Recommendation 4: mAb now being commercially produced by the mouse ascites method should continue to be so produced, but industry should continue to move toward the use of tissue-culture methods.

In a few circumstances, the use of the mouse ascites method for the production of mAb might be required. We suggest the following as examples of criteria to be used by an IACUC in establishing guidelines for the production of mAb in mice by the ascites method.

    1.  

    When a supernatant of a dense hybridoma culture grown for 7–10 days (stationary batch method) yields an mAb concentration of less than 5 µg/ml. If hollow-fiber reactors or semipermeable-membrane systems are used, 500 mg/ml and 300 mg/ml, respectively, are considered low mAb concentrations.

    2.  

    When more than 5 mg of mAb produced by each of five or more different hybridoma cell lines is needed simultaneously. It is technically difficult to produce this amount of mAb since it requires more monitoring and processing capability than the average laboratory can achieve.

    3.  

    When analysis of mAb produced in tissue culture reveals that a desired antibody function is diminished or lost.

    4.  

    When a hybridoma cell line grows and is productive only in mice.

    5.  

    When more than 50 mg of functional mAb is needed, and previous poor performance of the cell line indicates that hollow-fiber reactors, small-volume membrane-based fermentors, or other techniques cannot meet this need during optimal growth and production.

    We emphasize that those criteria are not all-inclusive and that it is the responsibility of the IACUCs to determine whether animal use is required for scientific or regulatory reasons. Criteria have not been developed to define a cell line that is low-producing or when tissue-culture methods are no longer a useful means of producing mAb.



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