Stability studies product optimisation

The evolution and optimisation of a formulation is an experimental stage that will be conducted on small batches of the material. For a drug with a tablet weight of 250 mg, test batches would t)rpically be 0.5-1 kg, providing up to 4000 tablets for analysis, performance testing and initial stability studies. Similar scales will be used in the optimisation of the product s packaging. 

At the completion of product optimisation, when the best product variant has been selected, it is a good idea to summarise the work conducted in a Product Optimisation Report. The report should reference the primary data from preformulation, product optimisation and stability studies, cross-referencing other investigational reports where necessary. It should clearly justify the recommendations for the quantitative formula and the excipient, component and product specifications. Such a document can be very useful to aid smooth technology transfer into production and for writing regulatory submissions. 

The FDA may also want to audit R D to gain assurance that the product development has been done satisfactorily. In particular, the FDA may wish to see data that support the manufacturing process and controls from preformulation, product/process optimisation, clinical trials process validation and stability studies. 

Our research in this field, which is summarised in this chapter, has been directed at obtaining a sensor modified with PB as electrochemical mediator which could avoid electrochemical interferences and could also couple the advantages of the screen-printed electrodes. For this purpose, an in-depth study of the modification procedure for PB deposition on the electrode surface was first conducted and then when an optimised procedure capable of providing an efficient and stable PB layer was obtained, it was applied with screen-printed electrodes in real analytical systems. Thus, our main goal has been not only to obtain a PB modification procedure suitable for a mass production of modified screen-printed electrodes, as already pointed out above, but also to achieve a stable PB layer in terms of operative and storage stability. 

A useful approach to process optimisation is to identify all the critical process parameters that could potentially affect product quality or performance and prepare a Process Optimisation Protocol. Typically, data used to identify critical process parameters will be derived from laboratory or pilot-scale batches, and do not need to be confirmed on full-scale batches unless the control of the particular parameter can only be evaluated on a production scale. There is good incentive to use the production facilities at the earliest opportunity, drug availability permitting, to iron out any transfer difficulties. Manufacture of the stability batches to support Phase III studies, and also the Phase III clinical batches, at the final commercial site should minimise any questions from the FDA during PAI about possible differences between R D and Production process used. 

---