The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and the practice of medicine and regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology and combination product fields) in a concise, abbreviated manner for all the major world market countries.
As when teaching on the subject of drug safety evaluation, the approach I have taken here is to first address the broadest scope "general case" for the regulatory nonclinical safety evaluation by ICH and ISO adhering countries, then to branch out to cover the differences in requirements associated with specific therapeutic areas (such as oncology), major routes of administration (with oral being the general case, other routes starting with parenteral, dermal, and inhalation are addressed). Large molecules biotechnology products are then considered, followed by special courses of product marketing approval, and finally the remaining national differences.
As will be seen, even for ICH countries there is (in mid-2009) continuing modification of the basic M3 guidance for small molecule drugs (R2 being released in step 2 in August of 2008) and S6 (for protein therapeutics) series guidances, and it is not expected that the situation captured and guidance offered in this volume will long withstand the need for regular updating. The drivers for such need will be new science, new ways of using therapeutic products, new concerns, and the influence of new major markets. Also, there will be new real or perceived drug safety concerns. Much of these effects translate to "regulatory creep" (unpublished changes in practice and expectations by different parts of regulatory agencies that proceed in an undocumented fashion almost from the moment a new regulatory guidance comes out), and tracking these changes in a published text approaches is a hopeless task.
It is also not intended that this volume addresses the specifics of study design and interpretation. There are several current texts which perform these tasks well (Gad and McCord, 2008 for devices, Gad 2009 for drugs, and Cavanaro 2008 specifically for biotechnology products) and in the details required. Adequate references are provided to guide the reader (user) of this volume directly to the details required.
- The Author -
Contents
Introduction to Safety Assessment in Drug and Medical
- Device Development
- Global Pharmaceutical and Medical Device Markets
- Legislative Considerations
- Regulations: Human Pharmaceuticals
- Special Cases: Biologics and Combination Products
- Strategies for Development Drugs
- What You Need to Know to Start
- Devices
- References
Drugs: The General Case
- IND/FIM Enabling
- To Support Continued Clinical Development
- To Support Marketing Approval
- Subset: Special or Hazard Studies
- ICH Requirements: The Global General Case
- The First Rule
- References
IND-Enabling Toxicology Programs
- Toxicity Testing: Traditional Pharmaceuticals
- Common Mistakes
- Toxicity Testing of Pharmaceuticals: The General Approach
- Developmental and Reproductive Toxicity Studies
- Genetic Toxicity Assessment
- Safety Pharmacology Studies
- Toxicity Testing: Biotechnology Products
- Toxicology Testing: Special Cases
- Oral Contraceptives
- Life-Threatening Diseases (Compassionate Use)
- Antibiotics and Anti-Infectives
- Special Cases
- Direct to FIM Trials: Imaging Agents
- Gene Therapy
- Cellular (Stem Cell) Therapy
- Excipients
- Pediatric Claims and Juvenile Animal Studies
- Exploratory INDs
- References
Nonclinical Safety Evaluation Studies Conducted to Support
- Continued Clinical Development
- Repeat Dose Toxicity
- Developmental and Reproductive Toxicology (DART)
- Impurities, Degradants, and Residual Solvents
- Impurities
- Residual Solvents
- Extractables and Leachables
- Residual Metals and Metal Catalysts
- Safety Assessment of Metabolites (Metabolites in Safety Testing – MIST)
- Local Tissue Tolerance
- Nonclinical Abuse Liability
- Drug Registration in Japan
- Drugs in China; Pharmacology and Toxicology Study Information
- References
Supporting Marketing Applications
- Non-Traditional (Other than NDA/505b (1)) Approval Routes and Requirements
- Carcinogenicity
- Pre- and Post-natal Development
- Pediatric Population Studies
- Special Cases
- References
Special Therapeutic Category and Route of Administration Cases
- Specific Therapeutic Classes
- Oncology Drugs
- Activity Profile and Mechanism of Action
- Mechanism(s) of Resistance
- Special Considerations for Biopharmaceutical Studies
- Nonclinical Data Evaluation to Support Clinical Trial Design
- Start Dose for First Administration in Human
- Dose Escalation and the Highest Dose in a Clinical Trial
- Duration and Schedule of Toxicology Studies to Support
- Initial Clinical Trials
- Duration of Toxicology Studies to Support Continued Development
- Combinations of Pharmaceuticals
- Studies in Pediatric Populations
- Special Considerations for Biologics
- Conjugated Agents
- Liposomal Formulated Products
- Evaluation of Drug Metabolites
- Evaluation of Impurities
- Other Life-Threatening Chronic Diseases
- Imaging Agents
- Antibiotics
- Vaccines
- Routes and Regimens Other than Oral and Daily
- Combination Products
- Historical Background
- References
Device Safety Evaluation
- Introduction
- Regulatory Definition of Medical Devices
- International Standards Organization
- Topical Devices
- Blood Path Direct
- Japan
- Other Regulatory Guidances
- Biological Tests
- References
About the Author
Appendix A Notable Regulatory Internet Addresses
Index
About the Author
Shayne C. Gad, B.S. (Whittier College, Chemistry and Biology, 1970) and Ph.D. in Pharmacology/Toxicology (Texas, 1977) DABT, ATS, is the principal of Gad Consulting Services, a 17-year-old consulting firm with 6 employees and more than 450 clients (including 120 pharmaceutical companies in the USA and 50 overseas). Prior to this, he served in director-level and above positions at Searle, Synergen, and Becton Dickinson. He has published 39 books and more than 350 chapters, articles, and abstracts in the fields of toxicology, statistics, pharmacology, drug development, and safety assessment. He has more than 33 years of broad-based experience in toxicology, drug and device development, statistics, and risk assessment.
He has specific expertise in neurotoxicology, in vitro methods, cardiovascular toxicology, inhalation toxicology, immunotoxicology, and genotoxicology. Past President of the American College of Toxicology, the Roundtable of Toxicology Consultants and three of SOT’s specialty sections, and recipient of the American College of Toxicology Lifetime Contribution Award. He has direct involvement in the preparation of INDs (90 successfully to date), NDA, PLA, ANDA, 510(k), IDE, CTD, clinical data bases for phase 1 and 2 studies, and PMAs. He has consulted for FDA, EPA, and NIH, and has trained reviewers and has been an expert witness for FDA. He has also conducted the triennial toxicology salary survey as a service to the profession for the last 22 years.
Product Details
- Hardcover: 140 pages
- Publisher: Springer; 1st Edition (2011)
- Language: English
- ISBN-10: 1441974482
- ISBN-13: 978-1441974488
- Product Dimensions: 9.2 x 6.1 x 0.5 inches
List Price: $139.00