Risk-based control of critical phases and assurance of data integrity in an etmaben safety pharmacology study

Aim. To develop and apply a risk-based framework for identifying and controlling critical study phases and for assuring data integrity and traceability in an etmaben safety pharmacology study. Materials and methods. The study workflow was decomposed into four functional blocks: organisational and preparatory activities, exposure-forming procedures, primary data-generating procedures, and data processing and reporting. A phase was considered critical when an error could affect test-item exposure, animal or sample identification, the assessment of one or more physiological systems, raw-data traceability, or the final interpretation of the study. For each critical phase, the potential risk, control parameters, supporting records, and actions under the Good Laboratory Practice principles and the quality assurance programme were defined. Criticality was assessed using the risk priority number, RPN = P × D × S, where P represented the probability of an error, D the difficulty of its timely detection, and S the scope of its potential impact on the data. Each criterion was scored on a scale from 1 to 5. RPN values of ≥30, 17–29, and ≤16 was classified as high, medium, and low criticality, respectively. Results. Ten critical phases were identified: study planning; receipt and identification of the test item; animal housing and use; suspension preparation and dose calculation; etmaben administration; recording of physiological endpoints; behavioural and neuromuscular testing; biochemical testing; statistical analysis; and final report preparation and archiving. Eight phases were classified as highly critical and two as moderately critical. The highest RPN values were assigned to etmaben administration (48), recording of physiological endpoints (45), study planning (40), and statistical analysis (40). System-specific critical phases and control parameters were defined for the cardiovascular, respiratory, central nervous and neuromuscular systems, as well as for additional biochemical endpoints. The corresponding GLP actions included study-based and process-based inspections, verification of equipment and personnel records, assessment of raw-data traceability and deviations, and comparison of the final report with the original study records. Conclusion. The proposed framework links each critical phase to a potential risk, a control parameter, a supporting raw record, and an action within the quality assurance programme. This approach supports risk-based planning of quality assurance activities and provides documented traceability of safety pharmacology data from study planning and test-item administration to statistical analysis and final reporting.