NECC Tragedy: Lessons Learned about Cleanroom Environmental Conditions

As the pharmaceutical community takes on board the sheer scale of disaster wrought by the case of the New England Compounding Centre (NECC), there are critical lessons we can learn that will make decontamination more effective. Beneath the profiteering, gross negligence and other layers of criminal activity that led to this ‘killer pharmacy’ manufacturing and distributing deadly medicines, it was the cleanroom contamination by a specific fungus that caused the agonising deaths of 64 people and infected over 800 more. Aspergillus fumigatus is a fungus that is usually found in decaying organic matter like a compost heap. In this case, it came from a recycling plant situated nearby the illegal NECC manufacturing site. But how did this lethal fungus find its way into the so-called cleanroom? Among the facts brought to light by massive investigations led by the United States federal and state health officials, the Justice Department and Congress, were the discovery of: A dirty mat leading into the cleanroom area. A leaky boiler standing in a pool of stagnant water. Air intake vents positioned about 30 yards (27.4 meters) from a dust-spewing recycling plant. These points alone show how microscopic fungus particles from the external environment found their way into the cleanroom and, once there, found hospitable environments in which to thrive. Poor decontamination processes did the rest. Fungus is only one potentially deadly contaminant of course. Bacteria, viruses and chemicals must all be taken into account as well. However, fungus may be of particular concern to cleanroom decontamination. Microbiologist and journalist, Tim Sandle, wrote in 2014 for the European Pharmaceutical Review, that as much as 21% of pharmaceutical products were recalled between 2000 and 2012 due to fungal incidents. He warned, “…The contamination risk posed by fungi to pharmaceutical products is greater than the level of industrial and academic interest would suggest.” Sandle went even further, to warn that, ‘Pharmaceuticals, cosmetics, food and other products are at risk because fungi are extremely versatile and adaptive in their ability to synthesise degradative enzymes.” The tragic consequences of the NECC case make it abundantly clear that every cleanroom team, from managers to maintenance, must possess the knowledge to evaluate all environmental factors that could impact the efficacy of decontamination. In practical terms, there are five key areas that must be assessed, understood and prepared for: 1. Types of contaminants present in environment Sticking to the validated amount of time and cleaning solution should be standard practice. Where unusual types or quantities of contaminants are found to be present, revalidation of the usual cycle might be required or changes made. In the case of the NECC cleanroom, surface and air sampling over the 20 weeks before the incident detected contamination in the air and on the surfaces and even on the hands of staff. The source was traced back to a recycling plant. In another case it could be a seemingly innocuous surrounding environment such as farm land. 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. The combination of chlorine and formaldehyde for instance is well known to be a toxic cocktail, but it certainly is not the only one. The bottom line is that standard decontamination and cleaning practices should be heightened and processes revalidated until the source of unusual contamination has been found and eliminated. 2. Forces that affect distribution of fumigants The standard rule of switching electrical equipment off for the decontamination period exists for several good reasons. Most staff will be aware of the risk of mixing fluids (fumigants) and electricity, but they might 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 generally switched off, operators must be aware of the impact that exceptions to these rules could have on their decontamination cycle. 3. Soiling and spills Gaseous decontamination methods, including fumigation, vapour, spraying, and fogging, are a good solution to decontaminating hard to reach nooks and crannies in the cleanroom. At the same time, most of these will not be able to penetrate deep spills or to dislodge particles. A covering of dirt and debris will prevent the area underneath that dirty spot being decontaminated during a fumigation. This is why it’s essential for operators to be aware of the presence of contaminants that cannot be removed by air handling. In these cases, soiling and spills, if safe to do so, must be cleaned and particles removed prior to setting up for decontamination. 4. Loss of control over environmental conditions, including temperature and humidity It might seem to be stating the obvious if I point out the importance of following the manufacturer’s instructions to a ‘T’ when using any type of decontamination device (i.e. fogging, fumigation, vapour, and spraying devices). But there are less obvious factors that could be overlooked if you’re not careful. 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 getting the formula right. Measuring these two factors under stable conditions is easy enough. The tricky part is predicting the room’s condition after the cleanroom systems have been shut down for decontamination, when temperature and humidity are no longer being controlled. Operators can ensure the validity of their decontamination formula by taking into account 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 of the primary data inputs for calculating the variables of any decontamination cycle. Like any of the factors mentioned above, (presence of unusual contaminants, loss of control over temperature and humidity, etc.), the validated decontamination cycle is bound to be affected by a creep in surface parameter above a certain level. While the addition of a small stool is not likely to result in a significant change, operators must take note of the addition of any larger pieces of furniture to the cleanroom such as big work benches. Wherever the cleanroom setup has been changed or added to, 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. 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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