of environmental risks and containment of biotechnological scaled-up processes
The introduction of recombinant DNA techniques into large-scale bioprocessing
has raised safety concerns, and in particular those about the risks of
exposure of the operator and environment. Public perception of this risk
is preventing more rapid adoption of recombinant DNA bioprocesses. The
most common form of occupational exposure is from air via the respiratory
route into the lungs. Although the micro-organisms used in the majority
of biotechnological processes are unlikely to be pathogenic in themselves,
the molecules they produce or express may in some cases present a health
risk if the micro-organism is able to colonise the body following inhalation.
Approach and methodology
Technical information about bioprocessing safety is an integral part of
the developing regulatory framework in biotechnology. A review of risks
associated with bioprocessing revealed equipment and processing operations
where problems might occur. The project developed and used methods to
assess risk and containment for selected unit operations and components.
Main findings and outcome
The evaluation of risks in biotechnology is far more difficult than that
for the chemical industry. This is mainly due to the lack of reliability
of data and gaps in knowledge about fundamental mechanisms underlying
the properties of fugitive micro-organisms and their products. Various
methods involving the use of aerobiological samplers and particle monitors
were applied to containment testing of bioprocess unit operations. The
project identified the need for rapid and sensitive methods for detecting
breaches of containment. Indeed, tests carried out during the project
identified difficulties with fermenter off-gas filters, cell disrupters,
and a continuous centrifuge.
The application of a biochemical method, the ATP assay, to aerobiology
was found to be particularly effective for the rapid determination of
microbiological emissions from equipment. The fermenter air filtration
test apparatus was acknowledged by industrialists to be an excellent design
which addressed many of the problems limiting previous research work in
the field and the testing procedure has recently (2000) been submitted
to EHEDG (European Hygienic Equipment Design Group) to become a standard.
J., Deans J.S., Logtenberg M.T., Hesselink P.G.M., Stewart I.W.,
Risk Assessment in Industrial Biotechnology.
Agro-Industry Hi-Tech, May 1992, pp. 26-28.
Hesselink P.G.M., Kastelein J. and Logtenberg M.T., Biosafety
Aspects of Biotechnological Processes; Testing and Evaluating Equipment
and Components, in Fermentation Technologies: Industrial
Applications, edited by Pak-Lam YU, Department of Biotechnology,
Massey University, Palmerston North, New Zealand, Elesevier Applied
Science, London and New York.
Kastelein J., Logtenberg M.T. and Hesselink P.G.M., Testing
and Evaluation of off-gas filters for bioreactors by a new bacterial
aerosol challenge test method (TBAC).
Enzyme Microb. Technol., 1992, vol. 14 July, pp. 553-560.
June 1986 December 1989
TNO Environment, Energy and Process Innovation