Your Environmental Monitoring System (EMS): the frontline between your product and contamination. Or, at least, letting you know there is contamination so you can determine what the problem is and fix it!
This means that an effective EMS is able to recognize when things are going wrong. The cornerstone of this process is conducting a Performance Qualification (PQ) that forces it into operational errors to ensure the system is handling and notifying operators of these errors. You should test your Standard Operational Procedures (SOPs) against the error to validate the effectiveness and how the event is handled.
A Performance Qualification (PQ) verifies that the EMS works properly and detects issues. A high-quality EMS is conducted from both a science- and risk-based approach, based on product and process knowledge, to define qualifications. An in-depth assessment allows you to understand the system in a real-world context. While the vendor for your EMS will usually conduct the PQ, you should be there to witness it and truly experience your system. This is an opportunity for everyone involved to understand the system truly and learn valuable information.
So what exactly goes into a PQ?
This is one of the most significant PQ tests. In real-time monitoring, alarm limits are set based on particle counter flowrate and update rate. EU GMP Annex 1 cGMP states that the sample volume should not be that which is used in Cleanroom Certification following ISO 14644-1, and the update rate should be based on the sample period time of the particle counter. That time period is usually about one minute.
Incorrectly applying the particle count and volume count thresholds from ISO 14644-1 to real-time monitoring puts you at risk for setting your alarming system up with an unworkable sensitivity.
This validation serves to determine the probability of events. Thus, we recommend using a risk assessment to produce a science-based approach to set your probability. This validation defines two probabilities: an event will turn into a detrimental trend that affects product quality and the probability of an event having viable particles in the environment.
So long as no one is in the cleanroom and the filing line and air barriers are working, the probability of viable particles is low. This can be backed up during the PQ with an active air sample and settle plate data. The air sampling should be downstream of the process.
Here at Lighthouse, we offer testing to verify this down to the microbe level using air sampling monitoring data.
This verification depends on the location of the particle counter sample probe. The location should be near critical zones. There are two major considerations to consider when placing your Isokinetic Sample Probe (ISP): its height and interference in process or airflow.
Its placement has a major impact on meaningful data collected. So it should not interfere with your process or airflow and be at the appropriate height for your industry.
Since you and your vendor will be purposely generating alarms, you will have the opportunity to learn how your system reports on real-time events and the process dynamics. This includes understanding what type of reports should be generated in different scenarios. These reports go very in-depth, and understanding the process can answer questions like:
- Do we need to cover data analytics?
- Can we find the root cause confidently and without bringing in the whole micro team?
- Do you see the same particle signature when one operator is in the cleanroom? And is that operator a repeat offender?
- Is the probability strategy working effectively?
- Are you confident if you have 5 out of 7 high alarms that the probability of product contamination is low?
- Do alarms need to be adjusted?
To an auditor, how you react to an event is more important than the event itself. That is where this part of the PQ for your Environmental Monitoring System comes into play. Did you follow an SOP once an EMS alarm is recorded? Did you note if this event is a trend or a one-time occurrence? How effective was your SOP? What decisions were made within and outside of the SOP? How were the decisions made? Are operator training records up-to-date? Have operators been properly trained?
An excellent vendor will not gloss over this component of the PQ. While this is testing personnel more than the equipment itself, understanding the combination will make or break the system. If your SOPs are not working correctly with the EMS, one or the other needs to be addressed.
The operator is the most significant risk to the filling line during the filling process. To test how effective operator interventions are, you should conduct simulation or real-time media testing runs during the PQ of the Environmental Monitoring System. These interventions should only be required when absolutely necessary, for example, in the event of a broken piece of equipment. Whatever intervention occurs, it should be validated. Additionally, particle count data and microbial data should be evaluated to determine the impact of the intervention. Tag your comments in your EMS to organize them.
Particle counters - like any other piece of equipment - require regulation calibration. Unfortunately, this is often overlooked in PQs but is critically important. These calibrations should be done annually, at the bare minimum, based on manufacturer and GMP requirements. Routine service should be an SOP to record that the particle counter has been put into service status through the EMS software. To complete the calibration, carefully remove the particle counter and send it out for service. Use a spare unit to test the location while that is out for serving.
Here at Lighthouse, we offer location IDs embedded in our smart bracket technology. This means that we can offer a true plug-and-play validated system that assures the data is always from that particular location.
What happens if you lose all your data and audit trails? Your backup and recovery process is a critical part of your Environmental Monitoring System (EMS) and needs to be carefully examined during the PQ.
Particle monitoring data is GMP data, which means there should be a couple of layers for the data backup. We recommend using a particle counter with data buffers built into it. This will ensure a few days’ worth of data is stored. With the correct integrations, the data can be automatically uploaded to a secure (21CFR11 compliant database. Manual options exist, as well. As you determine what your backup and recovery strategy is, consider these questions:
- Is the EMS software or external vacuum used to pull samples through remote particle counters on a redundant system?
- Are these on the facility UPS grid?
- What happens in the event of an EMS server failure?
- Is there an automatic redundant EMS server running in the background waiting to take over?
- Is the system set up on a virtual server?
- What is the business impact?
- How long does this recovery take?
- Is it automatic, and will the data be purged from the backup server to the secure data server?
- Does the EMS or particle counter vendor have remote technical or on-site technical services available?
- Are they 24/7?
- Are we in compliance with GMP Annex 11?
- Do we have spare instruments and parts to minimize downtime?
- Is the system a plug-and-play setup?
- How much manual technical support do you need?
- Do you have a Service Level Agreement in place?
- What is the escalation process?
Change control documentation is a critical part of an audit trail. The last thing you want is an auditor looking at your EMS audit trail and noticing alarm limits were changed six months ago, but no change control documentation is there to support the change. This is NOT a process you want to rush or skip over to get the cleanroom up and running. It’ll only cause problems later on. Implementing a strong Change Control process will mitigate against overlooked issues around the system changes.
The validation process of an Environmental Monitoring System is what sets you up for success. After spending the time and money on the right EMS, you don’t want to skip this part to get production going. More than that, you want to make the most of the PQ process so you can learn and understand your system.
While we think that DIY-ing things around your home is great, we highly recommend working with a thorough professional to validate your EMS. Having someone walk you through this process and genuinely acquaint you with your system is the difference between a successful cleanroom and midnight calls to several different IT departments.
So if you’re ready to set your cleanroom up for ease-of-mind success, give us a call.
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