Development of a Continuous Flow Grignard Reaction to Manufacture a Key Intermediate of Ipatasertib

25 Jun 2024 | Contributor(s): Kaldre, Dainis, Stocker, Severin, Linder, David, Reymond, Helena, Schuster, Andreas, Lamerz, Jens, Hildbrand, Stefan, Püntener, Kurt, Berry, Malcolm, Sedelmeier, Jörg

This article outlines the development of a continuous flow process for the manufacture of a key intermediate of the active pharmaceutical ingredient ipatasertib for the treatment of metastatic castration-resistant prostate cancer and triple-negative metastatic breast cancer. The reaction sequence...

Innovation and Continuous Improvement in Pharmaceutical Manufacturing

28 Mar 2024 | Document | Contributor(s): Ajaz Hussain (Chairperson) Raafat Fahmy (CVM), William Bargo (CVM), Robert Coleman, Robert (ORA), Elise Murphy (ORA), Frank Holcombe Jr (CDER), Chris Watts (CDER), See Lam (CDER), Jon Clark (CDER), Christopher Joneckis (CBER), John Dietrick (CDER), Diana Kolaitis (ORA), Vilayat Sayeed (CDER), Mai Huynh (CVM), Norman Schmuff (CDER), Andrew Chang (CBER)

The PAT Team and Manufacturing Science Working Group Report: A Summary of Learning, Contributions and Proposed Next Steps for Moving towards the "Desired State" of Pharmaceutical Manufacturing in the 21st Century

A Perspective on Quality by Design: A Preclinical Opportunity

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

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

The Subcommittee on Process Analytical Technologies (PAT): Closing Remarks

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

The Process Analytical Technology Initiative: PAT and the Pharmacopeias

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

The PAT Initiative A part of the Pharmaceutical Quality for the 21st Century Initiative  PAT and the USP Opportunities for the USP to support the PAT Framework

Utilizing PAT to Monitor and Control Bulk Biotech Processes

27 Mar 2024 | Document | Contributor(s): Rick E. Cooley

1.What is and isn’t PAT? 2.Implementing PAT in Manufacturing: What does it take? 3.Characteristics of bulk, biotech API processes 4.Why PAT? 5.Review of PAT technologies utilized 6.PAT application examples

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...

The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Dadou, SM, Tian, YWLi, S, Jones, DS, Andrews, GP

Complications associated with uncontrolled hypertension are considered the major cause of premature death worldwide. Fixed-dose combinations (FDCs) offer an alternative approach to polypharmacy with the aim to improve patient compliance. Process Analytical Technology (PAT) is gaining momentum as...

The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Andres, G.P., Jones D.S., Senta-Loys Z., Almajaan A., Li S., Chevallier O., Elliot C., Healy A.M., Kelleher J.F., Madi A.M., Gilvary G.C., Tian Y.a

Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To...

The Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Adam C Fisher, Mark-Henry Kamga, Cyrus Agarabi, Kurt Brorson, Sau L Lee, Seongkyu Yoon

There is a trend across the pharmaceutical sector toward process intensification and continuous manufacturing to produce small-molecule drugs or biotechnology products. For biotechnology products, advancing the manufacturing technology behind upstream and downstream processes has the potential to...

The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Dadou, Suha, Senta-Loys, Zoe, Almajaan, Ammar, Li, Shu, Jones, David, Healy, Anne, Tian, Yiwei, Andrews, Gavin

Continuous processing is superseding conventional batch processing as a means of manufacturing within the pharmaceutical Research Article/industry. This paradigm shift has led to the implementation of Process Analytical Technology (PAT) as a semi-automatic, predictive tool offering real-time...

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...

Spectroscopic characterization of tablet properties in a continuous powder blending and tableting process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nagy, Brigitta, Farkas, Attila, Magyar, Krisztina, Démuth, Balázs, Marosi, György

By the advent of continuous pharmaceutical manufacturing, fast and accurate characterization of product quality has become of a major interest. Although it also promotes the real-time release testing approach, so far mainly content uniformity studies were performed by near-infrared (NIR)...

Spray granulation for drug formulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Loh, Zhi Hui, Er, Dawn Z. L., Chan, Lai Wah, Liew, Celine V., Heng, Paul W. S.

Introduction: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration...

Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and sustainable Fine-Chemical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Morin, Mathieu, Zhang, Wenyao, Mallik, Debasis, Organ, Michael G

Process analytical technology (PAT) is a system designed to help chemists better understand and control manufacturing processes. PAT systems operate through the combination of analytical devices, reactor control elements, and mathematical models to ensure the quality of the final product through...

Risk Considerations on Developing a Continuous Crystallization System for Carbamazepine

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yang, Xiaochuan, Acevedo, David, Mohammad, Adil, Pavurala, Naresh, Wu, Huiquan, Brayton, Alex L., Shaw, Ryan A., Goldman, Mark J., He, Fan, Li, Shuaili, Fisher, Robert J., O'Connor, Thomas F., Cruz, Celia N.

Continuous manufacturing (CM) is an emerging technology in the pharmaceutical manufacturing sector, and the understanding of the impact on product quality is currently evolving. As the final purification and isolation step, crystallization has a significant impact on the final physicochemical...

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...

Recent progress in continuous manufacturing of oral solid dosage forms

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

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

09 Jun 2023 | Peer-reviewed journal | 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 Process Analytical Technologies of Pharmaceutical Secondary Manufacturing

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

Process analytical technology for continuous manufacturing tableting processing: A case study

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

The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...

Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Malwade, CR, Qu, HY

Background: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities....

Process Analytical Technology Tools for Monitoring Pharmaceutical Unit operations: A Control Strategy for Continuous Process Verification

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kim, Eun, Kim, Ji, Kim, Min-Soo, Jeong, Seong, Choi, Du

Various frameworks and methods, such as quality by design (QbD), real time release test (RTRT), and continuous process verification (CPV), have been introduced to improve drug product quality in the pharmaceutical industry. The methods recognize that an appropriate combination of process controls...