The impact of the changing regulatory environment on the approval of new medicines

The Centre for Innovation in Regulatory Science (CIRS) has released a new R&D Briefing 59 titled, “The impact of the evolving regulatory environment on the approval of new medicines across six major authorities 2006-2015”.

  • This is an annual CIRS regulatory approvals briefing, which evaluates 2015 approvals for new active substances (NAS) approved by the US Food and Drug Authority (FDA), the European Medicines Agency (EMA) via the centralized system and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA); in addition to the three ICH countries, approval activities for Health Canada, Swissmedic and Australian Therapeutic Goods Administration (TGA) were also included in this briefing
  • The analysis looks back over the last decade and provides a view on approval trends 2006-2015, particularly regarding the various review types, facilitated regulatory pathways, therapy areas and common approvals for the six agencies

The key messages from this Briefing are: 

Convergence of approval times

The convergence and decrease in median approval time observed in the previous years (R&D Briefing 55 and 57) continued in 2015, when the difference in the median approval time between the fastest and the slowest agency decreased from 530 days in 2006 to 180 days in 2015.

This may reflect the improving quality of submissions from companies, as well as implementation of various quality measures by agencies, such as pre-submission activities in order to verify the quality of the dossier ahead of the review. Interestingly, the gap between FDA and PMDA for the overall time taken for review has further increased in 2015. Amongst the cohort of EMA, Health Canada, TGA and FDA the gap is similar at 66 days, but this gap has been narrowing.

The large drop in the PMDA approval times that has occurred since the beginning of the decade reflects the continual improvements and resource commitments made by the agency. Although the FDA timing has increased slightly since 2013, this likely reflects the pre-Prescription Drug User Fee (PDUFA) two-month filing period introduced to the review timeline under the fifth iteration of PDUFA. This modification aims to enable further improvements to the quality of company submissions and ultimately to optimise the FDA review process and increase the number of one-cycle approvals.

Internationalisation of products

Convergence in approval times has resulted in more compounds being internationalised in a shorter time frame in the recent years across the six agencies.

 It can be argued that a true comparison of regulatory performance can be derived from studying the review of compounds that were approved by all compared agencies. We identified 18 NASs that were approved by the six agencies in 2006-2010, and 36 NASs that were approved in 2011-2015, which suggests that more products are being internationalised in the same timeframe.

Unsurprisingly, the quickest rollout was to US for both 2006-2010 and 2011-2015. Although the rollout to Japan occurred last out of the six countries for both time periods, both submission gap and approval time have decreased from 2006-2010 to 2011-2015. This reflects both PMDA efforts to speed up the review of medicines as well as changes in companies' strategies, which now include earlier submissions to PMDA.

The submission gap and approval time for each agency for these compounds uncovered some of the factors that affect the time medicines take to reach the market, which may include company strategy to submit a product, agency review timelines, as well as compound-specific factors. Those include the specific therapy area or whether the product aims to address unmet medical need, which in turn affects whether or not the approval of the drug can be expedited. Indeed, the second half of the decade, 2011-2015, saw a major increase in the number of approvals of anti-cancer and immunomodulator NASs compared with 2006-2010, and these now constitute approximately a third of all NAS approvals across the six agencies. Overall, the anti-cancer and immunomodulator therapy area was the second fastest in terms of approval time (with anti-infective therapies in first place) for the six agencies with a median of 351 days, which likely reflect the more frequent usage of expedited review pathways.

Leveraging of product information
Three types of products were identified based on the submission/approval timing of the compounds to the six agencies. The products approved between 2014-2015 were characterised as those that received approval in only one jurisdiction (type 1), those that were approved concurrently with another agency where submission occurred prior to first-in-world approval (type 2) and those that were follow-on approvals following first-in-world approval (type 3). This typology was shown to affect the time to approval for NASs approved by the six agencies 2014-2015 and this may relate to whether or not agencies can leverage what is already known about the product based on previous reviews.

FDA and PMDA approved the largest number of NASs out of the six agencies that were only approved by each of the jurisdictions (type 1). EMA approved mostly products that were approved concurrently with another jurisdiction(s), where submission occurred prior to first-in-world approval (type 2). PMDA, Health Canada, Swissmedic and TGA approved the largest proportion of NASs where the submission occurred following first-in-world approval (type 3). 

In general, type 1 products had the longest approval time, except for Health Canada, as well as TGA which did not approve any NASs that were unique to Australia. For Swissmedic and PMDA, type 3 NASs had the shortest approval time, which may indicate that those agencies are perhaps leveraging what is known about the compound during review.

Download the full free report here for more trends in the number of approvals and approval times
for new medicines such as:

  • Common approvals by all six regulatory authorities
  • Review type analysis
  • Focus on compound type and therapy areas
  • At the back of the briefing we also attach the 2015 Regulatory Metrics Snapshots, which are graphic summaries of regulatory agency statistics for the six agencies.

CIRS - The Centre for Innovation in Regulatory Science - is a neutral, independent UK-based subsidiary company, forming part of the Intellectual Property and Science business of Thomson Reuters. The mission of CIRS is to maintain a leadership role in identifying and applying scientific principles for the purpose of advancing regulatory and HTA policies and processes. CIRS provides an international forum for industry, regulators, HTA and other healthcare stakeholders to meet, debate and develop regulatory and reimbursement policy through the innovative application of regulatory science. It is governed and operated for the sole support of its members’ activities. The organisation has its own dedicated management and advisory boards, and its funding is derived from membership dues, related activities and grants. For more information, go to