Conference/Seminar: Design and Optimization of Pharmaceutical Products and Processes: Challenges and Opportunities

The $600 billion/year pharmaceutical industry is an important sector in which the U.S. remains a global leader. In the last few years, however, there has been growing recognition that the industry is facing a crisis. Indeed, the Critical Path Initiative of the FDA has identified the lack of innovation in pharmaceutical manufacturing science as one of the key impediments to the delivery of safe and cost-effective medicines to the patient.

There are a number of challenges that the industry faces in order to transition towards more competitive, systematic and efficient manufacturing. Regulatory authorities have recognized the deficiencies of pharmaceutical product manufacturing and aim to enhance process understanding through Quality by Design (QbD) and Process Analytical Technology (PAT) tools. As a result of this current effort to change the mindset in order to mimic the rest of the chemical industry, an additional transition is becoming more and more appealing: production from batch to continuous mode. However, continuous manufacturing requires detailed process understanding in terms of the evolution of all critical material properties as a function of its operating parameters and environmental conditions. Once process knowledge is translated into models, computer aided dynamic simulation tools will allow the design, analysis and optimization of continuous integrated processes.

In this talk I will discuss the work that has been done in my lab towards the development of an integrated platform that will enable the efficient flowsheet simulation and analysis, the assessment of design alternatives, the feasibility analysis of the production line, and the control and optimization of process design and operations.

The developed flowsheet model includes modules for all the necessary unit operations, namely powder feeding, mixing, roller compaction, tablet press and milling integrated to represent a tablet manufacturing line. Models used to represent each unit operation vary from empirical, first-principle or hybrid. Population balance models are developed in order to track the composition and particle size changes throughout complex powder processes dynamically. The developed flowsheet simulation is used to predict the propagation of upstream disturbances to final product quality, the assessment of recycle stream benefits, the identification of process integration bottlenecks and evaluation of different control strategies in order to retain the process within its design space. In addition, global dynamic sensitivity analysis is performed to identify critical process parameters not only within each unit operation, but also between different processes. Finally, simulation based optimization techniques enable the identification of the optimal operating conditions, as well as the optimal design sequence which leads to pharmaceutical tablets with desired characteristics. This work aims to merge knowledge, experience, experimental results and modeling tools for developing a dynamic simulation platform that will enable the safe implementation of the transition towards continuous pharmaceutical manufacturing.

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About the speaker

Marianthi Ierapetritou is a Professor in the Department of Chemical and Biochemical Engineering at Rutgers University in Piscataway, New Jersey. She obtained her BS from National Technical University in Athens, Greece, her PhD from Imperial College (London, UK) in 1995 and subsequently completed post-doctoral research at Princeton University (Princeton, NJ) before joining Rutgers University in 1998. Among her accomplishments is the Outstanding Faculty Award this year, the Rutgers Board of Trustees Research Fellowship for Scholarly Excellence, and the prestigious NSF CAREER award.

Marianthi research focuses on the following areas: 1) Process operations; (2) design and synthesis of flexible manufacturing systems; 3) modeling of reactive flow processes; and 4) metabolic engineering. She has published 152 papers and presented in national and international conferences (147 presentations). She was invited to present her work in a number of universities and conferences around the world (47 invitations). She is also a member of AIChE, INFORMS and SIAM and an active participant in the scientific advising committees of ESCAPE 16, 17, 21, 22, 23, PSE 2006, 2009, 2012, FOCAPD 2009, and FOCAPO 2012. In 2008 she was the organizer of the fifth international FOCAPO conference. She is an active educator both in the classroom teaching graduate and undergraduate classes in the Chemical Engineering department and as an advisor currently supervising the Ph.D. of 7 students and 1 postdoctoral fellow. Her research work is supported by federal (NSF, ONR, PRF, EPA, NIH) and industrial support (Pfizer, ExxonMobil, BOC).

Marianthi has been active in CAST division of the AIChE as a program director for the last two years and she was last year elected as a vice chair. In her role as a second vice-chair last year, she initiated an enhancement of the Student travel award to include the Student presentation award, which was implemented with great success. She has also been a chair for the area 10A programming in 2006 and is an elected Trustee of CACHE for the last 7 years where last year was elected as vice president.

Email: marianth@soemail.rutgers.edu

http://sol.rutgers.edu/staff/marianth/