Upstream Processing

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…

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…

Raman Spectrometric PAT Models: Successful Transfer from Minibioreactors to Larger-Scale, Stirred-Tank Bioreactors

Spectroscopic sensors are powerful tools for bioprocess monitoring within the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA). The PAT framework includes process understanding based on scientific background with the aim of monitoring and controlling critical process parameters (CPPs) that influence critical quality attributes (CQAs) of final biological products. The driving force for PAT implementation is a need to realize consistent product quality, process intensification, and real-time manufacturing control (1, 2). Using real-time spectroscopic measurements…

Deriving Mesenchymal Stromal Cells from Umbilical Cord Lining and Wharton’s Jelly: A Comparative Study of Extraction Methods and Culture Media

Mesenchymal stromal cells (MSCs) are multipotent, self-renewing progenitor cells that can differentiate into adipocytes, chondrocytes, and osteocytes (1). Cultured MSCs are plastic-adherent and spindle-shaped, and they express cell-surface markers CD44, CD73, CD90, and CD105, but not CD14, CD34, CD45, CD11b, CD79a, CD19, or HLA-DR (2, 3). First isolated from bone marrow (BM), human MSCs have been investigated extensively in clinical studies. MSCs also have been isolated from adipose tissue (4) and peripheral blood (5). Perinatal organs and tissues such as…

Analytical Tools for Improving Up- and Downstream AAV Process Development

During a May 2022 Ask the Expert presentation, Ivana Petrović Koshmak (head of upstream process development at BIA Separations, part of Sartorius) highlighted the gene- therapy industry’s need for fast, reliable analytics that work with both up- and downstream samples. High-performance liquid chromatography (HPLC) methods can fulfill that need, but process development (PD) scientists would need to account for the complexity of bioreactor samples to make such methods feasible for end-to-end analytics. Koshmak described a novel instrument that is designed…

Using Cutting-Edge Tools to Optimize Cell-Culture Media Development

Although culture-media optimization accounts for a relatively small part of process development, selections made at that stage strongly influence overall bioprocess productivity. Yaron Silberberg (chief scientist at the Ajinomoto Genexine CELLiST Solution Center) joined BPI in July 2022 to present strategies for enhancing media performance. He focused on how emerging tools for statistical analysis and process control facilitate media development for cultures based on Chinese hamster ovary (CHO) cell lines. Silberberg’s Presentation Because materials applied during cell-line development are not…

A Flexible, Intensified Seed Train to Boost Upstream Productivity

Biopharmaceutical companies continue to invest significantly in technologies that support process intensification (PI), including equipment for high-density and perfusion-mode cell cultures. During a July 2022 Ask the Expert webinar, Yuliya Mikhed (product manager for Biostat RM bioreactors at Sartorius) highlighted drivers for PI solutions, then described how an intensified modular seed train could help users to increase cell culture productivity and flexibility while reducing cost of goods (CoG). Mikhed’s Presentation Sartorius customers have identified several drug development “pain points.” Biologics…

BioProcess Insider Interview: Greg Bleck, Catalent

Moderator: Dan Stanton, Co-founder and Editor, BioProcess Insider. Featuring: Greg Bleck, Vice President of Research and Development, Catalent. In July 2021, Catalent released its GPEx Lightning expression construct for Chinese hamster ovary (CHO) cell-line development (CLD). Bleck characterized it as a novel combination of the company’s original GPEx retrovector gene-insertion technology, a glutamine synthetase (GS) knockout sequence, and a recombinase gene-insertion system. A key advantage of the platform, Bleck explained, is that it can reduce CLD timelines by three months.…

Intensifying Bioprocessing: Profiling 20 Years of Advances Driven By Single-Use Technologies

A long-time editorial advisor for BPI, Miriam Monge is head of marketing for fluid-management technologies (FMT) at Sartorius, where she works to develop sustainable growth strategies for single-use bioprocessing. Over the past 20 years, she has played a significant role in championing development, promotion, analysis, and adoption of single-use technologies (SUTs). We asked her to share her experiences and to offer additional thoughts about current and future industry trends. Science and Technology From a technological perspective, without a doubt, I…

Biomanufacturing from 2002 to 2022: How Far the Biopharmaceutical Industry Has Come

It has been two decades since the theatrical release of the first Spider Man film with Tobey Maguire, the euro became the official currency for the European Union, and Anne Montgomery and Cheryl Scott began piecing together the inaugural issue of BioProcess International. In celebration of the 20th anniversary of this staple publication in the bioprocessing arena, we compared products and manufacturing capacity in 2002 with those in 2022 and delved into what has driven the changes that have occurred.…