New drug applications to Health Canada cancelled and refused: Cross-sectional study

Abstract

Objectives

This study looks at the number of cancellations by companies and refusals by Health Canada of new drug applications from 1 June 2019 to 1 July 2025 and the amount of information given for the decisions taken.

Design

Cross-sectional.

Setting

Canada.

Participants

New drug applications.

Main outcome measures

Number of applications cancelled or refused and reasons for decisions.

Results

There were 270 regulatory decisions of which 33 (12.2%) were either cancelled by the company (30) or refused by Health Canada (3). In 10 of the 30 cases where the submission was cancelled, there was no information about the reason for the company's decision. In the remaining 20 cases, the website just said that a decision had been made by the company. Two of the three refusals by Health Canada were because of concerns about safety and efficacy and quality-related issues. The third refusal was due to deficiencies and/or significant omissions in the clinical and non-clinical information. In the 30 submissions cancelled by the company, there was no information about what Health Canada thought in 6 cases. In 16 cases, Health Canada had not completed its evaluation, and in the remaining 8, the evaluation was completed.

Conclusion

Over 12% of new drug submissions to Health Canada are either cancelled or refused. Health Canada does not always fully communicate the information that it has regarding the reasons for these decisions and needs to be much more transparent about its decision-making.

Keywords

Health Canada new drug applications cancelled refused

Introduction

Before a new active substance (NAS, a molecular never marketed before) can be sold in Canada, it must go through the Health Canada regulatory process to evaluate efficacy, safety and manufacturing quality. At times, submissions are either cancelled by the manufacturer or refused by Health Canada.

This study looks at the number of cancellations by manufacturers and refusals by Health Canada and the amount of information given for the decisions taken.

Methods

List of drugs with withdrawn or refused submissions

Health Canada maintains a webpage that lists all the drugs with a completed regulatory process starting from 1 June 1 2019.¹ (Prior to 1 June, Health Canada did not publish the names of new drug applications that were not approved.) NAS that either had a cancelled or rejected submission up until 1 July 2025 were identified, and the following information was recorded: the URL that hyperlinks to the reasons for the decision; and the dates that the submission was filed and the submission was either cancelled or refused.

Therapeutic classification

The second-level therapeutic classification was derived from the Anatomic-Therapeutic-Chemical database maintained by the World Health Organization and the Norwegian Institute of Public Health.²

Reason for company and Health Canada decisions

The hyperlinks were used to examine the information given for the company and Health Canada decisions,³ the information was summarised and recorded verbatim.

All data were entered on an Excel spreadsheet.

Data analysis

Counts were made of the total number of drugs with regulatory decisions, the number with cancelled and refused submissions and their second-level ATC classifications. The median time (interquartile range, IQR) between submission and cancellations and refusals was calculated in days using the function in Excel. No statistical testing was undertaken.

Patient involvement, ethics, and reporting

No patients were involved in this study; all data were publicly available, and ethics approval was not required. Data were gathered by a single individual between September 10 and 15, 2025. The 2007 STROBE guidelines for cross-sectional studies were followed.⁴

Results

There were 270 regulatory decisions for NAS between 1 June 2019 and 1 July 2025, out of which 33 (12.2%) submissions were either cancelled by the company (30) or refused by Health Canada (3). Withdrawals and refusals were clustered between 2022 and 2024. Eleven submissions cancelled by the company were for products related to COVID-19 (Table 1 and Supplementary File 1). The median time between submission of the application and both cancellations and refusals was 303 days (IQR 184, 306). The median time between submissions and cancellations was 303 days (IQR 184, 321) and for refusals it was 193 days (IQR 91, 304).

Table 1.

Number of regulatory decisions, cancellations and refusals.

