Protein Vaccine

Development and manufacturing of recombinant-protein–based vaccines has in the past few years become very similar to that of other well-documented and well-characterized biological drugs. For investigational vaccines, chemistry, manufacturing, and controls (CMC) information is critical for a successful regulatory filing. The process development and CGMP manufacturing of a recombinant protein drug is on the critical path toward clinical phase 1 dosing and safety studies as well as proof-of-concept clinical studies (1, 2). However, resources invested in this process may be…