Safety and efficacy of radiopharmaceuticals

391 Pages·1983·10.701 MB·English

by  Knud Kristensen, Elisabeth Norbygaard (auth.), Knud Kristensen, Elisabeth Nørbygaard (eds.)

SAFETY AND EFFICACY OF RADIOPHARMACEUTICALS
DEVELOPMENTS IN NUCLEAR MEDICINE
Series editor Peter H. Cox
Other titles in this series
Cox, P.H. (ed.): Cholescintigraphy. 1981. ISBN 90-247-2524-0
Cox, P.H. (ed.): Progress in radiopharmacology 3. Selected Topics. 1982.
ISBN 90-247-2768-5
Jonckheer, M.H. and Deconinck, F. (eds.): X-ray fluorescent scanning of the
thyroid. 1983. ISBN 0-89838-561-X
Safety and efficacy of
radiopharInaceuticals
edited by
KNUD KRISTENSEN
ELISABETH N0RBYGAARD
The Isotope-Pharmacy
The National Board of Health
Copenhagen
Denmark
1984 MARTINUS NIJHOFF PUBLISHERS ~.
a member of the KLUWER ACADEMIC PUBLISHERS GROUP ...
BOSTON / THE HAGUE / DORDRECHT / LANCASTER .~
Distributors
for the United States and Canada: Kluwer Boston, Inc., 190 Old Derby Street,
Hingham, MA 02043, USA
for afl other countries: Kluwer Academic Publishers Group, Distribution Center,
P.O.Box 322, 3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
Safety and efficacy of radiopharmaceuticals.
(Developments in nuclear medicine; v. 4)
Tncludes index.
1. Radiopharmaceuticals--Safety measures, 2. Drugs-
Effecti veness. 3. Drug trade--Quality concrol.
I. Kristensen, Knud. II. N~rbygaardJ Elisabeth.
III. Series. [DNLM: 1. Quality control--Congresses.
2. Radiation protection--Standards--Congresses.
3. RadioisotopeG--Congresses. Wl DE998kf v. 4 I
WN 420 8128 1983J
RM852.S2 1984 615.8'42 83-21938
I SBN-13: 978-94-009-6755-7 e-ISBN -13: 978-94-009-6753-3
DOl: 10.1007/978-94-009-6753-3
ISBN -13: 978-94-009-6755-7
Copyright
@ 1984 by Martinus Nijhoff Publishers, Boston.
Softcover reprint of the hardcover 1st edition 1984
All rights reserved. No part of this puhlication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, mechanical,
photocopying, recording, or otherwise, without the prior written permission of
the publishers,
Martinus Nijhoff Publishers, 190 Old Derby Street, Hingham, MA 02043, USA.
v
PREFACE
Safety and efficacy of radiopharmaceuticals are elements of
great importance in nuclear medicine. Since the first meeting
in 1965 in Oak Ridge with the title Radiopharmaceuticals
tremendous developments have taken place. In 1965 the whole
technetium-99m area was just in its very beginning. Safety and
efficacy of the non-radioactive pharmaceuticals have attracted
great attention during the last 10 years and so have similar
aspects of radiopharmaceuticals during the later years.
Regulatory agencies are extending their work also to the
preparation of radiopharmaceuticals at hospitals and to
requirements for registration of radiopharmaceuticals. In a
fast developing field there might be tendencies to
confrontation between interests and there have certainly been
some tendencies to put undue restrictions on the use of radio
pharmaceuticals due to the lack of understanding between the
industry and the regulatory authorities and between regulatory
authorities and hospitals. Much of this may have been due to
lack of information and certainly is due to the lack of
fundamental scientific knowledge in many radiopharmaceutical
aspects. A fast and safe introduction of new radio
pharmaceuticals and the proper handling of these requires a
lot of development work, but also an understanding of how
general principles from the non-radioactive drug field may be
sensibly transformed into the radiopharmaceutical area. It may
even require compromises between requirements for safety in
different areas such as radiation protection and
pharmaceutical aspects.
Two of the most important areas in these years seem to be
the approval of new radiopharmaceuticals and the preparation
of radiopharmaceuticals at hospitals with the use of kits and
generators. In order to give an up to date survey of these
areas and to include relevant aspects from the registration
VI
procedure for non-radioactive drugs a group of experts were
invited to prepare review papers under the two main themes:
Development of the documentation for efficacy and safety of
radiopharmaceuticals and Design of laboratory facilities for
preparation of radiopharmaceuticals at hospitals.
Summaries of these review papers were presented and
discussed at the first European Symposium on Radiopharmacy and
Radiopharmaceuticals, Elsinore, Denmark. 27. - 30. March,
1983. This meeting was organized by the Danish Society of
Clinical Physiology and Nuclear Medicine under the auspicies
