AIM OF THE PAPER The aim of the research was to develop and validate analytical methods for determining the residues of the active substances 6-marcaptopurine and valganciclovir hydrochloride on surfaces made of different materials. Onwards, using developed and validated analytical methods and using defined procedures for cleaning production equipment, production and non-production rooms and external/non-contact parts of equipment and devices, carry out decontamination process of the pharmaceutical plant for the production of cytotoxic drugs and document that the contaminants 6-mercaptopurine and valganciclovir hydrochloride have been removed below prescribed acceptance limits. A successfully completed decontamination procedure is a guarantee of safe repurposing of rooms, equipment and devices for other production purposes. MATERIALS AND METHODS Cytotoxic drugs stop the proliferation of cells in a certain cycle of their growth. They are used in the fight against rapidly growing cells such as cancer cells, but also in autoimmune diseases such as different types of arthritis. Cytotoxic drugs are highly potent substances that require special procedures during production and preventive measures during occupational exposure. Also, a high degree of caution is required while implementing the regular procedures for production equipment and premises cleaning, especially in the case of their repurposing for other production activities. Development and validation of two HPLC methods for the determination of 6-mercaptopurine and valganciclovir hydrochloride residues on surfaces after cleaning in the production plant SOO2B, Pliva Croatia d.o.o. was performed in accordance with internal protocols and ICH guidelines. Validation procedure of HPLC methods for the analysis of 6-mercaptopurine and valganciclovir hydrochloride tested their selectivity, linearity, accuracy, stability of solutions and swab samples and finally, their detection and quantification limits. The most critical locations were determined where the sampling procedures were carried out after the performed cleaning, including production equipment, production and non-production rooms, and external/non-contact parts of the devices. Each sampling location was assigned a unique code for further monitoring and evaluation during the procedure. As part of the decontamination process, all single-purpose and difficult-to-clean equipment, accessories and auxiliary equipment were removed from the production plant. The mentioned equipment is excluded from the sampling procedure due to the aforementioned characteristics and the high degree of cross-contamination risk. On the rest of the dismantled production equipment, devices and auxiliary equipment, several consecutive cycles of cleaning were carried out, as well as sampling and analysis of swab samples collected from defined, representative locations after each performed decontamination cleaning. Consecutive cleaning and sampling were carried out until the defined acceptance limits were achieved, i.e. the values of the analysis results lower than or equal to the detection limit of the validated HPLC methods for the analysis of 6-mercaptopurine and valganciclovir hydrochloride. After achieving the defined acceptance limits for all defined items in the cleaning process, the final phase of decontamination was performed, which included dismantling the filters of the production premises. After that, final cleaning and sampling of filter removal locations was carried out with the aim to verify the final state of contamination. DISSCUSSION Validation procedure of HPLC methods for the analysis of 6-mercaptopurine and valganciclovir hydrochloride tested and proved their selectivity, linearity, accuracy, stability of solutions and swab samples, detection and quantification limits. An evaluation of the obtained results of the samples analysis using HPLC methods for the determination of 6-mercaptopurine and valganciclovir hydrochloride was performed and final conclusion on the success of the cleaning procedures of the cytotoxic drugs production plant was made. The process of cleaning the plant after the production of cytotoxic products was a project that required extensive, precise and conscientious work, a detailed approach, analytical and production experience, an engineering approach, knowledge of the chemical properties of the analysed compounds and potential interactions and it represented an unusual and very specific pharmaceutical-engineering challenge. CONCLUSION Cleaning validation of the plant after the production of pharmaceutical forms with cytotoxic active substances (decontamination procedure) was carried out by successive cleaning of all production and non-production rooms and external/non-contact surfaces of the devices and their sampling until achieving analytical results lower than or equal to the detection limits of validated analytical methods for the determination of 6-mercaptopurine and valganciclovir hydrochloride. Based on all the obtained results, the production, non-production rooms and external/non-contact surfaces of the devices in the SOO2B plant are considered to be successfully decontaminated from the residues of 6-mercaptopurine and valganciclovir hydrochloride contaminants. The performed cleaning validation as well as the decontamination procedure itself are considered to be successfully completed, and, therefore, safe repurposing of all rooms and devices for other production purposes is possible.