The Learning Portal will be under maintenance Saturday, 8 August between 6 AM and 6 PM EST. Portal functionality will be unavailable during this window.
We apologize for any inconvenience caused during this time.

RAPS is closely monitoring developments in the Coronavirus (COVID-19) outbreak. See our public safety page for the latest updates.

Regulatory Focus™ > News Articles > European Regulatory Roundup: Clinical Trial Delays Prompt EMA to Consider Revising Guidance (18 Augu

European Regulatory Roundup: Clinical Trial Delays Prompt EMA to Consider Revising Guidance (18 August 2016)

Posted 18 August 2016 | By Nick Paul Taylor 

European Regulatory Roundup: Clinical Trial Delays Prompt EMA to Consider Revising Guidance (18 August 2016)

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.

Complaints About Delayed Clinical Trial Starts Prompt EMA to Consider Revising Guidance

The European Medicines Agency (EMA) is considering revising its guidance on clinical trial reference safety information (RSI) after drug developers complained the current situation is delaying the start of studies. In response to the grievances, EMA has encouraged the industry to discuss the concerns with the Heads of Medicines Agencies’ (HMA) Clinical Trial Facilitation Group (CTFG).

Drug developers brought up the topic at meeting with EMA about pharmacovigilance last month, a summary of which has just been released by the regulator. The complaint was prompted by an uptick in the number of questions and objections relating to the RSI parts of trial applications and updates to investigator brochures. RSI is a list of the medical reactions a sponsor expects to see when a drug is given in a clinical trial. Sponsors have been required to submit this information for some time, but as they see it, the demand, or, more accurately regulators’ responses to it, has become a burden.

As the industry sees it, the problems stem from the lack of aligned, detailed guidelines across the EU. Drug developers want to see such a document brought into force. While regulators are working on the document, the industry is asking for a transition period to be implemented to prevent the existing guidance from causing any more delays to the initiation of clinical trials.

Whether regulators meet the industry demands remains to be seen. EMA, which wrote up the exchange in the minutes to the pharmacovigilance meeting, said the next step is for the industry to raise its concerns with CTFG, a group HMA set up to coordinate the implementation of the clinical trial directive. Now, CTFG also serves as a place industry can discuss the need for principles that apply across the European regulatory network. EMA is advising industry to use this existing forum to discuss RSI, specifically the need to update guidance.

The topic was one of many discussed at the EMA-industry pharmacovigilance meeting. Among the notable issues raised by the industry was the adoption of safety features to comply with the Falsified Medicines Directive. Again, harmonization is a concern. EMA is seeking to allay the worries by talking to the European Commission. The talks will focus on the need to ensure the safety feature rules are applied consistently across the EU.    

Meeting Highlights

Novo Nordisk, EFPIA Call for Harmonization of HTA Clinical Assessments Across EU

The European Federation of Pharmaceutical Industries and Associations (EFPIA) and Novo Nordisk have met with the Directorate General for Health and Food Safety (DG Sante) to talk about health technology assessment (HTA).

Novo Nordisk requested the meeting to give it a chance to explain its views on cooperation on relative effectiveness assessment (REA) in the EU. In DG Sante’s write up of the meeting, which took place in June but came to light this week, EFPIA is said to have called for more cooperation across the EU on REAs. HTAs use REAs to compare the effectiveness of different medical interventions, making it an important tool for reimbursement decisions.

The question posed by EFPIA and Novo Nordisk is whether the same results can be achieved while burdening drug manufacturers less. “A big concern for industry are the different procedures and methodologies applied by national HTA agencies. Multiple requests for evidence were also a reason causing delays in patients' access, as well as increasing costs,” DG Sante wrote in its summary of the views expressed by EFPIA.

EFPIA thinks EU officials can alleviate these burdens. The trade group is advocating for HTA agencies to cooperate and harmonize aspects of their assessments that relate to clinical effectiveness. To date, the pace of HTA harmonization has been restricted by member states’ desires to retain full control over their reimbursement decisions. In focusing on the clinical rather than economic aspects of the assessments, EFPIA and Novo Nordisk could potentially face less resistance from HTA agencies. 

DG Sante published details of the meeting at the same time it released minutes covering talks with the European Patients’ Forum (EPF). The meeting with EPF focused on the potential for it to play a role in the European network for HTA (EUnetHTA). “EPF potentially foresees a cross cutting involvement in the different work packages,” DG Sante wrote. “Nevertheless EPF considers that the patient perspective should be specifically included in the work package on national implementation.”

Meeting Notes, More

Austria Joins EMA-FDA Generic Facility Inspection Cooperation Initiative

Austria has joined a cooperation initiative between EMA, certain EU member states and the US Food and Drug Administration (FDA). The initiative began early in 2014 to eliminate some of the duplicated regulatory work involved in the processing of generic marketing applications.

Starting out with just the involvement of France, Germany, Italy, the Netherlands and the UK, the pilot project established a framework for sharing information on bioequivalence testing facilities. In April 2014, Spain joined the scheme, since when the list of member states participating in the project has been unchanged. Now, with the addition of Austria to the program, EMA and FDA have taken another small step toward their objective of bringing member states into the initiative.

The desire to involve member states is a consequence of the role national regulators play in generic marketing authorizations in the EU. While innovative drugs typically follow the centralized approval procedure, generic drugs are often handled on a national level. As such, MHRA and its peers play a major role in the inspection of bioequivalence testing facilities in Europe, making their involvement in the initiative essential to its effectiveness.

With France, Germany and the UK involved with the program from day one, the initiative has always had the support of the region’s major drug markets. In adding Spain and now Austria, the project has continued to extend its reach. 

EMA Update

Glaxo Recalls and Pulls Drug from UK After Failing Impurity Tests

GlaxoSmithKline has recalled four batches of Respontin Nebules after routine stability testing showed out of specification results for impurities. The recall marks the end of the product’s availability in the UK.

The UK Medicines and Healthcare Products Regulatory Agency (MHRA), which shared details of the recall, told healthcare professionals the products are being discontinued. As such, alternative batches of either of the pack sizes affected by the recall will not be available to replace those now being quarantined and pulled from the market. Respontin Nebules is a formulation of ipratropium bromide designed for delivery via a nebulizer to reverse obstruction of airways. 

While no new batches of Respontin Nebules will be available and MHRA has not received reports of any adverse events, it is nonetheless asking healthcare professionals to stop using the product. The regulator is advising people to switch over to alternative versions of both pack sizes that are sold by suppliers other than Glaxo. Actavis, Boehringer Ingelheim and Concordia International are among the manufacturers listed as selling ipratropium bromide formulations in the UK.

MHRA Alert

Other News:

MHRA has issued a warning about blood glucose test strips from Nipro Diagnostics. The alert tells patients to stop using certain lots of the strips because a manufacturing fault has created a risk they could deliver false, low readouts. Patients who possess the test strips are being advised to return them to Nipro. MHRA Notice

Regulatory Focus newsletters

All the biggest regulatory news and happenings.