Risk management by the marketing authorisation holder in product quality review

Abstract

Product Quality Reviews, forming part of the current Good Manufacturing Practices, are periodic product quality assessments of all authorised pharmaceutical products, including those intended for export only. Product Quality Reviews are performed to ensure that the current specifications for raw materials and final products are appropriate, reliable and to identify any trends, that the current manufacturing procedure is consistent, and to determine ways to enhance both the product and the process. The Marketing Authorisation Holder is responsible for conducting routine product reviews and audits of the manufacturing processes in addition to adhering to Good Manufacturing Practice. The aim was to carry out a risk assessment, using Failure Mode and Effect Analysis, on the Product Quality Reviews performed by the Marketing Authorisation Holder to identify the risk imposed if any of the current checks are not executed. The reviews done by the Marketing Authorisation Holder were identified and for each identified review, the potential failure modes, their associated effects and their risk priority numbers were determined to derive a risk score for each component under review. The classification of the ‘severity’, ‘occurrence’ and ‘detectability’ was presented in the form of a five-point Likert Scale. Each factor was scored on a scale of 1 to 5, where a score of 1 denotes a low risk score. All three parameters were then multiplied to obtain the Risk Priority Number. Each review was ranked as ‘low risk and should be considered for delegation’ if the risk score fell between 1 and 12, ‘moderate risk and may be considered for delegation’ if the risk score fell between 13 and 35 and ‘high risk and not to be delegated’ if the risk score fell between 36 and 125. This risk assessment was compiled into a quality report, which was validated, reviewed and approved by managerial personnel and other relevant personnel within the Marketing Authorisation Holder. The areas for which the Marketing Authorisation Holder is directly responsible for were also taken into consideration, where these areas were considered as not delegable. The outcome of the risk assessment resulted in one review ranked as ‘low risk’ with a score of 10, ten reviews as ‘moderate risk’ with scores ranging between 18 and 32, and seven reviews as ‘high risk’ with scores ranging between 40 and 48. Three reviews were determined to be delegated by the Marketing Authorisation Holder to the batch release site. In case the batch release site and the manufacturer are the same, these reviews are to be reviewed by the Marketing Authorisation Holder during planned external audits. By adopting this risk-based approach, resources can be more effectively allocated by the Marketing Authorisation Holder, allowing time previously spent on Product Quality Reviews to be redirected toward addressing other critical quality issues.