Safety Evaluation of Pharmaceuticals and Medical Devices: International Regulatory Guidelines PDF
Preview Safety Evaluation of Pharmaceuticals and Medical Devices: International Regulatory Guidelines
Safety Evaluation of Pharmaceuticals and Medical Devices wwwwwww Shayne C. Gad Safety Evaluation of Pharmaceuticals and Medical Devices International Regulatory Guidelines Shayne C. Gad Gad Consulting Services Cary, NC USA [email protected] ISBN 978-1-4419-7448-8 e-ISBN 978-1-4419-7449-5 DOI 10.1007/978-1-4419-7449-5 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2010937640 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connec- tion with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Photo credit: Peter Atkins - fotolia.com Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) To my baby brother, Scott Michael Gad (1950-2010) wwwwwww Preface 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 regula- tion 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 combina- tion 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 modi- fication 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 prac- tice and expectations by different parts of regulatory agencies that proceed in an * Alder, S. and Zbinden, Z. (1988) National and International Drug Safety Guidelines, M.T.C. Verlay Zollikon, Zollikon, Switzerland. vii viii Preface 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 refer- ences are provided to guide the reader (user) of this volume directly to the details required. Cary, North Carolina Shayne C. Gad Gad Consulting Services Contents Introduction to Safety Assessment in Drug and Medical Device Development ........................................................................................ 1 Global Pharmaceutical and Medical Device Markets .................................. 2 Legislative Considerations ........................................................................... 6 Regulations: Human Pharmaceuticals .......................................................... 8 Special Cases: Biologics and Combination Products................................... 10 Strategies for Development .......................................................................... 10 Drugs ....................................................................................................... 10 What You Need to Know to Start ................................................................. 12 Devices ......................................................................................................... 13 References .................................................................................................... 15 Drugs: The General Case ............................................................................... 17 IND/FIM Enabling ....................................................................................... 19 To Support Continued Clinical Development .............................................. 19 To Support Marketing Approval .................................................................. 20 Subset: Special or Hazard Studies ........................................................... 20 ICH Requirements: The Global General Case ........................................ 21 The First Rule .......................................................................................... 21 References .................................................................................................... 21 IND-Enabling Toxicology Programs ............................................................. 23 Toxicity Testing: Traditional Pharmaceuticals ............................................. 26 Common Mistakes ....................................................................................... 27 Toxicity Testing of Pharmaceuticals: The General Approach ..................... 29 Developmental and Reproductive Toxicity Studies ..................................... 30 Genetic Toxicity Assessment ....................................................................... 31 Safety Pharmacology Studies ....................................................................... 33 Toxicity Testing: Biotechnology Products ................................................... 34 ix
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