Designing out contamination

Effective microbiological control is key to ensuring product safety, quality and image. In the event of a contamination incident the advice is to focus on looking for changes in raw material specs, equipment design failure, formulation or process error. While cleaning and sanitisation systems are crucial, preventative measures such as careful design of pipework and operation of supporting services, such as vacuum and vent systems, can radically reduce the risk of microbiological contamination

Recent events in the food sector have shown that product recalls can destroy companies in a few weeks. Susan Birks reports on the recent Pharmig conference in Oxford, UK, which looked at ways of preventing, anticipating and also managing damaging recalls in the cosmetics and toiletries industry.

Product recalls were fresh in delegates’ minds at the recent Pharmig conference, as the ‘horsemeat in beefburgers scandal’ was still making newspaper headlines. The conference, aimed at the personal care industry but of relevance to pharma and food sectors too, covered several topics including: recent legislative changes; microbiological and contamination issues; and managing product recalls – so it had a particular poignancy.

Brand image is crucial to all these sectors and effective microbiological control is key to ensuring product safety, quality and image – thus protecting a company’s bottom line. But speaker David Keen, Microbiology Manager, GlaxoSmithKline (GSK), highlighted the unique difficulties that microbiology departments face in communicating contamination risks to other departments.

‘Factory managers find microbiology issues the most difficult to comprehend,’ he said. This is in part due to the fact that, in all other areas ‘an issue is an issue’ but in the case of microbiology, products can rapidly change from being ‘in spec’ to ‘out of spec’ and back in spec. ‘Deciding if there is an issue is complex, even for a microbiologist,’ Keen admitted.

By the time any microbiological results come through in the event of an issue, it will be too late, as the product would be on the shelves

Nor can industry rely on sampling, as by the time any microbiological results come through in the event of an issue, it will be too late, as by then the product would be on the shelves – hence, manufacturers have to take preventative measures.

Microbes can also react in unusual ways, making product spoilage unpredictable, and while preservative systems are often present, delegates were reminded that these are employed to cover ‘product use by the consumer’ and should not be relied upon to kill contamination during production.

In spite of a growing understanding and experience of microbes within research institutions, these tiny organisms maintain the ability to surprise. Microbes can survive in the most unexpected and hostile environments, including soap bars, talc, or in some cases, the very disinfectants used to clean facilities. Microbes can also form biofilms that, once formed, will not be removed by the usual disinfection action.

Willy Verstraete of LabMET, University of Ghent, Belgium, shared some of the latest research that suggests microbes evolve and organise themselves into teams (microbiomes) and are capable of sending chemical signals to each other. The signals may be used to tell other microbes to move closer so that they can exchange metabolites. The result can be a change of behaviour and biofilm formation can be the result.

Resistance is futile

The realisation that microbes work in teams (or exist in microbiomes) has led to a better understanding of population dynamics and why some microbes thrive in the company of others. Their complexity is only just being understood. Verstraete talked of a future in which we will manage microbes and microbiomes, using them to address everything from health issues – such as autism – to climate change. And with up to 10,000 microbes per 1g of soil, there are plenty of subjects to work with.

Unfortunately microbes often seem to be one step ahead of humans, and their ability to build resistance to preservatives and sanitisers makes the microbiologist’s job more difficult

Unfortunately microbes often seem to be one step ahead of humans, and their ability to build resistance to preservatives and sanitisers makes the microbiologist’s job more difficult – as highlighted by Alan Whipple, Microbiology Lead, GSK Microbiological. If bacteria find dilute product lying around in a production system they will breed and grow resistance to the diluted preservative system, he said, and this could mean that on starting the next batch of shampoo, for example, the bacteria would be able to grow unchecked.

Whipple looked at how gross failures most often occur and should be dealt with. ‘A typical reaction to product contamination is to do a lab investigation and go out and swab everything, or review environmental monitoring data,’ he said. But this won’t tell us what happened because the air around the product is unlikely to be the cause. This is because processes are usually closed and the organisms in the environment are unlikely to survive the preservative.

The environment is only a concern when linked to other GMP issues, such as storage of wet equipment, or open processing. ‘This is something we need to recognise when setting up monitoring plans,’ he said. His advice was to focus on looking for changes in raw material specs, equipment design failure, formulation or process error.

One area Whipple highlighted as a frequent culprit was the design and operation of supporting services, such as vacuum and vent systems (see Figure 1). These are designed to draw the materials away from the production system but, if they fail, there can be problems of suck back. He also believes that use of non-return valves is effectively shutting the door after the horse has bolted: ‘They do not close quickly enough and you will find unwanted product in them.’

