Table Of ContentANIMAL CELL
TECHNOLOGY:
Developments, Processes
and Products
Editors
R. E. Spier
Department of Microbiology, University of Surrey,
Guildford, Surrey, UK
J. B. Griffiths
PHLS CAMR, Porton, Salisbury, Wilts, UK
C. MacDonald
Department of Immunology, University of Strathclyde,
Glasgow, UK
ESACT
EUROPEAN SOCIETY
FOR ANIMAL CELL TECHNOLOGY
THE 11th MEETING
Butterworth-Heinemann Ltd
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t^· PART OF REED INTERNAΉONAL BOOKS
OXFORD LONDON BOSTON
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First published 1992
© Long term stability of expression of humanized monoclonal antibody campath
1-Hin Chinese hamster ovary cells (pp. 51-3)
The effect of tetramethyl urea oc-interferon production by namalwa cells
(pp. 89-91)
The effect of sequential induction of oc-interferon production by namalwa cells
(pp. 92-4)
The effect of reduced temperature on oc-interferon production bynamalwa cells
(pp.189-91)
The above articles, The Wellcome Foundation Ltd 1992
All other articles, Butterworth-Heinemann 1992
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British Library Cataloguing in Publication Data
Animal Cell Technology: Developments,
Processes and Products
I. Spier, R. E.
660.6
ISBN 0 7506 0421 2
Library of Congress Cataloguing in Publication Data
Animal cell technology: developments, processes, and products/
editors, R.E. Spier, J.B. Griffiths, C. MacDonald.
p. cm.
Includes bibliographical references and index.
ISBN 0 7506 0421 2
I. Animal cell biotechnology-Congresses. I. Spier, R. (Raymond)
II. Griffiths, J.B. III. MacDonald, C. (Caroline)
TP248.27.A53A544 1992 92-15733
660'.6-dc20 CIP
Printed and bound in Great Britain
Organizing Committee
Caroline MacDonald, Chairperson
Malcolm Brattle
David Broad
Julian Burke
Celia Caulcott
Bryan Griffiths
Nigel Jenkins
Chris Mannix
Lynne Mayne
Ray Spier
Sponsors
Academic Press Life Technologies Ltd
Alfa-Laval Engineering Ltd MBR Bio Reactor AG
Amicon Ltd Macmillan Journals
B. Braun Microbiological Associates
Becton Dickinson Mycoplasma Experience Ltd
Bibby Sterilin New Brunswick Scientific (UK) Ltd
Bioengineering Pall Process Filtration Ltd
Butterworth-Heinemann Ltd Pharmacia LKB Biotechnology AB
Canberra Packard Quality Biotech Ltd
Carl Zeiss (Oberkochen) Ltd Quantum Biosystems Ltd
Cellon Sari Receptor Technologies Ltd
Celltech Biologies Sartorius
Coulter Electronics Ltd Scotlab
ECACC Sera-Lab Ltd
Elsevier Trend Journals Serotec Ltd
Eurobio S.G.L
F.T. Applikon Sigma Chemical Co. Ltd
Glaxo Group Research Ltd Smithkline Beecham
Hamosan Sorebio
Hazleton UK Ltd Technology Partnership
Hyclone AB Tissue Culture Services Ltd
ICN Flow University of Strathclyde
Imperial Laboratories (Europe) Ltd Verax Corporation
Intergen Waitaki International Biosciences
Inveresk Research International Wellcome Foundation Ltd
LH Fermentation Ltd Wisepress
Life Sciences Laboratories Ltd
ESACT Executive Committee
Wolfgang Berthold
Coen Beuvery
David Broad
Pierre CrOOy, Secretary
Bryan Griffiths
Caroline MacDonald,
Meeting Secretary
Ray Spier, Chairperson
Pierre Trotemann
Vil
llth ES ACT Meeting, Brighton,
United Kingdom
Session officials
Chairpersons
R. E. Spier J-M Engasser
N. Jenkins D. Broad
J. Lehmann W. Berthold
A. Doyle R. Häuser
C. MacDonald M. Carondo
W. Scheirer C. Caulcott
J. Lupker J. Birch
D. Onions H. Blachere
C. Mannix J. B. Griffiths
A. Dixon T. Cartwright
F. Hof mann K. Konopitsky
Concluding remarks
W. Berthold
CHAIRMAN'S STATEMENT.
It comes as a surprise to most non-Animal Cell Biotechnologists that the
revenue raised by the sale of products derived from animal cells in culture can
account for over half of the revenues generated by the sale of all the products
resulting from the application of the new biotechnologies. With many new
products waiting in the wings and with the increasing realisation that the
natural post-translational modifications offer the most realistic route to
injectable materials it is likely that this ascendency will be maintained for some
time yet. This should not be a cause for complacency. We still have many areas
where incremental improvements can yield disproportionate advantages in the
efficiency and facility with which products can be generated.
Following the need for serum-free media we have learned how to adapt cells to
grow and produce in protein-free media. Such media result in advantages in
downstream processing as well as in overcoming the reservation of regulators
who judge sera as necessary evils at the best. Cells that have never been
exposed to animal sera would clearly be classed as the most propitious for the
development of a process but such cells are rare when compared with the cells
that have been adapted or which are found to perform at maximal levels when
they have been grown to a sufficiently high concentration that they can
dispense with the need for such complex materials in later parts of the process.
