The shifting regulatory landscape impacts the review of new medicines


Major improvements in the regulatory environment in the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) countries over the last decade has led to a decrease in the time to approval as well as an increase in the number of medicines that have become available.

This is one of the key findings in a new report from The Centre for Innovation in Regulatory Science (CIRS) titled “New drug approvals in ICH countries 2007-2016.”

In its annual briefing on regulatory approvals, CIRS looked at approvals for new active substances (NASs) approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency’s (EMA) centralized system and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) from 2007-2016.

The analysis provides a view on approval trends, particularly regarding the various review types, facilitated regulatory pathways, therapy areas and common approvals for the three agencies.

CIRS analysts made these additional findings:

FDA and PMDA NAS median approval times converged in 2007-2016, with PMDA the fastest of the three agencies studied for a third year in a row.


Although Japan historically had the longest regulatory approval times, this has decreased following the creation of the PMDA. With its increase in resources and commitment, the PMDA’s review timing is now equivalent to the FDA’s. In 2016, the FDA overall median approval times decreased slightly from 2015 by 14 days. Nevertheless, when comparing 2007-2011 with 2012-2016, the median FDA approval times increased by 29 days, which is likely due to the process changes introduced under the Prescription Drug User Fee Act (PDUFA) V legislation. Europe, within the confines of its legislative approval procedures and processes, has had the slowest approval times out of the three agencies since 2011. Nevertheless, EMA approval times have been consistently lower for the last three years, by approximately 70 days compared with 2012-2013.

In 2016, the PMDA approved the greatest number of NASs (48) of the three agencies, approximately double the NASs compared with the EMA (28) and the FDA (22)


Following a spike in approval numbers in 2014 and 2015 for the three agencies, where 2014 marked a record year in the decade for FDA and PMDA and 2015 for EMA, in 2016 22 NASs were approved by the FDA and 28 by the EMA (Figure 2).

According to the FDA, this drop occurred for several reasons, including a natural fluctuation of the timing of application submissions which meant there was a smaller pool of novel drug applications to review, as well as a large number of deficiencies, as a result of which the FDA issued a higher number of complete response letters for novel drugs in 2016.1 However, although the PMDA approved the largest number of NASs of the three agencies in 2016, 71% of these NASs had been approved previously by the FDA or the EMA prior to PMDA submission. NAS approvals increased from 2007-2011 to 2012-2016 across all three agencies: a 50% increase for the FDA, 42% for the PMDA and 21% for the EMA.


The decrease in the overall median approval time for the EMA from 2014 onwards compared with 2012-2013 was driven largely by the decrease in company response time


Overall, the median company response time decreased by 39 days in 2016 compared with 2012; the median EMA review time remained the same with 245 days in 2016 compared with 243 in 2012; and the European Commission time decreased by 10 days for the same time period with 57 days in 2016, which is the lowest in the decade (Figure 3).


The number of the FDA CDER NASs approved after one cycle increased from 68% to 83% from 2007-2011 to 2012-2016


FDA’s Center for Drug Evaluation and Research (CDER) has been seeking to further optimize its review process, particularly by increasing the number of one-cycle approvals. An improvement in the number of one-cycle reviews may suggest better quality of dossiers, which in turn has a positive impact on review efficiency. It is important to note that this analysis (Figure 4) only includes approvals; inclusion of compounds that have not (yet) been approved may generate a different perspective, particularly in that CDER, as noted by the FDA, issued 14 complete response deficiency letters for novel drugs in 2016, which is higher than in the recent years, and consequently may be reflected in the number of review cycles in the coming years.1


The overall rollout time to Japan doubled in 2016 compared with 2012-2015 (Figure 5), which is due to an increase in the submission gap to Japan in 2016 (Figure 6)

This may reflect the fact that a number of products approved in 2016 were legacy products the availability of which to Japanese patients was facilitated through government programs as well as issues in the local development rights among sponsors (domestic versus foreign). Submission gaps also appeared to be related to company origin, with NASs from Japanese companies having experienced the longest submission gap in 2016. In addition, compounds that were designated as orphan experienced the longest submission gap during 2012-2016, which may be related to sponsor size where “large Japanese companies are developing orphan drugs after initial approval or at a later stage of development than in the USA or EU.”2 Interestingly, the PMDA approved the highest number of orphan medicines in 2016, which may also partially explain the increase in lag time in 2016.





  1. Jenkins J. 2017. A Review of CDER’s Novel Drug Approvals for 2016. FDA Voice. Available at: [Accessed April 6, 2017]
  2. Murakami M, Narkuawa M. 2016. Matched analysis on orphan drug designations and approvals: cross regional analysis in the United States, the European Union, and Japan. Drug Discov Today. 2016;21:544-549. doi: 10.1016/j.drudis.2016.02.016.

The Centre for Innovation in Regulatory Science – CIRS – is a neutral, independent U.K.-based subsidiary company, forming part of Clarivate Analytics. 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 organization has its own dedicated management and advisory boards, and its funding is derived from membership dues, related activities and grants.

Download the full free report, “New drug approvals in ICH countries 2007-2016,” here for definitions and more trends for new medicine approval such as:

  • Common agency approvals
  • Facilitated regulatory pathways and orphan designation approvals
  • A comprehensive list of approvals by each agency in 2016.

Region-specific “Regulatory Metrics Snapshots” for 2016 are also available here.