Guidance on amendments to the Food and Drug Regulations for drugs for use in relation to COVID-19: Preparing a submission or supplement

On this page

• Submission scenarios
• Modified requirements
• Format and structure for filing
• Content and requirements for filing
• Risk management plan
• Labelling
• Notice of compliance (NOC) for a COVID-19 drug
• Drug identification number (DIN)
• Market notification
• Transparency
• Performance standards
• Fees

Submission scenarios

The Governor in Council introduced amendments to the Regulations to provide a mechanism for COVID-19 drugs to be authorized through the issuance of an NOC, based on modified requirements that have been transferred from the ISAD IO.

Table 1 provides an overview of the modified requirements for COVID-19 drugs in the Regulations.

The "NDS CV" submission type has been created for NDSs that seek approval on the basis of any of the requirements in subsections C.08.002(2.1), C.08.002(2.2) or C.08.002(2.3) of the Regulations. To make use of any of the alternative requirements, the manufacturer must make the statements required by paragraphs C.08.002(2.4)(a) and meet the requirement in C.08.002(2.4)(b). To meet the requirements in subsection C.08.002(2.1), the manufacturer must also make the statement required by paragraph C.08.002(2.1)(a) and meet the requirement in C.08.002(2.1)(b). Manufacturers should ensure that all statements required are made in module 1.2.3, "Certification and Attestation Forms."

For more details, please refer to submission scenarios. NDS CV submission type means NDS [COVID].

Table 1: Overview of modified requirements for COVID-19 drug submissions

Scenario	Submission type	Available modified requirements	Terms and conditions
New drug with same data as filed under IO (and possible additional data)	NDS	C.08.002(2.1): supportive evidence C.08.002(2.2): draft label C.08.002(2.3): rolling submission	Yes
New designated COVID-19 drug (not previously filed under the ISAD IO)	NDS	C.08.002(2.1): supportive evidence C.08.002(2.2): draft label C.08.002(2.3): rolling submission	Yes
Marketed drug adding additional indication for COVID-19	SNDS	Modified requirements (as above)	Yes
Supplemental new drug submissions adding additional indication for COVID-19 following authorization of the NDS for a designated COVID-19 drug	SNDS	Modified requirements (as above)	Yes

Timelines within which to file a submission under the Regulations to obtain a notice of compliance

The amendments to the Regulations provide that an ISAD IO authorization will be revoked unless a submission is filed within:

• 90 days following the coming into force of the amendments, if the drug was authorized under the ISAD IO before the amendments came into force or
• 90 days following the issuance of an authorization under the ISAD IO, if the drug was authorized after the amendments came into force

Where a submission has been filed within these timelines, the COVID-19 drug may continue to be sold under the ISAD IO authorization until the submission has been approved, rejected or withdrawn. This is the case even after the ISAD IO ceases to have effect.

If a manufacturer fails to file a submission under the Regulations within the prescribed timelines, the manufacturer will have to wait until the product is authorized under the Regulations to resume sale.

Manufacturers are encouraged to submit a submission under the Regulations before the 90-day deadline to ensure the submission has met the requirements for filing (detailed in the section below).

Modified requirements

Manufacturers of COVID-19 drugs will have the option to follow similar requirements under the Regulations to those under the ISAD IO, as set out in paragraphs C.08.002(2.1) to (2.3). To make use of these alternate requirements, manufacturers must include a statement identifying that the purpose and conditions of use specified in the NDS relate only to COVID-19.

Manufacturers should ensure that all statements required are made in module 1.2.3, "Certification and Attestation Forms." Manufacturers are also encouraged to identify in a cover letter the modified requirements they intend to follow.

Modified requirements include:

• ability to file a rolling submission(C.08.002(2.3))
• exemption from submitting detailed reports of tests made to establish the safety and clinical effectiveness of the new drug under C.08.002(2)(g) and (h)
  • however, the manufacturer must provide sufficient evidence that the benefits of the drug outweigh the risks, taking into account uncertainties as well as the public health need due to COVID-19 (C.08.002(2.1)(b))
• exemption from being required under C.08.002(2)(j.1) to provide a mock-up label if the manufacturer provides a draft of the label
  • submission must also include any package insert and document provided upon request that sets out supplementary information on use of the drug (C.08.002(2.2))
• exemption from being required under C.08.002(2)(o) to conduct an assessment as to whether there is a likelihood the new drug will be mistaken for another drug due to a resemblance between the brand names
  • commonly referred to as a brand name assessment

The options available in subsections C.08.002(2.1), C.08.002(2.2) and C.08.002(2.3) only apply if the manufacturer has met the requirements outlined in subsection C.08.002(2.4).

