Guidelines for Good Manufacturing Practices (or GMP) require that a production zone for sterile drug manufacturing is subject to environmental monitoring. The goal of environmental monitoring is to assure that the cleanroom meets its specifications (according to ISO 14644-1) and the risk of contamination of the final product is minimal (routine monitoring).
Certain critical locations in the cleanroom might require daily routine monitoring by a combination of environmental monitoring tests such as active air sampling, settle plate sampling, contact plates, swabs etc.
This leads to complex sample plans in which there are dozens of daily samples to be taken, analysed, reported, reviewed, and trended. Unfortunately, this environmental monitoring sampling process is mostly done manually and managed on paper, which is outright burdensome for the cleanroom operators and is often a source of data integrity issues.
Digitalisation, a no-brainer?
Because of its highly routine and standardised nature, environmental monitoring sampling is a prime candidate for digitalisation.
For example, in the MyCellHub EM module, a digital master sampling plan can be generated based on a floorplan of the facility. By making use of tablets, operators are actively guided to the right sampling location and receive interactive work instructions that are appropriate to the classification of the zone where they are in and the type of sampling they need to perform.
Instead of writing down the sampling location by hand on the lid of the sampling plates, operators can use the camera of the tablet to link the barcode on the environmental monitoring plates to the exact sampling action. Once sample results are known, they are automatically checked against the right specifications and a warning for any type of excursion versus the reference can be sent out to all stakeholders automatically. Eventually, all this collected data is automatically turned into a trending report per room and sample point with the single click of a button.
Digitalisation of environmental monitoring workflows can clearly provide value. The value of digitalising GMP workflows lies generally on 3 levels:
One: Reduction of errors
By making use of interactive work instructions, operators are proactively warned about sample points that are skipped, contact plates that might be used twice by accident, settle plates that need to be closed in time, or the use of plates that are past their expiry date, etc. Every prevented error is a win for product safety and significantly reduces the workload of downstream effects of dealing with corrective and preventive actions.
Two: Streamlining compliance
By working digitally, a built-in computer-generated audit trail makes it 100% irrevocable who did what and when. Since data is accessible to all stakeholders the moment it is entered into the system, this also allows for the QC and QA departments to observe closely and react rapidly.
Three: Time gains
While time gains are often secondary to product safety for many cleanroom manufacturing processes, in the case of environmental monitoring they go hand in hand. Speed is critical, especially for the detection of viable contaminations in the environmental monitoring samples. The bioburden in the form of bacteria or yeasts often grows exponentially at a certain sampling location.
With this type of growth dynamics, detecting contamination just one day earlier can make a significant difference to product safety.
Therefore, having access to environmental monitoring (trending) data as close as possible to the moment of sampling is important. When working on paper, collecting all this data from all sample points in the whole facility and manually entering sample results in a spreadsheet to make the (regulatory required) trending of the environmental data per room and per sample point is a mind-numbing task that often takes weeks to complete.
As a result, some cleanroom facilities only look quarterly at their trending data, while clearly, more frequent trending could potentially signal issues earlier. Additionally, enabling highly skilled cleanroom operators to carry out boring and repetitive jobs faster and effortlessly directly frees up time for more value-added tasks which benefits both operator and employer.
From operational efficiency to operational agility
While digitalising environmental monitoring workflows makes sense from an operational point of view, the paradigm shift in value creation comes when data silos are broken down and data from different sources get integrated to make better informed decisions about cleanroom operations.
Take the example where a vial is dropped by accident during production. Manufacturing operators will report the event in the batch record, the operators doing the environmental monitoring will record an out-of-spec value in the particle counts and the cleaning team will report that they had to do an additional cleaning task.
Take the example where a vial is dropped by accident during production...
In a paper system where these three records each have their own chain of custody that gets reviewed and approved at different times, it might result in three separate incident reports that each generate work downstream. In a horizontally integrated system where electronic batch records, digital environmental monitoring reports and digital cleaning reports are available, these three elements would be flagged automatically, making it significantly easier for a reviewer to see that these are related which drastically reduces the time spent on the downstream paperwork.
With the right amount of contextualised data gathered by working digitally, the integration can be pushed even further.
For example, it’s not unthinkable that with the help of a dedicated algorithm, the software decides automatically that an additional cleaning task needs to be scheduled after a spill is reported and wraps up the required documentation about the spill, the resulting particle count excursion, and the additional cleaning task without the need for direct operator involvement.
It’s not unthinkable that with the help of a dedicated algorithm, the software decides automatically that an additional cleaning task needs to be scheduled after a spill
By combining the data of batch records and environmental monitoring data, the most likely sources of contamination (either human or technical) can be identified algorithmically, and proactive measures can be taken to prevent them.
Or to stress the need for fast trending of environmental monitoring data even more, again here with sufficient data on environmental monitoring results from the various locations of the cleanroom, it’s not unlikely that algorithms can predict which zones are at risk even before the contamination is detectable by the routine environmental monitoring and issues can be prevented by proactively updating the cleanroom cleaning schedule or cleaning agent rotation.
It’s this type of data-driven methodologies that enables our customers to unlock operational agility and streamline operations in GMP to ultimately drive down costs of manufacturing without making concessions on product quality. Check out how to get started with digitalising environmental monitoring, cleanroom cleaning and batch records with MyCellHub.
