The European Medicines Agency encourages early stage engagement with drug developers, in advance of filing an application for a marketing authorisation. Seeking scientific advice well before completing the clinical testing programme can help the developer to tailor its proposed programme of tests and studies towards gaining approval and focus its investment and activity accordingly. Not only does this streamline the costly and time-consuming development process, getting medicines into the clinic sooner, it also helps to avoid unnecessary clinical testing on volunteers and patients. In addition, there are obvious benefits to ensuring that clinical testing is focused on activity that is really necessary and relevant to the approvals process.
Similar processes of engagement are used in other countries, notably the US, Canada, Switzerland, Japan and Australia.
Whilst scientific advice from experts designated by the EMA can offer support in designing and carrying out clinical trials in a way that will best demonstrate the safety and efficacy of the medicine, once the developer brings forward an application for marketing authorisation, involvement of the same experts could lead to a perceived conflict of interest or bias if a decision in favour of granting the approval is made. This risk of how things may be perceived is an issue which those working within medical regulation are keenly aware of, and development of a best practice framework will hopefully give re-assurance to all those involved, regulators, industry and the public.
European Ombudsman review
The European Ombudsman has carried out an in-depth review of the practice. Views submitted by representatives of both industry and patient groups supported the use of pre-submission advice and indicated that the level of transparency was sufficient. Concerns over the practicality of using ‘firewalls’ were expressed. Complete separation of pre-submission advice and formal evaluation will not always be possible – in the case of orphan conditions or advanced therapies relevant expertise may be scarce. Publication of the detail of pre-submission meetings could inappropriately expose commercially confidential information.
The Ombudsman has now issued its final advice to the EMA on how to avoid the risk or perception of bias. A set of best practice recommendations call for the following:
- The EMA should aim for maximum separation between experts providing pre-submission advice and those involved in evaluating the medicine once a marketing authorisation application has been filed.
- Appointment of rapporteurs by the EMA's Committee for Medicinal Products for Human Use (CHMP) should take into account whether particular individuals have been involved as coordinators in providing pre-submission advice.
- Where, in an exceptional case, there is no other option than to appoint an expert who had a prominent role in pre-submission advice, the reasons should be documented and published with the European Public Assessment Report (EPAR).
- At least one of the two rapporteurs should have had no prominent role in the pre-submission activities.
- The EMA should publish with the EPAR a log all relevant pre-submission activities and the experts involved.
In its response the EMA highlights its existing efforts both to improve transparency and ensure independence, and re-emphasises the benefits to patients of bringing new medicines to market quickly and efficiently. The Agency will consider what further steps are necessary to meet the Ombudsman’s recommendations.