Cleanroom environmental monitoring system

01

Set the grades, locations and limits

EU GMP Annex 1 (August 2022) Table 5 sets maximum total particle concentrations for monitoring: grade A 3,520/m³ (≥0.5 µm) and 29/m³ (≥5 µm) at rest and in operation; grade B 3,520 and 29 at rest, 352,000 and 2,930 in operation; grade C 352,000 and 2,930 at rest, 3,520,000 and 29,300 in operation; and grade D 3,520,000 and 29,300 at rest, with in-operation limits set by the manufacturer from risk assessment. [1]

Annex 1 says alert levels and action limits should be set for viable and total particle monitoring, with Table 5 and Table 6 as maximum action limits and stricter limits allowed from trend data; monitoring locations in grade A should be at the points of highest contamination risk, and other characteristics such as temperature and relative humidity should be controlled within ranges that support the defined cleanliness. [1]

For US products, FDA's 2004 guidance on sterile drugs produced by aseptic processing uses ISO classes. Its Table 1 lists ISO 5 (Class 100) at 3,520 particles ≥0.5 µm per m³ with a recommended active-air action level of 1 cfu/m³, ISO 6 at 35,200 and 7 cfu/m³, ISO 7 at 352,000 and 10 cfu/m³, and ISO 8 at 3,520,000 and 100 cfu/m³. It says an ISO 5 concentration approximately equals EU grade A. The guidance recommends particle counts in the critical area at locations “normally not more than 1 foot away from the work site”, within the airflow, during filling and closing. [2]

Editorial note: list every room and critical zone with its grade, the parameters to monitor at each point, and the alert and action limits in the contamination control strategy before asking for a quotation.

Give the supplier the cleanroom layout and grades, number and location of particle sampling points, viable sampling points, temperature, humidity and differential-pressure points, sampling flow and frequency, alert and action limits, alarm outputs, software and data-integrity requirements (audit trail, electronic records), integration with BMS or SCADA, validation documents and quantities.

02

Specify sampling, alarms and trending

Annex 1 requires grade A to be monitored continuously for particles ≥0.5 µm and ≥5 µm for the full duration of critical processing, at a sample flow rate of at least 28 L (1 ft³) per minute, with each result correlated against alert and action limits and alarms triggered when alert levels are exceeded; a similar system is recommended for grade B at a lower frequency. [1]

It also requires continuous viable air monitoring in grade A during critical processing, procedures for trending that look at repeated excursions and changes in microbial flora, and investigation when action limits are exceeded; it notes that occasional ≥5 µm counts in grade A may be false counts from electronic noise or stray light, while repeated low counts should be investigated. [1]

Editorial calculation: at 28.3 L/min a counter samples 1 m³ in about 35 minutes, so the grade A limit of 29 particles ≥5 µm per m³ equals less than one particle per one-minute sample; ask how the software handles single counts and consecutive counts so alarms match your procedure. [1]

Room pressures are part of the same monitoring. FDA's guidance gives, as an example, a positive pressure differential of at least 10–15 Pa between adjacent rooms of different classification with doors closed. It says every monitoring location should be described in SOPs in enough detail for reproducible sampling. Written SOPs should also cover sampling frequency, timing, duration, sample size, equipment and techniques, alert and action levels, and responses to deviations. US rule 21 CFR 211.42(c)(10) requires aseptic processing areas to have, as appropriate, temperature and humidity controls, HEPA-filtered air under positive pressure, and a system for monitoring environmental conditions. [2] [3]

For the temperature and humidity channels, a sensor maker's product page shows what to specify. Vaisala lists its HMP110 humidity and temperature probe at ±1.5 %RH accuracy over 0–100 %RH and −40 to +80 °C, with a HUMICAP 180R sensor for stability and chemical tolerance, an IP65 polyurethane-filled stainless steel housing, a detachable M8 cable, three voltage-output options or an RS485 Modbus RTU version, optional dew-point calculation, low power and fast start-up for battery-powered loggers, a calibration certificate with every probe, and a replacement-probe service for maintenance. It names stability chambers, incubators and glove boxes among its uses. [4] Editorial calculation: ±1.5 %RH is 3 %RH wide, so a room controlled to 45 ± 5 %RH has 3.5 %RH of margin each side after sensor tolerance; ask the supplier for the temperature accuracy too and for the calibration interval and certificate traceability the validation needs. [4] [1]

03

Find cleanroom environmental monitoring system manufacturers

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04

Trace the system components

This is a functional reference built from the sources cited; it is not one maker's design.

05

Fill the specification fields with values for your cleanroom

An environmental monitoring system quotation needs values for your cleanroom. The table explains each field, gives published values where a reviewed source states them, and says what to obtain from the supplier.

06

Send the cleanroom, limits and data needs together

Paste it into your enquiry below or into an email to a maker, then replace every bracket.

Cleanroom: [rooms; grades; layout]
Points: [particle; viable; T/RH; pressure]
Limits: [alert; action; per grade]
Sampling: [flow; frequency; continuous zones]
Data: [software; audit trail; BMS]
Supply: [validation documents; quantity]

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