(6ib) Process System Engineering (PSE): Continuous Pharmaceutical and Bio-Pharmaceutical Manufacturing

Authors: 
Singh, R., Rutgers, The State University of New Jersey
My main research focus is process system engineering (PSE) and current application domain is continuous pharmaceutical and bio-pharmaceutical manufacturing. However, the PSE methods and tools that I developed are generic and can be applied to any manufacturing industries. Currently, pharmaceutical and bio-pharmaceutical industries are going through paradigm shift from conventional batch to continuous manufacturing process in which PSE can play a very significant role. Furthermore, there is a need of advanced modular continuous manufacturing platform technology for fast and robust development of pharmaceutical and bio-pharmaceutical products. Master formulations, process models, standardized sensing and control architecture, superior automation and novel methods and tools need to be developed to enable platform technology. This area of research and education are highly encouraged and supported by pharmaceutical and biopharmaceutical companies, academic institutions, regulatory authority (FDA) and national science foundation (NSF).

In this work, a scientific foundation for the optimal design, optimization and control of the modular continuous process involving structured organic particulate systems has been developed. The mathematical models for continuous manufacturing of active pharmaceutical ingredients and final product tablet, has been developed for virtual experimentation and applied for plant design, optimization and control. The developed continuous tablet manufacturing plant and process model has been adapted by several pharmaceutical companies. A flexible monitoring and control system incorporating different PAT techniques and tools and control strategies for continuous pharmaceutical manufacturing process has been designed and implemented to Rutgers pilot-plant. Different control strategies such as PID, PID coupled with dead time compensator, and MPC has been compared and evaluated practically for pharmaceutical process control. A new hybrid MPC-PID control strategy has been developed and implemented into the pharmaceutical tablet manufacturing plant and its performance has been found better than the other control strategies. A novel RTD based control system has been developed and implemented into the pilot-plant. Novel sensing methods have been developed for real time measurements of powder density and powder level. Feedforward control system has been integrated with feedback control system to take proactive mitigation actions on raw materials and process variability. A moving horizon based Dynamic Real Time Optimization (MH-DRTO) method has been also developed to provides the optimal operational set points for the control system. The developed control architecture has been implemented into pilot-plant.

Biosketch: I am working as an Assistant Research Professor at C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers University, NJ, USA. I am the recipient of prestigious EFCE Excellence Award given in Recognition of an Outstanding PhD Thesis, from European Federation of Chemical Engineering. I received several grants as a PI/Co-PI and have well stablished research group. I have published more than 60 scientific research papers, written 12 book chapters, presented at over 95 international conferences and edited one pharmaceutical book published by Elsevier. I am actively serving as a conference session chair, Journal reviewer and editor.

Research Interests: My main research area is process system engineering with focus on continuous pharmaceutical and biopharmaceutical manufacturing. I have contributed significantly in the field of process monitoring and control, process modelling and simulation, optimization, PAT, QbD, new methodology and software tools development.

Teaching Interests: My teaching experience that I acquired serving as a teaching assistant, lecturer, and research assistant professor makes me confidant to develop and teach any courses of chemical and biochemical engineering. The industrial invited crash courses that I have given provide me opportunity to extend my teaching skills to cover more applied courses and to interact with highly experienced scientist and operators from manufacturing companies. I demonstrated my skills to instruct hands-on exercise through several workshops that I conducted. Several training courses that I conducted for industrial and academic participants make me instrumented with additional capability of building highly skilled workforce. I developed two online course modules for FDA where I learn how to develop and give online courses. I have dual ability to teach theoretical as well as practical courses. I am open to teach any courses that your university will assign me. If needed then I can develop new courses based on my research outcomes.

Grants: Extensive experience in funding proposals writing.

(1). 2018 Glaxo Smith Kline (GSK) (granted)

Development of Computational Models for Continuous Tablet Manufacturing

Role: PI. Source: GSK Company. Amount: $539,991 (1st year); Total: $2.5 Million.

(2). 2018 Siemens (granted)

Cyber-physical attack in the Pharmaceutical Manufacturing Process

Role: PI. Source: Siemens Company. Amount: $78,750.

(3). 2018 Diversitech Corporation (granted)

Fluid bed drying trials

Role: PI. Source: Diversitech Company. Amount: $1600.

(4). 2018 Rutgers Global International Travel Grant (granted)

Role: PI. Amount: $750.

(5). 2018 CNH (granted)

Wear prediction and validation with fine particle interaction

Role: Co-PI. Source: CNH Company. Amount: $118608.

(6). 2017 Glaxo Smith Kline (GSK) (granted)

Development of tablet press feed frame RTD model and BU to CU relation

Role: Co-PI. Source: GSK Company. Amount: $150000.

(7). 2017 Grant to stablish international collaboration (granted)

Grants to Support the Initiation of International Collaboration.

Role: Co-PI. Source: Hamburg University of Technology. Amount: €1610.

(8). 2016 Integra Continuous Manufacturing Systems (granted)

Development of sensing and control strategy for direct compaction continuous pharmaceutical tablet manufacturing process. Role: PI. Source: Acumen Company. Amount: $5114.

(9). 2016 Research Council Grant Award (granted)

Development and validation of advanced model predictive feedforward/feedback control strategy for pharmaceutical process. Role: PI. Source: Rutgers. Amount: $3800.

(10). 2018 Food & Drug Administration (FDA) (submitted)

Advanced Bio-manufacturing

Role: Co-PI. Source: FDA. Amount: $1.8 Million

(11). 2018 Food & Drug Administration (FDA) (submitted)

Industry 4.0 Implementation in Continuous Pharmaceutical Manufacturing

Role: Co-PI. Source: FDA. Amount: $3.96 Million

Publications: Scientific articles (59); Book (1); Book chapters (12); International conference presentations (95); Citations>984, h-index>17, i10-index >26.

Activities in AIChE 2018 conference

Session chair/co-chair

  1. Chair: Predictive Control and Optimization II
  2. Chair: Big Data in Chemical and Pharmaceutical Processes
  3. Co-chair: Integrated Product and Process Design.

Oral presentations

  1. Singh, R., Muzzio, F. J. (2018). RTD Based Control System for Continuous Pharmaceutical Manufacturing Process. Oral presentation at AIChE, Pittsburgh, USA, 28 October - 2 November, 2018.
  2. Singh, R. (2018). Implementation of Advanced Process Control System into Continuous Pharmaceutical Manufacturing Pilot-Plant. Oral presentation at AIChE, Pittsburgh, USA, 28 October - 2 November, 2018.

Contact:

Email: ravendra.singh@rutgers.edu, Phone: (001)848-445-4944; Fax: (001)732-445-2581

Websites: http://cbe.rutgers.edu/faculty; http://ravendrasingh.wixsite.com/ppse