of the European Joint Committee on Radiopharmaceuticals of
European Society of Nuclear Medicine and the Society of
Nuclear Medicine, Europe with the support of the Danish
Medical Research Council. The Isotope-Pharmacy, The National
Board of Health, Copenhagen, provided the secretariate for the
meeting.
This book contains the full text of the review papers in
part 1 and 2. It also contains in part 3 introductory papers
prepared for a panel discussion on Quality control of radio
pharmaceuticals prepared from generators and kits.
It is hoped that the review papers will be useful as
reference papers for future development in this field and the
editors should like to thank all the authors for their
willingness to contribute and for the meticulous care with
which they all prepared the reviews.
Thanks are also due to the secretariat staff of the
Isotope-Pharmacy: Anne Andersen, Bente Hansen, Inge Kornerup
and Irma 0stergard who with great care prepared the manuscript
for reproduction.
May 1983
Elisabeth N0rbygard
Knud Kristensen
VII
CONTENTS
Preface V
Contributors XI
Part 1:
Development of the documentation for efficacy
and safety of radiopharmaceuticals. 1
Introduction 3
Chapter 1
Structure/distribution relationship in the design
of Tc-99m radiopharmaceuticals. 5
Gopal Subramanian, J.G. McAfee, R.F. Schneider
Chapter 2
Physical/chemical description "
Jiri Cifka
Chapter 3
Analytical quality control 66
Gertrude Pfeiffer
Chapter 4
Pharmaceutical form - packaging 85
Per Bremer
Chapter 5
Stability of radio pharmaceuticals 99
Charles Fallais and Francis Smal
Chapter 6
Prod uc t ion des ign - GMP ind us try 107
Maurizio Villa
Chapter 7
The design of radiopharmaceuticals
Pharmacology and toxicology 117
Peter Cox
Chapter 8
Animal models for efficacy studies -
a practical approach 130
Gerhard Kloss
VIII
Chapter 9
Human pharmacology - pharmacokinetics 1~
Yves Cohen
Chapter 10
Radiation dosimetry U8
Hans Detlev Roedler
Chapter 11
Clinical trials of radiopharmaceuticals 179
Per Juul
Chapter 12
Evaluation of clinical information In
Harriet Dige-Petersen
Chapter 13
Com par at i vee val u a t ion 0 f d rug s 203
Rolf de Jong and Wim B. Huising
Chapter 14
"The paperwork" with applications for registration of
radiopharmaceuticals in Denmark 213
Thomas Muller
Chapter 15
Drug-radiopharmaceutical interactions and other
possible modifications in radiopharmaceutical
b i 0 dis t rib uti 0 n 230
Martin Woldring
Chapter 16
Adv er se re act ions to r ad io ph a rm ace ut ic a 1 s 240
David H. Keeling
Chapter 17
Drug defects 251
Bente Pedersen
Chapter 1B
Ethics - responsibility in development, clinical trials
and mar ket i ng 263
Ole Weis-Fogh
Chapter 19
United Kingdom regulations relating to the control of
safety and efficacy of radiopharmaceuticals 270
Rosemary J. Smith
Chapter 20
Regulatory aspects in the Federal Republic of Germany 280
Hans Detlev Roedler
Chapter 21
Regulatory aspects - examples from Sweden 2~
Bertil Nosslin
IX
Chapter 22
Licensing of radiopharmaceuticals in european countries
1982 299
Knud Kristensen
Part 2:
Design of laboratory facilities for preparation of
radiopharmaceuticals at hospitals 307
Int roduct ion 309
Chapter 23
Design criteria in relation to protection of the
product 311
Neil Bell
Chapter 24
Design criteria in relation to protection of the
personnel aDd the environment n6
Klaus R. Ennow
Chapter 25
Present status of recommendations for the design
of laboratory facilities 333
Colin R. Lazarus
Part 3:
Quality control of radiopharmaceuticals prepared from
g en era tor san d kit s 349
Introduction nl
Chapter 26
Generator quality industry points of view n3
Yves Jean-Baptiste
Chapter 27
Generator - hospital points of view n6
Sten-Ove Nilsson
Chapter 28
Kit - in d u s try poi n t s 0 f vie w 360
Derek E. Lovett
Chapter 29
Kit - hospital points of view 364
J0rgen Marqversen
Chapter 30
United Kingdom Drug control point of view 3n
Rosemary J. Smith
INDEX379
XI
CONTRIBUTORS
Neil Bell
University of Strathclyde
Glasgow, Scotland
Per O. Bremer
Institute of Energy Technology
Kjeller, Norway
Jiri Cifka
Nuclear Research Institute
Rez, Czechoslovakia
Yves Cohen
Universite de Paris-Sud
Chatenay-Malabry, France
Peter H. Cox
Institute of Radiotherapy
Rotterdam, The Netherlands
Harriet Dige-Petersen
Glostrup Hospital
Glostrup, Denmark
Klaus R. Ennow
National Institute of Radiation Hygiene
Copenhagen, Denmark
Charles Fallais
Institut National des Radioelements
Fleurus, Belgium
Wim B. Huising
Byk-Malli nckrodt
Petten, The Netherlands
Yves Jean-Baptiste
Commisariat a l'Energie Atomique
Saclay, France