During 30 years’ experience in medicines and device development it has been my observation that insufficient attention is paid to the importance of quality and manufacturing strategy during product development planning. In particular, the need to generate the required information for submission in regulatory applications. The focus early on is placed firmly on clinical development. How soon can we obtain proof of concept in the proposed indication? What precise indication do we want to register? Which patient populations should we focus on? How should we consider the paediatric development in the context of studies in adults? What’s the fastest route to approval?
But how often do people ask these questions: at what point will we scale up to commercial production capacity, what packaging materials will we need for commercial presentation and what pack sizes and stability data will we need? When will formulation development be optimised, and will it be ready for phase III clinical trials? Will a new formulation be needed for paediatric trials? Will the manufacturing facilities we are using be suitable for FDA, PMDA and EMA approval? How will we handle storage conditions in transportation? What if we have to change manufacturing methods to scale up? How will bridging strategy work to link product used in clinical trials with commercial supply? What is our environmental strategy, and have we done the correct studies to meet all prevailing regulatory requirements? Is our validation strategy acceptable?
Failure to pay as much attention to quality documentation as clinical documentation is also a common obstacle to regulatory approval. I have lost count of the number of times the quality questions arising from regulatory review run into the hundreds compared with many fewer clinical and safety questions. This often occurs because project plans are driven on the clinical path and then pressure is placed on staff to short cut the quality and manufacturing steps to meet a submission date. So, what holds up the regulatory process? It is rarely the clinical and safety profile because companies do not submit their dossier knowing the clinical and safety profile are entirely insufficient for approval. Yet it seems commonplace to submit with a less than complete CMC package hoping to gain approval with a host of post approval commitments.
Yet it does not need to be this way. Having experienced staff who understand the complex interaction between clinical, regulatory, quality and manufacturing pathways will mean the entire product development strategy is well integrated such that all the necessary information will be available to support an on time regulatory submission and minimise the hold ups during the assessment caused by missing information. So, if you find your Company operating in functional silos, obtaining advice from experts capable of integrating your functional plans for improved first time approval success may well be beneficial. Such bespoke services are available from Fusion Pharma Limited.