Process validation in manufacturing of biopharmaceuticals: guidelines, current practices, and industrial case studies

602 Pages·2005·4.049 MB·English

by  Anurag S Rathore, G K Sofer

PROCESS
VALIDATION IN
MANUFACTURING OF
BIOPHARMACEUTICALS
Guidelines, Current Practices,
and Industrial Case Studies
BIOTECHNOLOGY AND BIOPROCESSING SERIES
1. Membrane Separations in Biotechnology, edited by
W. Courtney McGregor
2. Commercial Production of Monoclonal Antibodies: A Guide for
Scale-Up, edited by Sally S. Seaver
3. Handbook on Anaerobic Fermentations, edited by Larry E. Erickson
and Daniel Yee-Chak Fung
4. Fermentation Process Development of Industrial Organisms,
edited by Justin O. Neway
5. Yeast: Biotechnology and Biocatalysis, edited by Hubert Verachtert
and René De Mot
6. Sensors in Bioprocess Control, edited by John V. Twork
and Alexander M. Yacynych
7. Fundamentals of Protein Biotechnology, edited by Stanley Stein
8. Yeast Strain Selection, edited by Chandra J. Panchal
9. Separation Processes in Biotechnology, edited by Juan A. Asenjo
10. Large-Scale Mammalian Cell Culture Technology, edited by
Anthony S. Lubiniecki
11. Extractive Bioconversions, edited by Bo Mattiasson and Olle Holst
12. Purification and Analysis of Recombinant Proteins, edited by
Ramnath Seetharam and Satish K. Sharma
13. Drug Biotechnology Regulation: Scientific Basis and Practices,
edited by Yuan-yuan H. Chiu and John L. Gueriguian
14. Protein Immobilization: Fundamentals and Applications,
edited by Richard F. Taylor
15. Biosensor Principles and Applications, edited by Loï'efc J. Blum
and Pierre R. Coulet
16. Industrial Application of Immobilized Biocatalysts, edited by
Atsuo Tanaka, Tetsuya Tosa, and Takeshi Kobayashi
17. Insect Cell Culture Engineering, edited by Mattheus F. A. Goosen,
Andrew J. Daugulis, and Peter Faulkner
18. Protein Purification Process Engineering, edited by Roger G. Harrison
19. Recombinant Microbes for Industrial and Agricultural Applications,
edited by Yoshikatsu Murooka and Tadayuki Imanaka
20. Cell Adhesion: Fundamentals and Biotechnological Applications,
edited by Martin A. Hjortso and Joseph W. Roos
21. Bioreactor System Design, edited by Juan A. Asenjo
and José C. Merchuk
22. Gene Expression in Recombinant Microorganisms, edited by
Alan Smith
23. Interfacial Phenomena and Bioproducts, edited by John L. Brash
and Peter W. Wojciechowski
24. Metabolic Engineering, edited by Sang Yup Lee
and Eleftherios T. Papoutsakis
25. Biopharmaceutical Process Validation, edited by Gail Sofer
and Dane W. Zabriskie
26. Membrane Separations in Biotechnology: Second Edition,
Revised and Expanded, edited by William K. Wang
27. Isolation and Purification of Proteins, edited by Rajni Hatti-Kaul
and Bo Mattiasson
28. Biotransformation and Bioprocesses, Mukesh Doble,
Anil Kumar Kruthiventi, and Vilas Gajanan Gaikar
29. Process Validation in Manufacturing of Biopharmaceuticals:
Guidelines, Current Practices, and Industrial Case Studies,
edited by Anurag Singh Rathore and Gail Sofer
30. Cell Culture Technology for Pharmaceutical and Cell-Based Therapies,
edited by Sadettin S. Ozturk and Wei-Shou Hu
BIOTECHNOLOGY AND BIOPROCESSING SERIES
1. Membrane Separations in Biotechnology, edited by W. Courtney
McGregor
2. Commercial Production of Monoclonal Antibodies: A Guide for
Scale-Up, edited by Sally S. Seaver
3. Handbook on Anaerobic Fermentations, edited by Larry E. Erickson
and Daniel Yee-Chak Fung
4. Fermentation Process Development of Industrial Organisms,
edited by Justin O. Neway
5. Yeast: Biotechnology and Biocatalysis, edited by Hubert Verachtert
and René'e9 De Mot
6. Sensors in Bioprocess Control, edited by John V. Twork and
Alexander M. Yacynych
7. Fundamentals of Protein Biotechnology, edited by Stanley Stein
8. Yeast Strain Selection, edited by Chandra J. Panchal
9. Separation Processes in Biotechnology, edited by Juan A. Asenjo
10. Large-Scale Mammalian Cell Culture Technology, edited by
Anthony S. Lubiniecki
11. Extractive Bioconversions, edited by Bo Mattiasson and Olle
Holst
12. Purification and Analysis of Recombinant Proteins, edited by
Ramnath Seetharam and Satish K. Sharma
13. Drug Biotechnology Regulation: Scientific Basis and Practices,
