(7bk) Pharmaceutical System Engineering

Authors: 
Singh, R., Rutgers, The State University of New Jersey
Research Interests:

My main research area is process system engineering with focus on continuous pharmaceutical 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.

Process system engineering (PSE) is a very advanced field and has been very successful in solving complex problems of chemical based product manufacturing. However, the particulate systems are still poorly understood and there is different level of complexities involved, therefore new techniques and tools need to be developed for pharmaceutical manufacturing through extensive fundamental and applied research.

Currently, major pharmaceutical industries are shifting toward continuous manufacturing technology 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 solid oral 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. Author’s main research area is pharmaceutical system engineering (PSE). This area of research and education are highly encouraged and supported by pharmaceutical companies, academic institutions, regulatory authority (FDA) and national science foundation (NSF). For example, national science foundation of USA has established a 100 million dollar research center for structured organic particulate systems (C-SOPS) at Rutgers University New Jersey. Furthermore, more than 40 companies are supporting this center economically and providing scientific inputs so that the research outcomes can be directly applied to the companies.

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. Advanced modelling techniques such as PBM, DEM and CFD have been applied for pharmaceutical process modeling. 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 in terms of set point tracking and disturbances rejection ability, robustness, and stability/instability. 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. For the first time, the closed-loop operation of the tablet manufacturing plant using NIR sensor has been demonstrated, which is a significant advancement in pharmaceutical manufacturing as endorsed by the Food and Drug Administration (FDA) and other regulatory authorities as part of the Quality by Design (QbD) paradigm. For the first time NIR has been applied for real time monitoring of powder bulk density. Feedforward control system has been integrated with feedback control system to take proactive mitigation actions on raw materials and process variability. A systematic generic framework including the methods and tools through which the cost and profit can be estimated and the Dynamic Real Time Optimization (DRTO) can be integrated with hybrid control system has been also developed. The integrated DRTO provides the optimal operational set points for the plant control system in real time optimizing an objective function. DRTO integrated with hybrid control strategy ensures the maximum possible profit irrespective of the market demand fluctuations.

Presently, I am working a research assistant professor at Department of Chemical and Biochemical Engineering of Rutgers University and currently managing and leading ten projects funded by NSF, industries and regulator with total grants exceeding 18 million USD. I was involved in proposal writing of these projects and I am PI/Co-PI of some of these projects. Prior to this, I worked in a large scale European pharmaceutical project (F3 Factory project), which involves 25 partners from industry and Academia; where my responsibility was to manage and lead the DTU’s parts of the F3 Factory project and also to coordinate with the other partners associated with it. My doctoral research work, done at Department of Chemical and Biochemical Engineering, Technical University of Denmark, has been awarded for prestigious “EFCE Excellence Award 2010”, given in Recognition of an Outstanding PhD Thesis, from European Federation of Chemical Engineering. I have exemplary academic records, previous teaching experiences, and an established trail of valued research accreditations’. I have published more than 48 scientific articles, wrote 10 book chapters and presented in more than 90 international conferences. I have edited one book on pharmaceutical system engineering to be published by Elsevier. I am actively serving as a conference session chair, guest editor of Journal, manuscripts reviewer and bachelor, master and PhD projects supervisor.

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. In my department, I am a lead organizer of postdoctoral training program with the aim of building highly skilled workforce for industry and academia. I developed two online course modules 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. I am especially interested to teach courses related to process control, process modeling and simulation, process monitoring, chemical reaction engineering, process and tool integration and pharmaceuticals. If needed then I can develop new courses based on my research outcomes.

Grants: Extensive experience in funding proposals writing. Wrote several grants proposals for national science foundation (NSF), FDA, and pharmaceutical industries. 11 projects with total grant more than 18 million USD got funded.

Publications: Scientific articles (48); Book chapters (10); International conference presentations (90); Edited Book (1), Invited industrial/academic lectures (>8); Workshops (5); Thesis (3); Supervised Thesis (1 completed + 4 on going); Citations>656, h-index>15, i10-index >17.

Activities in AIChE 2017 conference

Session chair/co-chair

1. Co-chair: Advances in process control (35660: 10/29/2017, 3.30 - 6.00 PM, 103 E).

2. Co-chair: Dynamic simulation and optimization (35672: 11/01/2017, 3.15 - 5.45 PM, 103 E)

3. Chair: Big Data in Process Modeling, Estimation and Control (36339: 11/02/2017, 8.00-10.30 AM, 103 F).

4. Chair: Integrated Product and Process Design (35676: 11/02/2017, 8.00 - 10.30 AM, 103 C)

5. Chair: Economics and Process Control (35674: 11/02/2017, 12.30 – 3.00 PM, 103 C)

Presenter (Oral presentations)

1. Singh, R., Muzzio, F. J, Ierapetritou, M., Ramachandran, R. (2017). Advanced model predictive control of powder level in continuous pharmaceutical manufacturing pilot-plant. Oral presentation at AIChE annual meeting, Minneapolis, MN, USA, 29 October – 3 November. Paper 492410: 11/03/2017, 10.05-10.30 AM, 101E.

