© 2019

The Science and Regulations of Naturally Derived Complex Drugs

  • Ram Sasisekharan
  • Sau L. Lee
  • Amy Rosenberg
  • Larry A. Walker

Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 32)

Table of contents

  1. Front Matter
    Pages i-vi
  2. Larisa C. Wu, Andre Raw, Werner Knöss, Michael Smith, Wei-Dong Zhang, Y. S. Bedi et al.
    Pages 17-44
  3. Tai-Ping Fan, Yingli Zhu, Christine Leon, Gerhard Franz, Andreas Bender, Xiaohui Zheng
    Pages 59-77
  4. Marco Guerrini, Timothy R. Rudd, Edwin A. Yates
    Pages 115-137
  5. Sarah Rogstad, Michael Boyne, Ashley Ruth
    Pages 139-155
  6. Suman Chandra, Donald Stanford, Edward Fletcher, Larry A. Walker
    Pages 175-190
  7. Yuanyuan Zhu, Fuming Zhang, Robert J. Linhardt
    Pages 191-206
  8. Daniel S. Marsman, Amy L. Roe
    Pages 207-217
  9. Roshni Rao, Daniela Verthelyi
    Pages 219-244
  10. Jinhui Dou, Julie Beitz, Robert Temple
    Pages 245-264
  11. Melissa Jacob, Xing-Cong Li, Larry A. Walker
    Pages 297-310
  12. Rahul Raman, Zachary Shriver, Thomas Clark, Ram Sasisekharan
    Pages 311-327
  13. Back Matter
    Pages 329-331

About this book


This volume in the AAPS Advances series covers various quality, safety and clinical aspects of drug development that are relevant to new and/or generic drugs containing a complex mixture of molecules. Specific topics discussed include: raw materials sourcing; manufacturing controls; characterization; identification of critical product quality components and attributes; identification of impurities, particularly as they bear on toxicity and immunogenicity; clinical trial study design considerations, and the regulatory science applications to development of such complex mixtures. Complex mixtures are challenging to characterize and analyze using standard methods. Further challenges extend throughout the product development cycle from raw material control to clinical study design.  The regulatory landscape is rapidly changing as new types of complex mixtures are introduced into clinical trials and to the market (e.g., traditional Chinese medicines and medical marijuana products), while older products are facing generic competition for the first time (e.g., enoxaparin). The future outlook for complex generic drug products, as opposed to the more commonly developed targeted single agent drug products is not clear.  The risks pertaining to lack of a full understanding of raw material control, process and controls in manufacture, as well as characterization of a complex mixture were seen vividly during the heparin crisis of 2008. As such powerful lessons have been learned about the regulatory science specific to complex products. The Science and Regulations of Naturally Derived Complex Drugs addresses the interests among industry, academics, and government on the issues surrounding the future development of mixtures for medicinal use.


complex mixtures toxicity immunogenicity drug manufacturing single agent drug plant-derived natural products

Editors and affiliations

  • Ram Sasisekharan
    • 1
  • Sau L. Lee
    • 2
  • Amy Rosenberg
    • 3
  • Larry A. Walker
    • 4
  1. 1.Department of Biological EngineeringKoch Institute of Integrative Cancer Research, Massachusetts Institute of TechnologyCambridgeUSA
  2. 2.Office of Pharmaceutical Quality, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  3. 3.Office of Pharmaceutical Quality, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  4. 4.Director Emeritus, National Center for Natural Products Research, School of PharmacyUniversity of MississippiOxfordUSA

About the editors

Amy Rosenberg received her medical degree from Albert Einstein College of Medicine and is Board Certified in Internal Medicine. She was a post-doctoral fellow in Al Singer’s Laboratory in the NCI before coming to CBER, FDA in 1988. She became Director of the Division of Therapeutic Proteins, CBER/CDER in 2000. Her division (now DBRR3 in the Office of Biotechnology Products, CDER) regulates diverse protein therapeutics, including monoclonal antibodies and fusion proteins, enzyme replacement therapies, hematologic and somatic cell growth factors, and immunomodulatory agents. She has been a driving force in risk evaluation and mitigation pertaining to the immunogenicity of therapeutic proteins (Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products) and in the elucidation and implementation of immune tolerance induction protocols in clinical settings. She previously co-edited the AAPS/Springer Book “Biobetters: Protein Engineering to Approach the Curative”. 

Larry A. Walker is Director Emeritus of the National Center for Natural Products Research (NCNPR) at the University of Mississippi, having retired at the end of 2016 after 15 years as director.  He has been a member of the faculty of the School of Pharmacy at Ole Miss for 37 years.  He took his undergraduate pharmacy training at Mercer University (1975), and his doctorate in Pharmacology from Vanderbilt University School of Medicine in 1979, He has worked for much of his career on natural products drug discovery, pharmacology, toxicology and metabolism. Dr. Walker is a co-author of more than 200 papers in peer-reviewed journals in pharmacology, toxicology, and natural products discovery and development.  He is a member of the American Society of Pharmacognosy, American Society of Pharmacology and Experimental Therapeutics, American Society of Microbiology, American Society of Tropical Medicine and Hygiene, American Association of Pharmaceutical Scientists. He has served on editorial boards of the Journal of Pharmacology and Experimental Therapeutics, Phytotherapy Research, and was the editor-in-chief of the Journal of Biomolecular Screening from 1999-2007. He received the University’s second Distinguished Research and Creative Achievement Award in 2009, and the School of Pharmacy’s Researcher of the Year Award in 2003.  He works presently on development of strategic partnerships for the University of Mississippi, and as a senior science advisor with ElSohly Laboratories, Inc. in Oxford, MS, and consultant for pharmaceutical and botanical supplement industries.  




Bibliographic information

  • Book Title The Science and Regulations of Naturally Derived Complex Drugs
  • Editors Ram Sasisekharan
    Sau L. Lee
    Amy Rosenberg
    Larry A. Walker
  • Series Title AAPS Advances in the Pharmaceutical Sciences Series
  • Series Abbreviated Title AAPS Adv. Pharmaceutical Sciences
  • DOI
  • Copyright Information American Association of Pharmaceutical Scientists 2019
  • Publisher Name Springer, Cham
  • eBook Packages Biomedical and Life Sciences Biomedical and Life Sciences (R0)
  • Hardcover ISBN 978-3-030-11750-4
  • eBook ISBN 978-3-030-11751-1
  • Series ISSN 2210-7371
  • Series E-ISSN 2210-738X
  • Edition Number 1
  • Number of Pages VI, 331
  • Number of Illustrations 20 b/w illustrations, 41 illustrations in colour
  • Topics Pharmaceutical Sciences/Technology
  • Buy this book on publisher's site