Bioquell has launched a white paper discussing the role and requirements of a modern bio-decontamination solution.
It explores the key areas that need to be considered when seeking a solution and provides an illustration of the application of hydrogen-peroxide vapour bio-decontamination technology within the biological production industry.
According to Richard Lucas of Bioquell, the utilisation of mammalian or bacterial cell lines in the production of modern drug or cellular therapies represents a considerable challenge to the maintenance of clean facilities.
The conditions required for the growth, culture and maintenance of these cellular factories present an ideal environment for the accidental culture of extraneous, undesired biological contaminants such as viruses and microbes as well as material such as spores, fungi and mycoplasma.
The increase in size and scale of bioprocessing also presents a challenge.
Traditional methods of sterilisation such as steam and manual cleaning become increasingly difficult to deploy in large, complex production areas in a controlled and regulatory compliant manner.
Historically, the production of classic small-molecule drug products has predominantly been performed chemically, in an environment hostile to the presence and culture of most biological contaminants.
These products are commonly amenable to terminal gamma or steam sterilisation ensuring the integrity of the product at the point of final packing or filling.
Modern biopharmaceuticals present a multiple challenge when considering the need to present a safe and defined final product at the point of patient contact.
Biological products are manufactured in complex production lines commonly involving seeding trains, bioreactors and numerous clearing and filtration steps in order to produce the desired final product.
A number of these production steps present opportunities for contamination to be introduced or even cultured alongside the desired cell line.
The contamination may be critical to process integrity or may merely reduce cell titre in seeding.
However, modern in-line process monitoring and recording has raised the challenge of maintaining critical parameters across a production line to ensure batch-to-batch consistency in order to meet increasing levels of regulatory compliance.
Although a particular contaminant may be the specific cause for concern, a bio-decontamination method should ideally display broad spectrum efficacy against any potential contaminant, minimising the need for additional cleaning procedures.
The commonly employed Geobacillus stearothermophilus biological indicators are representative of the most difficult classification of organisms to kill; they are bacterial endospores and thus act as a strong surrogate for evidence of deactivation of other biological entities.
Deployment of a bio-decontamination technique in these heavily regulated environments increasingly requires the use of controlled and monitored processes that by definition can be validated to ensure efficacy.
This is in strong contradiction to the formaldehyde fumigation method of room and facility decontamination.
This inherently uncontrolled and unmonitored process presents challenges in generating data on actual contact times of the biocide with the environment, as well as presenting a considerable risk to the health of staff - formaldehyde being recently classified by WHO as a human carcinogen.
Maintenance of clean-room conditions is inherently dependent on appropriate operator protection and a sizable effort is employed in ensuring that the workforce minimises contaminants brought into monitored environments.
Of equal concern is the movement of materials into and out of clean rooms - both in terms of the prevention of outside contaminants entering a cleanroom through, for example, maintenance equipment, monitoring equipment and support equipment.
In many instances this equipment is not amenable to steam sterilisation - for example in an autoclave.
There are a number of both in-house and external benefits to carrying out a proactive decontamination - namely the preparation of plans for facility decontamination are already in place so any emergency work required following the outbreak of contamination can be deployed more rapidly.
The ability to synchronise any scheduled maintenance downtime with a decontamination cycle also ensures minimisation of the risk of contamination of an area by any maintenance work, while also ensuring that bio-burden levels are proactively kept to an absolute minimum.
From a regulatory standpoint, having a bio-decontamination plan in place prior to any outbreak reassures the regulator that the plan of action was put together in a defined and logical manner, and prior validation of the efficacy of a cycle assists in demonstrating efficacy of decontamination.
As transfer in and out of production areas comes under regulatory supervision and classical spray-and-wipe manual methods face the challenge of validation, Bioquell provides equipment for the rapid entry and exit of equipment and materials into and out of areas through whole solution material-transfer products.
Load presentation is critical to successful validation of these processes and represents a significant part of the validation procedure for material transfer solutions; validation of 'worst case' loads ensures confidence in this critical process.
The regulatory aspects of qualification (validation) generally relate to being able to prove in a definitive way, typically by documented evidence, that the equipment complies with the specifications; that the critical parameters of the processes are under control; that the process parameters are repeatable and that there is an adequate margin of safety in the process to take account of minor variations in the process performance or environmental conditions.
The paper concludes that hydrogen-peroxide vapour represents a rapid, integratable technique for the residue-free bio-decontamination of both routine and challenging areas within a Biotech production facility, while allowing the maintenance of clean-room integrity, the protection of workforce and the protection of product through integrated material-transfer solutions.
