Abstract
The application of the lifecycle model to the pharmaceutical products has modified existing approaches to quality assurance. The quality of a product is not simply the outcome of a GMP-compliant manufacturing, but the result of a GMPcompliant lifecycle. Product development means devising a formula and a manufacturing process, but most importantly, understanding thoroughly the product. This, known as quality by design, goes from defining its quality target profile to identifying the quality attributes of the starting materials and the quality parameters of the manufacturing process. Critical variables are the hallmark of a product during its lifecycle. They are identified and studied during the development stage and knowledge on them is increased during the product’s lifetime. Technological transfer means confirming that what worked in the development center will also work in the manufacturing plant, but also increasing and improving knowledge on the critical variables under industrial-scale conditions. Validation means verifying that the production process can be successfully controlled by means of the critical variables and that if these remain within proven acceptable ranges the process can be deemed under control and consequently yielding quality products. Thus, by monitoring critical variables each batch can be considered concurrently validated. The application of the above described approaches will enhance the level of quality insurance of the new products, but what happens with legacy ones? The model can be usefully applied to these latter too by using the same principles but proceeding step by step in a reverse approach, from knowledge to development instead of development to knowledge.
Keywords: Analytical validation, commercial manufacturing, computerized systems validation, CPP, CQA, critical variable, DAME, design space, development, discontinuation, DoE, evaluation, monitoring, PAT, process validation, proven acceptable range, QbD, QTPP, RTRT, technological transfer.