Health Canada intends to assess the requirements of subsections C.08.002(2.1), C.08.002(2.2), C.08.002(2.3) and C.08.002(2.4) in screening.

In accordance with C.08.002(2.5), the amended regulations do not apply if the manufacturer is seeking a notice of compliance for a COVID-19 drug on the basis of a direct or indirect comparison between the COVID-19 drug and another COVID-19 drug (for example, a generic or biosimilar submission). Submissions will be assessed under C.08.002(2.5) before a submission receives a filing date.

Safety and efficacy: C.08.002(2.1) as an alternative to C.08.002(2)(g) and C.08.002(2)(h)

The Regulations were amended to allow manufacturers who seek approval for a COVID-19 drug to file a submission with an alternative data package where justified based on the urgent public health needs resulting from COVID-19. As more products emerge to address the public health needs brought upon by COVID-19, manufacturers should discuss data requirements with Health Canada before filing. A data package based on C.08.002(2.1) may only be appropriate in some circumstances.

Following discussion with Health Canada, a manufacturer may file an NDS for a COVID-19 drug without complying with the requirements set out in paragraphs C.08.002(2)(g) and C.08.002(2)(h). To do so:

• the manufacturer must state that the NDS is for a COVID-19 drug (C.08.002(2)(2.1)(a))
• the NDS must contain sufficient safety, efficacy and quality evidence such that the benefits of the new drug outweigh the risks (C.08.002(2)(2.1)(b))

Manufacturers should make the required statement in module 1.2.3, "Certification and Attestation Forms." Manufacturers are encouraged to specify in a cover letter that the NDS relies on subsection C.08.002(2.1) of the Regulations to facilitate processing.

A manufacturer who relies on C.08.002(2.1) to provide evidence of safety and efficacy will be subject to any terms and conditions that might be imposed on an NOC issued for the COVID-19 drug. (See paragraph C.01.014.21(1)(b).) In the context of the public health need related to COVID-19, the manufacturer is required to include in the NDS sufficient safety, efficacy and quality evidence showing that the drug's benefits outweigh the risks. Health Canada reviews the NDS and will apply terms and conditions on the authorization to require the manufacturer to address risks and uncertainties after authorization.

If the manufacturer has a full data package to support the NDS, then they may choose not to rely on C.08.002(2.1).

For more information, see the following guidance documents on:

• Evidence requirements for COVID-19 vaccines
• Evidence requirements for COVID-19 drugs

Product labels

C.08.002(2.2) provides for exemption from the requirement in C.08.002(2)(j.1) to provide a mock-up of labels of the drug.

However, the submission must contain a draft of every label to be used with the new drug. This includes any package insert and any document that sets out supplementary information on the use of the new drug.

Health Canada will accept text-only labels and/or mock-up labels (if available). Sponsors should refer to sections 3, 9 and 10 of the Food and Drugs Act as well as related provisions of the Regulations to ensure they are complying with the labelling requirements. You may also refer to the following for more information:

• Guidance document: Labelling of pharmaceutical drugs for human use
• Guidance for market authorization requirements for COVID-19 vaccines: Labelling and post-market requirements

Sponsors are also encouraged to contact Health Canada in advance to discuss their labelling proposals. When modified requirements are sought, sponsors should include a rationale and 'note to reviewer' in the submission.

Manufacturers are encouraged to specify in a cover letter that the NDS relies on subsection C.08.002(2.2) of the Regulations to facilitate processing.

Rolling submissions

After September 15, 2021, a sponsor cannot submit anything under the ISAD IO, even if it was in the plan for a rolling submission. No ISAD IO authorization can be granted after September 16, 2021.