This development has led to considerable decreases in the cost of medium
(assuming that in-house formulations are used) but we can expect even further
decreases in cost by more carefully tailoring the composition of the medium
used in perfusion processes by replenishing selectively only those components
that are consumed.
The production of the flagship product, EPO, in roller bottles must give us
cause for thought. The urgency to be the first into the market place creates a
situation where any process that can be immediately, reliably and simply be put
into use to generate materials in sufficient quantities for the safety and clinical
tests is the one that is inevitably chosen; hence the popularity of the roller
bottle process. Clearly we need to provide workers at the research stage of a
project with a means of producing animal cells in culture that can be translated
to the large scale by the increase in the size of the culture system rather than
the multiplication of the units of that system. It will have to be simple, cheap,
effective and offer some advantage over the roller bottle. Therefore it cannot
use pumps, control systems, moving parts, stands and tubes, it could be
disposable or recylable. But it has to be available in large numbers so that
investigators can set up a series of reactors under different conditions and
arrive at optimal performance when selecting a cell (clone), medium
IX
composition and the procedures for the process. Were we to neglect this scale-
down requirement, our field will continue to persevere with primitive
technologies that belie the genius that has already been amply demonstrated
through the plethora of bioreactor designs available at scales too large for
bench work and needing peripherals that militate against simplicity and
cheapness.
A Chairman's Statement that did not comment on developments in the rapidly
(by past performance), changing field of regulations and licences would be
incomplete. It does seem that the points to consider that are to be issued shortly
from the FDA of the USA may recognise that;
* a tumerogenicity assay is not required when it is
recognised that the cell line is known to be
tumerogenic,
* the exhaustive virus testing of accepted cell lines of
known and accountable provenance may also be
waived,
* the amount of DNA in the final product is likely to be
set at less than 100 pg/dose,
* characterisation of cells using isoenzyme analysis,
species specific serology and DNA fingerprinting will
be emphasised,
* cell age and passage number may not be defined,
* determinations of vims contamination may depend on
the cost-benefit analysis of the situation into which the
product material is likely to be used,
* there is a probability that tests effected and accepted
under the aegis of one international regulatory agency
would not have to be repeated to gain acceptance by
another regulatory agency except where unique local
condition create special circumstances.
We have also to acknowledge the great achievement of the Centocor company
that has just received (on last day of this conference), the approval of the
Advisory Committee to the FDA for the production of an IgM humanised
mouse monoclonal which eliminates gram negative bacterial caused sepsis.
This material is produced by a large scale (over 100L) perfusion system that
generates materials over 50 days. This demonstrates that the definition of a
batch can be achieved in such a system and that the necessary characterisations
and controls can be provided to satisfy a licensing authority of the safety,
efficacy and controlability of the product and the process by which it is
generated.
The future will have two aspects that have not figured to major extents in our
considerations. Firstly, we will begin to recognise the physiological importance
of die large molecules that the cell secretes. These are becoming more apparent
as the move to protein-free media continues and the proteins that are made by
the cell and secreted become more noticeable. Secondly, and to some extent as
a consequence of the situation just described, we will be beset by a plethora of
molecules that will have effects on animal cells in culture but whose benefit to
therapeutic medicine will yet have to be determined. This is a complex
probiem because of the uniqueness of individual disease states and the
complexity of dealing with a therapeutic of multiple components. These
individual components may well have to be presented in the correct ratios for a
specific condition. This may only be achievable if we have an effective
overarching theory to arrive at a formulation for any one clinical case. There is
more than a decade of research in this area that will seriously challenge the
minds of researchers in many disciplines not excluding those engaged in
making and characterising such materials, viz. the animal cell biotechnologists.
On the international scene ESACT is well recognised by the European
Federation of Biotechnology (EFB), to be an effective organisation covering
the area of Animal Cell Biotechnology. It is about to set up a working party to
cover the area of Plant Cell Biotechnology. Your Chairman is also Chairman of
the Animal and Plant Cell Tissue Culture Technology Working Party of the
EFB which seeks to relate the practices and problems found in the respective
areas so as to obtain a "new view" of one's own problems. This has proved
mutually fruitful in the past (Enzyme and Microbial Technology, vol 13 pp
602-604), and has interesting prospects for the future.
XI
Additionally, EFB has set up a Task Group to examine the Biotechnology/
Medicine interface. Your Chairman along with the Chairmen of the Working
Parties of Applied Molecular Genetics and Safety are examining this area. The
outcome of such an examination will be reported in the new year.
It will be of interest to those pursuing the more engineering aspects of
biotechnology to learn that efforts are under way to include in the 4th
Framework programme for research a recognition of the need to make progress
in the area of Bioprocess Technology. Your Chairman has been active in this
area and he wishes to recognise the support of ESACT members in this quest.
Recognising the crowded timetables and diaries that are the vogue in our
thrusting world let us also look to a future when we will have our 12th meeting
in Wurtzburg, Germany (17th-21st May, 1993) to be followed a year and a half
later with our 13th meeting in Holland which will be held jointly with the
Japanese Association for Animal Cell Technology, (JAACT).
R.E. Spier
Chairman,
European Society for Animal Cell Technology, (ESACT).
Xll
