There is not a single pharma or biotech company involved in product development that is not acutely aware of the huge levels of investment in financial and human resources that is required. And, of course, the time that it takes from early stage concept development to obtaining a marketing authorisation.
A whole sub-industry has evolved around the development of new therapies which is dedicated to accelerating the process, either to a successful conclusion, or more rapidly identifying those therapies which are not likely to succeed.
The pinnacle, in every sense, of product development is the clinical trial programme for investigational medicinal products for human use (IMPs) which is of course itself subject to a well-defined and rigorous regulatory regime. It is therefore surprising that of, the 1,000 or more clinical trial authorisation applications received by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, more than half of the applications are inadequate and require additional information before they can be approved.
The issue has become so pressing that the MHRA has now issued a guidance document "Common issues identified during clinical trial applications". The guidance sets out the common issues the MHRA has encountered with clinical trial applications under four broad headings: validation; non-clinical; clinical; and pharmaceutical. In all, across all four headings, the MHRA has identified 31 common failings, any of which can cause an application to receive a request for further information or a "grounds for non-acceptance" (GNA) notice. The issues are encountered across applications for all phases of clinical trials. This can lead to an aggregate several weeks of delay in obtaining the MHRA's formal acceptance.
The MHRA identifies the following issues:
Common failings here include failing to provide mandatory documentation, failure to complete all of the relevant sections of the documentation, documents in the wrong formats and even inconsistencies across the documentation.
The most prevalent deficiencies are inadequate information about pivotal safety studies, a lack of proper contraception recommendations and even (surprisingly) a lack of justification of the starting dose in humans from a safety perspective.
Problems here include a lack of reference safety information or a lack of information about risk mitigation strategies.
This is probably the most remarkable section in terms of the common failings of the IMP dossier: missing or inadequate physiochemical and/or biological characterisation data; missing or inadequate batch analysis data for each manufacturing site; and even inadequate data on straightforward matters such as IMP shelf life and labelling.
The MHRA's findings demonstrate a remarkable and, for the most part, avoidable waste of time, all of which further reduces the term of patent protection of the IMP after it has been approved.
The MHRA, of course, deals with UK applications but it is highly likely that its experience is not confined to the UK.
EU clinical trials portal and database go-live postponed to 2019
The EMA has recently announced that, due to technical difficulties in developing the IT system for the new EU clinical trial portal and database, the go-live date has been postponed and so the entry in to force date of the new EU Clinical Trial Regulation will be pushed back from October 2018 to 2019. A further update on the delivery timeframe will be provided in October 2017.
The portal will be a single point of submission and maintenance of clinical trial applications and authorisations and is a hugely ambitious project.