Year	Number of regulatory decisions	Number (%) of cancellations	Number (%) of refusals	Number (%) of cancellations related to products for COVID-19
2019 (Starting 1 June)	16	0 (0)	0 (0)	0 (0)
2020	36	0 (0)	0 (0)	0 (0)
2021	52	8 (15.4)	1 (1.9)	0 (0)
2022	51	6 (11.8)	1 (2.0)	4 (66.7)
2023	52	8 (15.4)	0 (0)	4 (50.0)
2024	36	6 (16.7)	1 (2.7)	3 (50.0)
2025 (Ending 1 July)	27	2 (7.4)	0 (0)	0 (0)
Total	270	30 (11.1)	3 (1.1)	11 (36.7)

One NAS (finerenone) was submitted a second time and was approved, and one product (SARS-CoV-2 prefusion spike delta TM protein, recombinant) was cancelled twice. Six drugs were vaccines, five were antineoplastic agents and immune sera and immunoglobulins, and the remaining 17 were in 12 ATC categories.

In 10 of the 30 cases where the submission was cancelled by the company, there was no information about the reason for the company's decision. In the remaining 20 cases, the website just said that a decision had been made by the company, except in one case where the decision seems to have been made because Health Canada and the company could not agree on the content of the Product Monograph. (The Product Monograph is the document that contains detailed data on the drug's identity, therapeutic classification, clinical pharmacology, and clinical trial findings.)

Two of the three submissions refused by Health Canada had had their initial reviews completed. Health Canada refused one submission because of an inadequate response from the company to its initial concerns about safety and efficacy. A second submission was refused because of quality-related issues. The review of the third submission was not completed when it was refused, but Health Canada had identified deficiencies and/or significant omissions in the clinical and non-clinical information.

In the 30 submissions that were cancelled by the company, there was no information about what Health Canada thought in 6 cases. In 16 cases, Health Canada had not completed its evaluation of the submission when the company made the decision to cancel it. In those cases, Health Canada usually just said that it had identified deficiencies in the application but gave no further details. In those 16 cases, it was not clear if Health Canada had communicated its concerns to the company involved. In 8 cases, Health Canada had completed its initial evaluation and gave detailed information about the deficiencies in the clinical studies, which seemed to trigger the company's decision to cancel the submission (Table 2).

Table 2.

Reasons for company and Health Canada decisions.

