A modeling and control framework for extraction processes

05 Sep 2024 | Peer-reviewed journal | Contributor(s): Peter Neugebauer, Jakob Rehrl, Peter Poechlauer, Dirk Kirschneck, Martin Horn, Martin Steinberger, Stephan Sacher, Joscha Boehm, Daniel Moser

Many continuously operated pharmaceutical process routes have been presented recently. Most of these cover the synthesis of the active pharmaceutical ingredient (API) or solid dosage processing. However, the API purification is also gaining attraction. One widespread and waste-intensive unit...

The Rise of Continuous Manufacturing in Pharma

13 Aug 2024 | Website | Contributor(s): Editorial Team

"Mr Indu Bhushan, CEO and Director of STEERLife shares his insights on the transformative journey of continuous manufacturing, and the advanced technologies that have propelled this paradigm shift. He also throws light on how continuous manufacturing has accelerated drug development...

The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Peer-reviewed journal | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

Continuous Manufacturing in the Pharmaceutical Industry: Enhancing Drug Production

23 Jul 2024 | Website | Contributor(s): Timmerman, Siebe

A significant shift towards continuous manufacturing (CM) is currently underway in the pharmaceutical industry. Unlike the more commonly used batch processing, CM operates continuously. This method potentially offers increased efficiency, agility, and flexibility in the manufacturing of drug...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Peer-reviewed journal | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

Process Intensification via End-to-End Continuous Manufacturing of Atorvastatin Calcium Using an Integrated, Modular Reaction-Crystallization-Spherical Agglomeration-Filtration-Drying Process

23 Jul 2024 | Peer-reviewed journal | Contributor(s): Parvaresh, Rojan, Nagy, Zoltan K.

Continuous manufacturing can show potential benefits over batch processing in lower turnaround times and smaller footprint in addition to higher productivity, adaptability, and consistent product quality. Although these possible benefits exist, there are also challenges in integrating the various...

Development and Application of Control Concepts for Twin-Screw Wet Granulation in the ConsiGmaTM-25: Part 2 Granule Size

04 Jun 2024 | Peer-reviewed journal | Contributor(s): Selma Celikovic, Johannes Poms, Johannes Khinast, Martin Horn, Jakob Rehrl

Traditional operation modes, such as running the production processes at constant process settings or within a narrow design space, do not fully exploit the advantages of continuous pharmaceutical manufacturing. Integrating Quality by Control (QbC) algorithms as a standard component of...

Compact NMR Spectroscopy for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals (On-Demand)

31 Jan 2024 | Seminars | Contributor(s): Klas Meyer

Chemical companies are under constant pressure to improve productivity while cutting costs. Flexible and modular chemical plants can produce high-quality products using multi-purpose equipment with short downtimes, reducing time to market for new products. Intensified continuous production...

MOOC I Control Strategy - Process Control

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Control Strategy - Examples

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Control Strategy - Introduction

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Control Strategy - Quality Control

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Madarasz, L, Kote, AGyurkes, M, Farkas, A, Hambalko, B, Pataki, H, Fulop, G, Marosi, G, Lengyel, L, Casian, T, Csorba, K, Nagy, ZK

The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles...

Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Clive Badman, Charles L.Cooney, Alastair Florence, Konstantin Konstantinov, Markus Krumme, Salvatore Mascia, Moheb Nasr, Bernhardt L. Trout

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.

The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Monteyne, Tinne, Heeze, Liza, Mortier, Severine Therese F. C., Oldorp, Klaus, Nopens, Ingmar, Remon, Jean-Paul, Vervaet, Chris, De Beer, Thomas

Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential...

The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

The effects of unintentional and intentional process disturbances on tablet quality during long continuous manufacturing runs

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Niinikoski, Hannes, Ketolainen, Jarkko, Korhonen, Ossi

Several kinds of process disturbances can occur during (continuous) tablet manufacturing, i.e. unintentional or intentional disturbances. Long run-time continuous manufacturing studies are used to investigate the effects of intentional and unintentional deviations. In this study, the horizontal...

The Application of an Automated Control Strategy for an Integrated Continuous Pharmaceutical Pilot Plant

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Lakerveld, R, Benyahia, BHeider, PL, Zhang, HT, Wolfe, A, Testa, CJ, Ogden, S, Hersey, DR, Mascia, S, Evans, JMB, Braatz, RD, Barton, PI

Continuous manufacturing offers potential opportunities for the improved manufacturing of pharmaceutical products. A key challenge is the development of an appropriate control strategy. The experimental application of an automated control strategy is presented for an end-to-end continuous...

Tableting model assessment of porosity and tensile strength using a continuous wet granulation route

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Wang, Li Ge, Omar, Chalak, Li, Jianfeng, Mitchell, Niall, Bellinghausen, Stefan, Barrasso, Dana, Salman, Agba, Slade, David

This paper presents a comprehensive assessment of the most widely used tablet compaction models in a continuous wet granulation tableting process. The porosity models, tensile strength models and lubricant models are reviewed from the literature and classified based on their formulations i.e....

Supervisory Control System for Monitoring a Pharmaceutical Hot Melt Extrusion Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Markl, Daniel, Wahl, Patrick R, Menezes, José C, Koller, Daniel M, Kavsek, Barbara, Francois, Kjell, Roblegg, Evaa, Khinast, Johannes G.

Continuous pharmaceutical manufacturing processes are of increased industrial interest and require uni- and multivariate Process Analytical Technology (PAT) data from different unit operations to be aligned and explored within the Quality by Design (QbD) context. Real-time pharmaceutical process...

Simulation-Based Design of an Efficient Control System for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R

In this study, an efficient system-wide controlsystem has been designed for the integrated continuous purification and processing of the active pharmaceutical ingredient (API). The control strategy is based on the regulatory PID controller which is most widely used in the manufacturing industry...

Sample Mass Estimate for the Use of Near-Infrared and Raman Spectroscopy to Monitor Content Uniformity in a Tablet Press Feed Frame of a Drug Product Continuous Manufacturing Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Hetrick, Evan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Myers, David P

Recently, feed frame-based process analytical technology measurements used to assure product quality during continuous manufacturing processes have received significant attention. These measurements are able to accurately determine uniformity of the powder blend before compression, and in these...

Robustness of a continuous direct compression line against disturbances in feeding

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Karttunen A.-P., Poms J., Sacher S., Sparén A., Ruiz Samblás C., Fransson M., Martin De Juan L., Remmelgas J., Wikström H., Hsiao W.-K., Folestad S., Korhonen O.

The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term...

RTD modeling of a continuous dry granulation process for process control and materials diversion

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kruisz, Julia, Rehrl, Jakob, Sacher, Stephan, Aigner, Isabella, Horn, Martin, Khinast, Johannes G., Krumme, Markus

Disturbance propagation during continuous manufacturing processes can be predicted by evaluating the residence time distribution (RTD) of the specific unit operations. In this work, a dry granulation process was modelled and four scenarios of feeding events were simulated. We performed...

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

09 Jun 2023 | Peer-reviewed journal | 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...