The impact of the changing regulatory environment on the approval of new medicines, 2007-2016

Over the last decade, 2007-2016, convergence in approval times as well as changes in strategies of multinational pharmaceuticals have resulted in more new active substances (NASs) being internationalized, referring here to receiving marketing authorization in six major regulatory agencies, namely the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), the Japan Pharmaceuticals and Medical Devices Agency (PMDA), Health Canada, Swissmedic and the Australian Therapeutic Goods Administration (TGA).

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 six major authorities 2007-2016: Focus on the internationalisation of medicines.”

CIRS analysts made these additional findings:

In 2016, the PMDA approved the highest number of NASs (48), followed by Swissmedic (40), Health Canada (33), the TGA (32), the EMA (28) and the FDA (23) (See Figure 1). Despite these numbers varying on an annual basis, the overall number of NASs approved by the six agencies has increased, as shown by the three-year moving average.

A comparison of numbers of NASs approved by each agency during the two parts of the decade, 2007-2011 and 2012-2016, showed that the biggest difference in the number of approvals was seen for the FDA, with a 51% increase, followed by the TGA (45%), the PMDA (42%), Swissmedic (41%), Health Canada (40%) and the EMA (21%). The year-on-year variance across countries in the number of products approved by each agency may be explained by a number of factors, such as different submission strategies to each agency, which in turn varies according to sponsor R&D budget size and unmet medical need as well as agency review speed that can also vary according to therapeutic area and the use of expedited pathways.

Figure 1: Number of NASs approved by six regulatory authorities by approval year, 2007-2016.

The convergence in median approval time observed in previous years (See R&D Briefing 55 and 59) continued in 2016, when the difference in the median approval time between the fastest and the slowest agency decreased from 356 days in 2007 to 170 days in 2016 (See Figure 2).

In 2016, the PMDA was the agency with the shortest median approval time (311 days), followed by the FDA (333), Health Canada (351), the TGA (372), the EMA (422) and Swissmedic (481). Besides a decrease in variability in approval times across the six agencies, the past years have also seen a decrease in variation in approval time within the six agencies, especially for the TGA, the EMA and the PMDA, which have established even more consistency in review timing in the last five years. This may be a result of a number of factors, such as the legislation of approval procedures and processes within the EMA and TGA, 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 and to ultimately improve process consistency and timeliness. Where there is variance, this may be due to the use of standard or expedited pathways by the agency in order to prioritize the review of certain NASs.

Figure 2: New active substance (NAS) median approval time for six regulatory authorities in 2007-2016

The number of products approved by all six agencies in a two-year period increased from four NASs in 2011-2012 to 13 NASs in 2015-2016, which indicates that more products are becoming internationalized within the same time frame (See Figure 3).

The breakdown of the overall time to registration into submission gap and approval time uncovered potential limiting factors for registration of NASs. This may include company strategy to submit later or long approval times at a particular agency. The quickest time to registration was at the FDA for all three time frames (2011-2012, 2013-2014 and 2015-2016) as a result of companies submitting there first as well as quick regulatory review times by the agency. Submissions to the EMA occurred almost simultaneously with the FDA, and the overall time to registration decreased over the last six years for those common products, as a result of shorter median EMA approval times. This reflects increased use of expedited pathways for important products by the EMA, particularly in 2015-2016. Following EMA and FDA submissions, the submission gap to Health Canada, Swissmedic and the TGA was around ~60 days. This gap varied for the three time periods but the longest submission gap occurred in 2015-2016 for all three agencies.

Although the longest submission gap occurred at the PMDA and has increased steadily over the last few years (as discussed in more detail in R&D Briefing 62), the overall time to registration was quicker for Japan compared with Switzerland as a result of faster approval time at the PMDA. This reflects the Japanese regulator’s efforts to speed up the review of medicines, where the most notable changes made by the agency included an increase in resources, the introduction of prior-evaluation meetings to discuss clinical trial study results, as well as the prior-assessment consultations approximately six months prior to submission of a new drug application.

Figure 3: Median submission gap and median approval time for NASs approved in all six authorities in 2011-2012 (4), 2013-2014 (7) and 2015-2016 (13).

High unmet need and sponsor pharmaceutical company size were seen as key drivers for internationalization.

A greater proportion of anti-cancer and immunomodulating NASs and, in particular, products given a Breakthrough Designation by the FDA, obtained marketing authorization in the six agencies compared with the rest of NASs. The size of sponsor also had an effect; companies with large R&D budgets (>3 billion USD) were more likely to internationalize their products and also submitted to the six agencies earlier. Such integration of worldwide drug development and registration by companies, as well as more efficient reviews within agencies, enable NASs to be made available to wider patient populations globally in a timely manner.

Download the full CIRS analysis here for definitions and more trends for new medicine approvals such as:

  • therapy area approval
  • common agency approvals
  • review type
  • facilitated regulatory pathways.


Region-specific “Regulatory Metrics Snapshots” for 2016 are also available here. The list of NASs included in the analysis is available here. 

The Centre for Innovation in Regulatory Science 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.

To access other CIRS R&D Briefings and Reports, please click here.

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