Rigorous modeling of lyophilization for botanicals and biologics process integration

Klepzig, L.; Strube, Jochen

doi:10.1002/cite.201855362

Cited by 3 publications

(2 citation statements)

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“…The heat transfer coefficient of the vial (0. Efforts are about 1 week with 50 vial a 2 ml and about 150 g feed material [116][117][118].…”

Section: Lyophilizationmentioning

confidence: 99%

“…The benefits of appropriate USP and DSP integration have been demonstrated before [12,13,106,119]. Besides, USP modeling with Monod kinetics including reduced metabolomics [52,[120][121][122][123] enable to integrate USP into total process design as well as lyophilization as the final steps towards formulation [116][117][118]. The process sequences are evaluated by cost estimation tools added in process modeling easily [86,90].…”

Section: Industrializationmentioning

confidence: 99%

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Accelerating Biologics Manufacturing by Modeling or: Is Approval under the QbD and PAT Approaches Demanded by Authorities Acceptable without a Digital-Twin?

et al. 2019

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Innovative biologics, including cell therapeutics, virus-like particles, exosomes,recombinant proteins, and peptides, seem likely to substitute monoclonal antibodies as the maintherapeutic entities in manufacturing over the next decades. This molecular variety causes agrowing need for a general change of methods as well as mindset in the process development stage,as there are no platform processes available such as those for monoclonal antibodies. Moreover,market competitiveness demands hyper-intensified processes, including accelerated decisionstoward batch or continuous operation of dedicated modular plant concepts. This indicates gaps inprocess comprehension, when operation windows need to be run at the edges of optimization. Inthis editorial, the authors review and assess potential methods and begin discussing possiblesolutions throughout the workflow, from process development through piloting to manufacturingoperation from their point of view and experience. Especially, the state-of-the-art for modeling inred biotechnology is assessed, clarifying differences and applications of statistical, rigorousphysical-chemical based models as well as cost modeling. “Digital-twins” are described and effortsvs. benefits for new applications exemplified, including the regulation-demanded QbD (quality bydesign) and PAT (process analytical technology) approaches towards digitalization or industry 4.0based on advanced process control strategies. Finally, an analysis of the obstacles and possiblesolutions for any successful and efficient industrialization of innovative methods from processdevelopment, through piloting to manufacturing, results in some recommendations. A centralquestion therefore requires attention: Considering that QbD and PAT have been required byauthorities since 2004, can any biologic manufacturing process be approved by the regulatoryagencies without being modeled by a “digital-twin” as part of the filing documentation?

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“…The heat transfer coefficient of the vial (0. Efforts are about 1 week with 50 vial a 2 ml and about 150 g feed material [116][117][118].…”

Section: Lyophilizationmentioning

confidence: 99%