M knots' cl .il S.tlc IiiiiIi\’IiiihIiii:\ 
In dealing with these biologically active microbial 
products the biotechnology industries have an advan- 
tage in that their processes arc carried out under 
controlled conditions which allow the detection of 
such products and permit their containment or 
removal to whatever standards are found to be 
necessary. 
In many countries codes of practice arc agreed 
with the authorities to ensure that processes and 
products are safe. 
The farming and food preparation industries have 
been remarkably successful in handling the problems 
presented by biologically active microbial products. 
Nevertheless, the contamination of some farm prod- 
ucts by fungal toxins cannot be entirely prevented and 
sporadic food poisoning incidents also remain a 
problem associated with the improper handling of 
foods. 
Finally, it should be mentioned that the contain- 
ment standards for biotechnology processes are likely 
to be superior to those attainable in fanning, where 
the annual release of pollens heralds the onset of 
disabling allergies for large numbers of people. 
Again, the quality control systems in the biotech- 
nology industries are always likely to be superior to 
those attainable in catering where the operating 
conditions are so diverse. 
5.3 Problems associated with handling bulk quantities 
of microorganisms 
In some processes bulk quantities of microorganisms 
remain after the desired product has been separated, 
and these require safe disposal. If they are pathogenic 
they are killed by physical or chemical means or by a 
combination of such methods. 
There then remains only a disposal problem, the 
nature of which is determined by the composition of 
the cell mass. 
5.4 The stability and purity of process strains 
A biotechnology process will remain stable only so 
long as the microorganism(s) on which it is based 
remain unchanged. Changes in the properties of the 
organisms and in the composition of tlfefr products do 
fake place in response to the growth conditions 
employed but all such changes will be monitored by 
the manufacturer in the interests of maintaining an 
efficient and profitable process. They will be cor- 
rected long before Ihey pose a safety problem. For a 
longer discussion on “phenotypic” changes, see the 
paper by Sargeant and Evans [8]. 
Of greater significance is (he possibility 'that a 
process becomes contaminated with one or more 
organisms, most probably from the factory environ- 
ment. It is in the interest of manufacturers to protect 
industrial processes from such contamination. It has 
been suggested that mutation of a process strain 
might occur and that the mutant might be pathogenic. 
The DECHEMA report |2| deals with this subject at 
some length and concludes that this possibility is 
extraordinarily remote. Moreover, from a theoretical 
point of view, such a mutation of a Class 1 microor- 
ganism to pathogenicity is highly unlikely and has 
never been observed. 
The cultivation of attenuated strains, however, 
needs to be monitored closely to detect back-muta- 
tion to virulence. This is the usual practice where such 
strains are used in the manufacture of vaccines. 
6. Conclusions and recommendations 
1. Biotechnology, as properly practised, is safe. 
2. Processes where pathogenic microorganisms are 
used are being contained to such an extent that 
experience shows that risks to man, animals, and 
plants are minimal. 
3. An EFB classification of microorganisms is .pro- 
posed in which one class contains organisms that /re 
harmless to man and the other classes include 
organisms in Increasing order of risk. This is intended 
to harmonise the descriptions of risk classes in the 
various national classifications. A fifth Group, E, has 
been added and this contains organisms that offer a 
more severe threat to the environment than to 
ipan. 
4. Improved techniques should be developed for the 
detection of contaminating organisms in processes 
(particularly those based on animal cell cultures) and 
in products (particularly food and feeding stuffs). 
5. Development should be directed towards reducing 
the number of processes that employ disease-pro- 
ducing microorganisms, c.g, by: 
— selecting harmless rather than hazardous micro- 
organisms for process use. In such cases experimental 
methods should be devised to detect pathogenic 
properties and to obtain assurance that new process 
strains do not present a hazard; 
— transferring genetic information related to process 
needs from harmful to harmless organisms or by 
introducing synthetic genes into harmless hosts; 
— attenuating virulent strains. 
6. In cases where the use of hazardous organisms is 
unavoidable it is recommended that: 
— the related regulations and guidelines are harmon- 
ised; 
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Recombinant DNA Research, Volume 13 
