Guidance on management of drug submissions and applications: Review
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The review process
The review 1 period begins immediately after the screening acceptance letter (SAL) is issued. Health Canada will evaluate the submission or application as per the performance standards.
The reviewer examines and analyzes the information submitted to ensure the product meets the requirements set out in the applicable sections of the Food and Drug Regulations.
The regulatory project manager (RPM) or senior regulatory affairs officer (SRAO) coordinates the review timelines and is the sponsor’s initial point of contact.
Visit:
For information on the scientific review process of clinical trial applications (CTAs) and amendments to clinical trial applications (CTA-As), consult section 2.5.2 in:
Screening solicited and unsolicited information
During the scientific review process, we may screen solicited and unsolicited information submitted by the sponsor to ensure that:
- a cover letter is provided with the information and includes the control number of the submission or application
- the purpose of the correspondence is clearly stated as solicited or unsolicited and
- the information is in an acceptable format (for example, question-and-answer, side-by-side comparison), is referenced to the applicable section in the electronic submission or application and is complete for the intended purpose
Refer to the following sections on this page:
Cancellation letter during the scientific review
You must send a signed letter if you wish to cancel your submission or application during the review stage to the Office of Submissions and Intellectual Property (OSIP). The letter must be submitted in the same format as the original submission or application before a decision is made to issue any of the following:
- notice of compliance (NOC)
- notice of deficiency (NOD)
- notice of non-compliance (NON)
- notice of compliance with conditions - qualifying notice (NOC/c-QN)
- notice of deficiency - withdrawal (NOD-W) or
- notice of non-compliance - withdrawal (NON-W)
The status of the submission or application will be changed to “Cancel Science” as the scientific review has started.
The senior RPM or SRAO will issue a cancellation acknowledgment letter.
Submissions or applications that are cancelled by a sponsor do not affect refiling.
Learn more about refiling.
Pause-the-clock during the scientific review
Pause-the-clock allows the review clock to be paused under specific circumstances. When there is a pause, the target date is shifted to account for the amount of time the clock has been paused.
The review clock can pause only during the review period (for example, review 1 and review 2) for cost-recovered submissions and applications. Administrative submissions and applications are excluded.
Pauses may occur under 2 circumstances:
- a sponsor requests an extension to respond to a clarification request, including pre-market testing information in accordance with the Guidance for sponsors: Lot Release Program for Schedule D (biologic) drugs or
- Health Canada wishes to seek advice from an external advisory committee
1. Sponsor requests an extension to respond to a clarification request
You should submit the extension request as soon as possible in the form of a letter and written rationale. The clock will pause if:
- the request is beyond the number of days allocated to respond to a clarification request:
- 15 days for submissions with a 180- to 300-day performance standard
- 10 days for submissions and applications with a 91- to 179-day performance standard
- 5 days for submissions and applications with a 0- to 90-day performance standard
- the request is a minimum of 5 days but not beyond 90 days (applies to each clarification request)
- Health Canada approves the extension in writing to the sponsor
The review clock pauses once Health Canada approves the extension and after the standard clarification response time has elapsed. The target date is then changed. Note: There may be situations when we would not approve an extension or grant an extension to an existing pause.
The review clock resumes at the end of the approved extension period.
If the response to a clarification request is not satisfactory or not submitted within the specified time to respond, an NOD or NON is issued.
For example, if we issue a clarification request with a 10-day response time for a submission with a 91- to 179-day performance standard, the following happens:
- if an 8-day extension is requested beyond the standard 10-day response time and the extension request is approved, the review clock will pause for 8 days beginning on day 11 and the response is due on day 18
- if a 2-day extension is requested beyond the standard 10-day response time, and the extension request is approved, the review clock will not pause
2. Health Canada seeks advice from an external advisory committee
If an external advisory committee is required during the review period (this need will be identified as early as possible in the review), we will:
- notify you if a pause is required
- include the nature of the questions for the committee in the notification
The review clock resumes once we receive the committee’s final recommendations. We will confirm the revised target date at this time.
