3R Research Foundation Switzerland - Front page

3R-INFO-BULLETIN 2 - September 1994

 Technical consulting for mAb in vitro production on behalf of the Foundation is accomplished by Mr. René Fischer, ETH Zurich. As a project leader of two previous 3R-projects he evaluated and compared various methods for producing monoclonal antibodies in vitro. His main interest is to provide technical experience concerning various methods for mAb production in vitro.
Furthermore he is setting up a laboratory for mAb production as a service for the university.

René FischerRené Fischer. For information on mAb production and trouble shooting please contact
Mr. R. Fischer:
Phone 01-632 31 40
Fax 01-632 11 21 (new)
E-mail fischer@bc.biol.ethz.ch


Is it possible to give up monoclonal antibody production in "ascites-mice"? To address this controversy FOUNDATION RESEARCH 3R launched a validation study for the in vitro production of monoclonal antibodies (mAbs).

A Validation Study for Swiss Francs 350'000.-

The 3R validation study was initiated in 1993 and will be completed at the beginning of 1995. 27 research facilities in Switzerland were supplied with electronically controlled bioreactors for mAb production. The first feedback from the users clearly documented the basic feasibility of in vitro monoclonal antibody production. Besides remaining technical difficulties of in vitro antibody production the study has practically already achieved its goal: now all monoclonal antibodies in Switzerland are produced in vitro!

The Ascites-Mouse

Ten years ago the Swiss scientific community used approximately 10'000 mice yearly to produce monoclonal antibodies in vivo. The antibody producing cancer cells were thereby injected into the inflamed mouse peritoneum resulting in an abundant growth of the tumor cells (hybridomas) and large quantities of antibody, but with a strong distress to the animal.
Since 1994, in vivo mAb production was only exceptionally permitted by the Swiss authorities. Thereby a situation was created where most scientists felt that these new regulations requested alternative in vitro methods actually not yet validated.

Purpose of the Validation Study

Among the scientific community there was only a limited interest in validating new methods (that create an additional financial burden). Thus, the Foundation decided to provide for free a critical number of bioreactors to scientists in different research centers all over Switzerland. This idea was well accepted, and within short notice 29 bioreactors were under evaluation.

Methods of Hybridoma Cultivation

Besides the traditional stationary culture for antibody producing hybridomas there existed different culture systems at the onset of the validation study. Low density cell cultures were already frequently in use, including roller-bottles, spinner cultures, T-flasks, airlift systems (with and without microcarriers), etc. with the inherent disadvantage of producing only low quantities of mAbs.
On the other hand there existed at that time also high density cell cultures based on hollow fiber reactors or ceramic modules, that promised the production of higher concentrations of mAbs.
The Foundation decided to evaluate two of (at that time) the most advanced hollow fiber culture systems: BioFarm 2000 (Digitana AG) and Tecnomouse culture system (INTEGRA Biosciences AG).


Participation: Of the 29 bioreactors 6 devices were placed in industry and 23 in academic or other non profit organisations.
22 bioreactors were assessed for first validation round up (88 cell lines have been analysed):
12 participants had typical yields 0.5-30mg mAb/week, 9 participants had typical yields 30-90mg mAb/week,
1 participant had typical yields 90mg mAb/week.


A majority of participants were pleased, agreed or said yes:

A majority of participants were negative:



Participation is still possible! The Foundation still has available a limited number of devices. Applications are treated on a first come, first served basis.

BioFarm2000 (CP System 1000) manufactured by ARCOS Engineering and distributed locally by Digitana AG (general distributor: UniSyn Technologies, San Diego CA, USA). Automated pH and temperature control, O2-, CO2 delivery, pump for air and medium supply to the hollow fiber reactor allow the mAb production with up to three Cell-Pharm bioreactors.
Phone: 01 - 725 61 91

Tecnomouse culture system manufactured and distributed by INTEGRA Biosciences AG, Wallisellen. The Tecnomouse allows the simultaneous cultivation of up to 5 different cell lines. Exchangeable culture cassettes incorporating novel oxygenation and hollow fiber technology guarantee the optimal use of media whilst enabling tissue like density.
Phone: 01 - 830 22 77