Are Regulators Talking to Each Other Across Borders?

Clinical Pharmacology & Therapeutics, vol. 107, pp. 481–483

Abstract

Few people would disagree with the cliché that “the world is becoming more global.” At the same time, perhaps as a reaction to this, in recent years, various economic and political frameworks for international collaboration and alignment seem to have been under increasing pressure. Arguably, one of the most striking examples of this in our discipline of clinical pharmacology and drug development is the relocation of the European Medicines Agency (EMA) due to Brexit.1 In this issue of Clinical Pharmacology & Therapeutics, colleagues from EMA and the US Food and Drug Administration (FDA) ask the question if international regulators are talking to each other.2 They conclude that the answer to this question is “yes,” indeed that cross-border dialogue between international regulatory agencies is a well-established and near-daily activity (Figure 1). Through a survey, they identified 30 clusters for scientific collaboration and information exchange in certain disease areas or specific topics such as biosimilars,3 pediatric medicines,4 pharmacogenomics,5 and real-world evidence/big data.6 Two recent,7, 8 independent comparisons between outcomes of reviews by the FDA and EMA showed a high degree of concordance, which could indicate that such international collaboration has a positive impact on the consistency of regulatory decision making. In the January issue of Clinical Pharmacology & Therapeutics, Kondo et al.9 from the Japan Pharmaceutical and Medical Devices Agency (PMDA) also addressed the subsequent question: Why is it important that regulators talk to each other? They compared the definitions of regulatory science among the PMDA, FDA, and EMA and concluded that they have many common elements. Despite the similarities in approach and tools, different answers may be obtained to similar questions around the world, because regulatory science should also accommodate the local social, medical, and economic environment.9 As a result, the authors concluded that opinions about current and potential roles for regulators have diverged in different parts of the world and make a plea that it is time to emphasize the common ground and redefine regulatory science as a patient-centric discipline contributing to society and human welfare. Indeed, Zineh and Hartman10 recently stated that one of the two major ways in which clinical pharmacology can enable new therapies for unmet medical needs on a global scale is “the advancement and harmonization of regulatory science innovation and policies across global regulatory authorities.” An example of the impact of a concerted international effort is the EudraVigilance signal management system.11 In its first 6 years, it recorded nearly 15 million individual case safety reports, resulting in more than 26,000 potential signals reviewed and 453 confirmed signals assessed by the European Union Pharmacovigilance Risk Assessment Committee.12 This has resulted in the ability to detect and evaluate new safety signals that should improve the effective use of medicines across Europe. For example, in 2015, a routine search retrieved 148 cases of diabetic ketoacidosis in association with sodium-glucose transporter protein 2 inhibitors.12 Another example of the power of international collaboration involving regulatory agencies to develop consensus on approaches in the area of safety is the recent White Paper on general principles for the validation of proarrhythmia risk prediction models.13 Song et al.14 further corroborate Zineh and Hartman’s viewpoint10 by demonstrating the negative consequences of an isolated approach to regulatory science. Their recent analysis showed significant discrepancies in labeling of the most commonly used drugs in children between Korea and the United States, highlighting a consistent insufficiency in pediatric label information in the former country. Thus, although pediatric drug development is often global in scope, in the absence of global regulatory science collaboration, drug labels, and consequently the effectiveness and safety of therapies in young patients, may vary widely across regions. Another example of an area with room for improvement is consistency of pharmacogenomics drug labeling. Shekhani et al.15 found that of 54 drugs with actionable gen-drug interactions in the Clinical Pharmacogenetics Implementation Consortium16 and Dutch Pharmacogenetics Working Group guidelines, only 50% had actionable pharmacogenomics information in the label and different regulatory agencies were in agreement in only 18% of the cases. I believe these reflections on regulatory science can be condensed into a straightforward message: It is all about the patient.17, 18 In the drug development arena, there is always a temptation to shift the focus toward local regulatory processes, rules, and regulations, and there is a risk that we forget about the fact that collaborative innovative regulatory science is a key enabler of bringing life-changing medicines to patients.9, 19 Sir Alasdair Breckenridge, who passed away in December last year, was a founder and champion of regulatory pharmacology20 and the field of regulatory sciences owes much to him. He was an outstanding and influential member of our Editorial Board and Clinical Pharmacology & Therapeutics will continue to build on his legacy and aims to maintain its leading role as the journal for the dissemination of the most impactful regulatory science.

Authors 1

1. Piet H. van der Graaf corresponding Aachen

   Leiden University

   Affiliation as printed

   Certara Canterbury UK

   University of Leiden Leiden The Netherlands

   Certara, Canterbury, UK

   University of Leiden, Leiden, The Netherlands