A PAT-based qualification of pharmaceutical excipients produced by batch or continuous processing

09 Jun 2023 | Contributor(s): Hertrampf A., Müller H., Menezes J.C., Herdling T.

Pharmaceutical excipients have an influence on the main requirements for medicinal products (viz., quality, safety and efficacy) but also on their manufacturability. During product lifecycle it may become necessary to introduce minor changes (e.g., to continuously improve it) or major changes in...

A Perspective on Quality by Design: A Preclinical Opportunity

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Laske, Stephan, Paudel, Amrit, Scheibelhofer, Otto, Sacher, Stephan, Hoermann, Theresa, Khinast, Johannes, Kelly, Adrian, Rantannen, Jukka, Korhonen, Ossi, Stauffer, Fanny, De Leersnyder, Fien, De Beer, Thomas, Mantanus, Jerome, Chavez, Pierre-Francois, Thoorens, Benjamin, Ghiotti, Patrizia, Schubert, Martin, Tajarobi, Pirjo, Haeffler, Gunnar, Lakio, Satu, Fransson, Magnus, Sparen, Anders, Abrahmsen-Alami, Susanna, Folestad, Staffan, Funke, Adrian, Backx, Ivo, Kavsek, Barbara, Kjell, Francois, Michaelis, Marc, Page, Trevor, Palmer, John, Schaepman, Alexander, Sekulic, Sonja, Hammond, Steve, Braun, Birgit, Colegrove, Brenda

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological and mathematical) methods for material (e.g. materials,...

A Shared Vision for Pharmaceutical Development and Manufacturing in the 21st Century: Contributions of the PAT Initiative

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

An agile and robust in-line NIR potency deviation detection method for monitoring and control of a continuous direct compression process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alam, Md Anik, Liu, Yang Angela

Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in...

An Innovative Sampling Interface for Monitoring Flowing Pharmaceutical Powder Mixtures

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Martínez-Cartagena, Pedro, Romañach, Rodolfo J., Sierra-Vega, Nobel O; Alvarado-Hernández, Bárbara B; Méndez, Rafael

A chute was designed following the principles of the Theory of Sampling to minimize the variations in powder flow and provide all particles in the flowing blends with the same opportunity of being selected as a sample. The design also reduces the thickness of the chute to allow the analysis of a...

An Overview of Pharmaceutical Manufacturing for Solid Dosage Forms

09 Jun 2023 | Chapter Book | Contributor(s): Sacher, Stephan, Khinast, Johannes G.

In this chapter, the main processing steps and manufacturing aspects of solid dosage forms are described and the relevant literature is reviewed. Starting with powder feeding, powder blending, granulation (dry and wet), and drying the most important unit operations to make compactable granules...

Application of Continuous Crystallization in an Integrated Continuous Pharmaceutical Pilot Plant

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Zhang, Haitao, Lakerveld, Richard, Heider, Patrick, Tao, Mengying, Su, Min, Testa, Christopher, D’Antonio, Alyssa, Barton, Paul, Braatz, Richard, Trout, Bernhardt, Myerson, Allan, Jensen, Klavs, Evans, James

Real-time control using process analytical technology (PAT) tools is required for the implementation of continuous crystallization within integrated continuous manufacturing (ICM) of pharmaceuticals. However, appropriate selection of PAT tools is challenging, and the design and operation of...

Assessment of blend uniformity in a continuous tablet manufacturing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sierra-Vega, Nobel, Román-Ospino, Andrés, Scicolone, James, Muzzio, Fernando, Romañach, Rodolfo, Mendez, Rafael

Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing blends and compared to the drug concentration in the tablets. The NIR spectra were obtained through the chute after the blender and within the feed frame,...

Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Simon, Levente L, Pataki, Hajnalka, Marosi, György, Meemken, Fabian, Hungerbühler, Konrad, Baiker, Alfons, Tummala, Srinivas, Glennon, Brian, Kuentz, Martin, Steele, Gerry, Kramer, Herman J. M, Rydzak, James W.

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in...

At-line monitoring of salification process of the antiretroviral lamivudine-saccharinate salt using FT-MIR spectroscopy with multivariate curve resolution

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Mazivila, SJ, Castro, RAELeitao, JMM, da;Silva, JCGE

This article presents a promising application of Fourier transform-mid infrared (FT-MIR) spectroscopy with multivariate curve resolution - alternating least-squares (MCR-ALS) as an at-line process analytical technology (PAT) to enhancing the understanding and continuous control of a...

Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alam, MA, Liu, YADolph, S, Pawliczek, M, Peeters, E, Palm, A

A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to...

Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Velez, Natasha L., Drennen, James K., Anderson, Carl A.

Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...

Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Harms, Zachary, Shi, Zhenqi: Kulkarni, Rajesh, Myers, David P.

