November 17, 1997

Subject: Production of Monoclonal Antibodies Using Mouse Ascites Method

Dear Colleague:

This letter provides guidance to Public Health Service (PHS) awardee institutions and Institutional Animal Care and Use Committees (IACUCs) on avoiding or minimizing discomfort, distress, and pain in the care and use of

animals for the production of monoclonal antibodies using mouse ascites antibody production. The Public Health Service Act, the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, the PHS Policy on Humane Care and Use of Laboratory Animals, the Guide for the Care and Use of Laboratory Animals, and the Animal Welfare Act provide statutory and policy bases for the expectations in these areas (see enclosure for citations).

There is evidence that the mouse ascites method of monoclonal antibody production causes discomfort, distress, or pain. Practical in vitro methods exist which can replace the ascites method in many experimental applications without compromising the aims of the study.

Accordingly, IACUCs are expected to critically evaluate the proposed use of the mouse ascites method. Prior to approval of proposals which include the mouse ascites method, IACUCs must determine that (i) the proposed use is scientifically justified, (ii) methods that avoid or minimize discomfort, distress, and pain (including in vitro methods) have been considered, and (iii) the latter have been found unsuitable. Fulfillment of this three-part IACUC responsibility, with appropriate documentation, is considered central to an institution's compliance with its Animal Welfare Assurance and the PHS Policy.

The federal mandate to avoid or minimize discomfort, pain, and distress in experimental animals, consistent with sound scientific practices, is, for all practical purposes, synonymous with a requirement to consider alternative methods that reduce, refine, or replace the use of animals. Consideration of these issues should be incorporated into IACUC review, investigator training, research proposals, and ongoing monitoring of the institutional animal care and use program. IACUCs, acting as agents of institutions, are expected to implement and routinely evaluate these aspects of the institutional animal care and use program to ensure compliance with the PHS Policy.

Because these longstanding requirements are central to the federal oversight of all animal-related activities in research, testing, and training, this guidance may also be applied more generally to other PHS-supported and non PHS-supported activities involving animals. Additional references to resources relevant to this issue are enclosed for your information.

Thank you for your attention to these matters. As always, please feel free to contact OPRR at 301-496-7163 if you have questions regarding this correspondence.

/s/ /s/

Gary B. Ellis, Ph.D. Nelson L. Garnett, D.V.M.

Director Director, Division of Animal Welfare

Office for Protection from Research Risks Office for Protection from Research Risks