THE ANALYSIS OF CONTAINMENT PROBLEMS IN BIOPROCESSING INDUSTRIES IN ALL EEC NATIONS SHOULD IDENTIFY THE MOST PROBLEMATIC AREAS (COMPONENTS AND UNIT OPERATIONS) IN BIOPROCESSING METHODOLOGY. PROCESS COMPONENTS OF DIFFERENT MANUFACTURERS WILL BE TESTED IN AN AD HOC LABORATORY UNIT AND THEIR RELIABILITY ASSESSED. CONTAINMENT BREACHES WILL BE DETECTED UNDER DIFFERENT PROCESSING MODES TO INCREASE RELIABILITY.
THIS PROJECT APPEARS TO BE PARTICULARLY IMPORTANT FOR THE IMPROVEMENT OF CONTROL AND CONTAINMENT IN BIOPROCESSING.
The effectiveness of small off gas filters from five different manufacturers were tested by bacterial challenge in a specially designed test rig. The results showed that, under specified test conditions, filter penetration can be less than five particles (viable and non viable) per test. Filters from one manufacturer gave deviant results, indicating that the effectiveness of new filters should be checked on a routine basis.
The containment of a continuous centrifuge has also been analysed using a variety of techniques. These tests showed that no breach of containment is likely from the centrifuge itself, but problems have been found in the peripheral equipment and components.
The application of recombinant deoxyribonucleic acid (DNA) techniques to large scale bioprocessing has raised safety concerns in terms of exposure risk to the operator and the environment. Public perception is preventing a more rapid adoption of recombinant deoxyribonucleic acid (rDNA) bioprocesses. The possible effects on living material are not well understood. The most common form of occupational exposure is via the aerosol route into the lungs. Although the microorganisms used in the majority of biotechnological applications are unlikely to be pathogenic in themselves, the compounds they produce or express may present a risk to health, especially if the microorganism is able to colonize the body after inhalation.
Technical information on bioprocessing safety is an integral part of developing a regulatory framework in biotechnology. A review of bioprocessing risks revealed equipment and processing operations where problems might occur. The containment and risk assessment of selected unit operations and components were evaluated using methods developed in the project.
The quantification of risks in biotechnology is far more difficult than for the chemical industry, due to the lack of reliability data and gaps in the understanding of fundamental mechanisms underlying the properties of fugitive microorganisms and their products. Methods, involving the use of aerobiological samplers and particle monitors, have been applied to the containment testing of bioprocess unit operations. The need for rapid and sensitive methods to detect breaches of containment was highlighted. Tests carried out during the project have identified difficulties with fermenter off gas filters, cell disrupters and a continuous centrifuge.
THE OVERALL PROGRAMME IS DIVIDED EQUALLY BETWEEN WARREN SPRING LABORATORY (WSL,UK) AND THE INSTITUTE OF APPLIED CHEMISTRY (TNO,NL).
THE MAIN OBJECTIVES OF THE RESEARCH PROPOSAL ARE :
1-DEVELOPING MONITORING METHODS TO DETECT THE RELEASE OF MICRO-ORGANISMS FROM PROCESS PLANT.
2-TESTING CONTAINMENT PROCEDURES.
3-IMPROVING COMPONENT DESIGN AND MANUFACTURING.
4-ASSESSING RELEVANCE OF DATA FROM NUCLEAR AND CHEMICAL INDUSTRIES TO BIOPROCESSING.
5-ESTABLISHING A POOL OF INFORMATION ON RELIABILITY AND SAFETY IN BIOPROCESSING.
THE CONTRACTANT WILL UNDERTAKE TWO RESEARCH ACTIVITIES SUMMARIZED AS FOLLOWS :
ACTIVITY ONE : QUALITATIVE AND QUANTITATIVE ANALYSIS OF CONTAINMENT PROBLEMS IN LARGE SCALE BIOPROCESSING . DEVELOPING OF A GENERAL RISK ASSESSMENT MODEL FOR BIOPROCESS ACTIVITIES.
ACTIVITY THREE : DETERMINATION OF THE NATURE AND PHYSICAL MECHANISMS OF THE FAILURE FOR THE COMPONENTS OF THE BIOPROCESSES. ESTABLISHING OPERATING GUIDELINESS FOR THE CONSTRUCTION, INSTALLATION AND USE OF PROCESS COMPONENTS IN ORDER TO SAFEGUARD CONTAINMENT INTEGRITY AND TO CONTROL BREACHES OF CONTAINMENT.