C.08.002(2.3) carries over a manufacturer's ability to file a rolling submission, as permitted in the ISAD IO. Health Canada recognizes that the submission may not contain all of the information otherwise required by section C.08.002 at the time it is filed. Health Canada will begin its review using the information submitted by the manufacturer and accept new evidence as it becomes available. When providing the balance of the remaining missing information, the sponsor should confirm that it considers all missing information to have been provided. A manufacturer may file an NDS for a new COVID-19 drug without including some of the data otherwise required under:

• paragraphs C.08.002(2)(e) to C.08.002(2)(k), C.08.002(2)(m) and C.08.002(2)(n)
• paragraph C.08.002(2.1)(b) or
• subsection C.08.002(2.2)

This rolling review process can reduce the time it takes to authorize these critical new drugs while maintaining appropriate standards of safety, efficacy and quality.

To file a rolling submission, the manufacturer must include all applicable forms and other administrative components. The NDS must also include a plan identifying the missing parts of the submission. This plan must specify how and when the missing information or material will be provided to the Minister during the review period. (See C.08.002(2.3).)

The plan should be up-to-date and complete. The manufacturer should discuss and agree upon the plan in advance with Health Canada. Some elements of the plan may be more appropriate to file as an SNDS following approval of the NDS, rather than as part of a rolling submission. Health Canada recommends a pre-submission meeting to discuss efficient filing strategies for changes, such as chemistry, manufacturing and control changes.

Manufacturers are encouraged to specify in a cover letter that the NDS relies on subsection C.08.002(2.3) of the Regulations to facilitate processing. As with other NDSs under Division 8, the filing date refers to the date that:

• the NDS is deemed administratively complete by Health Canada
• all the elements and forms required for processing are completed and submitted to Health Canada

The filing date may differ from the date of original receipt if the submission is considered to be administratively incomplete at that time. Data or information that is subsequently provided in a rolling submission will be considered solicited information under the NDS and will not change the filing date of the submission.

The process for establishing a filing date has not changed from the standard process outlined in the Guidance document: The management of drug submissions and applications.
As with other NDSs under Division 8, the filing date refers to the date that:

• the NDS is deemed administratively complete by Health Canada and
• all the elements and forms required for processing are completed and submitted to Health Canada

This is typically the same day the regulatory activity is received by Health Canada.

For a submission to be considered administratively complete under Division 8 of the Regulations, it must meet the requirements of the data protection provisions of the Food and Drug Regulations and the Patented Medicines (Notice of Compliance) Regulations. It must also contain forms such as the:

• Regulatory Enrolment Process (REP) Regulatory Transaction (RT) File
• REP Product Information (PI) File
• REP RT Form – Fee Section
• Submission Certificate

Sufficient information must be submitted within a reasonable timeframe. The Minister reviews the NDS based on the requirements and makes a decision, as per section C.08.004 of the Regulations.

The plan should contain:

• a list of the non-clinical, clinical and quality data to be provided (planned and in progress)
• a timeframe for when this clinical and quality data will be available
• a timeframe for when this clinical and quality data will be filed for review

If the missing information outlined in the plan will be submitted as multiple packages, the plan must clearly specify what information will be contained in each data package. For example:

• data package A will be submitted on DD/MM/YYYY and contains results from studies XX, YY and ZZ
• data package B will be submitted on DD/MM/YYYY and contains results from studies MM, NN and OO

Pre-submission meetings provide an opportunity to discuss the plan in detail. These meetings should be used to:

• establish submission content and timelines
• determine the data that will be submitted when the submission is filed
• determine the data that will be provided at a later date

The cover letter should refer to the plan. If changes are required to labelling to reflect the new information, annotated and clean copies of the drug labels should be included.

Health Canada will:

• review the submission to ensure it includes the detailed plan
• assess the information submitted by the manufacturer
• accept new evidence as it becomes available until the review has been completed

Any subsequent data or information sent later is considered solicited information under the NDS if the data or information is provided according to the plan or in response to Health Canada's request. There may be situations where an update to the plan is appropriate. Health Canada will assess these on a case-by-case basis. However, changes in the timing or content should be avoided if possible as they will impact the review timeline and efficiency. Information or data provided otherwise may be considered unsolicited information.

Health Canada will not issue an NOC unless the Minister is satisfied that the NDS complies with the requirements of C.08.002.

