Toward biotherapeutic product real-time quality monitoring

Guerra, Alaine de Brito; von, Stosch; Glassey, Jarka

doi:10.1080/07388551.2018.1524362

Cited by 45 publications

(23 citation statements)

References 160 publications

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“…Recent developments in many analytical techniques have provided some framework for this approach that also bodes well for a quality by design approach for mAbs. 187…”

Section: Discussionmentioning

confidence: 99%

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Das

Narhi

Sreedhara³

et al. 2020

Journal of Pharmaceutical Sciences

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The success of biotherapeutic development heavily relies on establishing robust production platforms. During the manufacturing process, the protein is exposed to multiple stress conditions that can result in physical and chemical modifications. The modified proteins may raise safety and quality concerns depending on the nature of the modification. Therefore, the protein modifications potentially resulting from various process steps need to be characterized and controlled. This commentary brings together expertise and knowledge from biopharmaceutical scientists and discusses the various manufacturing process steps that could adversely impact the quality of drug substance (DS). The major process steps discussed here are commonly used in mAb production using mammalian cells. These include production cell culture, harvest, antibody capture by protein A, virus inactivation, polishing by ion-exchange chromatography, virus filtration, ultrafiltration-diafiltration, compounding followed by release testing, transportation and storage of final DS. Several of these process steps are relevant to protein DS production in general. The authors attempt to critically assess the level of risk in each of the DS processing steps, discuss strategies to control or mitigate protein modification in these steps, and recommend mitigation approaches including guidance on development studies that mimic the stress induced by the unit operations.

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“…Recent developments in many analytical techniques have provided some framework for this approach that also bodes well for a quality by design approach for mAbs. 187…”

Section: Discussionmentioning

confidence: 99%

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Das

Narhi

Sreedhara³

et al. 2020

Journal of Pharmaceutical Sciences

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“… – [ 49 ] FT-NIR spectroscopy 750–2500 nm Chemical/biological compositions Brucker, USA [ 48 ] Raman spectroscopy 100–3500 cm –1 antibody concentration Pfizer, USA; GlaxoSmithKline, USA [ 50 ] Fluorescence spectroscopy Excitation: 240–300 nm; emission: 260–450 nm Cell metabolism, fluorescent compounds in media. Sartorius Stedim Biotech GmbH, Germany [ 28 ] DLS Visible light Macromolecule diffusion Colloid Metrix GmbH, Germany; Sanofi-Aventis Deutschland GmbH, Germany [ 9 ] SLS Visible light Size of macromolecules in solution Sanofi-Aventis [ 9 ] Multiangle light scattering Visible light Protein aggregation Merck & Co., Inc., USA; Wyatt Technology Corporation, USA [ 51 ] a See also [ 59. , 60.…”

Section: Downstream Processingmentioning

confidence: 99%

Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Maruthamuthu

Rudge

Ardekani

et al. 2020

Trends in Biotechnology

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Process analytical technology (PAT) for the manufacture of monoclonal antibodies (mAbs) is defined by an integrated set of advanced and automated methods that analyze the compositions and biophysical properties of cell culture fluids, cell-free product streams, and biotherapeutic molecules that are ultimately formulated into concentrated products. In-line or near-line probes and systems are remarkably well developed, although challenges remain in the determination of the absence of viral loads, detecting microbial or mycoplasma contamination, and applying data-driven deep learning to process monitoring and soft sensors. In this review, we address the current status of PAT for both batch and continuous processing steps and discuss its potential impact on facilitating the continuous manufacture of biotherapeutics.

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“…Previously, only a small number of so-called "process variables" were commonly measured online in bioreactors (e.g., pH, temperature, OD, stirring). The scope of available real-time probes has now been significantly expanded thanks to the recent advances in analytical technologies and the adoption of Process Analytical Technologies initiative 15,16 .…”

Section: Real-time Bioprocess Monitoring: Track To Better Controlmentioning

confidence: 99%

Towards a widespread adoption of metabolic modeling tools in biopharmaceutical industry: a process systems biology engineering perspective

et al. 2020

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In biotechnology, the emergence of high-throughput technologies challenges the interpretation of large datasets. One way to identify meaningful outcomes impacting process and product attributes from large datasets is using systems biology tools such as metabolic models. However, these tools are still not fully exploited for this purpose in industrial context due to gaps in our knowledge and technical limitations. In this paper, key aspects restraining the routine implementation of these tools are highlighted in three research fields: monitoring, network science and hybrid modeling. Advances in these fields could expand the current state of systems biology applications in biopharmaceutical industry to address existing challenges in bioprocess development and improvement.npj Systems Biology and Applications (2020) 6:6 ; https://doi.

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Toward biotherapeutic product real-time quality monitoring

Cited by 45 publications

References 160 publications

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Towards a widespread adoption of metabolic modeling tools in biopharmaceutical industry: a process systems biology engineering perspective

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