Design of an innovative laboratory dedicated to the analysis of conventional anticancer agents : CytoxLab

the ageing of the population, the number of patients with cancer and undergoing chemotherapy treatment is increasing. Even if new promising drug molecules (targeted therapies) are developed, conventional anticancer drugs (small molecules) still constitute the most prescribed chemotherapies. The consequence is a manipulation of these molecules at very high toxicity by all operators located along the process (reception, preparation, transportation, administration, and elimination).

Among the different strategies applied for the evaluation of exposure to these toxic molecules, the evaluation of surface contamination by conventional anticancer agents is particularly interesting, because it makes it possible to quickly identify contaminated places to undertake a suitable chemical decontamination. Few laboratories offer this service in Europe and only for a few molecules (a maximum of ten) and often at high cost.

In this context, the quality control laboratory of the pharmacy of the University Hospitals of Geneva has designed a laboratory adapted to the analysis of anticancer agents in trace amounts on surfaces: CytoxLab. During the design of this innovative laboratory, all the analytical stages, from the preparation of the samples to the processing of the generated data, were the subject of reflection aimed at guaranteeing the safety of operators and the environment as well as the quality of analysis performed. This room, under negative pressure, has sufficient ventilation to ensure the containment of the molecules and the safety of the operator. An intermediate airlock ensures the vacuum cascade and allows the operator to wear the Personal Protective Equipment (PPE) essential for handling toxic products. The entire room has sealed and glazed walls allowing the interior to be viewed. A precision analytical balance placed in the heart of a laminar flow containment enclosure with a HEPA filter is equipped with an automatic weighing system to reduce the emission of toxic solid particles into the environment. Most of the sample manipulations are carried out by an automated liquid handling workstation, the rest being carried out by the operator in a Type II Microbiological Safety Station equipped with 3 HEPA filters and an activated carbon filter, thus making it possible to filter solid particles and molecules in gas form. The analytical liquid chromatography instrument coupled with a mass spectrometer (LC-MS) is confined in a very large laboratory ventilation hood allowing the rapid evacuation of residual nebulisates of toxic agents.

An LC-MS method allowing the analysis of traces (of the order of ng per sample) of 24 cytotoxic agents commonly used in hospitals in less than 13 min has been developed and validated in this infrastructure. This method is used to regularly monitor the potential contamination of Cytoxlab surfaces by these cytotoxic agents. Critical points have been clearly identified: the racks of the automated liquid handling workstation, the sample racks for LC-MS analysis and the weighing area. Appropriate cleaning procedures combined with the use of automatic weighing system for powders allow us to reduce or even eliminate the presence of cytotoxic agents on these surfaces.

This method is also applied to sampling in the chemotherapy production unit of the pharmacy and in the oncology care units of our hospital, thus allowing active monitoring of the exposure of staff to these highly toxic agents. These sampling campaigns are associated with an improvement strategy including additional training and awareness actions.

This service is also offered to other Swiss and European health institutions with the primary objective of allowing a simple, rapid and low-cost assessment of the potential surface contamination of their structure (www.cytoxlab.ch).