Process intensification in the biopharma industry: Improving efficiency of protein manufacturing processes from development to production scale using synergistic approaches

Müller, Dirk; Klein, Lukas; Lemke, Johannes R.; Schulze, Markus; Kruse, Thomas; Saballus, Martin; Matuszczyk, Jens; Kampmann, Markus; Zijlstra, Gerben

doi:10.1016/j.cep.2021.108727

Cited by 39 publications

(39 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Continuous purification technologies impact both productivity and footprint. For example, continuous chromatography reduces resin and buffer consumptions as well as waste production 4,5 . Yang et al 6 published a review focused on economical evaluation that compared by different means batch and continuous manufacturing using different approaches.…”

Section: Introductionmentioning

confidence: 99%

“…For example, continuous chromatography reduces resin and buffer consumptions as well as waste production. 4,5 Yang et al 6 published a review focused on economical evaluation that compared by different means batch and continuous manufacturing using different approaches. Feasibility and advantages of continuous processing have been reported already several times in small-scale study reports.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous

Ferreira

Benlegrimet

Diane

et al. 2022

Biotechnology Progress

View full text Add to dashboard Cite

Implementation of continuous in lieu of batch upstream processing (USP) and downstream process (DSP) for the production of recombinant therapeutic protein is a significant paradigm change. The present report describes how the first kilograms of monoclonal antibody were produced with equipment originally designed for batch operations while using continuous manufacturing processes and principles. Project timelines for the delivery of clinical material have driven this ambition and helped the transition. Nevertheless, because of equipment availability, a tradeoff between the envisaged continuous downstream process (cDSP) operations and the ones described in this article had to be taken. A total of 2.1 kg of monoclonal antibody were produced in two GMP runs for clinical trials. For USP, a 200‐L single‐use pilot scale bioreactor was upgraded to enable perfusion operation. DSP steps were designed to be easily transferable to cDSP for later clinical or commercial productions. An in‐line conditioning buffer preparation strategy was tested in a discontinuous way to prove its efficiency and the purification cascade was structured in parallel to the continuous collection of antibody‐containing cell culture supernatant. This strategy will avoid any process change when later moving to the continuous equipment that is currently under qualification. Alignment between small‐scale references runs and the GMP runs in terms of productivity and quality confirmed that the presented approach was valid. Thus, we demonstrate that existing fed‐batch infrastructure can be adapted to continuous manufacturing without significant additional investments. Such approach is useful to evaluate next‐generation manufacturing processes before making large investments.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous

Ferreira

Benlegrimet

Diane

et al. 2022

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…However, the productivity of such a process can be significantly improved by implementing a continuous culture strategy to intensify the volumetric productivity. Such approach can lead to an increase up to 10-fold of space-time yields, therefore leading to a reduction of production time by 30% ( Müller et al, 2022 ). These improvements enable opportunity for much smaller facilities with similar or larger productivity outputs, limiting the capital investment (for facilities and raw material costs) and providing manufacturing flexibility and sustainability ( Bielser et al, 2018 ; Chen et al, 2018 ; Müller et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Model-based intensification of CHO cell cultures: One-step strategy from fed-batch to perfusion

Richelle¹,

Corbett²,

Agarwal³

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.

show abstract

“…However, the productivity of such a process can be significantly improved by implementing a continuous culture strategy to intensify the volumetric productivity. Such approach can lead to an increase up to 10-fold of space-time yields, therefore leading to a reduction of production time by 30% 10 . These improvements enable opportunity for much smaller facilities with similar or larger productivity outputs, limiting the capital investment (for facilities and raw material costs) and providing manufacturing flexibility and sustainability 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, scale-down models, decisional tools, equipment and procedures currently in place in most companies have been developed for fed-batch processes and cannot be transposed without significant changes. Therefore, this transition might be seeming a high cost and time demand investment to modify existing process development protocols 10,11,13 . In this context, advanced computational tools could be used to elucidate changes in process dynamics and assess the influence of varying operating scenarios.…”

Section: Introductionmentioning

confidence: 99%

Model-based intensification of CHO cell cultures: one-step strategy from fed-batch to perfusion

Richelle¹,

Corbett²,

Agarwal³

et al. 2022

Preprint

View full text Add to dashboard Cite

There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of CHO cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.

show abstract

Process intensification in the biopharma industry: Improving efficiency of protein manufacturing processes from development to production scale using synergistic approaches

Cited by 39 publications

References 41 publications

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous

Transfer of continuous manufacturing process principles for mAb production in a GMP environment: A step in the transition from batch to continuous

Model-based intensification of CHO cell cultures: One-step strategy from fed-batch to perfusion

Model-based intensification of CHO cell cultures: one-step strategy from fed-batch to perfusion

Contact Info

Product

Resources

About