New Drug Submission Process in Canada

NEW DRUG SUBMISSION PROCESS IN CANADA

 

In Canada, as in all countries with regulatory agencies, there are specific regulatory pathways and processes for health products to be authorized for use in clinical trials or to obtain marketing approval. If you are looking to conduct a clinical trial in Canada or submit for the marketing authorization of a new health product, it is important to be familiar with the new drug submission process and what other regulatory processes look like, including the pathways that are available to you to achieve this.

This article will discuss the principal regulatory process for drug approval in Canada. The regulatory process for other health products, including Medical Devices, will be covered in subsequent articles.

 

Regulatory affairs in Canada

Regulatory affairs in relation to clinical trials or investigational testing refers to the process of ensuring that a trial conducted with patients or healthy individuals adheres to all relevant laws and regulations during the drug, medical device, or other health product clinical development process. This includes getting necessary authorizations from regulatory agencies governing the country where the sponsors wish to launch a trial.

In Canada, that regulatory agency is Health Canada (HC). The goal of HC, its Food and Drug Regulations, and regulatory processes is to protect the health and safety of the participants in those trials and ensure the accuracy and integrity of the data collected; this includes the reporting of any serious adverse events that occur during the studies. HC is interested not only in the safety of trial participants; data accuracy and integrity are as important and are needed for the eventual market access application you will submit at the end of the clinical development process.

Most countries have their own regulating body, for example, the Food and Drug Administration (FDA) in the United States (US), European Medicines Agency (EMA) in the European Union, Therapeutic Goods Administration (TGA) in Australia and the Central Drugs Standard Control Organization (CDSCO) in India, to name a few.

What they have in common is that the approach to trials, drug development, and market access process be transparent and efficient whilst ensuring the safety, efficacy, and quality of the product for their citizens.

 

Regulatory and licensing pathways for drugs in Canada

In Canada, HC has various licensing pathways for drugs, medical devices and other health products and they continue to work towards different pathways to facilitate market access of key health products, particularly those for unmet medical needs.

The regulatory strategies and submission work are done by regulatory experts; professionals well-versed and experienced in how each regulatory body evaluates and approves New Drug Submissions (NDS), Medical Devices License Applications as well as other health product applications in Canada or their equivalent outside Canada.

Specifically, the drug approval pathways in Canada are summarized as follows:

Regular New Drug Submission – NDS:

NDS stands for “New Drug Submission” in Canada, other acronyms would apply outside Canada. It is the regulatory process that pharmaceutical companies are required to go through to bring their new drugs to the market. The submission must include all relevant data and information about the drug, including non-clinical, clinical, and quality data, which address safety and efficacy as well as the overall quality (chemistry, manufacturing, and controls) of that drug. HC reviews this information to determine if the drug is of good quality, safe and effective (positive benefit vs. risk ratio) for its intended use. Only then can it be approved for sale to the public.

The standard timeframe for scientific review of the NDS is 300 days, preceded by a screening period of 45 days and 10 days of technical processing, as indicated below:

 

 

Priority Review NDS:

A Priority Review (PR) New Drug Submission (NDS) is a type of regulatory filing submitted to HC for the review of a new drug, at the end of its clinical development program, that is considered to have the potential to provide significant benefit over existing therapies (when available) for serious or life-threatening conditions. PR NDSs are prioritized over standard NDSs and are scientifically reviewed within 180 days, rather than the standard review time of 300 days. This expedited review process is intended to help bring new, innovative treatments to patients in need more quickly.

To apply for a PR NDS, a sponsor must demonstrate that the drug is to be used for a serious, life-threatening, or severely debilitating condition when there is substantial evidence of clinical effectiveness that shows the following:

  • effective treatment, prevention or diagnosis of a disease, for which no therapy is available in Canada, or
  • significant increase of efficacy and/or decrease in risk, supporting an improved benefit/risk profile over available treatment, prevention, or diagnostic agent for a disease, not adequately managed by available agents in Canada.

