Table of Contents

Section I: Design and Control: Continuous Manufacturing of Small Molecule Drug Substances and Products

1. A Survey of Continuous API Syntheses: Insights at the Interface of Chemistry and Chemical Engineering.

2. Development of Continuous Pharmaceutical Crystallization.

3. Residence Time Distribution in Continuous Manufacturing.

4. Powder Electrostatics in Continuous Pharmaceutical Manufacturing.

5. Continuous Impregnation Processes

6. Leveraging a mini-batch wise continuous direct compression (CDC) approach to optimize efficiency in process development, on-demand manufacturing and continuous process verification (CPV).

7. Predictive In-Vitro Dissolution for Real-time Release Test (RTRT) for Continuous Manufacturing Process on Drug Product.

Section II: Design and Control: Continuous Manufacturing of Large Molecule Drug Substances and Products

8. Continuous Manufacturing of Biologics Drug Products: Challenges of Implementing Innovation in cGMP.

9. Modernizing manufacturing of parenteral products: from batch to continuous lyophilization.

Section III: Process Analytical Technologies

10. Near-infrared Spectroscopy as Process Analytical Technology in Continuous Solid Dosage Form Manufacturing.

11. The Role of Process Analytical Technology (PAT) in Biologics Development.

12. Moving to Manufacturing – Lessons Learned in A Career in Process Analytical Technology.

Section IV: Modeling, Design Space, and Future Outlook

13. End-to-end Design Space for Continuous Manufacturing of pharmaceuticals: Understanding interactions across integrated continuous operations.

14. Control strategies in continuous direct compression.

15. Framework for the validation of mechanistic and hybrid models as Process Analytical tools in the pharmaceutical Industry.

16. Understanding the History of Continuous Manufacturing in Other industries to Guide Future Development in Pharmaceuticals.

17. Process Systems Engineering Tools towards Digital Twins of Pharmaceutical Continuous Manufacturing Processes

About the Author

Dr. Ajit Narang

Ajit Narang works for the Small Molecule Pharmaceutical Sciences Department of Genentech, Inc., in South San Francisco, CA responsible for the pharmaceutical development of new chemical entities through preclinical and early clinical stages.

He holds about two decades of pharmaceutical industry experience in the development and commercialization of oral and parenteral dosage forms and drug delivery platforms across preclinical through commercialization stages for both small and large molecule drugs. In addition to Genentech, he has worked for Bristol-Myers Squibb, Co., in New Brunswick, NJ; Ranbaxy Research Labs (currently a subsidiary of Daiichi Sankyo, Japan) in Gurgaon, India; and Morton Grove Pharmaceuticals (currently, Wockhardt USA) in Gurnee, IL. He holds undergraduate Pharmacy degree from the University of Delhi, India and graduate degrees in Pharmaceutics from the Banaras Hindu University, India and the University of Tennessee Health Science Center (UTHSC) in Memphis, TN.

Dr. Ajit has contributed to several preclinical, clinical, and commercialized drug products including NDAs, ANDAs, and 505B2s. He is credited with 54 peer-reviewed articles; 22 editorial contributions; 5 books; 10 patent applications; 47 invited talks; and 85 presentations at various scientific meetings. His current research interests are translation from preclinical to clinical and commercial drug product design; incorporation of QbD elements in drug product development; and mechanistic understanding of the role of material properties on product performance.

Dr. Atul Dubey

Atul Dubey is the Director of Pharmaceutical Continuous Manufacturing (PCM) at the United States Pharmacopeial Convention (USP). Headquartered in Rockville, MD, USA, USP is committed to global public health and quality of medicines for 200 years.

At USP, his group is focused on supporting the ongoing adoption of CM through education programs, public standards and collaborative work for standardization and harmonization. Atul is involved in the development of training curriculum for industry personnel to bring about technological awareness about CM. He is also a part of the expert working group (EWG) for drafting the ICH Q13 guideline for CM. He collaborates with various stakeholders to carry out scientific research in various aspects of CM.

After earning his PhD degree in Mechanical Engineering, he carried out research in pharmaceutical manufacturing processes using modeling and simulation to understand and optimize unit operations such as continuous mixing, granulation and pan coating. He has authored several journal articles and book chapters in the domain.

After his stint at the C-SOPS (Rutgers University) he moved to India where he worked as a consultant to pharmaceutical companies, as well as a Sr. Scientist in the Aditya Birla Group in India. With a strong motivation to facilitate the access to quality medicines worldwide, he is interested in applied R&D towards development of new standards, training and guidelines for CM.