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Quantitative Bioprocess Containment Validation

Bradley, Michael Ian; (2000) Quantitative Bioprocess Containment Validation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The safe use of genetically modified micro-organisms (GMMOs) for the industrial manufacture of therapeutic and other products depends on the design, implementation and validation of effective containment principles. This project has established a test method that can generate quantitative data on bioprocess releases that can be used to validate the containment of bioprocess equipment. A standard tracer gas leak test has been correlated with a quantitative polymerase chain reaction (QPCR) assay for the detection of GMMOs. The QPCR assay for Escherichia coli RV308 pHKY531 has been shown to be specific and have a low limit of detection (less than 50 cells in 10 μL) with a range of 6 orders of magnitude and an error of ± 0.11 logs. This assay has been used to analyse bioaerosol samples collected by an Aerojet General Cyclone. Throughout the course of the project, work has been carried out to improve the collection efficiency of a cyclone sampler and to investigate the effects of various approaches to bioaerosol sampling in a process environment. Using this method a good correlation has been observed between the spatial location of the release point and the collection efficiency of the cyclone. The release of aerosols from leaks in bioprocess equipment has been simulated by capillary tubes of various diameters and lengths. From the data presented here a value below 6 x 10 -6 cm min-1 SF6 would be recommended for an acceptable level for apiece of bioprocess equipment at a differential pressure of 2 bar. For a 5 mm leak this value is equivalent to a 3 μm diameter hole, which has been shown not to transmit a suspension of micro-organisms. The implications of these findings are discussed in relation to the validation of bioprocess containment.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Quantitative Bioprocess Containment Validation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10121018
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