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

DOES HEALTH CANADA REQUIRE SEPARATE CLINICAL TRIAL APPLICATIONS FOR EACH PROTOCOL?

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 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.

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.

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 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 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 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.

Does Health Canada give approvals based on foreign decisions?

IS IT TRUE THAT HEALTH CANADA BASES THEIR DECISIONS IN GREAT PROPORTIONS ON FOREIGN DECISIONS?

This is a major miss-conception. We have seen in many instances, new drugs or new indications approved in Canada while the approval was on hold or refused in foreign countries. Health Canada makes their own independent decisions. However, it is possible (and recommended) to submit the major Q & As issued during the foreign review, along with the Foreign Agency Reviewers Reports. If the submission includes foreign review report, it is recommended to include a completed Foreign Review Attestation Template.  The extent to which Health Canada will use foreign reviews varies. The Canadian regulatory decision can be based on a critical assessment of the foreign reviews, on the Canadian review only or on a mixture of both.

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