ObjectiveTo compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.DesignUsing publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.ResultsIn 2014–2016, 115 NASs were approved by EMA or FDA or both; 74/115 were new chemical entities and 41 new biological/biotechnology entities; 82/115 were approved by both agencies, 24 only by FDA and nine only by EMA. Simultaneous submission occurred for 52/115; 13/52 received expedited review by both agencies and 18 only by FDA; 8/52 received conditional approval from both agencies, 2/52 only from FDA and 1/52 only from EMA; 17/52 were designated as orphans by both agencies and 10/52 by FDA only; 31/52 indications were approved as submitted and 21 changed by EMA and 29/46 were approved as submitted (six not assessed) and 17/46 changed by FDA. Median FDA review timelines were 319 days compared with 409 days for EMA.ConclusionsThere was general agreement in EMA / FDA conditional approvals. FDA used expedited pathways and orphan designation more often than EMA, suggesting stricter EMA criteria or definitions for these designations or less flexible processes. Despite consistency in submitted indications, there was lack of concordance in approved indications, which should be further investigated. FDA review times are faster because of a wider range of expedited pathways and the two-step EMA process; this may change with recent revisions to EMA accelerated assessment guidelines and the launch of Priority Medicines.

The US Food and Drug Administration (FDA) has four facilitated regulatory pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review (PR), and Accelerated Approval (AA). Only PR specifies an expedited review timeline (6 months). We sought to determine to what extent the combination of two or more FRPs influenced development and approval times. We developed a “metro map” to illustrate FRP elements and their influence on review times. We assessed 125 new active substances (approved January 2013 to December 2015) 74 of which used one or more FRPs. For these 74, development times ranged from 1,458 (BTD + PR + AA) to 3,515 days (PR). PR alone had a median approval time of 242 days. The most common combination was FT + PR (median approval 292 days, n = 21). The fastest approval times were for PR + FT + BTD + AA (145 days) and PR + BTD + AA (166 days). Our findings support the combination of FRPs for shortening development and review times beyond that provided by PR alone.

Background The certificate of pharmaceutical product (CPP) was implemented to accelerate the availability of new drugs in developing countries by providing evidence of the quality of products and reducing the time to market through reliance on a prior trusted analysis. However, the CPP format, issuing process and use have not been revised since 1997 and there are significant differences among countries in regard to requirements for CPP timing, terminology, and format. We sought to determine current CPP practices versus national regulatory guidelines and to inform recommendations for the efficient use of the CPP based on the needs of the modern regulatory environment. Methods We conducted a comparative analysis of company practice versus agency guidelines across 18 maturing pharmaceutical markets using data from the Cortellis for Regulatory Intelligence® (CRI) and the Centre for Innovation in Regulatory Science (CIRS) Emerging Markets Regulatory Review Times (EMaRReT) databases and regulatory authorities’ websites. Results Of the studied 18 countries, 16 require the CPP for submission of new registrations; many accept alternative documentation but most still require legalization of the CPP and many are not compliant with the complex CPP format. Additional complicating factors include language requirements and varying local guidelines for CPP submission timing and validity dates. Conclusions With the implementation of a number of suggested improvements, the CPP can continue to serve an important role in streamlining regulatory efficiency and provide confidence in new medicines, ensuring a more efficient and effective approval process and expediting patient access to safe and effective medicines worldwide.

Although it cannot be expected that different medicines' regulatory agencies always reach the same review outcome, it is important that decision making is documented and communicated to ensure transparency. This study examines whether justification for divergences between the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding approved indications could be identified from the agencies' public assessment reports (PARs). We focused on 9 products previously identified to have been submitted simultaneously to both agencies with the same indication but had a different indication approved; there were 15 differences in indications. Our analysis confirms that the rationale for observed divergent indication decisions was predominantly found in the benefit-risk section of the PAR (9 of 15 cases for the FDA and 10 of 15 for the EMA). If not found in the benefit-risk section, the rationale for these decisions was found in other PAR sections (eg, labeling or clinical efficacy section) or not at all. Our study found a small number of inconsistencies or gaps in how, where, and whether regulatory decision making on approved indications are documented by the FDA and the EMA. We believe it is important for regulators to standardize their approach and systematically and transparently document their rationale for the approved indication, using a structured benefit-risk assessment format within the PAR. This process is especially important for innovative products for which experience in evaluating similar products worldwide is limited, particularly as agencies are striving to build effective regulatory processes by leveraging assessments by trusted reference agencies through approaches such as reliance. Clear and systematic communication and documentation of the decisions in the PAR are central and should continue to evolve as a best practice; an enabling step toward this would be a harmonized PAR template for use by agencies globally.

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