Note: Expert advisory panels and committees are convened in accordance with our policy on external advisory bodies.
Solicited information
Solicited information during the scientific review is any information that we request. Examples of solicited information during a scientific review include clarification on a statistical analysis contained in the information package, the rationale for interim pivotal trials or changes to the proposed labelling material.
Clarification requests
A clarification request is issued when Health Canada wants the sponsor to expand on, clarify or re-analyze existing information in the submission or application during the scientific review. For example, a clarification request could be made to locate misplaced documents.
A clarification request should not be made to request missing documents or new data, such as new clinical or pre-clinical information, bioavailability studies or chemistry and manufacturing data not previously submitted.
Health Canada will email the request and sponsors must respond in writing. The review process does not stop if we receive a complete response within the requested timeframe.
When responding to a clarification request, you should clearly identify the:
- name of the drug
- dossier ID
- control number of the relevant submission or application and
- purpose of the correspondence
- for example, “response to a clarification request”
Submit your response in a question-and-answer format and reference the applicable sections in the submission or application.
For acceptable formats, refer to the appropriate section in Filing submissions electronically:
- Preparation of regulatory activities in eCTD format
- Preparation of regulatory activities in non-eCTD format
For questions on filing submissions or applications electronically, you may contact BFMD.
Submit the solicited information within 15 calendar days from the date of the request or as indicated in the clarification request. A response is complete if:
- all clarifications or questions identified in the clarification request have been addressed or
- the sponsor provided a sound scientific rationale as to why the requested information is not necessary
Note: The period during which you must respond to a clarification request does not include the day that the clarification request is issued. It does include all other days, including weekends and statutory holidays. For example, if a clarification request is issued on April 1 and you have 15 calendar days to respond, the deadline to submit the request is April 16.
If a clarification request is inquiring about the location of data in the submission or application, you should only include the location of the data or an explanation as to why the data is missing.
To clarify any items in the clarification request or the reason for issuing it, you should contact the RPM or SRAO.
There is no limit on the number of clarification requests that may be solicited for 1 submission. However, a particular issue will only be addressed once. Acknowledgment letters are not sent for information received in response to a clarification request.
Response to a clarification request
For acceptable formats, refer to the appropriate section in Filing submissions electronically:
- Preparation of regulatory activities in eCTD format
- Preparation of regulatory activities in non-eCTD format
The timeline to respond is between 2 and 15 calendar days and is based on the type of and performance standard for a submission or application:
- 180- to 300-day performance standard: 15-day response time
- 91- to 179-day performance standard: 10-day response time
- 0- to 90-day performance standard: 5-day response time
- CTAs and CTA-As: 2-day response time
These are guidelines only and can be adjusted to be longer or shorter based on the complexity of the request, communications with the sponsor or the particular review circumstances.
Note: During review of a clinical assessment package, the solicited information in a clarification request should be submitted within 2 business days from the date of the request.
For more information, consult:
The review of the submission or application will not be interrupted if a complete response is submitted within the given time period.
If the response to a clarification request submitted during the scientific review is not satisfactory or not submitted within the specified time, we may send the following to a sponsor:
- notice of deficiency (NOD)
- not satisfactory notice (NSN) or
- notice of non-compliance (NON)
Notice of deficiency (NOD) - NDS, SNDS, ANDS and SANDS, EUNDS, EUSNDS, EUANDS, EUSANDS, NDS-D, SNDS-D, SNDS-c, SANDS-c, or an application for a DIN (DINA, DINB, DIND)
A notice of deficiency (NOD) is sent when:
- deficiencies or significant omissions that preclude continuing the review are identified or
- during the review of an application for a DIN (DINA, DINB, DIND), the product is identified as a new drug and the sponsor is asked to file a new drug submission (NDS) or an abbreviated new drug submission (ANDS)
When an NOD is issued, all scientific review streams stop and the status changes to “Inactive 45” or “Inactive 90” in the DSTS (depends on the type of submission or application), even if the review in the other streams has not been completed. Deficiencies identified to date from all review streams are included in the NOD and only 1 NOD is sent for a submission or application.