In summary, PR NDSs are allowed for drugs with a complete clinical program that address important unmet medical needs. The sponsor has to apply for a PR through an official request supported by a Clinical Assessment Package, justifying scientifically and with sufficient data why the submission should be granted PR rather than following the standard NDS process.

The Priority Review process differs from the regular NDS process as presented below:

Notice of Compliance with Conditions – NOC/c NDS:

The Notice of Compliance with Conditions (NOC/c) pathway allows a sponsor to bring a new drug to market during the clinical development process, and therefore more quickly, in exchange for accepting to complete the clinical development program agreed to with HC. An approval under the NOC/c policy contains conditions that a sponsor needs to comply with after the drug approval.

Eligibility

Eligibility for advanced consideration for a NOC/c applies to NDSs and SNDSs for serious, life-threatening, or severely debilitating conditions when there is promising evidence of clinical effectiveness based on the available data that shows the following:

  • effective treatment, prevention, or diagnosis of a disease, for which no therapy is available in Canada, or
  • significant increase of efficacy and/or decrease in risk, supporting an improved benefit/risk profile over available treatment, prevention, or diagnostic agent for a disease, not adequately managed by available agents in Canada.

NOC/cs are possible for drugs with promising clinical data that addresses important unmet medical needs. The NOC/c process differs from the regular NDS process as presented below:

Drug Submissions Relying on Third-Party Data (Literature and Market Experience):

This refers to the use of existing scientific literature or third party published data in lieu of clinical study reports to support the safety and efficacy of a drug. Literature can be used to support a New Drug Submission (NDS) or a Supplemental New Drug Submissions (SNDS) in Canada.

This approach saves time and resources for both the sponsor and HC, provided that the submission complies with the criteria established by HC. The literature must be relevant, reliable, and adequate to support the safety and efficacy of the drug in question and meet current regulations, guidelines and recommendations. The chemistry, manufacturing and controls (quality) data requirements are the same as for any other NDSs or SNDSs.

In addition to the pathways summarized above, HC does explore additional pathways to facilitate drug development to address unmet medical needs and to streamline their own processes, for example: Australia-Canada-Singapore-Switzerland (ACSS) Consortium and use of foreign reviews and decisions.

Project Orbis is another example of an international partnership HC is a part of which is designed to give cancer patients faster access to promising cancer treatments, alongside the US FDA. Products eligible for Project Orbis include oncology products that are either new active substances or new indications for previously approved drugs. Project Orbis submissions are expected to meet the criteria for “FDA Priority Review” and Health Canada PR or NOC/c criteria.

The various programs or pathways presented above can be explored with the assistance of regulatory experts, when a sponsor wishes to obtain a marketing authorization for a new drug in Canada. The various submission types have to respect specific criteria established by HC, which further underscores the need to work with regulatory experts that can orient the sponsor towards the most relevant and efficient pathway to use.

After the Notice of Compliance – NOC

Once HC has reviewed the submission and determined that the drug is safe and effective for its population, they will issue a Notice of Compliance (NOC), which grants the sponsor permission to sell the drug in Canada.

After an NOC has been granted for a new drug in Canada, maintaining the drug on the market requires various compliance activities, including pharmacovigilance and lifecycle management to ensure that the drug continues to be compliant with the requirements of the Food and Drug Regulations. Life cycle management activities could include a Supplemental New Drug Submission with new data from clinical trials to support a new indication or other important changes to the labelling of the drug. Likewise, major changes to the manufacturing process, or adding new formulations or a new dosage form, for example, would also require a submission to HC to ensure compliance with the regulations. For major changes that require approval from HC, a new NOC will be issued once HC has reviewed the submission and supporting data and, determined that the changes are acceptable; only then these changes can be implemented.

The Role of Regulatory Experts

Whichever pathway you utilize, it is imperative that the approach be one that is streamlined, transparent, and efficient, while ensuring the quality, safety, and efficacy of the product. It is the role of regulatory experts to strategize with you about which pathway to follow, and to navigate these applications through HC or their equivalent outside of Canada, to liaise with regulatory body officials, and lead the submission process.

