at MEDICAL RESEARCH COUNCIL 
20 Park Crescent London WIN 4AL Telephone 01-636 5422 
GMAG NOTE 12 
LARGE SCALE USE OF THE PRODUCTS OF GENETIC MANIPULATION - WORK INVOLVING 
VOLUMES OF 10 LITRES OR MORE 
1. GMAG through its Note 8 (29 March 1979) and Note 7 (Revised May 1979) 
announced that it would wish to give special consideration to proposals to 
do scale-up work involving the growth of self-propagating products of genetic 
manipulation in volumes of 10 litres or more. 
GMAG has decided that it would wish to consider all proposals involving 
'scale-up' in conjunction with a site visit. As a consequence all work 
involving 'scale-up' will be considered on a case by case basis. Initial 
proposals should be submitted on either the proposal forms A and B detailed 
in the Genetic Manipulation Regulations (SI 1978 No. 752), or in the form of a 
detailed letter. The precise form of the submission should be discussed with 
the GMAG Secretariat before a formal request for advice is made. 
Guidance Notes 
2. It is important in the assessment of proposals to do scale-up work to 
use the term 'scale-up' with strict regard for its meaning in this context. 
The expression is usually applied in the development of chemical, pharmaceutical 
and biological production processes in which the scale of the operation, the 
same operation, is translated from that of the bench to the pilot plant and 
then to the full-scale industrial plant. In the context of the GMAG 
responsibility, scale-up will involve the very significant change from the 
manipulation of the genetic material to the use of the resulting host vector 
system. 
3. A consequence of the change from manipulation to use is that any risks 
involved will not necessarily remain the same and a different type of assess- 
ment will be required for these changed circumstances. 
4. It has proved possible and convenient to assess by various means the 
conjectural hazards of genetic manipulation and to assign the proposed 
experiment to specified conditions of containment in identified categories 
from I to IV. 
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