Convalida della metodica dì cleaning nell’industria farmaceutica

The work presented in this dissertation describes the activities carried out during the internship period I completed at the chemic-pharmaceutical company Farmabios located in Gropello Cairoli (PV). It focuses on the design and on the validation of a cleaning methodology for steroid active principles microionization devices employed in multi-purpose facilities. Such levels have been calculated on a solid scientific basis. As far as the residue quantification is concerned, an analytical method suited to the identification and quantification of the active principle was employed. The procedure was run after having executed the cleaning procedures of the working areas and of the devices employed in the pharmaceutical production. In particular, a report on the validated procedure of the cleaning methodology for the microionization equipments has been drafted. The formulas for the computation of the MACO are detailed and discussed in this dissertation. The validation of the cleaning procedure employed for the microionization of the Triamcinolone Acetonide is then detailed. The steroid is here taken as an example of a contaminating product. The corresponding analytical method quantifying its residual possibly still present over the whole microionization line is then described. A validation check is always performed after three different production runs. After an evaluation of the historical data and of the risk analysis in the steroid department, a cleaning check is performed every four years after a worst-case production run. In the particular case of the microionization department, cleaning validation and the drafting of the corresponding protocol has to be performed after three production runs. Its main points are: the cleaning Standard Operation Procedures (SOP) for the specific devices employed, the number of the cleaning procedures considered, the characteristics of each individual device, the sampling locations and methods, the validated analytical methods applied, the definition of the acceptable residues and the evaluation criteria of the results obtained. The cleaning validation has to be performed for all device surfaces which are in direct contact with the product and on all sampling tools. The sampling of the remaining residue at the end of the cleaning procedure is performed by means of two different techniques: - Rinsing: it consists in sampling a percentage of the solvent, or of the solvent mixture, at the end of the cleaning procedure for each equipment which has been in direct contact with the product. - Swabbing: it consists in rubbing the device surfaces by means of suitable swabs with precise chemical-physical characteristics so as to avoid erroneous analyses. The chemical analysis for the computation of the cleaning efficiency is then performed immediately after the sampling, so as to avoid possible contaminations or sample degradations during the storage; in case this is not possible, the stability of the sample needs to be evaluated. The quantification of the residue on the microionizator equipments has been performed using HLPC analysis. The results obtained from the analyses on rinsed samples, expressed in mg, are indicative for the computation of the actual residue. The preferred reference data are the ones obtained from the analyses performed on swabbing samples whose acceptability limits are lower and more restrictive. The results obtained in the production runs n°1 and n°2 show that the calculated residue is lower than the acceptability limit of 39 mg/dm2. As far as the production run n°3 is concerned, the residue is lower than the QL of the HPLC method, equal to 0.25 mg/ml. We thus decided to set to QL the residue in this case.