2. Singh, R., Muzzio, F. J, Ierapetritou, M., Ramachandran, R. (2017). Integrated control and data management system for continuous pharmaceutical manufacturing process. Oral presentation at AIChE annual meeting, Minneapolis, MN, USA, 29 October – 3 November. Paper: 493080: 10/31/2017, 5.05-5.27 PM, 203 A/B & 205 A/B.

Co-author

3. Maeda, J., Escotet-Espinoza, MS, Singh, R., Ierapetritou, M. (2017). Real-time monitoring and control of API concentration in a tablet press for continuous manufacturing of tablets. Oral presentation at AIChE annual meeting, Minneapolis, MN, USA, 29 October – 3 November. Paper 496960: 10/31/2017, 2:42-3:04, 204 A/B.

4. Román-Ospino, A. D., Oka, S., Mogthadernejad, S., Escotet-Espinoza, M. S., Singh, R., Ramachandran, R., Ierapetritou, M., Muzzio, F. J. (2017). Residence time distribution and segregation studies trough real time measurements by near infrared spectroscopy. Oral presentation at AIChE annual meeting, Minneapolis, MN, USA, 29 October – 3 November. Paper 498490: 11/01/2017, 12.35 - 12.55 PM, 201 A/B.

5. Shah, A., Ramachandran, R., Singh, R. (2017). Moving horizon based real time optimization and hybrid control of continuous pharmaceutical manufacturing process. Oral presentation at AIChE annual meeting, Minneapolis, MN, USA, 29 October – 3 November. Paper 499020: 10/31/2017, 1:58-2.20 PM, 203 A/B & 205 A/B.

Selected references

1. Haas, N. T., Ierapetritou, M., Singh, R. (2017). Journal of Pharmaceutical Innovation, 12(2), 110-123.

2. Ierapetritou, M., Escotet-Espinoza, M. S., Singh, R. (2017). Process Simulation and control for continuous pharmaceutical manufacturing of solid drug products. Chapter 2 of book “Continuous manufacturing of pharmaceuticals” edited by Peter Kleinebudde, Johannes Khinast and Jukka Rantanen. Publisher: Wiley-VCH, pp 33-106.

3. Oka, S, Escotet-Espinoza, M. S., Singh, R., Scicolone, J., Hausner, D., Ierapetritou, M., Muzzio, F. (2017). Design of an integrated continuous manufacturing system. Chapter 12 of book “Continuous manufacturing of pharmaceuticals” edited by Peter Kleinebudde, Johannes Khinast and Jukka Rantanen. Publisher: Wiley-VCH, pp 405-446.

4. Román-Ospino, A. D., Singh, R., Ierapetritou, M., Ramachandran, R. Méndez, R., Ortega, C., Muzzio, F. J., Romañach, R. J. (2016). International Journal of Pharmaceutics, 512 (1), 61-74. http://dx.doi.org/10.1016/j.ijpharm.2016.08.029

5. Wu, S., Panikar, S. S., Singh; R., Zhang, J., Donepudi, A., Glasser, B., Ramachandran, R. (2016). Advanced Powder Technology, 27 (4), 1115-1127.

6. Singh, R., et al. (2015). International Journal of Pharmaceutics, 495, 612-625.

7. Singh, R., et al. (2015). PROCESSES Journal, 3, 339-356.

8. Singh, R., et al. (2015). Journal of Pharmaceutical Innovation, 10 (3), 233-253.

9. Simon, L. L., .. Singh, R., et al. (2015). Organic Process Research & Development, 19, 3-62.

10. Singh, R., et al. (2014). International Journal of Pharmaceutics, 473, 38–54.

11. Singh, R., et al. (2014). Computers & Chemical Engineering Journal, 66, 186-200.

12. Singh, R., et al. (2014). Journal of Pharmaceutical Innovation, 9, 16-37.

13. Sen, M., Barrasso, D., Singh, R., et al. (2014). Processes Journal, 2(1), 89-111.

14. Sen, M., Singh, R., et al. (2014). Journal of Pharmaceutical Innovation, 9, 65-81.

15. Sen, M., Singh, R., et al. (2014). PROCESSES Journal, 2, 392-418; doi:10.3390/pr2020392.

16. Sen, M., Chaudhury, A., Singh, R., et al. (2014). American Journal of Modern Chemical Engineering, 1, 13-29.

17. Singh, R., et al. (2014). Advanced Control of continuous pharmaceutical tablet manufacturing processes. Book chapter 7, Publisher: Humana Press, ISBN: 978-1-4939-2995-5, 191 – 223.

