One Year After the Opening of a Cleanroom: What Is the Level of Chemical Contamination and How Should It Be Interpreted?

Introduction
A new cleanroom was commissioned within the pharmaceutical technology unit, equipped with four new isolators: two dedicated to cytotoxic preparations (CP), one dedicated to immunotherapy preparations (IP), and one dedicated to non-CP/non-IP preparations. One year after the opening of this cleanroom, an environmental chemical monitoring campaign was conducted in accordance with French Good Preparation Practices to address the following questions: 1) What is the level of environmental chemical contamination? 2) Is there any cross-contamination between the different isolators? 3) Is the cleaning protocol using an alkaline cleaning solution effective? To answer these questions, the raw environmental chemical monitoring data alone were insufficient. Therefore, this study presents the development of an analytical scoring system designed to facilitate the interpretation of the results.

Materials and Methods
Standardized self-sampling kits were used to quantify twenty hazardous drugs by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) (Centre Léon Bérard / Lyon Sud University Hospital). Six surface samples were collected: one from each of the four isolators and one from each of the two workbenches (drug picking and preparation packaging). An analytical score ranging from 1 to 100 was developed to establish a three-level criticality scale (low, intermediate, and high). The score incorporated not only the environmental chemical monitoring results but also factors related to the type of preparations, equipment characteristics, cleaning procedures, and isolator usage frequency.

Results and Discussion
Using the proposed scoring system and criticality scale, none of the sampled areas exceeded a score of 40/100, corresponding to an intermediate level of contamination, with the highest score observed in one of the cytotoxic preparation isolators. The scoring system also identified platinum salt contamination in the immunotherapy isolator, although at a low level (score below 32/100). The results suggest that the alkaline cleaning protocol could be improved for the cytotoxic preparation isolators. For platinum salts, only the rinsing step appears to require reinforcement.

Conclusion
The development of this analytical tool provides valuable support for tailoring corrective actions according to the contamination level observed. Potential improvements include enhanced decontamination of vials before transfer into the isolators, increased cleaning frequency of storage bins, and segregated storage of medicinal products. This tool will also facilitate the implementation of a risk-based environmental monitoring plan for future sampling campaigns and help assess the effectiveness of corrective measures over time.

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