Excerpt

The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) in early 1997 to prohibit the use of an animal in the production of mAb (monoclonal antibodies). NIH responded late in 1997, asserting that continued use of the mouse method for producing mAb was scientifically required. In a second petition, in early 1998, AAVS did not accept the NIH response. NIH asked the National Research Council to form a committee to study this issue. The Committee on Methods of Producing Monoclonal Antibodies was composed of 11 experts with extensive experience in biomedical research, laboratory animal medicine, pain research, animal welfare, and patient advocacy. The committee was asked to determine whether there is a scientific necessity for producing mAb by the mouse method and, if so, to recommend ways to minimize any pain or distress that might be associated with the method. The committee was also to determine whether there are regulatory requirements for the mouse method and to summarize the current stage of development of tissue-culture methods.

Contents

• COMMITTEE ON METHODS OF PRODUCING MONOCLONAL ANTIBODIES
• INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL
• COMMISSION ON LIFE SCIENCES
• THE NATIONAL ACADEMIES
• Preface
• Executive Summary
• Introduction
• 1. Generation of Hybridomas: Permanent Cell Lines Secreting Monoclonal Antibodies
• 2. In Vitro Production of Monoclonal Antibody
  • BATCH TISSUE-CULTURE METHODS
  • SEMIPERMEABLE-MEMBRANE-BASED SYSTEMS
• 3. Scientific Needs for Mouse Ascites Production of mAb
• 4. Summary of Advantages and Disadvantages of In Vitro and In Vivo Methods
  • ADVANTAGES OF IN VITRO METHODS
  • DISADVANTAGES OF IN VITRO METHODS
  • ADVANTAGES OF MOUSE ASCITES METHOD
  • DISADVANTAGES OF MOUSE ASCITES METHODS
• 5. Large-Scale Production of Monoclonal Antibodies
  • MONOCLONAL ANTIBODY PRODUCTION FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES
  • IN VIVO AND IN VITRO METHODS FOR COMMERCIAL PRODUCTION OF mAb
  • IN VIVO PRODUCTION
  • IN VITRO PRODUCTION
  • REGULATORY REQUIREMENTS
• 6. Animal-Welfare Issues Related to the Ascites Method for Producing Monoclonal Antibodies
  • AVAILABILITY OF DATA
  • ANIMAL-WELFARE ISSUES RELATED TO ASCITES METHOD
  • METHODS FOR MEASURING PAIN OR DISTRESS IN LABORATORY RODENTS
  • PRIMING
  • ASCITES
  • HARVESTING ASCITIC FLUID
  • FEEDER CELL HARVESTING AND SERUM SUPPLEMENTS FOR IN VITRO HYBRIDOMA CULTURE
  • SUMMARY OF ANIMAL WELFARE ISSUES
• 7. Conclusions and Recommendations
• References
• Appendix A Workshop on Methods of Producing Monoclonal Antibodies
• Appendix B Biographical Sketches of Authoring Committee

This study was supported by Contract No. N01-OD-4-2139 between the National Academy of Sciences and the National Institutes of Health.

Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.