 

FURTHER INFORMATION

For further information about the drug review & approval process in Canada, or to have a complementary discussion about your needs, please contact SPharm directly.

Featured Posts

Are separate Clinical Trial Applications required for each protocol?

Does Health Canada require separate Clinical Trial Applications for each protocol?

 

 

Does Health Canada require separate Clinical Trial Applications for each protocol is a question often asked. Presently, drug developers may submit more than one protocol into one single clinical trial application (CTA), when the Application is submitted to the Therapeutic Drug Directorate (TPD). Each protocol would then be considered a different dossier with a different control number per protocol; an approval per protocol would apply. When the CTA is submitted to the Biologic and Genetic Therapies Directorate (BGTD), one protocol only can be submitted per CTA. The upcoming electronic submission requirements for the CTA will likely impose the submission of one protocol per CTA for both Directorates.

Even with these differences, globally the process is quite similar in the US and Canada, however, the terminology used is different and this can cause some confusion.

In the U.S., we see one IND per product under clinical development, which is open to adding new protocol amendments etc… Clinical holds can apply to these INDs and the duration of the holds may vary. In Canada, there is a clinical trial application process, whereby one or more protocols can be submitted at once. New protocols are submitted as new CTAs. There are amendments and notifications that can be brought to clinical trial applications that are approved.

An amendment is considered a major change to an approved protocol or quality dossier, and therefore requires the same 30-day default review period. Minor changes are submitted as notifications within 15 days of the implementation of the change and no review period applies. Now, as mentioned, a new protocol must be submitted via a new clinical trial application. However, cross-referencing to an approved clinical trial application already on file for sections that are not changed, is possible. For example, cross-referencing to an approved investigator’s brochure or to an approved quality dossier. Therefore, it reduces the submission requirement and content. The process is simple and very similar to an IND amendment in the U.S., even if it’s classified as a clinical trial application in Canada.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Does Health Canada require all documents be translated to French?

 

Does Health Canada require that all documents be translated to French?

 

 

DOES HEALTH CANADA REQUIRE THAT ALL DOCUMENTS BE TRANSLATED TO FRENCH?

Not at all. Both official languages in Canada, that is English and French, are accepted. That being said, the regulatory dossiers are usually submitted to Health Canada in English. French dossiers, or the supporting documents that are in French, are also acceptable, however, the review could be a little more challenging since most of the Health Canada reviewers are Anglophone. Even if it is not required to submit French documents to Health Canada, the French translation of the informed consent form must be generated and available for francophone patients. Also, there are specific language regulations to respect on Canadian labels. That being said, Health Canada has established standard target review timelines that they respect, which is not influenced by the selected submission language.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Are Sponsors required to have a legal representative reside in Canada?

 

Does Health Canada require Sponsors to have a legal representative reside in Canada?

 

 

DOES HEALTH CANADA REQUIRE SPONSORS TO HAVE A LEGAL REPRESENTATIVE RESIDE IN CANADA?

A scientific or medical officer residing in Canada that represents the sponsor and who’s responsible for providing an attestation with respect to the clinical trial application or the amendment that is being filed, is required. There is no additional information available in the regulations or guidance related to the Canadian officer. Therefore, any Canadian scientific personnel that are authorized by the sponsor to submit the application on their behalf and to be the representative can be the signatory. Normally the regulatory agent or the CRO can sign the clinical trial application on behalf of the sponsor.

With respect to having Sponsors having a legal representative residing in Canada for the Registration Process, the answer is no, Health Canada does not require Canadian residence. Nonetheless, if the sponsor is not located in Canada, a Canadian importer must be determined and their Drug Establishment License (DEL) submitted or amended at least 3 months prior to the submission of the marketing authorization submission (NDS or ANDS) in Canada. This is one of the Good Manufacturing Practice requirements.

That being said, having a Canadian regulatory point of contact in Canada is an advantage for the Canadian regulatory language with Health Canada as well as for dealing rapidly with questions and being in the same time zone as the reviewing regulatory agency.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Clinical Trial Site Information Forms – a Health Canada update

 

Update: Clinical Trial Site Information Forms (CTSIFs)

We recently communicated with our clients and partners about the recent changes Health Canada has made regarding the electronic submission of Clinical Trial Site Information Forms (CTSIFs), and we share them now with you.

