Therapeutic protein drug products: Practical approaches to formulation in the laboratory, manufacturing, and the clinic

202 Pages·2012·3.613 MB·English

by  Brian K. Meyer

Therapeutic Protein Drug Products
Biohealthcare Publishing Series on Pharma, Biotech and
Biosciences: Science, Technology and Business
Volumes in the Series Industries. T. Cochrane
(ISBN 9781907568336).
1. C linical Research in Asia. U. Sahoo
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(ISBN 9781907568084).
R. Bouchard
3. P ractical Leadership for (ISBN 9781907568121).
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(ISBN 9781907568060)
9781907568374).
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H. Lutz
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6. T herapeutic Protein Drug Products.
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B. Meyer (ed.)
and Good Management Practices:
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Value Added Compliance for the

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12. T he Application of SPC in the of Biopharmaceuticals: Principles
Pharmaceutical and Biotechnology and Best Practice. Applied Strategies
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Manufacture. A. Newcombe et al. T.P.G. Fernandes et al.
(ISBN 9781907568640). (ISBN 9781907568886).
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(ISBN 9781907568664). and Biopharmaceutical
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24.A nnotating New Genes: From In
C. Herwig and J.C. Menezes
Silico to Validations by
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Experiments. S. Uchida
(ISBN 9781907568688). 35. Fed-Batch Fermentation: A
Practical Guide to Scalable
25.I mpact of Regulation on Drug
Recombinant Protein Production in
Development. H. Guenter Hennings
Escherichia coli. G.G. Moulton and
(ISBN 9781907568701).
T. Vedvick
26.T he Design and Manufacture of (ISBN 9781907568923).
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From the Laboratory to Clinical (ISBN 9781907568947).
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28. Developments in Tissue Engineered (ISBN 9781907568961).
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Life Science and Industry.
J. Basu and J.W. Ludlow
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30. Marine Enzymes for Biocatalysis. (ISBN 9781907568985).
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31. Recombinant Vaccines. S. Pincus et al. J.E. Aguilar-Diaz
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in the Eye: Their Role in Drug Systems. K. Shimuzu
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For Faye and Jake
And to my mother Diane and in loving memory of my father Jerry

Therapeutic Protein Drug
Products
Practical approaches to formulation in
the laboratory, manufacturing,
and the clinic
Edited by
Brian K. Meyer
Biohealthcare Publishing (Oxford) Limited
Hexagon House
Avenue 4
Station Lane
Witney
Oxford OX28 4BN, UK
Tel: [phone]; Fax: [phone]
Email: [email protected]
Website: www.biohealthcarepublishing.com
First published in 2012 by Biohealthcare Publishing (Oxford) Limited
ISBN: 978 1 907568 18 3 (print) and 978 1 9078818 10 2 (e-book)
© The editor, contributors and the Publishers, 2012
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Contents
List of fi gures and tables xiii
Preface xv
About the authors xvii
1 Commercial therapeutic protein drug products 1
brian k. meyer and mohammed shameem
1.1 Introduction 1
1.2 Lyophilized formulations 2
1.2.1 Lyophilized monoclonal antibodies and IgG fusion
proteins 2
1.2.2 Lyophilized proteins and peptides to 150 kDa 3
1.3 Liquid formulations 4
1.3.1 Monoclonal antibodies and IgG fusion proteins 4

1.3.2 Proteins and peptides to 150 kDa 4
1.4 Protein formulations for radiologic and diagnostic use 5
1.5 Summary 5
1.6 References 9
2 A formulation method to improve the physical stability
of macromolecular-based drug products 13
akhilesh bhambhani, santosh thakkar, sangeeta b. joshi, and
c. russell middaugh
2.1 Introduction 14
2.2 Common techniques used for the construction of EPDs 17
2.2.1 UV absorption spectroscopy 17
2.2.2 Far-UV circular dichroism 22
2.2.3 Fluorescence spectroscopy 23
2.2.4 Pressure perturbation calorimetry 25
2.2.5 Ultrasonic spectroscopy 25
2.2.6 Red-edge excitation shift spectroscopy 26
2.2.7 Time-correlated single photon counting 26
x Therapeutic Protein Drug Products
2.2.8 Dynamic light scattering 27
2.2.9 Miscellaneous techniques 28
2.3 The peptide drug pramlintide 29
2.4 Monoclonal antibodies at low and high concentration 35
2.5 Static vs. dynamic EPDs: a case study using a humanized
immunoglobulin (IgG1) 36
2.6 Conclusion and future studies 40
2.7 References 42
3 Properties of protein formulations 47
henryk mach, brian k. meyer, and mohammed shameem
3.1 Introduction 47
3.2 Opalescence 48
3.3 Phase separation 50
3.4 Color 51
3.5 Subvisible particles 51
3.5.1 Analytical methods 52
3.5.2 Immunogenicity 56
3.5.3 Trends and challenges 59
3.6 References 60
4 Material and process compatibility testing 67

brian k. meyer
4.1 Introduction 67
4.2 Material compatibility 69
4.2.1 Stainless steel and alloys 69
4.2.2 Plastic and other polymers 70
4.2.3 Tubing 71
4.2.4 Glass 72
4.2.5 Rubber closures 72
4.2.6 Silicone oil 73
4.2.7 Tungsten 74
4.2.8 Hydrogen peroxide 74
4.3 Process compatibility testing 74
4.3.1 Filtration 74
4.3.2 Pumping during manufacture of drug substance 75
4.3.3 Pumping during fi lling of drug product 75
4.3.4 Mixing and stirring 78
4.3.5 Shaking 78
4.3.6 Photostability 78