Cleanroom Particle Monitoring "What data means to you?"

Imagine you have such set of data for any location from your particle monitoring system;

Think about it for a second. What does this data alone mean for you? Is this data valuable as it is now? Or are there any other contributors you need to analyze and make useful for your cleanroom and production??

Most end users are collecting particle count data from their state-of-art online particle monitoring systems, however, due to a lack of data analysis and assessment, either they overestimate conditions and take unnecessary actions which creates another chain of failures, or neglect major issues and assume that they are safe, just because they have a monitoring system in place.

If you look at the table again, these numbers can be anything. Without proper records attached to these numbers such as units, time, location, cleanroom class, occupancy, location status (during active production or passive conditions), or data tags such as operators' alarm acknowledgment notes, this doesn’t mean anything to anyone. These numbers, in tandem, could be the author's mobile number too.

Even warning and alarm conditions as per predefined limits, data analysis, and assessment are critical. Let’s complete all missing parameters and analyze data again;

Now we have all we need to analyze and interpret this alarm condition. First of all; we got much valuable information about conditions during this alarm;

• This alarm happened at the turn table from aseptic vial production,
• It was during production,
• Alarm status caused by operators’ intervention, not due to routine production conditions,
• Alarm ended right after this intervention and particle counts back to their normal conditions

?We know now that this kind of alarm with known sources is easy to manage. The only thing, for now, is to monitor if this vial break has not become a route and operator interventions are not too often. Also, studying potential failure modes and testing them during media fill is critical here to determine alarms and their results on product quality and patient health. Try to limit your operator's alarm acknowledgment sentences. Good practice here is to limit them to predefined texts which are tested scenarios during media fill. Other alarm reasons will help you to investigate and address problems other than sweep them under the carpet.?

If the alarm is not addressed and repeats itself frequently, now this is something that you should investigate. Not because meet guideline and criteria, but to avoid potential risks for the patient and your product which can end up being fatal results. Having an online monitoring system, collecting data, printing them for batch records, and acknowledging alarms are not our ultimate targets.?

Trend Reports

The same approach is valid for trend reports. Trends are not just taking the same location data in certain time periods like year over year. It doesn't prove anything to anyone if you are just taking the same day in 2 different years. Also will not help you to identify system conditions and year-over-year status. However, if you apply trends to the same location for the same period of each batch and get the data with statistics such as average, mean, and standard deviation, this can help you to analyze data and to see the difference.

Searching peak repeats will help you to understand if they are just irregular peaks or happens right at the same time as the same event. For example, getting a peak every time at the stopper bowl location right after adding more stoppers indicates poor design and needs attention. Or peak counts at the turn table right after opening the depyranization tunnel shouldn't be repeating alarm conditions. As stated in GMP Annex 1; ” However consecutive or regular counting of low levels is an indicator of a possible contamination event and should be investigated. Such events may indicate early failure of the HVAC system, filling equipment failure or may also be diagnostic of poor practices during machine set-up and routine operation”. Standard deviation can help you to identify the trend of your average data. If your standard deviation increases event by event, this may help you to diagnose the early failure of your entire design.?

Data Tables and Graphs

Like in trends, having all location data printed for your batch records may not help you. Over 100 pages of data in your batch records may become a stack of papers in the long run. Since the entire software platform is validated and all data captured in your database securely, having alarm event report and audit trial printouts will assist you to evaluate current condition, production health, alarm conditions, and their acknowledgments; whether all alarms and their acknowledgments are based on what you study during media fill or something else that you need to take an action.?

Question : Can we extend our classification period if we have an online monitoring system in place?

Answer : At a certain level, yes, you can. For example, if your routine is every month, you can do it for 3 months first for the next 4 cycles, if data is okay (within limits without any deviation) then you can go 6 months, 8 months, etc, depending on your cleanroom Grade. However, you can't extend it more than 6 months for Grade A and B & 12 months for Grade C and D areas in GMP-regulated cleanrooms. You can consider it reverse; you can increase the frequency of your classification if you don't have a monitoring system in place. This will never cover you 100%, especially for critical operations, however, for Grade B and Grade C areas, you can rely on your classification data with an increased sampling period.

Our next newsletter will be covering cleanroom particle monitoring system maintenance. Please send your related questions so I can cover them in my coming newsletter too. If you know someone that might find this newsletter useful, please forward or notify them by simply tagging them in the comment section. See you again on the 27th of July!