Regulatory activity and transaction details for designated COVID-19 drugs

As noted above, modified requirements introduced through amendments to the Regulations are only available for an NDS. The "NDS CV" submission type has been created for NDSs that use any of the provisions in subsections C.08.002(2.1), C.08.002(2.2) or C.08.002(2.3) of the Regulations. The manufacturer must select the "NDS CV" submission type in the appropriate Regulatory Enrolment Process (REP) regulatory transaction template when submitting their NDS. "NDS CV" submission types are described as "Drug submission with modified requirements for Designated COVID-19 drugs."

To file an NDS that does not benefit from any of the modified requirements mentioned in the 3 subsections above, a manufacturer must select the regular NDS submission type when submitting its NDS.

Pre-submission meetings

Manufacturers are encouraged to have regular communications with Health Canada. Early and ongoing consultation(s) with Health Canada help ensure that regulatory requirements are met.

Before filing an NDS, manufacturers are encouraged to request a pre-submission meeting to discuss all aspects of their submission. At this meeting, Health Canada will expect you to describe your submission plan and indicate how and when you will provide the Minister with the missing information or material, if applicable (subsection C.08.002(2.3)).

To request a pre-submission meeting with the appropriate directorate, consult the guidance documents on the:

• Management of drug submissions and applications
• Management of regulatory submissions for veterinary drugs

For relevant contact information, please see key contacts.

Format and structure for filing

For general procedures on how to file applications, please also refer to the guidance documents on the:

• Management of drug submissions and applications or
• Management of regulatory submissions for veterinary drugs

Submissions for human drugs should be formatted, structured and filed as outlined in the:

• Guidance document on the preparation of regulatory activities in the eCTD format
• Organization and document placement for Canadian module 1
• Guidance document on the regulatory enrolment process (REP)

Manufacturers who cannot comply with the formatting requirements may contact the Office of Submissions and Intellectual Property for further options and guidance. Please send an email to ereview@hc-sc.gc.ca.

Submissions for veterinary drugs should be formatted, structured and filed as outlined in the following guidance documents on the:

• Preparation of regulatory activities in the non-eCTD format
• Regulatory enrolment process (REP)

Manufacturers who cannot comply with the formatting requirements may contact the Veterinary Drugs Directorate by email at vdd.skmd.so-dgps.dmv.cp@hc-sc.gc.ca.

Submissions filed under the Regulations for which an application was previously filed under the ISAD IO will receive a new dossier ID separate from the ISAD IO application. The new dossier ID must be requested using the dossier ID request forms.

Content and requirements for filing

Submissions made under the Regulations must be independent from any ISAD IO application. At a minimum, they must contain all relevant data that was included in the ISAD IO application, along with any required updates. The sponsor must include all the data they rely on to support their submission in the NDS. The sponsor should consult with Health Canada at a pre-submission meeting before filing.

For both the non-clinical and clinical information package, you may not need to include as much information at the time of filing as you do for a data package in a typical drug submission. This is balanced by additional information, which is to be provided as part of the rolling submissions as well as the terms and conditions of authorization.

Non-clinical information and requirements

Key non-clinical information may be required to:

• demonstrate the potential for clinical effectiveness under the proposed conditions of use
• support the safety of the COVID-19 drug

All key studies should be conducted in accordance with good laboratory practices.

For more information, consult the following guidance document:

• Non-clinical laboratory study data supporting drug product applications and submissions: Adherence to good laboratory practice

Clinical information and requirements

A manufacturer may submit an NDS relying on the modified requirements in C.08.002(2.1) to (2.3). All known information should be provided to support the safety and efficacy of the COVID-19 drug. This includes all available clinical trial data and the safety and efficacy summary documents.

For more information, consult the following guidance document:

• Evidence requirements for COVID-19 vaccines

Quality (chemistry and manufacturing) information and requirements

For further guidance on meeting application and information requirements, consult the list of guidance documents. Under section C.08.002(2.3) in the Regulations, the manufacturer may provide the information and material normally required under paragraphs (2)(e), (f) and (m) on a rolling basis. The manufacturer must specify in their plan how and when they will provide the missing information to Health Canada. Manufacturers should make sure that their plan is detailed and accurate. They should discuss the plan with Health Canada before submitting it. Health Canada will review the timing proposed in the plan as well as the chemistry and manufacturing information.

For more information, consult the following guidance document:

• Evidence requirements for COVID-19 vaccines

Comparative submissions for subsequent entry drugs

Under the Abbreviated New Drug Submissions (ANDS) and NDS pathways of the Food and Drug Regulations, manufacturers of subsequent entry drugs (generics and biosimilars) can seek an NOC on the basis of a comparison to a drug that has already received an NOC.