Generic name	Health Canada evaluation	Company response	Cancellation or refusal
Abaloparatide	No information	No information	Cancelled by company
Aducanumab	At the time of cancellation, Health Canada completed the assessment of the data provided to support the proposed indication. The clinical efficacy and safety data that were provided did not support the clinical benefit	Sponsor chose to cancel their submission	Cancelled by company
Amisulpride	At the time of the cancellation, the review of the submission was ongoing. Health Canada had identified deficiencies in the package that would have precluded issuing an approval.	Sponsor chose to withdraw their submission prior to sending a response	Cancelled by company
Avanafil	At the time of cancellation, the pre-clinical and clinical evidence with respect to the safety and efficacy of the drug had been reviewed and found to be acceptable. Health Canada had identified issues during the assessment of the quality data, regarding the lack of an assessment of the control for certain impurities. Health Canada issued a refusal for this submission on April 16, 2020. A response to the refusal was filed and reviewed by Health Canada but quality-related issues remained.	The sponsor subsequently decided to cancel the submission.	Refused by Health Canada
Bamlanivimab *For use in relation to COVID-19	At the time of cancellation, the review of the submission was ongoing	The sponsor chose to cancel the submission due to the changes in global variant landscape	Cancelled by company
Casirivimab, imdevimab *For use in relation to COVID-19	The review of the submission was ongoing at the time of cancellation	No information	Cancelled by company
Cefditoren pivoxil	At the time of the cancellation, the review of the submission was ongoing for most review components. Health Canada had identified major deficiencies and data gaps in the drug quality data that would have precluded conducting a meaningful quality assessment and hence issuing an approval. The submission review had not started for the drug quality component but focused only on the initial scoping. A refusal was recommended for this submission insofar as chemistry and manufacturing were concerned.	The sponsor chose to cancel their submission	Cancelled by company
Cevimeline hydrochloride	Overall, the lack of evidence to support efficacy of cevimeline as compared to placebo, the inconsistent results on subjective endpoints, and the lack of dose-response suggest an overall lack of efficacy. Explanations provided in the refusal do not sufficiently address the concerns identified during the review and do not provide confirmation of efficacy…Proposed labelling does not adequately address these safety issues especially in the context where there is a lack of substantial evidence supporting efficacy for the treatment of dry mouth in patients with Sjögren's Syndrome.	No information	Refused by Health Canada
Cilostazol	At the time of the cancellation, the review of the submission was ongoing. Health Canada identified some deficiencies in the package that would have precluded issuing an approval. Health Canada issued a refusal…and was awaiting a response to it.	The sponsor chose to cancel their submission prior to sending the response.	Cancelled by company
Copanlisib dihydrochloride	At the time of the cancellation, Health Canada had identified concerns during the review related to the product's efficacy and safety and was about to notify the sponsor of these concerns through the delivery of a clarification request.	The NDS was cancelled by the Sponsor	Cancelled by company
Daprodustat	No information	No information	Cancelled by company
Datopotamab deruxtecan	No information	No information	Cancelled by company
Diroximel fumarate	At the time of the cancellation, Health Canada was assessing the company response to its refusal	The sponsor chose to cancel their submission before a decision was issued.	Cancelled by company
Emapalumab	At the time of the cancellation, Health Canada had completed the assessment of the non-clinical data package and the review of the pivotal evidence supporting the safety and efficacy…The review of clinical pharmacology information was on-going. Health Canada had identified deficiencies in the clinical data that would have precluded issuing an approval.	The sponsor chose to cancel the submission	Cancelled by company
Enterococcus faecalis inactivated, Escherichia coli inactivated, Klebsiella pneumoniae inactivated, Proteus vulgaris inactivated	Health Canada's review of the submission was incomplete at the time of cancellation. During review, Health Canada identified that they were unable to entirely assess the chemistry and manufacturing of the product from the data that was available	Health Canada notified the sponsor of these issues, and the submission was subsequently voluntarily withdrawn.	Cancelled by company
Etesevimab *For use in relation to COVID-19	At the time of cancellation, the review of the submission was ongoing.	The sponsor chose to cancel the submission due to the changes in global variant landscape	Cancelled by company
Favipiravir *For use in relation to COVID-19	Based on the review of submitted evidence, Health Canada was not able to establish a positive benefit-harm profile for favipiravir in the acute treatment of mild to moderate COVID-19.	The sponsor was given an opportunity to provide additional supporting clinical trial evidence. However, on February 24, 2022 the sponsor opted to withdraw the submission from review.	Cancelled by company