The difference between an NOD and an NON is that the review of the submission or application is not complete when an NOD is issued.
To clarify items in the NOD or the reason for it being issued, you should contact the regulatory project manager (RPM) or senior regulatory affairs officer (SRAO).
For an NDS, SNDS, ANDS, SANDS, EUNDS, EUSNDS, EUANDS, EUSANDS, NDS-D, SNDS-D, SNDS-c, and SANDS-c, the response to an NOD is to be submitted within 90 calendar days (or the time that was agreed to by the review area and the sponsor) from the date the NOD was sent.
For applications for a drug identification number (DIN), the response to an NOD is to be submitted within 45 calendar days (or the time that was agreed to by the review area and the sponsor) from the date the NOD was sent.
Response to NOD
A response to an NOD is to be submitted in the same format as the original submission or application. Solicited information must include a copy of the NOD and should be submitted in a question-and-answer format and reference the applicable sections of the submission or application.
Sponsors who decide it is not necessary to file the solicited information must provide a sound scientific rationale as to why the requested information is not necessary.
You should send all requested information along with up-to-date documents, including an updated cover letter, in a single package to OSIP for processing. OSIP will process this information and send to the appropriate review area within 10 calendar days. When OSIP begins to process the response to an NOD, the status of the submission will be changed to “Process”. If OSIP determines that the response to the NOD is administratively incomplete, it will change the status to “Process Hold”.
Once OSIP verifies that the response to an NOD is administratively complete, it will notify the appropriate review area that the response has been processed.
When the response to the NOD is received, a new screening 1 period begins.
Note: Acknowledgment letters are not sent when a response to an NOD is received.
Acceptance of a response to an NOD
When the response to an NOD is screened and found acceptable for scientific review, a screening acceptance letter (SAL) is sent to the sponsor. Then, a new review 1 period begins.
The RPM or SRAO is the initial point of contact.
Following review of the response to the NOD, the sponsor may be sent a:
- notice of deficiency withdrawal (NOD-W)
- notice of compliance (NOC) or
- notice of non-compliance (NON)
Notice of deficiency withdrawal letter (NOD-W)
An NOD-W is sent to the sponsor if the:
- response to an NOD contains unsolicited information, is incomplete or is deficient (found during the screening process)
- sponsor does not submit the solicited information within the assigned time period
- Health Canada interprets this as a request to withdraw the submission or application
- submission or application is still deficient (found during the scientific review of the response to the NOD)
You may withdraw a submission or application without having an impact on refiling.
Learn about refiling.
You may file a request for reconsideration after an NOD-W letter has been issued.
Learn about reconsideration of decisions.
Unsolicited information
When you file unsolicited information, you should use the same format as the original submission or application (eCTD or non-CTD electronic only). Your cover letter should indicate the type of information being provided, the reason for filing and the date of filing. Send this information to OSIP for processing. The RPM or SRAO will be notified that unsolicited information has been received.
Unsolicited information may only contain the types of information indicated in this section. All other types of information are not acceptable and you will be asked to remove them from your submission.
For submissions filed in the eCTD format, you must submit a new eCTD sequence to withdraw the unsolicited information as follows:
- assign operations attribute “delete” on leaves provided as “new” or
- assign operation attribute “replace” on leaves provided as replace
- use file reuse to reinstate the previous document as the current submission content
If you require assistance, email us at ereview@hc-sc.gc.ca.
If you wish to include the unsolicited information in a future drug submission or application, you will need to resubmit the information. Your submission or application will be assigned a new control number.
All unsolicited information for a CTA or CTA-A should be submitted as CTA-notifications to either ORA in BRDD or OCT in PDD, unless otherwise directed.
