|
Table I: Application of Process Performance and Product Quality Monitoring
throughout the Product Lifecycle
|
Development |
Technology Transfer |
Manufacturing |
Product Discontinuation |
|
Quality risk management and monitoring conducted throughout development
can be used to establish a control strategy for manufacturing. |
Monitoring of scale-up activities can provide a preliminary indication
of process performance and the successful integration into
manufacturing. Monitoring of 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. |
ii) Corrective Action and Preventive Action System (CAPA)
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 root cause. The level of effort and
formality of the investigation should be commensurate with the level of risk.
CAPA methodology should result in product and process improvements and enhanced
product and process understanding.
Table II: Application of Corrective Action/Preventive Action throughout the
Product Lifecycle
|
Development |
Technology Transfer |
Manufacturing |
Product Discontinuation |
|
Product or process variability is explored. CAPA methodology can be
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, feed forward 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. |
iii) Change Management System
Innovation, continual improvement, the outputs of process performance and
product quality monitoring and CAPA drive change. In order to properly evaluate,
approve and implement these changes, 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 while providing 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:
(1) 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. There should be an assessment to determine whether a change to
the regulatory filing is required under regional requirements;
(2) All changes should be properly evaluated. Proposed changes should be
evaluated relative to the marketing authorisation, including design space, where
established, and / or current product and process understanding. As stated in
ICH Q8, movement 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;
(3) 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;
(4) 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;
(5) Regional regulatory submission/approval requirements should be assessed for a
proposed change to a marketed product.
Table III: Application of Change Management System throughout Product
Lifecycle
|
Development |
Technology Transfer |
Manufacturing |
Product Discontinuation |
|
Change is an inherent part of the development process and should be
documented; the formality of the change management process should
increase as the product moves through 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. |
iv) 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.
(1) The management review system should include:
(a) The results of regulatory inspections and findings, audits and other
assessments;
(b) Periodic quality reviews, that can include:
(i) Measures of customer satisfaction such as customer complaints and recalls;
(ii) Conclusions of process performance and product quality monitoring;
(iii) The effectiveness of process and product changes including those arising from
corrective action and preventive actions.
(c) Any follow-up actions from previous management reviews;
(2) The management review system should identify appropriate action, such as:
(d) Improvements to manufacturing processes and products;
(e) Provision, training and/or realignment of resources;
(f) Capture and dissemination of knowledge.
Table IV: Application of Management Review of Process Performance and Product
Quality throughout the Product Lifecycle
|
Development |
Technology Transfer |
Manufacturing |
Product Discontinuation |
|
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 complaints. |
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