The law needs to be changed to make it clearer to drugmakers when they should report new information which might influence the evaluation of a medicine’s risks and benefits to the Medicines and Healthcare products Regulatory Agency, the government has been told.

In particular, there is a need for more guidance on what to report within what timeframe, and for further clarity over use of the terms “promptly” and “due diligence,” respondents (mainly manufacturers) have told the public consultation held by the MHRA on the issue.

The consultation was launched to discover if the current law – The Medicines For Human Use (Marketing Authorisations, etc) Regulations 1994 – needed to be changed, following the MHRA’s report earlier this year of its investigation into whether GlaxoSmithKline had failed to inform it in a timely manner about information which it had on the safety of its antidepressant Seroxat (paroxetine) when used in patients aged under 18.

Based on the findings of the investigation and legal advice, government prosecutors decided that that there was no realistic prospect of a conviction and that the case should not proceed to criminal prosecution.
However, the legislation in force at that time was not sufficiently clear or comprehensive as to require companies to inform the regulator of safety information when the drug was being used for, or tested outside, its licensed indications, says the government, in its response to the consultation.

There have been several European Union developments since the Seroxat case, including the new clinical trials Directive and legislative changes to clarify the obligation to report, "promptly," relevant safety information arising from clinical trials using products outside their normal conditions of use.

The European Commission is also proposing to strengthen the EU system for monitoring the safety of medicines but, given the length of time that this may take, the MHRA has committed to changing UK legislation in the interim to clarify the requirements.

Therefore, the proposed changes to the 1994 Regulations will state explicitly, to ensure there remains “no room for doubt in industry’s and regulators’ minds,” that Marketing Authorisation (MA) holders should report information from both clinical trials outside the licensed indication and arising from third countries and to provide a timescale for reporting, says the government.

Points from the consultation
The MHRA’s review of the consultation says that a number of respondents - including the Faculty of Pharmaceutical Medicine (FPM), Wyeth, the British Association of Research Quality Assurance (BARQA), the Association of the British Pharmaceutical Industry (ABPI), the BioIndustry Association (BIO) and the mental health charity Mind – expressed concern over the use of the word “promptly.” As a result, it says, the proposed new legislation will use the term “as soon as reasonably practical” instead.

The ABPI also felt there should be guidance on what type of information is caught, in which time frames this needs to be reported and when the clock for such reporting starts, while the BARQA said the MHRA’s preparation of the new regulations should provide a clear audit trail of the underlying legislation, so that MA holders “could understand at a glance exactly what is required of them, especially when severely punitive sanctions apply to non-compliance.”

Among other comments: - the BIA called for guidance on the MA holder’s obligations for reporting safety information arising from non-company-sponsored trials; - Flynn Pharma Ltd pointed out that if the same products are marketed by different countries inside and outside the European Economic Area (EEA), UK-based MA holders might not be informed of problems occurring outside the EEA; and - Merck Sharp & Dohme noted that MA holders might not be made aware of the results of clinical trials sponsored by academic investigators which could affect the their product’s risk-benefit balance prior to such trials being made public and that, until they obtained such knowledge, they would be unable to report such results to the regulator. The BIA raised similar concerns, particularly in areas such as oncology, where trials are often designed and conducted by clinicians and academics acting independently from the MA holder.