Filgotinib	At the time of the cancellation, the review of the submission was nearing completion and Health Canada was planning to issue a refusal, based on clinical and non-clinical issues.	The clinical division met with the sponsor to discuss the NON issues and the need to complete the ongoing safety studies with filgotinib. The Sponsor chose to withdraw the submission before the NON was issued.	Cancelled by company
Finerenone	An initial review of the Fidelio renal outcomes trial was conducted and a number of uncertainties were identified and conveyed to the sponsor in a clinical clarification request… At the time of cancellation, Health Canada's review of the submission was not complete.	The NDS for Kerendia was cancelled by the sponsor	Cancelled by company
Gefapixant	At the time of the cancellation, Health Canada was finalizing its response to the company's reply to the reasons for refusal. Health Canada still had concerns regarding the robustness and clinical relevance of the efficacy data despite the additional information provided in the response to NOD.	No information	Cancelled by company
Lasmiditan	At the time of cancellation, the review of the submission was complete. Health Canada did not identify any deficiencies in the data packages that would have precluded issuing an approval. However, Health Canada and the sponsor could not reach agreement on the interpretation of the cardiovascular data and resulting content in the Product Monograph.	The sponsor made the decision to cancel the submission before a negative decision could be issued by Health Canada.	Cancelled by company
Marstacimab	No information	No information	Cancelled by company
Masitinib mesylate	Deficiencies and/or significant omissions were identified pertaining to clinical and non-clinical information that preclude continuing the review. Therefore, a refusal was recommended. The clinical, non-clinical, quality and labelling reviews were not completed at the time of the refusal and deficiency comments so far identified were included with the refusal.	AB Science S.A. submitted to Health Canada a request for reconsideration on May 9, 2024. While the reconsideration review was underway, the sponsor withdrew the reconsideration request	Refused by Health Canada
Molnupiravir *For use in relation to COVID-19	A refusal was issued for this NDS-CV on February 3, 2023, based on a negative outcome of the clinical review…Based on the data submitted in this NDS-CV, the efficacy of molnupiravir in the treatment of mild to moderate COVID-19 in adults who are at risk for progressing to severe disease has not been established and therefore, the benefit-harm-uncertainty profile of molnupiravir is negative.	The sponsor had an opportunity to provide additional evidence to support their proposed indication for molnupiravir. However, on April 26, 2023, the sponsor opted to withdraw the submission from review.	Cancelled by company
mRNA encoding haemagglutinin of B/Victoria lineage, haemagglutinin of influenza A/H1N1, haemagglutinin of influenza A/H3N2, SARS-CoV-2 spike protein NTD-RBD subdomains	No information	No information	Cancelled by company
Recombinant haemagglutinin-strain A (H1N1) virus-like particles, Recombinant haemagglutinin-strain A (H3N2) virus-like particles, Recombinant haemagglutinin-strain B (Victoria lineage) virus-like particles, Recombinant haemagglutinin-strain B (Yamagata lineage) virus-like particles	No information	No information	Cancelled by company
Regdanvimab *For use in relation to COVID-19	At the time of the cancellation, the review of the submission was ongoing.	The Sponsor chose to cancel their submission for business reasons.	Cancelled by company
Roxadustat	A refusal was previously issued for this product on January 25, 2021. A response to the refusal was filed and reviewed by Health Canada. Remaining issues were identified during the review of the response.	The sponsor subsequently decided to cancel the submission.	Cancelled by company
Sabizabulin *For use in relation to COVID-19	A refusal was issued on April 14, 2023. The sponsor asked for a 3-year extension to respond to the refusal which was denied due to the length of the requested extension.	The sponsor opted to withdraw the submission from review.	Cancelled by company
SARS-CoV-2 prefusion spike delta TM protein, recombinant *For use in relation to COVID-19	At the time of the cancellation, the review of the submission was ongoing and no decision or recommendations had been made.	The sponsor chose to cancel their submission	Cancelled by company
SARS-CoV-2 prefusion spike delta TM protein, recombinant *For use in relation to COVID-19	At the time of the cancellation, the review of the submission was in screening pending additional data from the sponsor	The sponsor chose to cancel their submission	Cancelled by company
Sotrovimab *For use in relation to COVID-19	The review of the submission was ongoing at the time of cancellation.	No information	Cancelled by company
Whole virion inactivated coronavirus *For use in relation to COVID-19	At the time of the cancellation, the review of the submission was nearing completion. Health Canada had identified some deficiencies in the data that would have precluded issuing an approval.	The sponsor chose to cancel their submission	Cancelled by company

