Risk analysis in the production of hard capsules under the conditional name “Praziquantel plus” using the Ishikawa diagram method

Abstract

This article explores the application of the Ishikawa (cause-and-effect) diagram as a risk analysis tool within a pharmaceutical quality system for the production of hard capsules under the code name "Praziquantel Plus". Aligned with the standards of ISO 9001, ICH Q10, and GMP, the study demonstrates how this method systematically identifies and analyzes potential risks across key production categories. The research provides a tailored Ishikawa diagram that facilitates the identification of critical parameters, supports process optimization, and enhances the overall quality assurance system for this specific medicinal product. The aim of the research was to analyze the risks in the production of hard capsules under the conditional name “Praziquantel Plus” using the Ishikawa diagram. The study was based on the analysis of a model industrial process for the production of Praziquantel Plus hard capsules. The materials for the risk analysis were the technological regulations, specifications for raw materials and finished product, as well as the requirements of GMP/ICH standards. The study employed a systematic approach to risk assessment in accordance with ICH Q9 guidelines. The primary methodology is centered on the construction of the Ishikawa diagram. The study is based on a systems approach, brainstorming, cluster analysis and cause-and-effect analysis. A comprehensive Ishikawa diagram was developed, structured around six pri­mary risk categories for pharmaceutical production: raw materials, production process, equipment, personnel, premises, and quality control. Critical risk factors were identified and prioritized. The most significant risks were found to be associated with: a) the quality of active pharmaceutical ingredients and excipients (e.g., inconsistency in quantitative content, impurities); b) critical stages of the technological process (e.g., weighing accuracy, mixture homogeneity, capsule filling flowability); and c) the specifics of pharmaceutical equipment qualification and operation. Detailed risk assessment tables were created for both raw materials and the technological process, outlining potential failures, their consequences, and proposed precautionary measures to mitigate each risk (e.g., enhanced incoming quality control, process validation, equipment calibration). An adapted, product-specific Ishikawa diagram was proposed for the industrial-scale production of “Praziquantel Plus”. This diagram details first- and second-order subcategories within the main "bones," reflecting the unique aspects of scaling up from laboratory to commercial manufacturing. The Ishikawa diagram method proves to be an effective and structured tool for pre-emptive risk identification in pharmaceutical process development and scale-up, aligning with GMP and ICH Q9/Q10 requirements. The study successfully mapped and systematized the key risk categories and their interrelations for the production of “Praziquantel Plus” hard capsules, providing a visual and analytical framework for quality management. The proposed tailored diagram and risk tables ser­ve as a practical foundation for implementing preventive actions, optimizing the technological process, and conducting root-cause analysis of potential defects, thereby strengthening the overall Pharmaceutical Quality System for this product.