18. Singh, R., et al. (2013). European Journal of Pharmaceutics and Biopharmaceutics, 85(3), Part B, 1164-1182.

19. Singh, R., et al. (2013). Computers & Chemical Engineering Journal, 58, 344 - 368.

20. Sen, M., Dubey, A., Singh, R., et al. (2013). Journal of Powder Technology, http://dx.doi.org/10.1155/2013/843784.

21. Sen, M., Chaudhury, A., Singh, R., et al. (2013). International Journal of Pharmaceutics, 445 (1-2), 29-38.

22. Sen, M., Rogers, A., Singh, R., et al. (2013). Chemical Engineering Science, 102, 56 – 66.

23. Singh, R., et al. (2012). International Journal of Pharmaceutics, 438 (1-2), 307-326.

24. Sen, M., Singh, R., et al. (2012). Chemical Engineering Science, 18, 349-360.

25. Samad, N. A. F. A., Singh, R., et al. (2011). Computers & Chemical Engineering Journal, 35(5), 828-843.

26. Singh, R., et al. (2011). Process and Product Modelling: A case study approach. Book chapters 12.2-12.6, Publisher: Elsevier, pp 380-430.

27. Singh, R., et al. (2010). Computers & Chemical Engineering Journal, 34(7), 1108-1136.

28. Singh, R., et al. (2010). Computers & Chemical Engineering Journal, 34(7), 1137-1154.

29. Singh, R., et al. (2009). Computers & Chemical Engineering Journal, 33(1), 22-42.

30. Singh, R. (2017). Advanced model predictive control of a novel continuous pharmaceutical manufacturing pilot-plant. Pharma, https://www.pharmafocusasia.com/. Accepted.

31. Singh, R., Muzzio, F., Ierapetritou, M., Ramachandran, R. (2016). Computer Aided Chemical Engineering, 38, 1473-1478.

32. Singh, R., Zhang, J., Ierapetritou, M., Ramachandran, R. (2015). European Pharmaceutical Review, 20(6), 37-41.

33. Sen, M., Singh, R., Ramachandran, R. (2015). The Medicine Maker, February, 05, 42-45.

34. Escotet-Espinoza, M. S., Singh, R., Sen, M., O’Connor, T., Lee, S., Chatterjee, S., Ramachandran, R., Ierapetritou, M., Muzzio, F. (2015). Pharmaceutical Technology 39 (4), 34-42.

35. Singh, R., Muzzio, F., Ierapetritou, M., Ramachandran, R. (2015). Computer Aided Chemical Engineering, 37, 2183 - 2188.

36. Karry, K. M., Singh, R., Muzzio, F. J. (2015). American Pharmaceutical Review, 18(4), 64 - 67.

37. Singh, R., Ierapetritou, M., Ramachandran, R. (2015). European Pharmaceutical Review 20(2), 76-80.

38. Singh, R., et al. (2013). Computer Aided Chemical Engineering, 32, 757-762.

39. Muzzio, F., Singh, R., et al. (2013). Pharmaceutical Technology magazine, 37(6), 40-41, 77.

40. Singh, R., et al. (2013). BioPharma magazine Asia, 2(5), 18-25.

41. Singh, R., et al. (2012). Computer Aided Chemical Engineering, 31, 715-719.

42. Singh, R., et al. (2012). PharmPro Magazine, Pharmaceutical Processing, 27(6), 22-25.

43. Singh, R., et al. (2012). European Compliance Academic (ECE), http://www.gmp-compliance.org/ecanl_503_0_news_3268_7248_n.html.

44. Samad, N. A. F. A., Singh, R., Sin, G., Gernaey, K. V., Gani, R. (2011). IEEE, 1-6.

45. Gani, R., Singh, R. (2011). GEN: Genetic Engineering & Biotechnology News, 31(6), 40-41.

46. Samad, N. A. F. A., Singh, R., et al. (2010). Computer Aided Chemical Engineering, 28, 613-618.

47. Singh, R., et al. (2010). Computer Aided Chemical Engineering, 29, 291-295.

48. Samad, N. A. F. A., Singh, R., et al. (2010). Computer Aided Chemical Engineering, 29, 86-90.

49. Singh, R., et al. (2009). Computer Aided Chemical Engineering, 26, 321-326.

50. Singh, R., et al. (2008). Computer Aided Chemical Engineering, 25, 423-428.

Contact: Email: ravendra.singh@rutgers.edu. Website: http://ravendrasingh.wixsite.com/ppse

NSF Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA
Email: ravendra.singh@rutgers.edu