For more information, consult:
Safety information
Information that may be submitted during the submission process
You may submit negative safety findings or risk information collected from animal studies or clinical experience at any time. This information should support additions or changes to the wording in the “contraindications”, “warnings and precautions”, and “adverse reactions” sections of the product monograph.
If you are revising the product monograph as a result of the unsolicited safety data, the revised monograph must appropriately reference the original monograph, include the proposed changes and accompany any unsolicited data being submitted. A mock-up label is also required if changes to the monograph result in changes to the label. The new information will not affect the performance standards for reviewing your submission.
When submitting negative safety information, be sure to include in the cover letter the following:
- name of the drug
- dossier ID
- control number of the relevant submission or application
- purpose of the correspondence
- statement that the information is unsolicited
Information that will not be accepted once submission is accepted for review
Unsolicited final reports of safety studies that do not require changes to the “contraindications”, “warnings and precautions” and “adverse reactions” sections of the product monograph will not be accepted for scientific review. You may, however, file this information in response to an NOD or NON, or include this data when you file an SNDS.
For more information, consult:
Foreign regulatory information
Assessment reports
We will accept assessment reports prepared by other regulatory authorities within 120 days of receiving the original submission or application. Assessment reports submitted outside the 120-day time period may not be used or considered. We will not accept reports that have been summarized.
Correspondence
We will accept copies of correspondence between the sponsor and other regulatory authorities at any time, but we will not accept summaries of the correspondence. Supporting data or appendices should not be included with the correspondence, but should be available if requested.
Reports from an expert or expert advisory committee
We will only accept reports from an expert or expert advisory committee at the time of filing or if submitted in a response to an NOD or NON.
Changes in name of sponsor or product during processing, screening or review
During the review of a submission or application for a new product that has not yet been issued a drug identification number (DIN), if the name of the sponsor or product changes, you should submit the applicable items to OSIP:
- letter stating the nature of the change
- Regulatory Enrolment Process (REP) Regulatory Transaction (RT) XML file, for submissions and applications
- If the new manufacturer name does not have a company identifier, it is necessary to complete a REP Company (CO) XML file before filling out the updated RT XML file. The CO XML file is processed separately from submission and application documents. For any questions about the CO XML file, contact the Client Information Unit at client.information@hc-sc.gc.ca.
- revised product monograph, package insert and labels, including mock-up labels
- brand-name assessment and mock-up labels for a product name change
- labels and packages certification form
- revised Certified Product Information Document (CPID)
- letter of authorization from the originating sponsor if the product is being transferred from 1 sponsor to another
If a product has already received market authorization (has been issued a DIN) and the name of the sponsor or product changes during the review of a subsequent submission or application, you must file a submission or application to make the necessary changes.
For information on the requirements for sponsor and product name changes, consult:
- Guidance document for industry: Review of drug brand names
- Frequently asked questions – Guidance document for industry – Review of drug brand names
- Guidance document: Questions and answers: Plain language labelling regulations for prescription drugs
- Guidance document: Questions and answers: Plain language labelling regulations for non-prescription drugs
- Guidance document - Administrative processing of submissions and applications: Human or disinfectant drugs
Efficacy data
Efficacy data will not be accepted at any point during the review unless it is solicited in an NOD or NON. You may file efficacy data as a supplement to a new drug submission, where applicable.
For more information, consult:
If you committed to providing additional efficacy data in a letter of undertaking prepared in response to an NOC/c qualifying notice, you should submit this data as an SNDS-c or SANDS-c.
Stability data
You should only submit updated stability information relating to the quality of the drug substance or drug product when requested.
Finalizing the review process
Finalizing the submission or application
After the review is completed and a decision has been recommended (either negative or positive), we will prepare and send 1 of the following decision documents.
Notice of compliance (NOC) - NDS, SNDS, ANDS, SANDS, EUNDS, EUSNDS, EUANDS, EUSANDS, NDS-D, SNDS-D, SNDS-c, SANDS-c
This section does not apply to CTAs and CTA-As.