Manufacturers must demonstrate similarity to an authorized reference drug (for example, in the case of generics, a Canadian reference product as defined in section C.08.001.1). This is done by filing a comparative submission that relies, in part, on the previously authorized evidence of safety and effectiveness for the previously authorized reference drug. The manufacturer may then submit a reduced data package in the submission.

The amendments do not extend the modified requirements provided under new subsections C.08.002(2.1), (2.2) and (2.3) to cases where manufacturers seek an NOC for a COVID-19 drug on the basis of a direct or indirect comparison between that drug and another COVID-19 drug.

The Regulations do not allow comparative submissions to be filed while benefitting from any of the modified requirements, even where consent from the reference product manufacturer is provided. Therefore, comparative submissions are expected to be filed as an ANDS or a comparative NDS.

Health Canada will apply subsection C.08.002(2.5) of the Regulations in processing and comparative submissions that seek approval on the basis of any of the new subsections C.08.002(2.1), (2.2) and (2.3) will not receive a filing date. When it appears that the filing of a submission is prevented, the manufacturer will be provided with a written preliminary decision and an opportunity to make representations in response. If, following consideration of the representations, Health Canada remains of the view that the submission cannot be filed, the manufacturer will be notified and the submission will not be processed further.

Manufacturers of subsequent entry products are prohibited from filing a submission on the basis of a direct or indirect comparison to a COVID-19 drug for which an authorization was issued under the ISAD IO (C.08.003.01(2)). Note that subsection C.08.003.01(2) is not intended to prevent the filing of a submission that contains new data from clinical trials comparing the efficacy of the new drug to an existing one. Also note that C.08.003.01 does not prevent the filing of a submission or supplement on the basis of a comparison to a COVID-19 drug that has received an NOC (C.08.003.01(3)).

Manufacturers who intend to file a submission seeking an NOC for a COVID-19 drug on the basis of a comparison with another COVID-19 drug are encouraged to contact Health Canada for a pre-submission meeting.

Information and requirements for veterinary drugs

A COVID-19 drug submission should contain all available information to help Health Canada assess the drug's safety, efficacy and quality. Information should include evidence of its efficacy in the target species, animal safety, human safety and quality.

For drugs used in a food-producing animal, information should be provided on the safety of drug residues in meat and other food products from the treated animal intended for human consumption.

Risk management plan

Manufacturers should submit a Risk Management Plan (RMP) for a COVID-19 drug. If an RMP has been filed as part of the ISAD IO application, an updated RMP with the most recent post marketing data, risk minimization measures and pharmacovigilance activities should be submitted.

The RMP should focus on the product's updated safety risks in the context of COVID-19 use to ensure that:

• the benefit-risk profile of the product is managed optimally during its life-cycle
• knowledge gaps at the time of authorization are described and risks are further quantified and characterized over time

It should:

• outline the product's safety risks related to COVID-19 use
• outline the pharmacovigilance activities and risk minimization activities used to identify, characterize, prevent or minimize risks
• contain an evaluation of the effectiveness of such risk minimization measures

For information on the scope of RMPs, please refer to the following guidance document:

• Submission of risk management plans and follow-up commitments

For COVID-19 drugs submitted for authorization, the RMP should include the following:

• safety specification section on the identified risks, potential risks and missing information for the product (for example, special populations where there is limited information or who were excluded from clinical trials), with a focus on risks in COVID-19 patients, where appropriate
• pharmacovigilance plan on the specific activities to be taken to identify and report safety issues, including expedited adverse reaction reporting, periodic reporting and ongoing/planned studies to quantify and characterize those risks (for example, registries, prospective cohort studies)
• risk minimization plan to manage the safety risks including routine risk minimization measures (for example, labelling) and additional measures beyond those considered routine (such as educational materials for health care professionals or patients, or a restricted access or distribution program), if needed
• plan to measure the effectiveness of additional risk minimization activities

An RMP that has been reviewed and accepted as part of the submission for a COVID-19 drug is expected to be implemented. If the manufacturer filed under the requirement in subsection C.08.002(2.1), any elements of an RMP that are essential for the safe and effective use of the product could be identified as terms or conditions and must be implemented.

