On September 24-25, 1997, over 110 participants from research, industry, government, and special interest groups attended the "Alternatives in Monoclonal Antibody Production" workshop, organized by The Johns Hopkins Center for Alternatives to Animal Testing and cosponsored by the National Institutes of Health's Office for Protection From Research Risks. The workshop examined in vitro alternative production techniques, cost, animal welfare, and Institutional Animal Care and Use Committee (IACUC) issues.
The workshop was prompted by the April 23, 1997, American Anti-Vivisection Society (AAVS) petition to the National Institutes of Health (NIH) and the U.S. Department of Agriculture (USDA), requesting that the two institutions follow in the footsteps of their European counterparts to ban in vivo monoclonal antibody (MAb) production. According to the AAVS, up to 1 million animals per year are sacrificed in the United States for antibody production. [Ed. note: According to a 1991 report by the Business Communications Company, an estimated 2.6 million mice were used worldwide for the production of MAbs. The United States share was estimated at 40 percent of the world total.]
Representatives from USDA and NIH were present at the workshop to make a formal response to the petition. Louis Sibal, D.V.M., Director of the NIH Office of Laboratory Animal Research concluded that although alternatives are "scientifically acceptable, reasonable, and practically available," NIH will not approve the ban. According to Jerry DePoyster, D.V.M., Veterinary Medical Officer, USDA, Animal Care, USDA expects its field personnel to make sure an alternatives search has been done if the researcher plans to work with a regulated animal covered by the Animal Welfare Act (AWA). However, USDA animal welfare regulations currently excludes rats and mice from coverage and USDA does not expect to be changing its list of regulated animals in the near future.
Several conclusions and recommendations were made at the workshop. First, in vitro alternatives for MAb production should be the accepted method, with the ascites method being the exception. If the ascites method must be used, the investigator should justify this carefully and take care to minimize stress and pain. Consequently, the role of the IACUC is becoming pivotal in advising and educating investigators about proper alternatives.
Another conclusion was that the procedure is painful and causes suffering. According to data presented, mice used for ascites production experience problems such as respiratory distress, circulatory shock, difficulty walking, anorexia, dehydration, and peritonitis. A topic of debate was (and still is) the permitted number of abdominal taps, since fluid removal may cause hemorrhage, edema, and death. Furthermore, many mice develop solid tumors during the process, rendering them useless for production.
The workshop also determined that alternatives not only produce adequate amounts of MAbs, but are also cost and time efficient. Leading researchers presented cost and production data from alternative in vitro methods such as hollow fiber bioreactors, the miniPERM bioreactor, and gas permeable tissue culture bags that confirmed the feasibility of these methods.
Unisyn Technologies (Hopkinton, MA) displayed the new Cell-Pharm System 100 hollow fiber bioreactor system and the miniPERM bioreactor. Leading researchers presented data which confirmed that on a cost per milligram basis, the miniPERM bioreactor is competitive or less expensive than ascites when factoring in mouse per diem costs and other associated costs such as investigator /IACUC time needed to write/review each ascites proposal. These data also indicated in vitro antibody concentrations equivalent to ascites, without the contamination of adventitious murine viruses or nonspecific proteins.
Another topic discussed was the increasingly important trend towards central hybridoma core facilities. More and more core facilities and contract laboratories are expanding their current services to include in vitro MAb production. Some offer in vitro production methods only. These core facilities offer in vitro services to researchers with personnel, cost, and/or space constraints.
The workshop not only confirmed the feasibility and easy availability of alternative methods, but also served as an excellent information resource for anyone interested in the 3Rs: reduction, refinement, and replacement. The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) hosts AltWeb, a website dedicated entirely to alternatives. The website contains links to many other related sites and can be reached at the address http://caat.jhsph.edu/ Another helpful resource is the August 1997 Information Resources for Adjuvants and Antibody Production: Comparisons and Alternative Technologies developed by USDA's Animal Welfare Information Center. This publication can be found at http://www.nal.usda.gov/awic/pubs/antibody
For additional information on Unisyn products, please contact Christina Goettel-Connolly, Unisyn Technologies, Inc., 25 South Street, Hopkinton, MA 01748-2217 USA, phone: (508) 435-2000, fax: (508) 435-8111, World Wide Web: http://www.unisyntech.com
[Ed. note: For additional information about other products or companies providing equipment or supplies for in vitro production of MAbs, please visit http://www.nal.usda.gov/awic/pubs/antibody/company.htm on the AWIC web site.]
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