Avaliação da interrupção com retomada de produção em campanha produtiva no emblistamento de comprimidos por validação de limpeza

Abstract

In the pharmaceutical industry, manufacturing campaign is used as an alternative in the search for robust production with lower production costs. This condition is characterized by the consecutive production of a certain number of batches. In order to guarantee and document that the manufacturing campaign process is carried out without the risk of cross­contamination, a cleaning validation study is carried out, in which the residual limits of the active substance, products provided with degradation, cleaning agent and microbiological are evaluated. In this way, we aim to evaluate the efficiency of cleaning procedures applied to equipment and parts used during the production of medicines, corroborating compliance with Good Manufacturing Practices and safety in the production of a diversified portfolio, once the equipment is shared during production. The strategy adopted in this paper was to evaluate the impact of the interruption of a manufacturing campaign for a determined time, with the resumption of production until the conclusion of the total number of batches foreseen in the campaign, to show that the interruption period does not promote possible contaminants to the batches involved in the process. This evaluation is justified in view of the need to make the manufacturing campaign schedules of batches more flexible, since the productions also take place on weekends, which leads to the need to interrupt cleaning procedures, making the equipment remain dirty until the beginning of the following week. Faced with this need, the industry performs excessive stops during production, increasing operating costs. The study was carried out in a packaging line (blistering) of oral solids (tablets) in a pharmaceutical company in the western region of Paraná. Among the drugs that pass through the production route of choice, the most critical product (worst case) was identified. In order to carry out the cleaning validation, it was defined that three manufacturing campaigns would be analyzed, each one composed of twenty batches of the product of choice. The established downtime (process interruption) within the manufacturing campaign was at least forty­eight hours, to reflect the downtime on a weekend. At the end of each studied campaign, after carrying out the general cleaning of the equipment and parts, collections were carried out at predetermined points and they were submitted to laboratory analysis. Among the analyses carried out, the detection of residues of the active substance, the presence of microorganisms and the presence of degradation products stand out. Thus, it was verified that the condition of applying a shutdown with the resumption of the process in a manufacturing campaign is safe and the equipment cleaning procedure was efficient in the removal of possible contaminant residues. It was noted that the time of an interruption to be used in the manufacturing routines, in the campaign, was 50 hours, in addition to the 20­batchmanufacturing campaigns, they must comply with the production time of a maximum of 9 days after the start of production or until completing the amount of batches foreseen in the campaign. This condition can be established from the results of the identification of residues from the sampled points, showing that the residues of possible contaminants in the equipment after general cleaning were below the limits of the acceptance criteria for the study, which validates the effectiveness and safety of the general cleaning performed in the equipment. Therefore, the use of this manufacturing campaign configuration with interruption for a determined time, meets the requirements of Good Manufacturing Practices, providing greater flexibility in production schedules.