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  1. Continuous Manufacturing in the Pharmaceutical Industry: Enhancing Drug Production

    23 Jul 2024 | 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...

  2. WHAT are sampling errors-and WHAT can we do about them? Part 1

    09 Jun 2023 | Contributor(s):: Romañach, Rodolfo J., Joubert Castro, Aidalu, Esbensen, Kim H

    The objective of this column is to provide easy-to-understand examples of sampling errors. Prompted by recent participationsand presentations at on-line conferences and meetings, we believe there is a need for a more fulfilling introduction andexemplification of the concept and real-world...

  3. Theory of Sampling (TOS): A necessary and sufficient guarantee for reliable multivariate dara analysis in pharmaceutical manufacturing

    09 Jun 2023 | Contributor(s):: Esbensen, Kim H, Romañach, Rodolfo, J.Ferrerira, Ana P., Menezes, Jose C., Tobyn, Mike, Román-Ospino, Andrés D.

    Multivariate Analysis in the Pharmaceutical Industry provides industry practitioners with guidance on multivariate data methods and their applications over the lifecycle of a pharmaceutical product, from process development, to routine manufacturing, focusing on the challenges specific to each...

  4. Pharmaceutical manufacturing and the quality by design (QBD), process analytical technology (PAT) approach

    09 Jun 2023 | Contributor(s):: Murphy, Trevor, O’ Mahony, Niall, Panduru, Krishna, Riordan, Daniel, Walsh, Joseph

    This paper is the result of a literature review focusing on the application of process analytical technology (PAT) for the pharmaceutical industry in conjunction with the quality by design (QBD) framework. PAT and the QBD framework put forward by the FDA, offer a holistic approach to...

  5. Near-Infrared Spectroscopy as Process Analytical Technology in Continuous Solid Dosage Form Manufacturing

    09 Jun 2023 | Contributor(s):: Peeters, M., De Beer, T., Narang, Ajit S., Dubey, Atul., Kumar, A

    In this chapter titled “Near-infrared Spectroscopy as Process Analytical Technology in Continuous Solid Dosage Form Manufacturing” the fundamentals of near-infrared spectroscopy (NIRS) and the mainstream and emerging NIRS analyzer technologies for process analytical technology (PAT) applications...

  6. Non-invasive, continuous, quantitative detection of powder level and mass holdup in a metal feed tube

    09 Jun 2023 | Contributor(s):: Louge, Michel Y, Mandur, Jasdeep, Blincoe, William, Tantuccio, Anthony, Meyer, Robert F

    We describe a quantitative, non-invasive capacitance detector providing a rapid signal that varies continuously with powder level and/or mass holdup in the metal feed tube of a tablet press. We outline the principle of its processing electronics, provide an algorithm for the accurate...

  7. Introduction to the Theory and Practice of Sampling

    09 Jun 2023 | Contributor(s):: Esbensen, Kim H

    Sampling is an important, but sometimes hidden, part of everyday life in science, technology, industry, society and commerce where decisions are made based on analytical results, which must be based on reliable samples. However, there is a very long and complex pathway from heterogeneous...

  8. Guidance for Industry PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance

    09 Jun 2023

    This guidance is intended to describe a regulatory framework (Process Analytical Technology, PAT) that will encourage the voluntary development and implementation of innovative pharmaceutical development, manufacturing, and quality assurance. Working with existing regulations, the Agency has...

  9. Holistic Control Strategies for Continuous Manufacturing

    09 Jun 2023 | Contributor(s):: Moore, Christine, Garcia, Thomas, Hausner, Douglas B., Ben-Anat, Inna

    Innovative technologies such as continuous manufacturing (CM) bring speed, efficiency, and agility to pharmaceutical manufacturing together with enhanced process robustness and assurance of product quality. During CM, material is simultaneously charged and discharged into process unit operations....

  10. Flexibility in Drug Product Development: A Perspective

    09 Jun 2023 | Contributor(s):: Kapoor, Yash, Ferguson, Heidi, Skomski, Daniel, Daublain, Pierre, Troup, Gregory, Dalton, Chad, Ramasamy, Manoharan, Templeton, Allen

    The process of bringing a drug to market involves innumerable decisions to refine a concept into a final product. The final product goes through extensive research and development to meet the target product profile and to obtain a product that is manufacturable at scale. Historically, this...

