NECC Tragedy: Lessons Learned about Cleanroom Environmental Conditions
By Andy Whittard
Industry needs to learn from NECC scandal
The New England Compounding Centre (NECC) scandal resulted in over 60 deaths and more than 800 cases of serious illness. Profiteering, negligence and other criminal activity were all contributory factors that led to this so-called “killer pharmacy” manufacturing and distributing deadly medicines, but it was cleanroom contamination that had the most serious impact, with products reaching consumers that contained a particular fungus. Critical lessons need to be learned and acted upon to make decontamination more effective, and avoid similar incidents occurring.
Aspergillus fumigatus is usually found in decaying organic matter, such as compost heaps. In the NECC case, the source was a recycling plant located near the manufacturing site. But the question is, how did this lethal fungus find its way into the company’s so-called cleanroom?
Investigations led by US federal and state health officials, the Justice Department and Congress discovered multiple issues. These included a dirty mat leading into the cleanroom area, a leaky boiler standing in a pool of stagnant water, and air intake vents positioned less than 30 meters from a recycling plant expelling large amounts of dust. These points of weakness enabled microscopic fungus particles to penetrate the cleanroom, where they found hospitable environments in which to thrive. Poor decontamination processes did the rest, with tragic consequences.
Fungi’s adaptability poses significant risk, all staff must be aware
In 2014, microbiologist and journalist Tim Sandle wrote in the European Pharmaceutical Review that, over 2000-2012, as much as 21% of pharmaceutical products were recalled due to fungal incidents. Sandle warned: “The contamination risk posed by fungi to pharmaceutical products is greater than the level of industrial and academic interest would suggest. [...] Pharmaceuticals, cosmetics, food and other products are at risk because fungi are extremely versatile and adaptive in their ability to synthesise degradative enzymes.”
While fungus may be of particular concern regarding cleanroom decontamination, it is only one potentially deadly contaminant: bacteria, viruses and chemicals must also be considered. The tragic consequences of the NECC case highlight the fact that every member of the cleanroom team, from managers to maintenance staff, must be sufficiently trained to be able to evaluate the environmental factors that could impact the efficacy of decontamination processes.
In practical terms, five key areas must be assessed, understood and prepared for:
1. Types of contaminants in the environment Adherence to the validated amount of time and cleaning solution used should be standard practice. Where unusual types or quantities of contaminants are discovered, revalidation of the usual cycle might be required, or changes necessary.
In the case of the NECC cleanroom, surface and air sampling conducted over the 20 weeks prior to the incident detected contamination in the air, on surfaces, and even on the hands of staff, with the source traced to the recycling plant mentioned above. Elsewhere, a seemingly innocuous nearby environment such as farmland could be the source of such contamination.
Chemical particles can affect the decontamination cycle by reacting with fumigants to create entirely new particles. These newly created contaminants could be poisonous and corrosive to cleanroom surfaces. Chlorine and formaldehyde is a well-known toxic combination, for example, but certainly not the only one. The bottom line is that standard decontamination and cleaning practices should be intensified and processes revalidated until the source of unusual contamination is identified and eliminated.
2. Forces affecting distribution of fumigants Switching off electrical equipment for the decontamination period is standard practise for several reasons. Most staff will be aware of the risks associated with mixing fluids (fumigants) and electricity, but may not be aware of the repelling effect that electrostatic charge could have on the distribution of fumigants.
While personal electronic devices are usually banned from the cleanroom, and equipment is generally switched off, operators must understand the impact that any failure to follow these practises could have on the decontamination process: personal equipment could represent a source of contamination, and the harsh chemicals used in cleaning could damage monitoring devices, potentially reducing their effectiveness and lifespan.
3. Soiling and spills Gaseous decontamination methods, including fumigation, vapour, spraying and fogging, are good solutions when seeking to decontaminate difficult-to-reach nooks and crannies in the cleanroom. Most of these will be unable to penetrate deep spills or dislodge particles, however. Layers of dirt and debris will prevent the area beneath the dirt being decontaminated during fumigation.
It’s therefore essential that operators are aware of the presence of contaminants that cannot be removed by air handling. In these cases, soiling and spills must be cleaned and particles removed prior to setting up for decontamination, if it is safe to do so.
4. Loss of control over environmental conditions, including temperature and humidity It’s important to follow the manufacturer’s instructions when using any type of decontamination device, whether fogging, fumigation, vapour or spraying – but there are less obvious factors that could be overlooked.
In the case of the Minncare Dry Fog systems, for example, the manufacturer supplies an automated calculation sheet that computes an effective decontamination formula (quantities of different solutions and decontamination period) based on cleanroom-specific data provided by the user. ‘Room temperature’ and ‘relative humidity in the room’ are two essential factors in achieving the correct formula.
Measuring these two variables under stable conditions is easy enough; the difficulty is in predicting the room’s condition after shutting down the cleanroom systems for decontamination, when temperature and humidity are no longer controlled. Operators can ensure the validity of their decontamination formula by considering external environmental conditions, and adapting the room’s conditions prior to decontamination accordingly.
5. Surface area parameters: furniture and large objects Surface area is another primary data input for calculating the variables of any decontamination cycle. Like any of the factors mentioned above, the validated decontamination cycle is bound to be affected by a creep in surface parameters above a certain level. While small items of furniture are unlikely to result in significant change, any more substantial pieces of furniture that may be introduced to the cleanroom, such as large workbenches, must be noted. Wherever the cleanroom setup has changed, the positioning of the decontamination unit should be reconsidered, and the cycle revalidated.
Stick to validated parameters and look out for anomalies
Cleanroom decontamination cycles are validated for specific parameters, including the normal range of environmental conditions. Educating staff, following procedures and adhering to best-practice guidelines are essential to avoiding further incidents with consequences like those arising from the NECC case. By being aware and proactive, operators can ensure that changes in the cleanroom and the broader environment are accounted for, and their impact on the decontamination cycle neutralised.
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