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order...

Combined feedforward/feedback control of an integrated continuous granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pereira, Glinka Cathy, Muddu, Shashank Venkat Román-Ospino, Andrés David Clancy, Don Igne, Benoit Airiau, Christian Muzzio, Fernando J Ierapetritou, Marianthi Ramachandran, Rohit, Singh, Ravendra

Continuous manufacturing offers shorter processing times and increased product quality assurance, among several other advantages. This makes it an ever-growing interest among pharmaceutical companies. A suitable efficient control system is however desired for continuous pharmaceutical...

Continuous direct compression as manufacturing platform for sustained release tablets

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vanhoorne, V, Holman, J., Cunningham, C., Kumar, A., Vercruysse, J., De Beer, T., Remon, J. P, Vervaet, C

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard...

Continuous Manufacturing for Pharmaceutical Solid Dosage Forms (On-Demand)

31 Jan 2024 | Seminars | Contributor(s): Atul Dubey, Fernando Muzzio, Gerardo Callegari, Lucy L. Botros, Ravendra Singh, James Scicolone, Andres Roman, Sonia Modarres Razavi

Course Description: This self-paced curriculum contains fourteen self-paced modules and three recordings of live virtual education on Pharmaceutical Continuous Manufacturing (PCM). Learners will have access to the following: A recording of the introductory session covering topics such as...

Continuous manufacturing of a pharmaceutical cream: Investigating continuous powder dispersing and residence time distribution (RTD)

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bostijn, N, Van, Renterghem, JVanbillemont, B, Dhondt, W, Vervaet, C, De;Beer, T

Recently, an innovative continuous manufacturing technology for a pharmaceutical oral suspension was proposed, based on two consecutive mixing units. A limitation of this technology is the need to dissolve or disperse powder-based raw materials in a liquid via a batch step before continuous...

Continuous Manufacturing of a Polymer Stabilized Emulsion Monitored with Process Analytical Technology

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Qwist, PK, Sander, CBostijn, N, Jessen, V, Rantanen, J, de;Beer, T

Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process...

Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Roggo, Yves, Pauli, Victoria, Jelsch, Morgane, Pellegatti, Laurent, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Krumme, Markus

The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties...

Control strategy definition for a drug product continuous wet granulation process: Industrial case study

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Chavez, Pierre-François, Stauffer, Fanny, Eeckman, Frédéric, Bostijn, Nils, Didion, David, Schaefer, Cédric, Yang, Hong, El Aalamat, Yousef, Lories, Xavier, Warman, Martin, Mathieu, Benoit, Mantanus, Jérôme

This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with...

Deep learning for continuous manufacturing of pharmaceutical solid dosage form

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Roggo, Yves, Jelsch, Morgane, Heger, Philipp, Ensslin, Simon, Krumme, Markus

Continuous Manufacturing (CM) of pharmaceutical drug products is a new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line for production of solid dosage forms was investigated. The line was composed of the subsequent continuous unit:...

Design and Commercialization of an End-to-End Continuous Pharmaceutical Production Process: A Pilot Plant Case Study

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Testa, Christopher J., Hu, Chuntian, Shvedova, Khrystyna, Wu, Wei, Sayin, Ridade, Casati, Federica, Halkude, Bhakti S., Hermant, Paul, Shen, Dongying Erin, Ramnath, Anjana, Su, Qinglin, Born, Stephen C., Takizawa, Bayan, Chattopadhyay, Saptarshi, O'Connor, Thomas F., Yang, Xiaochuan, Ramanujam, Sukumar, Mascia, Salvatore

The pharmaceutical industry faces multiple challenges (e.g., inefficient manufacturing techniques, quality control issues, and supply chain vulnerabilities) because of its current batch-wise approach to manufacturing. Recent regulatory support for continuous manufacturing and advances in...

Development and Application of a Business Case Model for a Stream Sampler in the Pharmaceutical Industry

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Fontalvo-Lascano, María A, Alvarado-Hernández, Bárbara B., Conde, Carlos, Sánchez, Eric J., Méndez-Piñero, Mayra I., Romañach, Rodolfo

Purpose: A template to prepare a business case for Process Analytical Technology (PAT) and Continuous Manufacturing (CM) projects is presented in this study. Business cases are necessary tools used in different organizations to present new projects for management evaluation. As new ways of...

Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press

09 Jun 2023 | Peer-reviewed journal | Contributor(s): De Leersnyder, Fien, Peeters, Elisabeth, Djalabi, Hasna, Vanhoorne, Valérie, Van Snick, Bernd, Hong, Ke, Hammond, Stephen, Liu, Angela, Ziemons, Eric, Vervaet, Chris, De Beer, Thomas

A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was...