The Science and Regulations of Naturally Derived Complex Drugs

Description

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. Front Matter ....Pages i-vi Evolving Challenges in Developing Naturally-Derived Complex Mixtures into Drugs: U.S. Experience and Perspective (Adam C. Fisher, Sau L. Lee)....Pages 1-15 Regulatory Landscapes for Approval of Naturally-Derived Complex Mixture Drugs (Larisa C. Wu, Andre Raw, Werner Knöss, Michael Smith, Wei-Dong Zhang, Y. S. Bedi et al.)....Pages 17-44 Complex Natural Product Heparin: Biosynthesis, Biology, and Application via Synthetic Heparins (Po-Hung Hsieh, Jian Liu)....Pages 45-58 Traditional Chinese Medicine Herbal Drugs: From Heritage to Future Developments (Tai-Ping Fan, Yingli Zhu, Christine Leon, Gerhard Franz, Andreas Bender, Xiaohui Zheng)....Pages 59-77 Analytics on Farm Dust Extract for Development of Novel Strategies to Prevent Asthma and Allergic Disease (Nathan Stebbins, Erika von Mutius, Ram Sasisekharan)....Pages 79-90 Analytical Tools for Physicochemical Characterization and Fingerprinting (David A. Keire)....Pages 91-113 NMR in the Characterization of Complex Mixture Drugs (Marco Guerrini, Timothy R. Rudd, Edwin A. Yates)....Pages 115-137 Mass Spectrometry in the Characterization of Complex Drugs (Sarah Rogstad, Michael Boyne, Ashley Ruth)....Pages 139-155 Scientific Considerations in the Approval of Complex Generics (Andre S. Raw, Larisa Wu)....Pages 157-173 Raw Materials Production and Manufacturing Process Control Strategies (Suman Chandra, Donald Stanford, Edward Fletcher, Larry A. Walker)....Pages 175-190 Heparin Contamination and Issues Related to Raw Materials and Controls (Yuanyuan Zhu, Fuming Zhang, Robert J. Linhardt)....Pages 191-206 Pharmacology and Toxicology Concerns of Impurities (Daniel S. Marsman, Amy L. Roe)....Pages 207-217 Immunogenicity Risks for Naturally Derived Complex Drugs (Roshni Rao, Daniela Verthelyi)....Pages 219-244 Development of Plant-Derived Mixtures as Botanical Drugs: Clinical Considerations (Jinhui Dou, Julie Beitz, Robert Temple)....Pages 245-264 A Totality-of-Evidence Approach to Ensuring Therapeutic Consistency of Naturally Derived Complex Mixtures (Sau L. Lee)....Pages 265-270 Economic Considerations for Complex Mixture Drugs (Sen Lin)....Pages 271-295 Drug Discovery from Complex Mixtures: Serendipity, Screening, and Characterization (Melissa Jacob, Xing-Cong Li, Larry A. Walker)....Pages 297-310 Integrated Approach for Characterization of Highly Heterogeneous Drugs (Rahul Raman, Zachary Shriver, Thomas Clark, Ram Sasisekharan)....Pages 311-327 Back Matter ....Pages 329-331