A Canadian addendum that demonstrates that the RMP meets Canadian regulatory requirements must accompany the core RMP. Information on these requirements are provided in the following guidance documents and recent notice:

• Evidence requirements for COVID-19 vaccines
• Notice of clarification to drug manufacturers and sponsors on Canadian-specific considerations in risk management plans

If you have a question about the type of quality, safety and effectiveness information required, please contact the appropriate directorate within Health Canada. Please refer to the key contacts for relevant contact information.

Labelling

Manufacturers of a COVID-19 drug must comply with all applicable labelling requirements in the Food and Drugs Act and parts A and C of the Regulations:

• A.01.014
• A.01.015
• A.01.60.1 to A.01.068
• A.01.065
• C.01.004 to C.01.011
• C.01.401
• C.03.202
• C.03.203
• C.03.206 to C.03.209
• C.04.019 and C.04.020

Existing regulatory provisions on the labelling of veterinary drugs also apply.

Manufacturers that file an NDS for a COVID-19 drug using the modified requirements may be asked to include a warning statement on the inner and outer labels. This statement may be displayed on any panel. The data submitted to support the NDS and any associated terms and conditions that the Minister places on the DIN will dictate this.

Drug products that are packaged in special and/or containers that are too small to accommodate the inner label requirements outlined in the Regulations may contain abbreviated labelling. But there must be an outer label that meets all regulatory requirements. Sponsors are encouraged to contact Health Canada to discuss their labelling proposals. When modified requirements are sought, sponsors should include a rationale and 'note to reviewer' in the submission.

The plain language labelling requirements for mock-up labels and a brand name assessment package do not apply (C.08.002(2)(j.1) and C.08.002(2)(o)).

While exempt from these requirements, manufacturers are strongly encouraged to complete and submit a brand name assessment package and to provide mock-up labels:

• at the time of NDS filing (if available) or
• at the earliest time after the NDS is filed

Manufacturers may also file these materials after the NOC is granted.

Health Canada may apply labelling terms and conditions as necessary. We will request that the sponsor submit a brand name assessment and final mock-up package labels at an agreed-upon time if the sponsor chooses to use the labelling modified requirements provided by the Regulations.

Manufacturers that are unable to provide a complete brand name assessment package at the time of filing or at the earliest time after the NDS is filed, may provide a package where simulation exercises are omitted.

Modified requirements to transition to Canadian specific labelling (including when final mock-ups are to be provided) will continue to be assessed based on the global supply and pandemic situation. Health Canada will work with manufacturers to develop an appropriate timeline to:

• submit the labelling materials to support their market authorization
• transition to the Canadian labelling at a point when the global supply and pandemic situation will make this possible

Plain language labelling and Look-alike Sound-alike components are not needed with respect to the labelling of veterinary drugs.

Consult the list of guidance documents for further guidance on labelling.

Filing a supplement to an NDS for a COVID-19 drug

A manufacturer of a COVID-19 drug that holds an authorization for a new drug under the ISAD IO may file an NDS under section C.08.002 of the Regulations. Once the manufacturer receives an NOC for the COVID-19 drug, they may file a supplement to that new drug submission (SNDS) for any changes post-NOC. Filing a supplement to an NDS for a COVID-19 drug depends on the situation. The SNDS relies on the original modified requirements on the NOC. Discuss with Health Canada before filing. Where applicable, the manufacturer may also be able to incorporate the change as part of its NDS.

Consult the following guidance documents on post-NOC:

• Framework document for pharmaceutical, biologic and radiopharmaceutical drugs for human use only
• Safety and efficacy document for pharmaceutical, biologic and radiopharmaceutical drugs for human use only
• Post-notice of compliance (NOC) changes: Quality document

Notice of compliance (NOC) for a COVID-19 drug

For Health Canada to issue an NOC (C.08.004) for the sale of a COVID-19 drug, the NDS must meet the requirements of section C.08.002. For drugs relying on the modified requirements in C.08.002 (2.1), the NDS must contain enough evidence to support the conclusion that the drug's benefits outweigh the risks when used as indicated. The evidence takes into consideration the uncertainties around the drug in the context of the public health need related to COVID-19.

