Abstract

Despite meeting qualification requirements under established standards such as ISO 14644 [1] and EU GMP Annex 1 [2], many cleanroom facilities fail to perform reliably during routine operation. This gap between qualification and performance remains a persistent challenge in pharmaceutical manufacturing, often resulting in deviations, inefficiencies, and increased regulatory risk. The root cause is not a lack of technology, but a disconnect between facility design, cleaning strategy, and operational execution.

This presentation is based on cross-project experience from cleanroom design, commissioning, and early manufacturing phases. It highlights three recurring gaps seen in practice: (i) User Requirement Specifications that do not sufficiently translate process and cleaning needs into design inputs, resulting in facilities that meet specifications but are difficult to clean or operate; (ii) commissioning and qualification (C&Q) activities introduced too late, limiting the ability to verify airflow behavior, cleanability, and system robustness before qualification; and (iii) validation documentation that meets inspection expectations but does not support day-to-day operations, leading to repeated deviations.

These observations are aligned with lifecycle guidance from ISPE [3] and PDA [4], and with the increased focus on contamination control strategy in Annex 1 [2]. In one aseptic manufacturing project, a traditional late-stage C&Q approach resulted in deviation rates of 18–22% during the first six months of operation; by integrating commissioning earlier and focusing on cleanability during design, deviation rates were reduced to below 10%, representing a 40–50% improvement.

The session translates these lessons into practical actions, including how to embed cleanability into URS, use commissioning as a risk-reduction tool, and align documentation with real operational needs. The objective is to support teams in transitioning from qualification-driven delivery to performance-driven cleanroom operation.

References

[1] International Organization for Standardization (ISO). (2015). ISO 14644-1.
[2] European Commission. (2022). EU GMP Annex 1.
[3] ISPE. (2019). Baseline Guide Volume 5.
[4] PDA. (2014). Technical Report No. 60.