In controlled environments such as cleanrooms, pharmaceutical manufacturing facilities and biotech laboratories, airborne particle sampling is not just a best practice — it is a regulatory necessity. With the publication of ISO/TR 14644-21:2023, the framework for particle sampling has been clarified and strengthened.
This article explains why this technical report matters, what is new compared to previous standards, and how to implement it effectively in GMP environments.
What is ISO/TR 14644-21?
ISO/TR 14644-21:2023 is a technical report published by ISO as part of the ISO 14644 cleanroom standard series.
While ISO 14644-1 defines cleanroom classification and maximum particle limits, the TR 14644-21 provides practical guidance on how to perform airborne particle sampling using discrete particle counters (DPC).
It helps bridge the gap between regulatory expectations and real-world implementation, especially in high-risk sectors like pharmaceutical aseptic production.
What is new in ISO/TR 14644-21?
Here are the key contributions of this new report:
- Clarifies the selection and use of sampling locations (risk-based, process-oriented)
- Describes how to determine sampling volume and time based on cleanroom class and particle size
- Defines terms like “most representative location” and “worst-case location”
- Explains how to calculate sampling uncertainty and interpret outliers
- Provides guidance on operating procedures (calibration, tubing, orientation, flow rate)
Compared to ISO 14644-1/-2, which define classification and monitoring respectively, TR 14644-21 focuses on the practical “how-to” of particle sampling.
Why this matters for GMP environments
In GMP-regulated production (e.g., sterile drug manufacturing), airborne particle control is a critical quality attribute (CQA).
Annex 1 of EU GMP guidelines (rev. 2022) requires:
- Justification of sampling strategy
- Defined sample volumes per grade
- Periodic re-evaluation of monitoring plans
ISO/TR 14644-21 supports Annex 1 compliance by offering a scientifically grounded method to select points, define frequency and volume, and interpret results with traceability.
Practical implications: how to apply ISO/TR 14644-21
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Evaluate your current sampling points
Are they based on risk? Do they cover worst-case conditions? -
Calculate appropriate sample volumes
Use formulas provided in the report (based on ISO Class and particle size). -
Review your SOPs for particle counting
Ensure procedures include tubing position, flow rate, counter calibration. -
Document uncertainty and corrective actions
Especially when outliers or unusual readings occur. -
Train personnel
The new approach requires clear understanding of rationale and methods.
Recommended equipment and support
To implement the new standard effectively, you will need:
- Validated airborne particle counters
- Flexible and compliant sampling probes
- Accurate flow control and calibration certificates
- A risk-based monitoring plan and audit-ready documentation
QSGroup supports clients with certified particle counters, technical training and development of Annex 1-compliant sampling plans.
Ready to upgrade your particle sampling strategy?
ISO/TR 14644-21 is not just a new guideline — it is a chance to align your cleanroom monitoring program with the latest best practices and regulatory expectations.
Contact QSGroup to request a technical assessment or receive our checklist for implementing ISO/TR 14644-21 in your facility.