Drug identification number (DIN)

When the manufacturer of a COVID-19 drug that was previously authorized under the ISAD IO submits an NDS to obtain an NOC, the DIN that was assigned under the ISAD IO remains active until the NDS has been approved, rejected or withdrawn. This ensures that all regulatory obligations associated with the DIN continue.

Once an NOC is issued for a COVID-19 drug, Health Canada may assign the same digits for the DIN under C.01.014.2 as were issued under section 7 of the ISAD IO.

If the submission that was submitted under the Regulations is rejected or withdrawn, the DIN will be revoked at that time.

For more information on DINs, refer to the:

• Guidance document on the regulatory requirements for drug identification numbers (DINs)

Terms and conditions on a DIN pertaining to a COVID-19 drug relying on modified requirements in C.08.002(2.1)

Health Canada may at any time impose or amend terms and conditions on a DIN (C.01.014.21(1)(b)) of a COVID-19 drug where the manufacturer relied on C.08.002(2.1) to obtain an NOC. If the manufacturer only used other provisions, then the terms and conditions power does not apply.

This authority allows Health Canada to issue an NOC for a COVID-19 drug while attaching additional conditions that the DIN holder must comply with. These terms or conditions are used to ensure appropriate oversight, manage uncertainties or mitigate risks. However, the terms and conditions on a DIN for a COVID-19 drug using the submission flexibility in C.08.002(2.1) will be based on what's needed when a submission is not able to meet the usual data requirements. Examples of anticipated terms and conditions include:

• specific pharmacovigilance and risk mitigation and management measures
• additional quality information
• confirmation of effectiveness
• drug shortage measures introduced to prevent or alleviate a shortage

The terms and conditions are on the DIN and remain on the DIN regardless of subsequent SNDSs (supplement to a new drug submission). The exception is if the Minister removes the terms and conditions as part of the (SNDS) process.

The terms and conditions may also apply to drugs authorized on the basis of a comparison to a COVID-19 drug, where the NOC of the comparator product had relied on these submission flexibilities (C.01.014.21(1.1)(b)). This ensures that any post-market commitments for a reference product may also be imposed on NOCs issued on the basis of a comparison.

Terms and conditions can be imposed or amended at any time on a DIN for a COVID-19 drug (C.01.014.21(1.1)(a)) that was filed as:

• an NDS under section C.08.002 relying on the data flexibility referred to in C.08.002(2.1)
• a supplement to an NDS for that new drug

They can also be imposed or amended at any time on a DIN for a COVID-19 drug (C.01.014.21(1.1)(b)) authorized on the basis of a direct or indirect comparison to another COVID-19 drug (see C.01.014.21(1.1)(a)) and filed as:

• an NDS filed under C.08.002
• an abbreviated new drug submission (ANDS) filed under C.08.002.1
• a supplement to a new drug submission or an abbreviated new drug submission that is filed under section C.08.003

Health Canada will discuss the terms and conditions with the sponsor prior to imposing them. All terms and conditions are enforceable under section 21.7 of the Act.

Terms and conditions do not apply to any drugs, including COVID-19 drugs, authorized through the existing NDS and SNDS pathway if the manufacturer:

• is able to satisfy the full data requirements (C.08.002(2)(g) and (h))
• has not relied on C.08.002(2.1)

Submitting information to fulfill terms and conditions

Information on the fulfilment of terms and conditions should be submitted as solicited information with an accompanying cover letter. The subject should state "Solicited information, fulfilling Terms and Conditions for COVID-19 drug." Supporting documentation is to be provided.

Health Canada will review the documentation to determine if the conditions have been met. Once we are satisfied that the manufacturer has complied with all the terms and conditions, we will indicate this in a letter and reference the original file/control number.

Market notification

A market notification for a drug authorized under the ISAD IO does not constitute market notification of a drug under the Regulations. This is the case even if the same digits have been issued to the drug as the DIN under both the ISAD IO and the Regulations.

The manufacturer of a COVID-19 drug authorized under the Regulations must notify Health Canada when they first sell the COVID-19 drug under an NOC. The manufacturer must complete, sign, date and return the Health Canada-issued drug notification form (DNF) within 30 days of the date of the first sale. All pages of the DNF must be returned to Health Canada.

The DIN assigned under the ISAD IO will be revoked once the same DIN is assigned to the drug under the Regulations. Our drug product database will indicate the DIN as "approved" until the manufacturer submits a completed DNF, at which point the DIN will be "marketed."

