Safety Evaluation of Biotechnologically-derived Pharmaceuticals: Facilitating a Scientific Approach PDF
Preview Safety Evaluation of Biotechnologically-derived Pharmaceuticals: Facilitating a Scientific Approach
Safety Evaluation of Biotechnologically-derived Pharmaceuticals: Facilitating a Scientific Approach CMRInternationalWorkshop Series MonitoringforAdverseDrugReactions Editors: S.R. WalkerandA. Goldberg Long-TermAnimalStudies TheirPredictiveValueforMan Editors: S.R. WalkerandAD. Dayan Medicinesand Risk/BenefitDecisions Editor: SR. WalkerandA.W. Asscher QualityofLife:AssessmentandApplication Editors: S.R. WalkerandRM. Rosser InternationalMedicinesRegulations AForwardLookto1992 Editors: SR. WalkerandJ.P. Griffin AnimalToxicityStudies: TheirRelevanceforMan Editors: CE. LumleyandS.R. Walker CreatingtheRight Environmentfor DrugDiscovery Editor: S.R Walker CurrentIssuesinReproductiveandDevelopmentalToxicology CananInternationalGuidelinebeAchieved? Editors: CE. Lumleyand SR. Walker TheCarcinogenicityDebate Editors:JAN. McAuslane, CE LumleyandS.R Walker TheRelevanceofEthnicFactorsintheClinicalEvaluationofMedicines Editors: S.R Walker, C.E. LumleyandJAN. McAuslane ImprovingtheRegulatory ReviewProcess: Industryand Regulatory Initiatives Editors: CE. LumleyandS.R. Walker Improvingthe Regulatory ReviewProcess:AssessingPerformanceand SettingTargets Editors:JAN. McAuslaneand S.R. Walker Workshop Series Safety Evaluation of Biotechnologically-derived Pharmaceuticals: Facilitating a Scientific Approach Ediled by Susan A. Griffiths and Cyndy E. Lumley Centre for Medicines Research International Carshalton, Surrey, UK Proceedings of a CMR IlItemational Workshop held al AslldoWlI Park Hotel, Wych Cross, UK, February 1997 SPRINGER SCIENCE+BUSINESS MEDIA, B.V. A catalogue record for this book is available horn the British Library ISBN 978-94-010-6043-1 ISBN 978-94-011-4876-4 (eBook) DOI 10.1007/978-94-011-4876-4 Copyright © 1998 by Springer Science+Business Media Dordrecht Origina1ly published by Kluwer Academic Publishers in 1998 Softcover reprint ofthe hardcover Ist edition 1998 Ali rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers, Springer Science+ Business Media, B.V. Lasertypeset by Martin Lister Publishing Services, Bolton-le-Sands, Camforth, Lancs. Contents Preface vii Foreword - ProfessorGiuseppeVicari xi Notes onContributorsandChairmen xiii 1 Designingnon-clinicalsafetyevaluationprogrammes: Theviewoftheclinician John Lipani 1 2 Designingnon-clinicalsafetyevaluationprogrammes: Theviewofthetoxicologist Maggie Dempster 7 3 Companystrategiesfor designingnon-clinicalsafety evaluationprogrammes: ResultsofaCMRInternational survey Susan Griffiths 17 4 Influenceofregulatorysystems: AviewpointoftheUS FDAprocess JoyA. Cavagnaro 31 5 Influenceofregulatorysystems: TheEuropeanCPMP perspective Per Sjoberg 39 6 Biotechnologically-derived pharmaceuticalsinJapan: Presentand future prospects Tohru Inoue 51 7 Designingnon-clinicalsafetyevaluationprogrammes for colonystimulatingfactors, growthfactors and hormones: Apersonalview DouglasM. Morton 65 v SafetyEvaluationofBiotechnologically-derivedPharmaceuticals 8 Designingnon-clinicalsafetyevaluationprogrammes for interferonsand interleukins: Apersonal view Grushenka H.I. Wolfgang, Sharon Chen, Martin Giedlin, 79 Rene Braeckmanand DaleJohnson (ThispaperwaspresentedattheWorkshopbyDaleJohnson) 9 Designingnon-clinical safetyevaluationprogrammesfor monoclonal antibodiesfor therapeutic use: Apersonal view PeterBugelski 103 10 Designingnon-clinical safetyevaluationprogrammesfor gene therapy products: Apersonal view James MacDonald, RichardMorrisseyandJames Patrick 115 11 Recommendationsand the way forward 129 12 Designingnon-clinicalsafetyevaluationprogrammesfor colonystimulatingfactors, growthfactors and hormones: Recommendationsand thewayforward Jennifer SimsandFelixdela Iglesia 133 13 Designingnon-clinical safetyevaluationprogrammesfor interferons and interleukins: Pastexperiencesand recommendationsfor future products Joy A. Cavagnaroand Timothy Anderson 139 14 Designingnon-clinical safetyevaluationprogrammesfor monoclonal antibodies: Recommendationsand theway forward James Green andJohn Purves 151 15 Designingasafetyevaluationprogrammefor gene therapy products: Recommendationsand theway forward Peter Harris andAnthony Dayan 159 Appendix1: PreclinicalSafety Evaluationof 169 Biotechnology-Derived Pharmaceuticals: ICHStep 4HarmonisedTripartiteGuideline AppendixII: ListofParticipants 189 Index 193 vi Preface The Thirteenth CMR International Workshop, held in February 1997, provided