edited by Yuan-yuan H. Chiu and John L. Gueriguian
14. Protein Immobilization: Fundamentals and Applications, edited
by Richard F. Taylor
15. Biosensor Principles and Applications, edited by Loï'efc J. Blum
and Pierre R. Coulet
16. Industrial Application of Immobilized Biocatalysts, edited by
Atsuo Tanaka, Tetsuya Tosa, and Takeshi Kobayashi
17. Insect Cell Culture Engineering, edited by Mattheus F. A. Goosen,
Andrew J. Daugulis, and Peter Faulkner
18. Protein Purification Process Engineering, edited by Roger G.
Harrison
19. Recombinant Microbes for Industrial and Agricultural Applications,
edited by Yoshikatsu Murooka and Tadayuki Imanaka
20. Cell Adhesion: Fundamentals and Biotechnological Applications,
edited by Martin A. Hjortso and Joseph W. Roos
21. Bioreactor System Design, edited by Juan A. Asenjo and José'e9
C. Merchuk
22. Gene Expression in Recombinant Microorganisms, edited by
Alan Smith
23. Interfacial Phenomena and Bioproducts, edited by John L. Brash
and Peter W. Wojciechowski
24. Metabolic Engineering, edited by Sang Yup Lee and Eleftherios
T. Papoutsakis
25. Biopharmaceutical Process Validation, edited by Gail Sofer and
Dane W. Zabriskie
26. Membrane Separations in Biotechnology: Second Edition, Revised
and Expanded, edited by William K. Wang
27. Isolation and Purification of Proteins, edited by Rajni Hatti-Kaul
and Bo Mattiasson
28. Biotransformation and Bioprocesses, Mukesh Doble, Anil Kumar
Kruthiventi, and Vilas Gajanan Gaikar
29. Process Validation in Manufacturing of Biopharmaceuticals:
Guidelines, Current Practices, and Industrial Case Studies
PROCESS
VALIDATION IN
MANUFACTURING OF
BIOPHARMACEUTICALS
Guidelines, Current Practices,
and Industrial Case Studies
edited by
Anurag Singh Rathore
Gail Sofer
Published in 2005 by
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2005 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
10 9 8 7 6 5 4 3 2 1
International Standard Book Number-10: 1-57444-516-2 (Hardcover)
International Standard Book Number-13: 978-1-57444-516-9 (Hardcover)
Library of Congress Card Number 2004065748
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Library of Congress Cataloging-in-Publication Data
Process validation in manufacturing of biopharmaceuticals : guidelines, current practices, and
industrial case studies / edited by Anurag Singh Rathore, Gail Sofer.
p. cm. -- (Biotechnology and bioprocessing series ; 29)
Includes bibliographical references and index.
ISBN 1-57444-516-2 (alk. paper)
1. Pharmaceutical biotechnology--Quality control. 2. Biotechnological process monitoring.
I. Rathore, Anurag S. (Anurag Singh), 1973- II. Sofer, G. K. III. Series.
RS380.P76 2005
615'.19--dc22 2004065748
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Dedication
To our family:
Bhawana, Payal, Bill, Gregg, and Douglas,
who contributed to this as much as we did.

Preface
Process validation continues to be a topic of much debate and con-
fusion for biopharmaceutical manufacturers. It is usually perceived
as a regulatory requirement and good business practice, since it can
prevent failed batches when based on science and risk assessments.
This book provides insights into the key aspects and current prac-
tices of process validation.
Chapter 1 addresses some of the current process validation con-
cerns. In Chapter 2, the use of a risk assessment method (failure
modes and effect analysis [FMEA]) is presented as a means to
prioritize process parameters for further process characterization
prior to validation. FMEA provides a logical approach that can aid
in establishing critical parameters and ensure process robustness.
Specific examples on the use of FMEA will aid readers to establish
this method in their own organizations.
Process characterization is a prerequisite for process validation.
In Chapter 3, a description of how to carry out thorough and con-
sistent process characterization is presented. “Precharacterization”
studies, which are used to help define the scope of the actual exper-
imental characterization work, are also discussed. The discussions
on timing of process characterization, needed resources, and a
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