If the manufacturer did not file mock-up labels during review, the manufacturer should submit final mock-ups or final printed labels when the COVID-19 drug is marketed or launched.

For more information on market notifications or notifications for the 'interruption of sale,' consult the:

• Guidance document on the regulatory requirements for drug identification numbers (DINs)

Changes in product ownership, mergers and buyouts or licensing agreements

Submissions proposing administrative changes should be filed within Administrative (Abbreviated) New Drug Submissions ((A)NDS).

If sponsors are proposing labelling changes along with the proposed administrative changes, they must file these changes within an (A)NDS 'labelling only' to obtain Health Canada authorization. They must do so before making any changes to labelling materials on the market.

Refer to the following guidance document for more information:

• Administrative processing of submissions and applications involving human or disinfectant drugs

Notification of discontinuation of sale

The manufacturer of a COVID-19 drug must submit the notification of discontinuation of sale to Health Canada within 30 days after the COVID-19 drug is permanently discontinued in Canada. The date of discontinuance is when the manufacturer last sells its drug, not when it is last sold at retail.

For information and general procedures on notification of discontinuance, authorization holders should consult the:

• Guidance document on the regulatory requirements for drug identification numbers (DINs)

For more information on additional requirements on how to report a discontinuance of sale, see the section on shortages or discontinuation of sale.

Transparency

Health Canada will continue to communicate up-to-date information about COVID-19 drugs under the amended Food and Drug Regulations.

You can find the following information online:

• COVID-19 product-related information can be viewed on the COVID-19vaccines and treatments portal and the drug and health product register
• submissions for COVID-19 drugs that have been accepted for review in the lists for drug and health product submissions under review
• regulatory decision summaries (RDS) and summary basis of decision documents (SBDs) for COVID-19 drugs in the drug and health product register
• clinical information used to seek approval of COVID-19 drugs can be viewed on Health Canada's clinical information portal
• drug inspection outcomes and measures in the drug and health product inspections database

In addition, Health Canada will continue to provide the most up-to-date approved Risk Management Plans for COVID vaccines and treatments in their entirety to external stakeholders upon request. Health Canada confirms that sponsors will be consulted before any risk management plan for COVID-19 vaccines and treatments is made public. For more information, please consult the:

• Labelling and post-market requirements section of the Guidance for market authorization requirements for COVID-19 vaccines
• Public release of clinical information

Performance standards

Health Canada aims to prioritize submissions for COVID-19 drugs. Drug submissions will be prioritized and reviewed to reflect the public health need.

The time required to review a submission will depend on the submission itself, the volume of data to be assessed and the ability of the manufacturer to submit the data as per the plan, where applicable. Published performance standards will apply to submissions related to COVID-19 drugs, other than rolling submissions, made under the Regulations.

Rolling submissions will not be subject to performance standards (in other words, credits to manufacturers due to missed performance standards). This is explained in the Fees section below.

For more information, refer to the following guidance documents on the:

• Management of drug submissions and applications
• Management of regulatory submissions for veterinary drugs

Fees

Submission fees

Pre-market evaluation fees will be remitted for human drug submissions filed under the Food and Drug Regulations seeking approval for a COVID-19 drug, provided that:

• an application was previously filed under the ISAD IO for the same drug and
• no submission was previously filed under the Food and Drug Regulations for that drug

Once a drug has received an NOC under the Regulations, the existing Drug Right To Sell (DRTS) fee will apply.

Where an application had not been filed under the ISAD IO, the following fees will apply to COVID-19 drug submissions filed under the Regulations:

• existing evaluation fees will be charged for submissions
• existing small business mitigation measures are available for COVID-19 drug submissions, and include
• full waiver of evaluation fee for the company's first drug submission with Health Canada
• a 50% reduction in all other evaluation fees as well as a 25% reduction in DIN and DEL fees

Please consult the following guidance document:

• Fees for the review of human and disinfectant drug submissions and applications

Submissions with fees have associated performance standards. Penalties may apply:

• Published performance standards will apply, but it's expected that most COVID-19 drug submissions will be managed and reviewed efficiently.
• Rolling submissions will not be subject to performance standards (in other words, the 25% remittance to manufacturers due to missed performance standards will not apply).