Innovation and access: Improving Europe’s pharmaceutical regulatory framework

EMA “lags behind” other international regulators when it comes to approval timelines, finds EFPIA analysis.

Only a regulatory framework that “embraces a culture of excellence and innovation” will make Europe a world leader in life sciences and ensure people can reap the benefits of life-changing new treatments.

That’s according to the EFPIA’s analysis of the region’s regulatory framework, which compares the timelines of national regulatory agencies, and suggests key areas for change as the European Commission (EC) prepares to review pharmaceutical legislation.

Innovation and unmet need

The EC’s upcoming review of pharmaceutical regulation, part of the EU Pharmaceuticals Strategy, comes as the region faces substantial unmet need in disease areas from cancers to Alzheimer’s, liver disease to CNS disorders.

The problem, though, is not a lack of innovation. Researchers and developers are working on a raft of cutting-edge therapies, all of which have huge potential.

Checkpoint inhibitor combinations have delivered lifesaving therapies for patients with non-small cell lung cancer (NSCLC) and are now being studied in other cancers. In addition, gene therapies offer fresh hope to those living with genetic conditions, while curative hepatitis B and HIV treatments could remove the need for life-long treatment altogether. At the same time, personalised mRNA vaccines and CAR-T treatments are promising to revolutionise the oncology landscape.

It’s an exciting time, and, as highlighted in the EFPIA report, the upward trend of new active substances (NAA) is a testament to the sector’s scientific achievements.

Half of all therapies currently in development are NAAs, a large proportion of which are for untreated or undertreated diseases, according to the report. Moreover, 40% of the industry’s pipeline is made up of orphan drugs.

Researchers are making huge strides towards creating the treatments of the future, offering people the opportunity to live longer, healthier lives. But innovation alone will not fulfil this mission.

Ensuring access

The stated aim of the EC legislation review is to build a “future-proof and crisis-resistant medicines regulatory system”.

Part of that is making the route from development to market as efficient as possible without compromising safety. This boosts market competitiveness and ensures speedy access to life-changing drugs.

Yet when the EFPIA compared the timelines of six regulatory agencies between 2011 and 2020, it found the European Medicines Agency (EMA) “lagged behind”.

“The median EMA approval time in 2020 was more than 400 days,” the publication reports. “Apart from Swissmedic, this is longer than other regulatory agencies.”

By contrast, the US Food and Drug Administration (FDA) had a median approval time of 244 days, Health Canada had a timeline of 306 days, Japan’s Pharmaceuticals and Medical Devices Agency recorded 313 days, and the Australian Therapeutic Goods Administration, 315 days.

At least six companies that took part in an EFPIA survey of 39 sponsors said the time from submission to approval for rare disease treatments was “significantly longer for EMA compared to the FDA”.

One said a product approved in the US within four months took almost a year to get through the process in the EU. Another said a “more conservative EU position” resulted in a “significant delay to the availability of the medicines for the EU patient community”.

A case study included in the Evidence MIX report listed a number of potential reasons for this disparity. The company said the process of bringing a treatment for neurotrophic tyrosine receptor kinase solid tumours and ROS1 NSCLC to the European market took nearly a year longer than it did in the US.

“Firstly, there was an additional inspection of the sponsor of the drug by EMA. EMA also requested data that was not scheduled to be reviewed in advance,” said the case study.

“Additionally, there were limited interactions with EU rapporteurs/co-rapporteurs and even fewer interactions with clinical reviewers. The FDA reviewers were available to meet more frequently with the company (than the EMA).”

Expedited pathways, such as the FDA’s Breakthrough Designation and Fast Track, and the EMA’s PRIME Status, have been designed to provide an alternative to the standard medicines’ development and registration cycle.

By encouraging early dialogue between companies and agencies, allowing for interactions based on evolving safety/efficacy data in the context of unmet need, and reducing cycle times for feedback, they have become an “enabler” of innovation.

Yet there is still room for improvement, the EFPIA analysis suggests. The report shows that in 2020, the FDA had the highest percentage of NASs approved via expedited reviews (74%), followed by Swissmedic (61%), and TGA (56%). The EMA had the second-lowest percentage (37%) of medicines approved through an expedited review.

Future-proofing the system

The EFPIA report makes a number of recommendations for overcoming these challenges, while still accounting for those of the future.

It suggests enabling a “more agile, centralised” framework by removing “unnecessary interfaces” between the EC, EMA, working parties, and committees, and allowing member states to “bring forward their expertise”. The authors suggest that the move would “ensure global competitiveness through enhanced expertise-based assessment, and an efficient and swift process for the legally binding decisions”.

“An example of more efficient decision making is a timeframe limit of seven days for the Commission Decision, instead of the current maximum 67 days, for new Marketing Authorisation Applications, and 44 days for an extension of indications with limited exceptions,” said the authors.

Enhancing expediting pathways that support innovation is also recommended in the report. The EC, it says, should address longstanding pathway issues, such as clarifying the criteria for entry, expanding PRIME eligibility, and introducing regulatory ‘sandboxes’ for highly-innovative products, development, and manufacturing methods.

The result, say the authors, would be a faster, more flexible process that supports a “wide range of treatments for unmet need in the pipeline today and into the future”.

Next-generation regulation

As we look forward to a golden age in medical science, it is essential that we secure European access to next-generation therapeutics.

As such, EFPIA Director General, Nathalie Moll, has described the review of the general pharmaceutical legislation as “a once in a lifetime opportunity to deliver safer, better medicines to patients, faster”.

Any new regulatory framework, she went on, must be globally competitive enough to stem the tide of cutting-edge technologies that are leaving Europe for the US, China, and other regions.

About the author

Amanda Barrell is a freelance health and medical education journalist, editor and copywriter. She has worked on projects for pharma, charities and agencies, and has written extensively for patients, HCPs and the public.