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QbD and PAT in Granulation
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
When process knowledge is not available during proposing a new process analyzer, the test-to-test comparison between an on-line or in-line process analyzer and a conventional analytical test method on collected samples may be the only available validation option. Transfer of laboratory methods to on-, in-, or at-line methods may not necessarily be PAT. Existing regulatory guidance and compendia approach to analytical method validation should be considered. Structured product and process development on a small-scale using experimental design and on- or in-line process analyzers to collect data in real-time can provide increased insight and understanding for process development, optimization, scale-up, technology transfer, and control. Moreover, continuous learning over the life cycle of a product is important when material attributes with respect to different suppliers and environmental processing parameters change over time.
Process Development and Validation
Published in Emmanuel Lesaffre, Gianluca Baio, Bruno Boulanger, Bayesian Methods in Pharmaceutical Research, 2020
Bayesian statistical methodology has two useful characteristics. It can make use of prior information, and most statisticians know this. Perhaps just as important though is that the Bayesian approach is very flexible for modeling complex (manufacturing or assay) processes or complex quantifications of such a process. In the act of such modeling, the Bayesian method also accounts for the uncertainties of the unknown model parameters. In addition, since posterior probabilities of events of interest can typically be quantified in a straightforward manner, Bayesian methods are also very useful and natural for risk quantification, an important aspect of quality-by-design. This chapter will review two important aspects of process development and validation. One development aspect to be reviewed is that of “design space” as defined in the International Conference on Harmonization Q8 regulatory guidance. The other aspect to be assessed (during late development or early validation), is the assessment of measurement system or assay robustness. An assay is robust if it is insensitive to small deviations in its basic operating factors. This chapter will also show that realistic, natural quality criteria may exist in complex quantitative forms. The flexibility of the Bayesian approach nonetheless adapts in a straightforward manner to these complexities.
Gaps and Future Considerations for Development of Transdermal and Topical Delivery Systems
Published in Tapash K. Ghosh, Dermal Drug Delivery, 2020
For many formulations the order of addition of components, mixing speed, temperature and time significantly affect the adhesive formulations. During process development, great care should be taken in determining the influence and importance of each parameter. Sampling for in-process testing of the adhesive mix should be from top, middle and bottom of the mixing vessel. Proper tests are product specific but may include a variety of identification and assay or potency methods, visual examination for color, clarity, air entrapment or undissolved particles or agglomeration of excipients or drug substances, and viscosity. Other tests may be applicable and all avenues and considerations for proper control of the mixing steps should be explored. As previously mentioned, the incorporation of PAT at this stage of the manufacturing process may prove beneficial. According to the Guidance for Industry – PAT a Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance, “a process end point is not a fixed time; rather it is the achievement of the desired material attribute.”3 During the blending process the use of infrared technology or other real-time monitoring methods may allow manufacturers to determine when solvation has been achieved or confirm when a homogenous blend of the drug/adhesive solution is obtained; thus the blend can then be moved to the laminating or casting stage of production.
10th antibody industrial symposium: new developments in antibody and adoptive cell therapies
Published in mAbs, 2023
Ana Antunes, Luis Alvarez-Vallina, Federico Bertoglio, Nicolas Bouquin, Stéphanie Cornen, Francis Duffieux, Pierre Ferré, Raphaëlle Gillet, Christian Jorgensen, Mark B Leick, Bernard Maillère, Hélène Negre, Mireia Pelegrin, Nicolas Poirier, Dietmar Reusch, Bruno Robert, Guy Serre, Alain Vicari, Martin Villalba, Christoph Volpers, Gavin Vuddamalay, Hervé Watier, Thierry Wurch, Lennart Zabeau, Stefan Zielonka, Baolin Zhang, Alain Beck, Pierre Martineau
During her presentation, Dr. Christelle Dagoneau (Head of Global Business Development, Just Evotec Biologics, Toulouse, France) described their unique platform that integrates the discovery, design, engineering, development, and manufacture of biologics in very flexible and easily deployable production facilities called J.POD®. C. Dagoneau showed how the intrinsic molecular properties of antibody sequences can result in lead candidates that are difficult to manufacture or keep stable in formulation. This translates into process development and manufacturing challenges that can substantially affect costs and timelines. Just-Evotec Biologics uses its Abacus™ software, an in-house suite of proprietary computational tools, to predict molecules and conditions for development. She also described how J.POD® accommodates perfusion, intensified fed-batch, semicontinuous, and end-to-end continuous biomanufacturing processes at a standard 500 L scale to deliver from few kilograms of antibodies for “first-in-human” studies to metric tons of drug substance (commercial biomanufacturing) for commercial supply.
Using online content uniformity measurements for rapid automated process development exemplified via an X-ray system
Published in Pharmaceutical Development and Technology, 2019
Bernhard Wagner, Thomas Brinz, Johannes Khinast
Obviously, there are several process parameters (i.e. CPPs), which may affect the CQAs. Likely, there are strong interactions between the CPPs of the different process steps. The CPPs influence each other. As such, rather than testing each single unit on its own, the combination of units should be examined as a whole via the RAPD. One example is given by the feeders that feed continuously into the blender. A fluctuation in the feed rate can induce variations in the final mixture. For some materials, feeding can be a challenging task and significant fluctuations may occur. However, whether these fluctuations are critical for the process cannot be determined without considering the subsequent process steps. For example, the blender may be able to dampen the fluctuations (Weinekötter and Reh 1995; Gao et al. 2011) or fluctuations in the feed may be acceptable, if their influence on the content uniformity is negligible (or below the pharmacopeia limits). This is why in terms of process development it is important to consider the process as a whole. Consequently, the combination of a content check and the RAPD can be a valuable solution for the development of a continuous-capsule filling process.
Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D
Published in mAbs, 2020
Suzanne S. Farid, Max Baron, Christos Stamatis, Wenhao Nie, Jon Coffman
The definitions of process development and its associated costs in biopharmaceutical product development vary between sources and organizations. In this model, process development was defined as the activity that establishes and optimizes the manufacturing for biopharmaceutical products for clinical and commercial purposes, and provides knowledge for regulatory compliance. The cost associated with process development was therefore distributed across strain development, process synthesis, design, optimization, characterization, validation, and the related analytical development activities. It should be noted that the cost of manufacturing clinical material was not included in the cost of process development and instead was included under manufacturing.