Monoclonal Antibody (Mab) Production
OPRR Policy
Recent guidance from the Office of Protection from Research Risks (OPRR) of the National Institutes of Health (NIH)(1) provides that prior to approval of protocols that propose the production of ascites fluid, the investigator must use the following criteria in order to be in compliance with OPRR and justify that the use of animals is necessary.
- The proposed use of animals must be scientifically justified.
- Methods that avoid or minimize discomfort, distress and pain (including in vitro methods) have been considered, and
- Have been found to be unsuitable.
IACUC Responsibility
It is the responsibility of the IACUC to critically evaluate these criteria and appropriately document that the three criteria have been fulfilled.(1)
- In most applications, in vitro alternatives produce adequate amounts of Mab.(2) The most recent workshop on alternatives in Monoclonal Antibody Production concluded that in vitro methods for Mab production should be the accepted method because the ascites method causes pain and suffering(1),(2). Thus, the use of the ascites method should be the exception and should require rigorous and scientific justification.(2) If adequate justification is not provided for an exception, then in vitro methods are required.(2)
- Justification should not be based on cost or convenience.
- Investigators must provide assurance that the antibody to be used is not commercially available.
- In vitro alternatives for Mab production should be the preferred method, with the ascites method being the exception.
- Acceptable exceptions to using in vitro alternatives may be instances where the hybridoma cells grown in culture either failed to produce Mabs or fail to produce Mabs with the proper reactivity needed to answer important research questions.
Information on Available Alternative Methods
- University Laboratory Animal Resources (ULAR) maintains a library of commercially available in vitro systems for production of monoclonal antibodies.
- Educational Web Site Resources
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- The John Hopkins Alternatives to Animal Testing Website http://altweb.jhsph.edu/
- Nature Buyers' Guide http://www.guide.nature.com/
- Antibody Resource Page http://www.antibodyresource.com
- Information Resources for Adjuvants and Antibody Production: Comparisons and Alternative Technologies http://www.nal.usda.gov/awic/pubs/antibody/
References
1 OPRR Reports, National Institutes of Health, 11/17/97.
2 Conclusions & Recommendations, Alternatives in Monoclonal Antibody Production Workshop of Johns Hopkins Center for Alternatives & OPRR, NIH.