Discussion

Over 12% of initial submissions are either cancelled by the company or refused by Health Canada, with very few drugs having repeat submissions. One third of cancellations were in NAS related to COVID-19, and therefore, this 33-drug sample may not have reflected the usual pattern of refusals and cancellations. There was generally not enough information available to determine the reason for the median 303-day interval between when a company submitted its application and then cancelled the submission.

When new drugs are approved by Health Canada, it publishes a Summary Basis of Decision document, which provides much more detail about the reasons for the decision than when NAS submissions are cancelled or refused. In contrast, the European Public Assessment Reports contain the same level of detail regardless of the decision by the European Medicines Agency.⁵

The FDA has released over 200 Complete Response Letters (CRL) outlining safety concerns, trial design flaws and manufacturing gaps in new drug applications. These CRLs provide more information than Health Canada documents, but they are not automatically available as is the information from Health Canada.⁶

The results from this study are markedly different from one that looked at drugs that failed their initial submission to the FDA between 2000 and 2012. Of 302 new drug applications, 151 (50%) were approved on their first submission compared to almost 88% for new drugs submitted to Health Canada. The main reasons why FDA submissions failed were uncertainties related to dose selection, study endpoints and poor efficacy – 13.2% each and inconsistent results – 11.3%. Granular detail from Health Canada was not available to repeat this type of analysis.⁷

Although NASs that have their submissions initially cancelled or refused are not going to be sold, it is still important to have detailed information as to why they were not approved. Related medicines may already be marketed and may exhibit the same problems. Occasionally, companies may resubmit products for approval, and it is important to be able to determine whether and how deficiencies were corrected. Finally, having the reasons publicly available may help other companies looking at similar drugs avoid making mistakes in their clinical trials and thereby not expose patients to harm and save on resources.

Limitations

The results only apply to cancellations and withdrawals of submissions for new drugs and not for subsequent indications of drugs or for generics and biosimilars. When Health Canada reviews were not complete, it was not clear if companies made their decision independently or after being alerted to deficiencies in their submissions by Health Canada. Health Canada may have communicated its reasoning privately to the companies. When companies cancelled their submissions, they may not always have provided Health Canada with the reasons for their decisions. Drugs may not be approved not because they are unsafe or inefficacious but because the information in the submission is inadequate to make a determination about safety and efficacy.

Conclusion

Over 12% of new drug submissions to Health Canada are either cancelled or refused. Health Canada does not always fully communicate the information that it has regarding the reasons for these decisions and should start issuing a Summary Basis of Decision document regardless of whether a drug is approved or not.

Supplemental Material

sj-xlsx-1-shr-10.1177_20542704261447654 - Supplemental material for New drug applications to Health Canada cancelled and refused: Cross-sectional study

Supplemental material, sj-xlsx-1-shr-10.1177_20542704261447654 for New drug applications to Health Canada cancelled and refused: Cross-sectional study by Joel Lexchin in JRSM Open

Footnotes

Declarations

Competing interest

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Between 2022 and 2025, Joel Lexchin received payments for writing a brief for a legal firm on the role of promotion in generating prescriptions for opioids, for being on a panel about pharmacare and for co-writing an article for a peer-reviewed medical journal on semaglutide. He is a member of the Boards of Canadian Doctors for Medicare and the Canadian Health Coalition. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. He has received funding from the Canadian Institutes of Health Research in the past.

Funding

The author received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

All data were publicly available, and ethics approval was not required.

Guarantor

JL.

Contributorship

JL conceived of the idea for the study, gathered and analysed the data, wrote the first draft of the manuscript and revised the manuscript.

Acknowledgements

None.

Provenance

Not commissioned: peer reviewed by Julie Morris.

Data availability statement

All the data for this study are in the tables and the supplementary file.

ORCID iD

Joel Lexchin

Supplemental material

Supplemental material for this article is available online.

References

Government of Canada. Drug and health product submissions under review (SUR): new drug submissions completed, https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review/new-drug-submissions-completed.html (2025, accessed September 10 2025).

World Health Organization and Norwegian Institute of Public Health. ATC/DDD Index 2025, https://atcddd.fhi.no/atc_ddd_index/ (2026, accessed October 1 2025).

Government of Canada. Drug and health product portal, https://dhpp.hpfb-dgpsa.ca/dhpp/search (2025, accessed September 11 2025).

Equator Network. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies, https://www.equator-network.org/reporting-guidelines/strobe/ (2023, accessed March 6 2025).

European Medicines Agency. European public assessment reports: background and context, https://www.ema.europa.eu/en/medicines/what-we-publish-medicines-when/european-public-assessment-reports-background-context (2025, accessed September 21 2025).

Tracy

. New FDA initiative reveals common reasons for drug application rejection, https://www.appliedclinicaltrialsonline.com/view/new-fda-initiative-reveals-common-reasons-drug-application-rejection (2025, accessed September 26 2025).

Sacks

Shamsuddin

Yasinskaya

, et al. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000–2012. JAMA 2014;311:378–384.

Supplementary Material

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