Pharmaceutical Quality System Elements & Change Management System As per ICH Q10
The elements described below might be, required in part under regional GMP
regulations. However, the Q10 model’s intent is to enhance these elements in order to
promote the lifecycle approach to product quality. These four elements are:
• Process performance and product quality monitoring system;
• Corrective action and preventive action (CAPA) system;
• Change management system; • Management review of process performance and product quality.
These elements should be applied in a manner that is appropriate and proportionate
to each of the product lifecycle stages, recognising the differences among, and the
different goals of, each stage. Throughout the product lifecycle, companies are
encouraged to evaluate opportunities for innovative approaches to improve product
quality. Each element is followed by a table of example applications of the element to the
stages of the pharmaceutical lifecycle.
Process Performance and Product Quality Monitoring System
Pharmaceutical companies should plan and execute a system for the monitoring of
process performance and product quality to ensure a state of control is maintained. An
effective monitoring system provides assurance of the continued capability of
processes and controls to produce a product of desired quality and to identify areas for
continual improvement. The process performance and product quality monitoring
(a) Use quality risk management to establish the control strategy. This can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, inprocess controls, finished product specifications, and the associated methods and frequency of monitoring and control. The control strategy should facilitate timely feedback / feed forward and appropriate corrective action and preventive action;
(b) Provide the tools for measurement and analysis of parameters and attributes identified in the control strategy (e.g., data management and statistical tools);
(c) Analyse parameters and attributes identified in the control strategy to verify continued operation within a state of control;
(d) Identify sources of variation affecting process performance and product quality for potential continual improvement activities to reduce or control variation;
(e) Include feedback on product quality from both internal and external sources,
e.g., complaints, product rejections, non-conformances, recalls, deviations,
audits and regulatory inspections and findings;
(f) Provide knowledge to enhance process understanding, enrich the design space
(where established), and enable innovative approaches to process validation
Table I: Application of Process Performance and Product Quality Monitoring System throughout the Product Lifecycle
|Process and product knowledge generated and process and product monitoring conducted throughout development can be used to establish a control strategy for manufacturing
|Monitoring during scale-up activities can provide a preliminary indication of process performance and the successful integration into manufacturing. Knowledge obtained during transfer and scale up activities can be useful in further developing the control strategy.
|A well-defined system for process performance and product quality monitoring should be applied to assure performance within a state of control and to identify improvement areas.
|Once manufacturing ceases, monitoring such as stability testing should continue to completion of the studies. Appropriate action on marketed product should continue to be executed according to regional regulations.
Corrective Action and Preventive Action (CAPA) System
The pharmaceutical company should have a system for implementing corrective
actions and preventive actions resulting from the investigation of complaints, product
rejections, non-conformances, recalls, deviations, audits, regulatory inspections and
findings, and trends from process performance and product quality monitoring. A
structured approach to the investigation process should be used with the objective of
determining the root cause. The level of effort, formality, and documentation of the
investigation should be commensurate with the level of risk, in line with ICH Q9.
CAPA methodology should result in product and process improvements and enhanced
product and process understanding.
Table II: Application of Corrective Action and Preventive Action System throughout the Product Lifecycle
|Product or process variability is explored. CAPA methodology is useful where corrective actions and preventive actions are incorporated into the iterative design and development process.
|CAPA can be used as an effective system for feedback, feedforward and continual improvement.
|CAPA should be used and the effectiveness of the actions should be evaluated
|CAPA should continue after the product is discontinued. The impact on product remaining on the market should be considered as well as other products which might be impacted.
Change Management System
Innovation, continual improvement, the outputs of process performance and product
quality monitoring and CAPA drive change. In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. There is generally a difference in formality of change management processes prior to the initial regulatory submission and after submission, where changes to the regulatory filing might be required under regional requirements.
The change management system ensures continual improvement is undertaken in a timely and effective manner. It should provide a high degree of assurance there are no
unintended consequences of the change.
The change management system should include the following, as appropriate for the
stage of the lifecycle:
(a) Quality risk management should be utilised to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk;
(b) Proposed changes should be evaluated relative to the marketing authorisation, including design space, where established, and/or current product and process understanding. There should be an assessment to determine whether a change to the regulatory filing is required under regional requirements. As stated in ICH Q8, working within the design space is not considered a change (from a regulatory filing perspective). However, from a pharmaceutical quality system standpoint, all changes should be evaluated by a company’s change management system;
(c) Proposed changes should be evaluated by expert teams contributing the appropriate expertise and knowledge from relevant areas (e.g., Pharmaceutical Development, Manufacturing, Quality, Regulatory Affairs and Medical), to ensure the change is technically justified. Prospective evaluation criteria for a proposed change should be set;
(d) After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and that there was no deleterious impact on product quality.
Table III: Application of Change Management System throughout the Product Lifecycle.
|Change is an inherent part of the development process and should be documented; the formality of the change management process should be consistent with the stage of pharmaceutical development.
|The change management system should provide management and documentation of adjustments made to the process during technology transfer activities.
|A formal change management system should be in place for commercial manufacturing. Oversight by the quality unit should provide assurance of appropriate science and risk based assessments.
|Any changes after product discontinuation should go through an appropriate change management system.
Management Review of Process Performance and Product Quality
Management review should provide assurance that process performance and product
quality are managed over the lifecycle. Depending on the size and complexity of the
company, management review can be a series of reviews at various levels of
management and should include a timely and effective communication and escalation
process to raise appropriate quality issues to senior levels of management for review.
(a) The management review system should include:
(1) The results of regulatory inspections and findings, audits and other
assessments, and commitments made to regulatory authorities;
(2) Periodic quality reviews, that can include:
(i) Measures of customer satisfaction such as product quality
complaints and recalls;
(ii) Conclusions of process performance and product quality
(iii)The effectiveness of process and product changes including those
arising from corrective action and preventive actions.
(3) Any follow-up actions from previous management reviews.
(b) The management review system should identify appropriate actions, such as:
(1) Improvements to manufacturing processes and products;
(2) Provision, training and/or realignment of resources;
(3) Capture and dissemination of knowledge.
Table IV: Application of Management Review of Process Performance and Product Quality throughout the Product Lifecycle.
|Aspects of management review can be performed to ensure adequacy of the product and process design.
|Aspects of management review should be performed to ensure the developed product and process can be manufactured at commercial scale.
|Management review should be a structured system, as described above, and should support continual improvement
|Management review should include such items as product stability and product quality complaints.