Wednesday, September 28, 2022 Daily Archives

Development of a Stand-Alone Monitoring Application for Purification Processes in Biomanufacturing

The ability to monitor unit operations in biomanufacturing is essential because it enables early fault detection and effective root-cause analysis. Below, we present a case study on the development of a stand-alone, data-driven, process-monitoring application for a biomanufacturing purification process. We review the application’s functionality and highlight its utility using a few examples from commercial manufacturing of a therapeutic protein. Lessons learned from the development of that application also are presented. The progress and performance of a purification process have…

Mechanistic Modeling for a Hydrophobic-Interaction Chromatography Process: Use in Vaccine Antigen Purification

Bioprocess models and simulations are the basis for digital twins, which are virtual representations of physical processes and enabling methods of biopharma 4.0. Early adopters in the industry have shown potential application of this approach in nearly all stages of a product development life cycle. Experts in academia and the biopharmaceutical industry have studied mechanistic modeling as the main method of chromatography modeling. Mechanistic models are mathematical descriptions of physiochemical phenomena. They are based on first principles and thus can…

Appropriate Estimation of Long-Term Variability: Using Biopharmaceutical Release and Stability Data

Numeric results from quality attributes testing of drug product and drug substance lots can be used for different statistical analyses. One study is the calculation of statistical tolerance intervals from lot-release data to assist in the determination of specification acceptance criteria (1). Data from manufactured batches placed on stability at the recommended storage condition (RSC) also can provide useful information to estimate long-term variation. Below, I address potential concerns associated with pooling disparate data sources and illustrate a technique to…

Increasing Reproducibility of Cell Culture Bioprocesses

Reproducible cell growth and reliable development of a desired product are ideal outcomes for a bioprocessing engineer. If reproducibility is poor, the risk of needing to discard a batch and repeat an entire bioprocess is high and results in a great loss of time and resources. Cells, culture media, and a bioprocess control system are required components of an upstream bioprocess. Each of those can be a source of variability that affects cell growth and viability as well as product…

eBook: Drug-Delivery Systems — Measurement-System Analysis Using Gauge R&R Studies

When a biological product requires a specialized delivery device, the resulting combination product can introduce new types of quality evaluation. Product development brings together regulatory requirements for biologics and drug-delivery systems, and for many people on the biopharmaceutical side, that includes a number of unfamiliar terms, processes, and procedures. Among those are gauge repeatability and reproducibility studies for measuring variations that arise from measurement devices and the operators using them. This eBook introduces the concept of attribute-data gauge repeatability and…

September 2022: From the Editor

Just coming off our big anniversary issue, we editors are still in a taking-stock mindset. That normally goes hand-in-hand with planning for the next publication year — which we can’t believe we’re doing already — but it feels more acute this time. And our 20th year has coincided with some pretty major current events, as the world begins to emerge from a pandemic amid a great deal of associated economic and sociopolitical turmoil. The effects of it all on the…

Building a Solid Foundation for a Pharmaceutical Quality System: Presenting QRM and KM As United Enablers

Risk, knowledge, uncertainty, decision-making: They are among the building blocks at the center of the biopharmaceutical industry that guide the daily operations of biopharmaceutical organizations, from the work of scientists during discovery to technicians manufacturing each batch. Indeed, the biopharmaceutical industry is a knowledge-based industry in which organizations satisfy patient needs while gaining competitive advantage by their ability to grow, transfer, and apply knowledge rapidly and effectively. Many people who read the word knowledge have a certain implicit interpretation of…

Hardware, Software, and Wetware: 20 Years of Advancements in Biopharmaceutical Production, Part 2

The past couple of decades have witnessed significant advances in upstream bioprocess technologies and approaches. Since its establishment, BPI has been a facilitator of discussion both in print and at professional conferences, as well as in webcasts and news online. To mark the 20th anniversary of the publication, we surveyed articles published over the past two decades and found hundreds that highlight significant advances in both emerging and established themes in biopharmaceutical production: • “hardware” technology (e.g., analytical instrumentation, bioreactors,…

Future Supply-Chain Needs for Allogeneic Cell Therapies: Why Strategic Partnerships Are Critical

Allogeneic products are an attractive option for cell-therapy developers because multiple batches can be manufactured using apheresis material collected from one healthy donor — and because the resulting therapies could be made available as off-the-shelf products. The appeal of this approach is apparent from growth in allogeneic-therapy development. According to the Alliance for Regenerative Medicine, the number of clinical trials for allogeneic cell-based cancer treatments has increased by 30% over the past five years. Early in 2022, allogeneic candidates accounted…

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…