Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies

09 Jun 2023 | Contributor(s): Chopda, Viki, Gyorgypal, Aron Yang, Ou Singh, Ravendra Ramachandran, Rohit Zhang, Haoran Tsilomelekis, George Chundawat, Shishir PS, Ierapetritou, Marianthi G

Continuous bioprocessing is significantly changing the biological drugs (or biologics) manufacturing landscape by potentially improving product quality, process stability, and overall profitability, as was similarly seen during the adoption of advanced manufacturing processes for small molecule...

Recent Developments in the Crystallization Process: Toward the Pharmaceutical Industry

09 Jun 2023 | Contributor(s): Gao, Zhenguo, Gong, Junbo, Rohani, Sohrab, Wang, Jingkang

Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building efficient manufacturing processes. In this paper, we review recent developments in...

Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review

09 Jun 2023 | Contributor(s): Tezyk, Michal, Ernst, Andrzej, Milanowski, Bartlomiej, Lulek, Janina

Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous...

Recent Progress in Continuous Crystallization of Pharmaceutical Products: Precise Preparation and Control

09 Jun 2023 | Contributor(s): Ma, Yiming, Joao Macaringue, Estevao, Zhang, Teng, Gong, Junbo, Wu, Songgu, Wang, Jingkang

Crystallization, as a solid−liquid separation process, is employed to purify and isolate a great diversity of crystalline pharmaceutical products. In recent years, continuous crystallization has attracted increasing attention because of the product and process robustness as well as higher...

Recent progress in continuous manufacturing of oral solid dosage forms

09 Jun 2023 | Contributor(s): Vanhoorne, Valérie, Vervaet, Chris

Continuous drug product manufacturing is slowly being implemented in the pharmaceutical industry. Although the benefits related to the quality and cost of continuous manufacturing are widely recognized, several challenges hampered the widespread introduction of continuous manufacturing of drug...

Reducing the mean size of API crystals by continuous manufacturing with product classification and recycle

09 Jun 2023 | Contributor(s): Griffin, DW, Mellichamp, DA, Doherty, MF

A continuous crystallization process is proposed that can produce active pharmaceutical ingredients with a small mean size and narrow distribution. The process flowsheet consists of a new product classifier configuration where the large crystals from the classifier are recycled to a dissolver...

Regions of attainable particle sizes in continuous and batch crystallization processes

09 Jun 2023 | Contributor(s): Vetter, Thomas, Burcham, Christopher L., Doherty, Michael F.

Process alternatives for continuous crystallization, i.e., cascades of mixed suspension, mixed product removal crystallizers (MSMPRCs) and plug flow crystallizers (PFCs), as well as batch crystallizers are discussed and modeled using population balance equations. The attainable region approach...

Regulatory and Quality Considerations for Continuous Manufacturing

09 Jun 2023 | Contributor(s): Allison, Gretchen, Cain, Yanxi Tan, Cooney, Charles, Garcia, Tom, Bizjak, Tara Gooen, Holte, Oyvind, Jagota, Nirdosh, Komas, Bekki, Korakianiti, Evdokia, Kourti, Dora, Madurawe, Rapti, Morefield, Elaine, Montgomery, Frank, Randolph, William, Robert, Jean-Louis, Rudd, Dave, Nasr, Moheb, Zezza, Diane

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including...

Residence Time Distribution (RTD)-Based Control System for Continuous Pharmaceutical Manufacturing Process

09 Jun 2023 | Contributor(s): Bhaskar, Aparajith, Singh, Ravendra

Residence Time Distribution as a Traceability Method for Lot Changes in A Pharmaceutical Continuous Manufacturing System

09 Jun 2023 | Contributor(s): Sánchez-Paternina, Adriluz, Martínez-Cartagena, Pedro Li, Jingzhe Scicolone, James Singh, Ravendra Lugo, Yleana C Romañach, Rodolfo J Muzzio, Fernando J, Román-Ospino, Andrés D

Residence time distribution (RTD) models were developed to track raw material lots and investigate batch transitions in a continuous manufacturing system. Two raw materials with similar physical properties (granular metformin and lactose) were identified via Principal Component Analysis (PCA)...

Residence time distribution modelling and in line monitoring of drug concentration in a tablet press feed frame containing dead zones

09 Jun 2023 | Contributor(s): Tanimura, Shinji, Singh, Ravendra Román-Ospino, Andrés D, Ierapetritou, Marianthi

The presence of a ‘significant dead zone’ in any continuous manufacturing equipment may affect the product quality and need to be investigated systematically. Dead zone will affect the residence time distribution (RTD) of continuous manufacturing and thus the mixing and product quality. Tablet...

Real-time feedback control of twin-screw wet granulation based on image analysis

09 Jun 2023 | Contributor(s): Madarasz, Lajos, Hoffer, Istvan, Szabo, Barnabas, Csontos, Istvan, Pataki, Hajnalka, Demuth, Balazs, Szabo, Bence, Csorba, Kristof, Nagy, Zsombor Kristof, Marosi, Gyorgy

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored...

Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy

09 Jun 2023 | Contributor(s): Vanarase, Aditya, Alcalà, Manel, Jerez-Rozo, Jackeline, Muzzio, Fernando, Romañach, Rodolfo

A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration...

Real-time monitoring of particle size distribution in a continuous granulation and drying process by near infrared spectroscopy

09 Jun 2023 | Contributor(s): Pauli, V, Roggo, YKleinebudde, P, Krumme, M

In continuous granulation, it can be important to control granules particle size distribution (PSD), as it may affect final product quality. Near infrared spectroscopy (NIRS) is already a routine analytical procedure within pharmaceutical continuous manufacturing for the in-line analysis of...

Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process

09 Jun 2023 | Contributor(s): Huang, Yan-Shu, Medina-González, Sergio Straiton, Benjamin Keller, Joshua, Marashdeh, Qussai, Gonzalez, Marcial, Nagy, Zoltan, Reklaitis, Gintaras V.

While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the...

Real-Time Monitoring of Powder Mixing in a Convective Blender Using Non-Invasive Reflectance NIR Spectrometry

09 Jun 2023 | Contributor(s): Bellamy, L. J., Littlejohn, D., Nordon, A.

A convective blender based on a scaled down version of a high shear mixer-granulator was used to produce binary mixtures of microcrystalline cellulose (Avicel) and aspirin, citric acid, aspartame or povidone. Spectra of stationary Avicel or aspirin powder provided an indication of the information...

Real-time monitoring of the moisture content of filter cakes in vacuum filters by a novel soft sensor

09 Jun 2023 | Contributor(s): Huttunen, Manu, Nygren, Lauri Kinnarinen, Teemu Ekberg, Bjarne, Lindh, Tuomo, Karvonen, Vesa, Ahola, Jero, Häkkinen, Antti

The moisture content of filter cakes is probably the most important characteristic that should be kept at a desired level in industrial cake filtration applications to maintain consistent product quality and minimize energy consumption. Most of the currently applied methods for contactless...

Real-time process monitoring in a semi-continuous fluid-bed dryer - microwave resonance technology versus near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Peters, Johanna, Teske, Andreas, Taute, Wolfgang, Döscher, Claas, Höft, Michael, Knöchel, Reinhard, Breitkreutz, Jörg

The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision...

Real-Time Quantification of Low-Dose Cohesive Formulations within a Sampling Interface for Flowing Powders

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel. O., Romañach, Rodolfo J., Mendez, Rafael

This study investigates the performance of a sampling interface for monitoring cohesive, flowing powder formulations with Hausner's Ratio and Carr's Index higher than 1.5 and 35%, respectively. The sampler device was operated in combination with near-infrared (NIR) spectroscopy to quantify...

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

09 Jun 2023 | Contributor(s): Schenck, L, Erdemir, DGorka, LS, Merritt, JM, Marziano, I, Ho, R, Lee, M, Bullard, J, Boukerche, M, Ferguson, S, Florence, AJ, Khan, SA, Sun, CC

Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining...

Quantitative Solution Measurement for the Selection of Complexing Agents to Enable Purification by Impurity Complexation

09 Jun 2023 | Contributor(s): Weber, CC, Wood, GPFKunov-Kruse, AJ, Nmagu, DE, Trout, BL, Myerson, AS

The removal of carboxylic acid impurities from amide targets has been accomplished through crystallization featuring a complexing agent in solution. The interaction between the complexing agents and impurities was examined using isothermal titration calorimetry and the free energy of association...

Raman Spectroscopy

09 Jun 2023

Standard highlights the use of Raman spectroscopy to ensure successful application for measuring pharmaceutical products.

Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing

09 Jun 2023 | Contributor(s): Esmonde-White, Karen A, Cuellar, Maryann, Uerpmann, Carsten, Lenain, Bruno., Lewis, Ian R.

Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data...

Raman Spectroscopy for Monitoring the Continuous Crystallization of Carbamazepine

09 Jun 2023 | Contributor(s): Acevedo, D, Mohammad, Adil, Pavurala, Naresh, Wu, Wei-Lee, O'Connor, Thomas F., Nagy, Zoltan K, Yang, Xiaochuan, Cruz, CN

Crystallization has a significant impact on the properties of the active pharmaceutical ingredient (API) since it is the final step in the manufacturing of the drug substance and determines particle size distribution, purity, shape, and polymorphs. Many publications have focused on the...

Raman Spectroscopy for Process Analytical Technologies of Pharmaceutical Secondary Manufacturing

09 Jun 2023 | Contributor(s): Nagy, Brigitta, Farkas, Attila, Borbás, Enikő, Vass, Panna, Nagy, Zsombor Kristóf, Marosi, György

As the process analytical technology (PAT) mindset is progressively introduced and adopted by the pharmaceutical companies, there is an increasing demand for effective and versatile real-time analyzers to address the quality assurance challenges of drug manufacturing. In the last decades, Raman...