Innovations in Pharmaceutical Manufacturing on the Horizon Technical Challenges, Regulatory Issues, and Recommendations (2021) / Chapter Skim
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Appendix D: Innovations in Pharmaceutical Manufacturing Proceeding of a Workshop - in Brief
Appendix D: Innovations in Pharmaceutical Manufacturing Proceeding of a Workshop - in Brief
Pages 84-96
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From page 84... ...
Almost 2 decades ago, CDER launched an initiative called Pharmaceutical Quality for the 21st Century with the goal of achieving an agile, flexible pharmaceutical manufacturing sector that reliably produces high-quality drugs without the need for extensive regulatory oversight. She noted that advanced manufacturing has moved from the laboratory feasibility stage to commercial applications, that innovative technologies are in the pipeline, and that proposals are being submitted to the CDER Emerging Technologies Team from all types of companies throughout the pharmaceutical sector.
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From page 85... ...
DRUG PRODUCT MANUFACTURING Daniel Blackwood, a research fellow in the Drug Product Design Group of Pharmaceutical Sciences–Small Molecule at Pfizer, began the session on drug product manufacturing by describing activities focused on continuous manufacturing in his company. He noted that interest in continuous manufacturing arose several decades ago as the industry began to prepare for patent expiry of its blockbuster, high-volume medicines.
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From page 86... ...
He said that his company wants to create flexible manufacturing with new technology that has the ability to produce small product batches. To achieve that goal, Merck will rely on portable manufacturing units, robotics to improve compliance, data analytics and information technology integration, and continuous manufacturing.
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From page 87... ...
Discussion To close the drug product session, Matthew DeLisa, William L Lewis Professor in the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell University, moderated a panel discussion with the speakers and the workshop audience.
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From page 88... ...
In closing, Braatz predicted that there will be advances in methods that combine data analytics and machine learning with first-principles models, increased use of tensorial data streams, and a broadening of the scope of data analytics and machine learning in pharmaceutical applications. He imagined that the industry will automatically archive data for process modeling and analysis and improving monitoring and control, use plantwide data to optimize operational models, use all available data to ensure that product quality specifications are met, and ultimately use ecosystem data to connect customer needs to manufacturing data.
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From page 89... ...
In closing, she emphasized the need to make the business case for investing in advanced process control and hoped that enhancing models with advanced sensor data to optimize feed control and ultimately product quality would be more common in the next 5–10 years. Jack Prior, head of Manufacturing Science, Global Manufacturing Science and Technology at Sanofi, provided his view of the current state of process data analytics.
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From page 90... ...
In one, Pfizer replaced end-product testing with a soft sensor to reduce drying-cycle time and increase productivity; in the other, Pfizer used advanced process control for fully automating and controlling pH in a production process and thus reducing product variabilities. In closing, Huang emphasized that accelerating process development will require aggregating data into a central repository that can be accessed by various users in development and manufacturing and require development of the analytics to leverage those data.
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From page 91... ...
An audience member raised the idea of an industry consortium to share process data as a possibility for improving models or data analytics. Schiel noted that process data are intimately tied to product data and that the industry would therefore not be eager to share.
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From page 92... ...
Tom noted that complex molecules, such as oligonucleotides and peptides, involve new regulatory challenges, including various issues associated with impurities and use of analytical methods different from those used to characterize traditional small molecules. As a final note on route invention, Tom mentioned co-processed APIs and the question, from a regulatory standpoint, of whether to treat them as drug substances or as drug-product intermediates.6 Regarding process invention, Tom acknowledged that innovations have been focused on continuous manufacturing and noted several challenges, including process-control complexities, lack of first-principle understanding, development of real-time feedback loops and predictive modeling, and uncertainties of regulatory requirements.
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From page 93... ...
Nyberg highlighted continuous manufacturing and noted that it is probably not going to decrease the cost of goods radically but will substantially change capital costs given the much lower costs of building a manufacturing facility. Other benefits of continuous manufacturing are that it allows companies to right-size manufacturing capacity and provides the ability to make a variety of molecules.
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From page 94... ...
Tom emphasized that there are challenges given the different regulatory requirements for various drug substances and products and mentioned again the issues that her company has faced with co-processed APIs. As a final note, Mascia raised the prospects of release testing only for the final drug product in a continuous manufacturing process; he asked, If the API is not isolated, why should a company have to release it for testing?
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From page 95... ...
Several audience members debated issues associated with data analytics and control. Braatz noted that digital twins constitute a technology that the committee will likely discuss in its report and encouraged the committee to define the term because there is much confusion about what it means.
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From page 96... ...
2019. Bayesian probabilistic modeling in pharmaceutical process development.
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