The main objective of the pharmaceutical industry is the production of high quality, safe and effective medicines, which is carried out in accordance with the principles and guidelines of good manufacturing practice, various regulatory directives and other good practices. In order to achieve this, pharmaceutical companies are constantly monitoring innovations and implement changes, following the scientific and technical progress and regulatory authority requirements. Changes are an inevitable occurrence through the pharmaceutical product’s lifecycle and represent a critical point in quality assurance, so it is important that the quality of the product is carefully planned, incorporated and controlled throughout the process – from conceptual design to its marketing stage.
In the Master's thesis we illustrated how complex and extensive the effective management of changes is after obtaining a marketing authorization. We presented a guideline of the International Conference on Harmonization ICH Q12, which aims to internationally unify the technical and regulatory requirements for managing the product’s lifecycle, unifying the process for filing variations and reducing the extensive regulatory review of changes. In our thesis we presented its concepts or rather individual tools by means of descriptive analysis and correlated them on an example of finished product by preparing a post-approval change management protocol for it. We described the proposed change, presented in tabular form the key differences between the current state and the state after the proposed change, identified critical quality attributes, critical and key process parameters, and performed a general risk assessment of individual technological stages on critical quality attributes. We also defined a control strategy for managing risks in the manufacturing process, proposed a stability testing program and recommended a reporting category for the proposed change. Given the results of the comparability of technological equipment, the envisioned manufacturing process and the justification of critical process parameters, we have estimated that the proposed change has no impact on product’s quality. Repeatable production of evaluated product of appropriate quality will be confirmed by process validation on three successively produced batches. As such, planned implementation of the change in manufacturing process is essential, since it lets us optimally introduce change implementation, helps reduce the number of inadequate batches of the finished product, avoid inadequate quality of manufactured batches and the need for additional batch testing.
During our thesis we found that despite efforts to globally approximate regulatory requirements and unify the management of post-approval changes, ICH Q12 does not currently show a significant contribution to the product’s lifecycle management. The key regulatory requirements that we must meet when submitting an amendment are not new, but already well established. To facilitate the implementation of the ICH Q12 guideline, we suggest that it should be more closely linked to the ICH Q8 and Q11 guidelines and to define some terms more clearly and unequivocally and illustrating the selected example directly in the guideline. Nonetheless, the guidance in ICH Q12 is not fully compatible with the legal framework in some regions and will need to adopt its existing legislation.
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