Continuous Bioprocessing

Synthetic Biology for Adapting CHO Cells to Challenging Bioprocesses

Biopharmaceuticals are produced mainly by Chinese hamster ovary (CHO) cell lines, for which advances in protein formats, bioprocesses, and bioprocess control are introducing novel challenges (1). Thus far, those challenges have been tackled either by technical innovations and media optimization or by advances in host-cell engineering (2, 3). Some technical innovations bring further challenges, such as those related to the compatibility of CHO cultures with highly automated bioprocesses and continuous high-density culture modes (4). With regard to host-cell engineering, most…

Proud Partners: Advancing Technologies Enable Collaboration and Innovation

Recent global events have demonstrated a growing demand for biologics to be made rapidly, cost-effectively, and in high volumes. There has been an urgent need to develop highly flexible and cost-effective next-generation biomanufacturing solutions that provide high yields of therapeutic proteins. Novel technology platforms such as single-use bioreactors and continuous bioprocessing technologies have contributed greatly to improvements in product quality and productivity while reducing cost of goods. Continuous Bioprocessing Expands Historically, continuous-culture processes were used for production of low-titer, low-stability,…

Biologics Manufacturing Without the Big Bioreactors

Over the past few decades, the biotechnology industry has brought to patients a medical revolution with the most advanced medicine ever seen. Yet much of the world‚Äôs population cannot afford or get access to these breakthrough therapeutics. That is in part a consequence of the high associated costs of development and biomanufacturing, extended times for regulatory review and approval, and a lack of regional manufacturing and dependable supply chains (because of facility costs and a scarcity of expertise). The recent…

eBook: A Dynamic Control Strategy for Downstream Continuous Bioprocessing

Continuous processes can have many sources of variability. In downstream unit operations, changes can arise because of feed material variability, resin fouling in chromatography columns, column compression or failure, membrane fouling, depth-filter clogging, and so on. The US Food and Drug Administration‚Äôs guideline for continued process verification encourages biomanufacturers to monitor their processes and keep them under a steady state of control. One way to achieve that in continuous downstream processes is to implement a dynamic control system that adapts…

eBook: Intensifying Processes for Monoclonal Antibodies

The commercial manufacturing success of monoclonal antibodies (MAbs) has become a touchstone of the biopharmaceutical industry. MAbs are so well established that they often are referred to as ‚Äútraditional‚ÄĚ biologics, and well-known MAb processing methods have become a model for processing of other ‚Äúadvanced‚ÄĚ or ‚Äúemerging‚ÄĚ therapies. But MAb processing continues to advance as biomanufacturers seek ways to improve efficiencies, lower costs, and (most recently) increase sustainability of facilities. Drug makers are particularly interested in strategies for MAb process intensification.…

Reducing Downstream Scale-Up Needs: Advances Toward Continuous Downstream Processing

The biopharmaceutical industry generally acknowledges that upstream and downstream aspects of drug-substance manufacturing are experiencing a capacity mismatch. Today, many recombinant proteins can be produced at expression titers of 3 g/L, with some yields exceeding 10 g/L. Such titers represent 100-fold increases in production capability compared with values from twenty years ago (1, 2). Increases in cell-culture density and improvements to perfusion-mode bioreactor systems hold promise for increasing yields further still. Such developments, combined with the broad availability of concentrated…

Practical Considerations for Statistical Analyses in Continued Process Verification

Several statistical techniques can be used to assist in monitoring biopharmaceutical product quality attributes as part of continued process verification (CPV) activities. These include run charts, control charts, and capability analyses. Below, I provide an overview and recommendations on statistical strategies when developing a CPV program, considering the expected behavior of manufacturing results in the biopharmaceutical industry. Presence of Autocorrelated Data In a previous study, I highlighted the tendency for data to be positively autocorrelated (values are closely related to…

The Crossroads of Academia, ‚ÄčIndustry, and Education: Modern Training Centers Are Pivotal to the Future of R&D

Global pharmaceutical industry research and development (R&D) investment has experienced steady growth over the past two decades, with an anticipated compound annual growth rate (CAGR) of 3.0% and projected 2024 investment of US$213 billion (1). Focused on developing innovative therapies for chronic, infectious, genetic, and lifestyle-related ailments, the fast-growing biologics segment has become a cornerstone of the pharmaceutical industry and healthcare sector. The demonstrated effectiveness and wide-ranging applicability of biopharmaceuticals also have brought considerable R&D in computational and biological technologies.…

Run Rules with Autocorrelated Data for Continued Process Verification

Control charts can be used to assist in monitoring of biopharmaceutical product quality attributes as part of continued process verification activities. A number of tests known as run rules have been developed to assess whether biomanufacturing processes remain in statistical control. In practice, results for such attributes can be positively autocorrelated. Simulated data are used to assess the performance of run rules with autocorrelated data to assist in determining risk‚Äďreward profiles for process monitoring. Autocorrelated Data The tendency for data…

Developing Process Control Strategies for Continuous Bioprocesses

Process control enables biomanufacturers to ensure that operating parameters are within defined specifications. A control strategy should be established during early stages of process development while process and product performance are being defined using risk-based methods such as quality by design (QbD) and process analytical technologies (PATs). Confirming process control as an essential part of product development creates greater process knowledge and understanding and provides the first steps toward process optimization. By understanding how process performance relates to product quality,…