Acceptance criteria Numerical limits, ranges, or other suitable measures for acceptance of results from analytical procedures that a drug substance, drug product, or materials at other stages of their manufacture should meet (1). Numerical limits, ranges, process signatures, or other suitable measures that are necessary for making a decision to accept or reject the result of a process, in-process variable, a product, or any other convenient subgroups of manufactured units (2). Numerical limits, ranges, or other suitable measures for acceptance…
March 2008 Supplement
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…
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…
Appendix 1: Designing for Process Robustness
A rich cup of coffee is what comes to mind for many people when you mention the word robust. For biotechnologists it is often a comfortable term, generally referring to the overall strength or ruggedness of a manufacturing process. However, the origin of the robustness concept for manufacturing is found in the field of robust design, which has for decades been a rigorous discipline with its own metrics, algorithms, and mathematical tools. Lately it has experienced a renewed interest in…
Automated Closed-Loop Solution for Bioreactors and Fermentors
Today, there is much discussion regarding the promise of improved insight into bioprocess industry processes. Look to the pages of industry publications such as this one, and you’ll see that industry leaders in process measurement and control have begun to discuss openly the potential for simulating and modeling bioprocesses. “Important opportunities such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process…
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…
The Biopharmaceutical Industry’s New Operating Paradigm
Currently the biopharmaceutical industry is transitioning to a new business model of production efficiency through implementing operational excellence (Op Ex). Borrowing from such principles as “lean manufacturing” and “Six Sigma” (6σ), and incorporating quality by design (QbD) (1), Op Ex is being applied through the implementation of such advanced enabling concepts and technologies as quality risk management (QRM) (2), process analytical technology (PAT) (3), and systems biology (SB) (4). Some people see a conflict here: This paradigm shift is occurring…