Article
Engineering, Chemical
Alex Juckers, Petra Knerr, Frank Harms, Jochen Strube
Summary: Lyophilization is commonly used for preserving thermolabile products, with the main drawback being the long processing time. By implementing the quality by design (QbD) approach and process analytical technology (PAT), the process duration can be optimized for increased productivity while maintaining product safety.
Article
Chemistry, Medicinal
Yan-Shu Huang, Sergio Medina-Gonzalez, Benjamin Straiton, Joshua Keller, Qussai Marashdeh, Marcial Gonzalez, Zoltan Nagy, Gintaras Reklaitis
Summary: Measurement and monitoring of powder/particulate mass flow rate play a key role in establishing process control and system design in continuous pharmaceutical tablet manufacturing. Due to the lack of established sensing technologies for measuring particulate flow rates, indirect strategies are used to monitor and control downstream flow.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Engineering, Chemical
Axel Schmidt, Heribert Helgers, Florian Lukas Vetter, Steffen Zobel-Roos, Alina Hengelbrock, Jochen Strube
Summary: Vaccine supply faces manufacturing capacity issues due to operation personnel and chemical demands. Continuous manufacturing processes, enabled by strict application of regulatory quality by design process based on digital twins, process analytical technology, and control automation strategies, can help improve manufacturing capacity, reduce batch failures, optimize personnel training and utilization of buffers and chemicals, and speed up product release.
Article
Pharmacology & Pharmacy
Michele Panzitta, Niccolo Calamassi, Cristina Sabatini, Marzia Grassi, Chiara Spagnoli, Vittoria Vizzini, Elisa Ricchiuto, Andrea Venturini, Andrea Brogi, Judit Brassier Font, Lino Pontello, Giorgio Bruno, Paola Minghetti, Maurizio Ricci
Summary: The European Pharmacopoeia includes chapters on Raman, NIR, and Chemometrics, and there is significant academia research on these topics. However, the implementation of spectroscopic techniques in the pharmaceutical industry is still slow. Successful applications of spectroscopy in pharmaceutical production departments highlight the need for industry-academia cooperation to expedite process innovation for the benefit of patients.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Applied
David J. Lamberto, Jeffrey Neuhaus
Summary: Sugammadex is a reversal agent for neuromuscular blockade drugs in anesthesia, with an open structure cyclodextrin molecule having multiple solid forms. A redesigned manufacturing process was developed to produce the thermodynamic form for improved robustness in meeting product demand, with a unique solvent removal mechanism independent of API crystallinity. A predictive model was created for successful drying, relying on displacement of solvent by water molecules regardless of crystal structure.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Biotechnology & Applied Microbiology
Letha Chemmalil, Dhanuka P. Wasalathanthri, Xin Zhang, June Kuang, Chun Shao, Robin Barbour, Sohil Bhavsar, Tanushree Prabhakar, Ryan Knihtila, Jay West, Neha Puri, Kyle McHugh, Matthew S. Rehmann, Qin He, Jianlin Xu, Michael C. Borys, Julia Ding, Zhengjian Li
Summary: The biopharmaceutical industry is shifting towards continuous bioprocessing to reduce costs and improve efficiency, with the support of process analytical technologies (PAT). Knowledge-based operations can integrate product quality into processes to achieve desired critical quality attributes and reduce variability.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Ole Jacob Boehl, Jana Schellenberg, Janina Bahnemann, Bernd Hitzmann, Thomas Scheper, Doerte Solle
Summary: The quality by design approach is widely used in monoclonal antibody production processes, but early process phases have not been thoroughly investigated. Through risk assessment and design of experiments, interactions between key parameters in the early process were identified and a design space was established.
ENGINEERING IN LIFE SCIENCES
(2021)
Article
Chemistry, Applied
Thierry Furrer, Michael Levis, Bernhard Berger, Maja Kandziora, Andreas Zogg
Summary: Minimizing the effort of pilot and laboratory-scale experiments for successful scale-up is a key challenge in process development. This article discusses innovative technologies, including a dynamic process model and a laboratory-scale reactor, which enable direct and efficient scale-up while optimizing scale-dependent parameters. Experimental evaluations and comparisons show excellent agreement between the scales, proving the effectiveness of these technologies in reducing costs, shortening timelines, and improving process understanding.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Applied
Amanda Jane Lyons, Adam Clarke, Heidi Fisk, Bethany Jackson, Peter R. Moore, Samantha Oke, Thomas O. Ronson, Rebecca E. Meadows
Summary: In this study, a targeted approach was used to redesign the C-H borylation process, minimizing the inherent risks associated with the reaction, and successfully transferring the final process to large-scale manufacturing.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Analytical
Gabriella Gerzon, Yi Sheng, Marina Kirkitadze
Summary: Process Analytical Technology (PAT) instruments optimize process controls by measuring parameters and attributes in real time, mainly applied in pharmaceutical manufacturing. PAT solutions aim to achieve quality control and real-time product release, promoting production efficiency and reducing production costs.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biotechnology & Applied Microbiology
Christopher Gillespie, Dhanuka P. Wasalathanthri, Diana B. Ritz, George Zhou, Keith A. Davis, Thomas Wucherpfennig, Nadine Hazelwood
Summary: The study evaluated the business value of PAT technologies in biotherapeutic development, highlighting the different values various PAT tools hold in upstream and downstream processes. The results aim to assist current practitioners and newcomers in prioritizing and steering their projects towards success.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Pharmacology & Pharmacy
Adam J. J. Rish, Samuel R. R. Henson, Yang Liu, James K. K. Drennen, Carl A. A. Anderson, Md. Anik Alam
Summary: As continuous manufacturing processes develop, near-infrared spectroscopy has become an important tool in process monitoring. Traditional Partial Least Squares (PLS) models require significant time and resources for development, leading to the increasing interest in calibration-free/minimal calibration approaches. This study demonstrates the success and value of iterative optimization technology algorithms for monitoring potency trends and API content in a continuous manufacturing system, with improved prediction performance using a novel wavelength method.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biotechnology & Applied Microbiology
Vishwanath Hebbi, Garima Thakur, Anurag S. Rathore
Summary: This study utilized a combined spectroscopic and statistical approach to monitor and control the PEGylation reaction for G-CSF using near infrared spectroscopy (NIRS). The online NIRS probe tracked the conversion of G-CSF into different PEGylated forms in real time, while the spectra were used to build a batch evolution model and detect deviations. The system successfully identified and corrected four common deviations in the PEGylation process, demonstrating the potential for quality by design framework in biotechnology manufacturing.
JOURNAL OF BIOTECHNOLOGY
(2021)
Article
Engineering, Chemical
Alex Juckers, Petra Knerr, Frank Harms, Jochen Strube
Summary: This paper introduces the application of emerging process analytical technology in freeze-drying process and outlines their potential for implementation in a control strategy.
Article
Engineering, Chemical
Alex Juckers, Petra Knerr, Frank Harms, Jochen Strube
Summary: Lyophilization, or freeze-drying, is commonly used to preserve thermosensitive products. It involves freezing, primary drying, and secondary drying. The freezing step is crucial for process efficiency and product quality, but control during freezing is challenging. This study compares different freezing methods and demonstrates their impact on primary drying experiments and simulations.