Tools for real time release testing (RTRt) in batch and continuous tablet manufacturing (original) (raw)
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International Journal of Pharmaceutics, 2020
In the last decade significant advances have been made in process analytical technologies and digital manufacturing of pharmaceutical oral solid dosage forms leading to enhanced product knowledge and process understanding. These developments provide an excellent platform for realising real-time release testing (RTRT) to eliminate all, or certain, off-line end product tests assuring that the drug product is of intended quality. This review article presents the state of the art, an RTRT development workflow as well as challenges and opportunities of RTRT in batch and continuous manufacturing of pharmaceutical tablets. Critical quality attributes, regulatory aspects and the scientific basis of enabling technologies and models for RTRT are discussed and a systematic development workflow for the robust design of an RTRT environment is presented. This includes the discussion of key considerations for the identification of the critical quality attributes and points of testing as well as the development of the sampling strategy, a hard and/or soft sensor approach and operational procedures. The final sections present two RTRT use cases in an industrial setting as well as critically discuss challenges and provide a future perspective of RTRT.
Manufacturing challenges in the production of high quality modified-release tablets
The Boolean: Snapshots of Doctoral Research at University College Cork, 2011
The pharmaceutical industry is obliged and regulated to ensure that manufactured medicines (i.e., tablets) meet the highest quality standards. However, no system is perfect. The European Medicines Agency (EMEA) state that somewhere between 5-10% of pharmaceutical production batches must be either reworked or discarded, because they do not fully meet the stringent final quality specifications. Poor production quality, often due to inflexible manufacturing and insufficient process understanding represents an unnecessary burden in both time and expense. According to Cedar Management Consulting, the bulk of the global top 16 pharmaceutical companies’ budgets are spent on manufacturing (~36%), whereas the research and development (R&D) expenses (often considered to be the major cost burden) can be less than half of this (~16%). Therefore, there is great interest in making manufacturing more effective and optimising processes in order to deliver consistent high quality. The goal of this r...
Process Analytical Technology for continuous manufacturing of solid-dosage forms
TrAC Trends in Analytical Chemistry, 2015
Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the advantages of continuous processing, so the critical quality attributes of continuously produced pharmaceuticals need to be monitored in real time. In 2004, the US Food and Drug Administration launched the process analytical technology (PAT) concept to stimulate the pharmaceutical industry to change from off-line to real-time quality testing. This review explores the implementation of PAT tools within continuous pharmaceutical processes (i.e., blending, spray drying, roller compaction, twin-screw granulation and compression), focusing on both opportunities and challenges.
Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study
Journal of Pharmaceutical and Biomedical Analysis, 2019
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Process analytical technologies and injectable drug products: Is there a future?
International Journal of Pharmaceutics, 2019
Parametric release was the first subset of real time release testing (RTRT), applied to terminally sterilised injectable drug products. The objective was to offer the industry an alternative to the time and money consuming sterility testing, without compromising the sterility of the products. The rationale was that quality cannot be tested into products, instead it must be planned (the principle of quality by design, QbD). This can be implemented by setting appropriate in-process controls supported on process analytical technologies (PAT). Two of the most versatile and promising PAT tools are the near infrared spectroscopy (NIRS) and the Raman spectroscopy. However, their application to injectable drug product development and manufacturing has been scarce. This review has the objective to provide a framework for the practical implementation of the QbD approach to injectable formulations, including application of diverse risk assessment and factorial design tools. Finally, the actual application of PAT, namely NIRS and Raman spectroscopy, to injectable drug product analysis is addressed.
Handbook of Pharmaceutical Manufacturing Formualtion Vol
Preface to the Series-Second Edition vii this work, for seeing an immediate value to the readers in publishing the second edition of this book and allowing me enough time to prepare this work. The diligent editing and composing staff at Informa, particularly Joseph Stubenrauch, Baljinder Kaur and others are highly appreciated. Regardless, all errors and omissions remain altogether mine. In the first edition, I had dedicated each volume to one of my mentors; the second edition continues the dedication to these great teachers.
AIChE Journal, 2017
A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of dispersed flow from the reaction engineering field. An estimability analysis was performed to understand the impact of the available measurements on the estimated parameters and suggest better ways to approach the parametrization. Predictions are successfully contrasted with experimental data. The model is used to produce residence time distributions at different process conditions and a graphical representation of the allowable range of disturbances in the feeders that can be mitigated by the process. The model was used in support of the method development for an online near infrared sensor. © 2017 American Institute of Chemical Engineers AIChE J, 64: 511–525, 2018
Dissolution Technologies
BACKGROUND T he International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Workshop on Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation was held on November 11-12, 2021, virtually using the WebEx video conferencing platform (1). Recordings of all podium talks and panel discussions have been made available by the IQ Consortium (2). The workshop was attended by 256 scientists representing 85 organizations from the pharmaceutical industry and academia as well as regulatory and standards agencies. Figure 1 shows the distribution of workshop registrants by organization type and by experience with dissolution real-time release testing (RTRT), based on their answers to the questionnaire provided electronically during registration. Of the registrants, 86% represented the pharmaceutical industry; additionally, of the 8% who identified as "other," most represented vendors to the pharmaceutical industry (e.g., equipment or software manufacturers, pharmaceutical testing laboratories). Less