  11. Effective Development of PAT Capability in Pharmaceutical Manufacturing

    09 Jun 2023 | Contributor(s):: Hammond, Steve

    Over the last ten years, the path to effective development of PAT has evolved, driven by the advent of continuous manufacturing. The development and deployment of PAT used for pharmaceutical manufacturing has arrived at a point where application development has been miniaturized and streamlined....

  12. Continuous Twin Screw Wet Granulation and Drying - Control Strategy for Drug Product Manufacturing

    09 Jun 2023 | Contributor(s):: Dahlgren, Gabriella, Tajarobi, Pirjo, Simone, Eric, Ricart, Brendon, Melnick, Jason, Puri, Vibha, Stanton, Courtney, Bajwa, Gurjit

    The use of continuous manufacturing has been increasing within the pharmaceutical industry over the last few years. Continuous direct compression has been the focus of publications on the topic to date. The use of wet granulation can improve segregation resistance, uniformity, enhance density,...

  13. Characterization of material properties

    09 Jun 2023 | Contributor(s):: Razavi, Sonia, Oka, Sarang, Escotet-Espinoza, M. Sebastian, Wang, Yifan, Li, Tianyi, Futran Mauricio., Muzzio, Fernando

    This chapter describes the importance of deepening our understanding of material properties and their effect on process performance. There are many measurement techniques to describe the complex nature of powders, some of which are provided in this chapter. Strong knowledge of multivariate...

  14. An ontological knowledge-based system for the selection of process monitoring and analysis tools

    09 Jun 2023 | Contributor(s):: Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul

    Efficient process monitoring and analysis tools provide the means for automated supervision and control of manufacturing plants and therefore play an important role in plant safety, process control and assurance of end product quality. The availability of a large number of different process...

  15. An automated modular assembly line for drugs in a miniaturized plant

    09 Jun 2023 | Contributor(s):: Hu, Chuntian, Testa, Christopher, Wu, Wei, Shvedova, Khrystyna, Shen, Dongying, Sayin, Ridade, . Halkude, Bhakti, Casati, Federica, Hermant, Paul, Ramnath, Anjana, Born, Stephen, Takizawa, Bayan, O'Connor, Thomas, Yang, Xiaochuan, Ramanujamd, Sukumar, Mascia, Salvatore

    We report here a fully automated, end-to-end, integrated continuous manufacturing process for a small-molecule generic medication with built-in quality assurance. The entire process fits into a box of 30.7 m2 modular footprint and a total residence time of less than 30 h, with a throughput up to...

  16. Adequacy and Verifiability of Pharmaceutical Mixtures and Dose Units by Variographic Analysis (Theory of Sampling) - A Call for a Regulatory Paradigm Shift

    09 Jun 2023 | Contributor(s):: Esbensen, Kim H, Román-Ospino, Andrés D., Sanchez, Adriluz, Romañach, Rodolfo J.

    In spite of intense efforts in the last 20 years, the current state of affairs regarding evaluation of adequacy of pharmaceutical mixing is at an impressive standstill, characterized by two draft guidances, one withdrawn, and the other never approved. We here analyze the regulatory, scientific...

  17. Achieving Continuous Manufacturing for Final Dosage Formation: Challenges and How to Meet Them

    09 Jun 2023 | Contributor(s):: Byrn, Stephen, Futran, Maricio, Thomas, Hayden, Jayjock, Eric, Maron, Nicola, Meyer, Robert F., Myerson, Allan S., Thien, Michael P., Trout, Bernhardt L.

    We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to...

  18. A Semi-Continuous Operations Model For Solid-Dose Manufacturing

    09 Jun 2023 | Contributor(s):: Pazhayattil, Ajay Babu, Sayeed-Desta, Naheed

    This article will explore the evolving generic drug environment in the U.S. It will also describe an operations model for semi-continuous manufacturing of generic solid-dose products that will improve flexibility and enable just-in-time production.

  19. A Framework for Representative Sampling for NIR Analysis – Theory of Sampling (TOS)

    09 Jun 2023 | Contributor(s):: Esbensen, Kim H, Ciurczak, Emil W., Igne, Benoît, Workman, Jr.,Jerome, Burns, Donald A., Romañach, Rodolfo J.

    This chapter deals with all critical steps before near-infrared spectroscopy (NIR) analysis, irrespective of whether the total sampling error contribution is large, intermediate, or small – all cases can be treated identically, including the widespread sensor-based solutions from the...