Joel Lexchin
Abstract
Background
Health Canada posts the outcomes of all New Drug Submissions. In some cases, companies have withdrawn submissions or submissions have been rejected by Health Canada for new active substances (NAS). This study explores the reasons for those decisions and compares them with decisions made by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Methods
This is a cross-sectional analysis. Submissions for NAS between December 2015 and December 2022 were identified along with the original indications for the NAS, the information that Health Canada had available and the reasons for its decisions. Similar information was sourced from the FDA and the EMA. Their decisions were compared to those made by Health Canada. The time between decisions by Health Canada, the FDA and the EMA were calculated in months.
Introduction
Before new active substances (NAS, new drugs that have never been marketed before in Canada in any form) can be approved, sponsors need to present Health Canada with evidence of their efficacy, safety and manufacturing quality [1]. (The equivalent of the NAS designation by the United States Food and Drug Administration (FDA) is new molecular entity.) Since December 2015, Health Canada has been posting the outcomes of New Drug Submissions on its Drug and Health Product Submissions Under Review website [2]. Outcomes include: canceled by sponsor; Notice of Compliance (market authorization); Notice of Compliance with conditions (market authorization with requirements for postmarket studies); Notice of Deficiency–Withdrawal (NOD-W, company has not adequately responded to Health Canada’s decision that there is insufficient evidence to proceed with the review); and Notice of Non-Compliance–Withdrawal (NON-W, after the review has been completed, the company has not adequately responded to Health Canada’s decision that the evidence does not warrant approval).
Material and methods
Health Canada data
NAS where the sponsors withdrew the submission or they received either a NOD-W or a NON-W were identified through the New Drug Submissions on its Drug and Health Product Submissions Under Review website and the generic name of the NAS, the month and year when the submissions were concluded and their indication [2] were recorded on an Excel spreadsheet. Dates were only given by month and year and decisions were assumed to take place on the first day of each month. Hyperlinks from the Drug and Health Product Submissions Under Review website to the Drug and Health Product Register [4] were used to retrieve the reasons for Health Canada’s decisions along with the key information that the companies provided for their drugs and this information was entered onto the same spreadsheet.
Results
Health Canada considered New Drug Submissions for 272 NAS from December 2015 until the end of 2022 and approved 257 of them. Fifteen NAS were not approved: sponsors withdrew 14 submissions for 13 NAS (a submission for ataluren was filed twice) and two submissions received a NON-W. One product, finerenone, was approved after a second submission. (There was no information about why the company withdrew the second submission for ataluren).
Discussion
Over a 7-year period, Health Canada approved 257 NAS, rejected 2 submissions and companies withdrew 14 submissions for 13 NAS. Nearly all the submissions to Health Canada were withdrawn because the agency identified data deficiencies although these deficiencies were not generally further specified. Despite all 15 drugs not reaching the Canadian market (one was approved on a subsequent submission), 7 were approved by the FDA and 6 were approved by the EMA. In one case (amisulpride), the indications were different and that could have been the reason for the different decisions by Health Canada and the FDA.
Conclusion
Differences in decision making by regulators are due to more than just the data which with they are presented, the timing of that presentation and the indications for the drugs. Recognizing that differences are also due to therapeutic culture needs to be taken into consideration when there are calls for Canada to automatically accept regulatory decisions taken in other jurisdictions.
Citation: Lexchin J (2023) New drug submissions in Canada and a comparison with the Food and Drug Administration and the European Medicines Agency: Cross-sectional analysis. PLoS ONE 18(6): e0286802. https://doi.org/10.1371/journal.pone.0286802
Editor: Hideki Maeda, Meiji Pharmaceutical University, JAPAN
Received: March 2, 2023; Accepted: May 23, 2023; Published: June 15, 2023
Copyright: © 2023 Joel Lexchin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its supporting information.
Funding: The author received no specific funding for this work.
Competing interests: In 2019-2022, Joel Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for two legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written.