an opportunity for international experts to discuss the approaches used, and difficulties encountered, in designing scientifically-based non-clinical safety evaluation programmes for biotechnologically-derived pharmaceuticals. This two-day meet ing brought together toxicologists and clinicians, from 32 pharma ceutical and biotechnology companies, and regulators and regula tory advisors from the European Medicines Evaluation Agency and 9countries: Denmark, France,Germany, Italy,Japan, theNeth erlands, Sweden, the UK and the USA. Ata time whena guideline to provide general principles for designing internationally accept able preclinical safety evaluation programmes for biotechnology products was being developed under the auspices of ICH (the International Conference on Harmonisation of Technical Require ments for Registration of Pharmaceuticals for Human Use), it was timely to debate the application of these principles to specific productclasses. The foundation for the discussions was setby a clinician and a toxicologist describing the information required from a safety test ing programme of biotechnologically-derived pharmaceuticals. This was followed by regulatory viewpoints from the USA, Europe and Japan. Four speakers then presented proposals on the design of non-clinical safety evaluation programmes for colony stimulating factors, growth factors and hormones; interferons and interleukins; monoclonal antibodies for therapeutic use; and gene therapy products. After the plenary discussion, the participants split up into four syndicate groups for several hours of further discussion and debate on the approaches that should be taken for each of these product classes. Although, inevitably, there were differences of opinion, the conclusions which were presented vii SafetyEvaluationofBiotechnologically-derivedPharmaceuticals subsequently to the whole group, were remarkably consistent. There was a general endorsement of the ICH draft guideline, which was at Step 3 of the ICH process at that time, and it was agreed that detailed annexes for different types of product are not feasible due to the diversity of biotech products. There was con sensus by both regulators and the industry that genotoxicity and carcinogenicity studies are not usually appropriate for biotech products. In addition, there was agreement on general principles for the safety testing of gene therapy products, which are not included in the ICH guideline. Finally, the participants recognised that companies should not contribute to increased regulatory expectations by conducting studies which are more suitable for small molecule chemicals, without adequate scientificjustification. These recommendations, arising from a forum in which experts from a wide range of companies and agencies were present, were taken into consideration for the final ICH S6 guideline which was agreed atICH4inBrusselsinJuly1997. The workshop also provided an opportunity for industry and regulatory experts to share their experiences of designing safety evaluation programmes for specific product classes. This type of interaction isparticularlyimportantbecauseindividualcompanies and regulatory authorities may have little experience with these compoundsdue tothe relatively smallnumber ofbiotechproducts which have been marketed to date. In addition, the case-by-case approach taken to designing safety evaluation programmes for biotechnologically-derivedpharmaceuticalshas led to inconsisten cies in the information on non-clinical safety testing requested by regulatorsintheUSA, EuropeandJapan. Theeditorshope that the publication of these proceedingswill provide support for industry toxicologists to press for a scientific approach to the safety evalu ation of biotech products, and give regulators the confidence not to requeststudies tobeconductedwhich are part ofthe traditional programme for smallmolecule chemicals,unless thereis appropri ate scientificjustification. We would like to thank all the Authors and Participants for making the meeting such a stimulating debate. Special thanks go viii Preface to the Rapporteurs andChairmen ofthe syndicate groupsfor pull ing together the views into the consensus recommendations docu mented in these proceedings. We are also indebted to Sandra Cox, whose work as administrator and compiler made a considerable contribution to the quality ofthis publication, and toSaraTownsend for so capably handling all the administrative arrangements for the meeting. Susan Griffiths CyndyLumley December 1997 ix
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