5.—(1) Non-pathogenic
The recipient or parental organisms can be classified as non-pathogenic if they satisfy the conditions of one of the following sub-paragraphs—
the recipient or parental strain should have an established record of safety in the laboratory and/or industry, with no adverse effects on human health and the environment;
the recipient or parental strain does not meet the conditions of sub-paragraph (a) above but it belongs to a species for which there is a long record of biological work including safety in the laboratory and/or industry, showing no adverse effects on human health and the environment;
if the recipient or parental organism is a strain which does not satisfy the conditions of sub-paragraph (a) above and belongs to a species for which there is no record of biological work including safe use in the laboratory and/or industry, appropriate testing (including, if necessary, animals) must be carried out, in order to establish non-pathogenicity and safety in the environment;
if a non-virulent strain of an acknowledged pathogenic species is used, the strain should be as deficient as possible in genetic material that determines virulence so as to ensure no reversion to pathogenicity. In the case of bacteria, special attention should be given to plasmid or phage-borne virulence determinants.
(2) No adventitious agents
The recipient or parental strain/cell line should be free of known biological contaminating agents (symbionts, mycoplasms, viruses, viroids, etc.), which are potentially harmful.
(3) The recipient or parental strain/cell line should have proven and extended history of safe use or built-in biological barriers, which, without interfering with optimal growth in the reactor or fermenter, confer limited survivability and replicability, without adverse consequences in the environment (applicable only for Type B operations).