Figure 1: A typical process set-up to consider how microbes could be introduced into the process. When vacuum and vent systems fail they can cause of microbiological problems
Slide: Alan Whipple, GSK Microbiological

Whipple said some 70% of failures he experienced have been from vacuum pumps. ‘They are poorly understood by operators and rarely monitored,’ he said.

He recommended:

  • Defined valve/vac pump sequences for vacuum
  • Sanitise vacuum pipework
  • Vacuum pumps on uninterruptible power supply
  • Independent vents/interlocking valves
  • Pressure recording

In terms of cleaning and sanitisation, if using steam, drainage is key. ‘Think of where condensates will form and design in drains and valves to run off condensate,’ he suggested. He also warned that when using steam, it condenses and causes a vacuum with the potential to draw in contaminated air, particularly at drain points. This risk can be avoided by ensuring air breaks with drains and by maintaining positive pressure with compressed air during cooling. He suggested that when using compressed air, avoid negative pressures, and filter the air.

Be wary of product formulation changes, as this can mean that production procedures also need changing

Another key point that Whipple raised was to be wary of product formulation changes, as this can mean that production procedures also need changing. He suggested that the recent rise in mouthwash recalls was because new alcohol-free products were being made on the same equipment as the alcohol-based formulations but ‘without the alcohol, the microbes were winning’.

Leigh Holt, EMEA Beauty Care Regional Microbiologist, P&G, looked at all aspects of cleaning and sanitisation and said the key to preventing contamination was making the plant ‘hygienic in design, cleanable- and sanitisable-in-place and drainable’.

Improve plant design

P&G is in the process of rationalising its equipment across all sites to make it easier to clean or cleanable in place. The company is moving to heat sanitisation, he said, because there is no guarantee that chemical agents will get to all the surfaces.

His department goes to great lengths in checking the plant design. His advice included: using a supplier’s mapping techniques to ensure spray balls reach all areas; check using spirit levels that pipes are sloping, as horizontal pipes will trap fluids; do not have pipes overhead where you can’t get at them to clean or sanitise them; avoid dead legs (branches of pipe blanked or not used, through which cleaning fluids cannot flow) or flat tops where microbes can gather; and avoid T configurations with valves.

GEA Hygienic Design’s Andrew Ball and Hisham Fyyaz gave further advice on designing out dead legs, ensuring good drainage and cleanability (see Figure 2).

Figure 2: GEA showed how to make pipework hygienic by avoiding dead legs and T connections that restrict the flow of cleaning agents

David Keen (GSK) advised delegates to be wary of environmental aerosols, which can be a vector for spreading microbes. ‘Aerosols created by a pressure hose when cleaning, for example, will spread microbes at a great rate into the air and around the plant.’ Even the air pistons used in doors have been known to spread mould, he said.

Most recalls happen on a Friday afternoon – not a good time to find out you that don’t know all the steps

Preparing for a recall sounds like being ultra cautious, but Breda Quinn, Seven Seas, (Merck CH), recommends from 20 years’ experience in the pharmaceutical industry that running a mock recall annually, and checking that traceability works, is well worth the effort. ‘Be sure to check that you have documented all the steps in your processes, especially any changes introduced,’ she said. ‘Most recalls happen on a Friday afternoon – not a good time to find out you that don’t know all the steps.’

When faced with a real recall situation, the clock is ticking, big money is at stake and decisions have to be made quickly, with sales directors, managers and delivery companies all wanting immediate answers. To manage the situation effectively, Quinn advises:

  • Gather a team to manage the issue and investigation
  • Gather the actual facts quickly – don’t make assumptions
  • Assign tasks based on skills and knowledge (this avoids duplication of work or worse, people assuming someone else is doing it)
  • Meet frequently – morning and evening
  • Keep good notes, as these will help when writing up the report afterwards

Quinn recommends a proactive risk-based approach to quality management rather than a reactive one – which will ultimately prevent recalls in the future.

The seminar ended with a presentation by Dr Anthony Hilton, Head of Biology & Biomedical Science, Aston University who featured in the UK TV series Grime Scene Investigation, a show that took a novel approach to engaging the public in the science of microbiology.

Dr Hilton and comedian Rufus Hound took a mobile lab round the country to reveal the hidden world of microbes. They found plenty of undesirable bugs lurking in ordinary family homes and in those of not so ordinary co-habiting students. Once again, microbe misconceptions were highlighted. The sampling found frequent contact points in urban locations thought likely to be swarming with microbes – doors, hand rails, cash points – were relatively clean, whereas families in country dwellings were more at risk from microbes arising from owning pet dogs or horses.

Male students were found to have a largely ambivalent attitude to hygiene, leaving food around and not cleaning surfaces, but girls were equally at risk from sharing very old make-up products with friends, such as mascara, which had over time become a breeding ground for microbes.

For details of the next conference visit the Pharmig website at www.pharmig.org.

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