First is a reminder that CTSIFs must be provided to Health Canada prior to commencement of the trial.

The new CTSIF is already available for submissions and will be mandatory as of January 2nd, 2020. The current form will not be accepted after that date.

3 changes:

There are 3 changes to be aware of in the new form and for online submissions:

  1. Drug Product and Sponsor information sections have been removed, as they are already found with the Clinical Trial Application.
  2. Previous versions of a completed form can be used to make revisions and it will be possible to identify precisely which sections of the form are revised.
  3. ‘Submit’ buttons on the form allow for direct electronic filing to Health Canada. An application control number is required prior to submitting a CTSIF, so that Health Canada can make the necessary link between the application and relevant CTSIFs.

Have questions?

Want to walk through the changes specifically for your trials? The experts at SPharm are available to discuss your needs.

What adjustments are made for Targeted Therapeutics?

 

What adjustments do drug developers make associated to Targeted Therapeutics?

 

 

WHAT ADJUSTMENTS HAVE DRUG DEVELOPERS HAD TO MAKE TO RESPOND TO CHALLENGES ASSOCIATED WITH TARGETED THERAPEUTICS?

The key adjustments for drug developers have been to increase transparency with the authorities and open up to pre-submission or scientific advice meetings. These meetings become even more efficient when you bring in local experts and key opinion leaders.

The purpose of this is to discuss strategies and requirements with the authorities and to come up with agreements for the drug development activities. Meeting with Health Canada is not a requirement, but it’s highly recommended for novel therapies that would not have the same clinical data package that would usually be required or expected in Canada for market access.

With regards to submission content, contrary to common belief, Health Canada follows similar requirements to those of the FDA and EMA, therefore, usually only minor adjustments are necessary from a FDA or EMA dossier when submitting a marketing application in Canada.

 

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Will Health Canada approve Trials with multiple investigational products?

Will Health Canada approve Clinical Trials designed with more than one investigational product?

 

WILL HEALTH CANADA APPROVE CLINICAL TRIALS DESIGNED WITH MORE THAN ONE INVESTIGATIONAL PRODUCT?

Yes, definitely. With the appropriate quality information for both investigational products, Health Canada will review the dossier and approve it if it meets the Canadian requirements, and that will be under the same 30-day default review period.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Does Health Canada prefer early phase or late phase trials?

 

Does Health Canada prefer early phase trials or late phase studies close to approval?

 

 

DOES HEALTH CANADA PREFER EARLY PHASE TRIAL DESIGNS OR LATE PHASE STUDIES CLOSE TO APPROVAL?

Health Canada is very open to all phases of clinical trials for both early and late phase. If the product is innovative or has the potential of being granted an NOC/c, we do recommend that sponsors meet with Health Canada early to ensure that the study trial design and the clinical development plan is aligned with the requirements for an accelerated access to market.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

 

Why does Health Canada ask for Foreign Reviews?

Why does Health Canada ask for Foreign Reviews?

 

 

 

WHY IS IT THAT HEALTH CANADA ASKS FOR FOREIGN REVIEWS?

The provision of foreign review reports in an NDS is not mandatory, but highly recommended. Indeed, they are usually requested at screening if not included within the original submission.

In addition, within the Screening Acceptance letter, Health Canada usually requests the sponsor to share the Questions from foreign regulatory agency reviews and the sponsor’s answers, during the review of the NDS.

In my experience and through my discussions with Health Canada, when the Canadian agency has questions that have already been addressed in a response to questions from a foreign agency, it likely reduces the number of questions to be raised to the sponsor, accordingly.

 

For questions about the Canadian Drug Review & Regulatory approval process that is not covered in this section, please go ahead and contact us directly.

Health Canada news on formatting of regulatory submissions

 
Health Canada now accepts Medical Device and Veterinary Drug regulatory activities in “non-eCTD electronic-only” format: