6.5.1. Shift of development focus from product performance and customer needs

Right from the start the focus of all development projects has to switch from the purely product related view to a customer related view. Setting up a QTPP, is required as soon as a drug compound has been nominated as a potential candidate for a FIH study. At this time the project team has to start assessing the necessary product performance for the next development steps, the pre-clinical safety studies in animals and the intended FIH study. When defining the QTPP the focus needs be on these first customers, the animal species for toxicology studies or the volunteers for a FIH study. The dosage forms used for each customer differ, reflecting the different needs such as dose strength, size of dosage form and packaging while the critical quality attributes concentrate on the most essential performance requirements for these types of studies to deliver the correct dose in a formulation providing representative bioavailability for the desired pharmacological effects and perspectives for further development. For phase II medication longer shelf life stability is needed than for FIH studies and patients may no longer be willing or able to swallow large, investigational dosage forms. And finally during phase III development of a dosage form quite similar to the commercial market form has to consider handling aspects, disease related attributes, potential misuse, and specific needs of the different patient segments. Therefore, QTPPs can either evolve throughout development or be replaced by new ones for each of the changing customer segments, to address the specific needs of each customer according to the development phase. Thereby, CQAs can also evolve throughout development to reflect these different QTPP requirements. While at the beginning only the most essential CQAs as required for this phase need to be addressed, CQAs are expected to increase or shift in their focus during later development phases. For example bioavailability and therefore drug dissolution will be a CQA for an oral drug product containing a poorly soluble drug compound right from the start already for pre-clinical studies, while other CQAs such as easy to swallow tablets or 2 years of shelf life stability at room temperature may not be required until phase III studies.

However, a CQA will always stay critical once it has been identified as such, irrespective of its probability, detectability or state of control. A derived Control Strategy lowers the risk of occurrence or impacts on the CQA but never the criticality of the CQA itself.⁶⁹

⁶⁹ ICH; Points to Consider; 2011