If a submission for a Division 8 product complies with the Food and Drug Regulations, you may receive:
- a DIN, in the form of a Drug Notification Form (DNF), in accordance with sub-section C.01.014.2(1) of the Food and Drug Regulations and
- an NOC once the requirements of the Patented Medicines (Notice of Compliance) Regulations and the data protection provisions in section C.08.004.1 of the Food and Drug Regulations have been met or
- a notification that the submission has been placed on Intellectual Property - Hold until the requirements of the Patented Medicines (Notice of Compliance) Regulations have been met or the term of market exclusivity for an innovative drug in accordance with the data protection provisions in section C.08.004.1 of the Food and Drug Regulations has expired
Before receiving an NOC, submissions may also be placed on Switch Hold or Regulatory Hold.
Learn more about types of holds.
No objection letter (NOL) - application for a DIN (DINA, DINB, DIND), NC, PDC, PDC-B, CTA, CTA-A
When the scientific review of an application for a DIN (DINA, DINB, and DIND) has been completed and found to be in compliance, you will receive:
- a DIN, via a Drug Notification Form (DNF), in accordance with subsection C.01.014.2(1) of the Food and Drug Regulations or
- an NOL for DINAs and DINDs or
- an approval letter for DINBs
An NOL will also be sent by the responsible review area for NCs, PDCs, PDC-Bs, CTAs or CTA-As when the submission or application has been found to be in compliance.
Not satisfactory notice (NSN) - NC, PDC, PDC-B, CTA, CTA-A
If deficiencies are identified during the review of an NC, PDC, PDC-B, CTA or CTA-A, the review area will send an NSN specifying the deficiencies to the sponsor. The review of the submission will stop on the date the NSN is sent.
You should contact the RPM or SRAO to clarify items in the NSN or the reason for issuing it.
If an NSN has been issued, you may refile the submission or application.
Learn about refiling.
If an NSN has been issued, you may file a request for reconsideration.
Learn about reconsideration of decisions.
Notice of compliance with conditions qualifying notice (NOC/c-QN)
This section does not apply to CTAs and CTA-As.
When it has been determined that data submitted for review qualifies under the NOC/c policy, the appropriate directorate will contact the sponsor to discuss the details of the submission, commitments and its potential consideration under the NOC/c policy. Following these discussions, we will issue an NOC/c–QN if appropriate.
The NOC/c-QN indicates that the submission qualifies for an NOC under the NOC/c policy. This notice also outlines the:
- additional clinical evidence to be provided in confirmatory studies
- post-market surveillance responsibilities and
- requirements related to advertising, labelling or distribution
The scientific review of the submission will stop on the date the qualifying notice is issued.
You should submit the appropriate information within 30 calendar days of receiving the NOC/c-QN. Responses to an NOC/c-QN should reference the submission control number and be sent to OSIP.
Once we receive a sponsor's response to an NOC/c-QN, we start the scientific review of the additional information provided. This stage is subject to a 30-calendar day performance standard.
If the information is acceptable, we will finalize (with the sponsor) the conditions associated with the NOC and the letter of undertaking (LOU).
For more information, consult:
If the information is not acceptable, we may issue an NON.
Note: Acknowledgment letters are not sent when we receive information in response to an NOC/c-QN.
Notice of non-compliance (NON) - NDS, SNDS, ANDS, SANDS, EUNDS, EUSNDS, EUANDS, EUSANDS or an application for a DIN (DINA, DINB, DIND)
This section does not apply to CTAs and CTA-As.
If after the scientific review, we find that a submission or application is incomplete or non-compliant with the requirements outlined in the Food and Drugs Act and its regulations, we will send an NON to the sponsor. (Note: The authorities are set out in sections C.01.014.2 (2), C.08.004 (1) and C.08.004.01 (1) of the Food and Drug Regulations.)
The NON will specify the issues that make the submission non-compliant.
After an NON is issued, the status of the submission or application status will change to “Inactive 45” or “Inactive 90” in the DSTS (depends on the submission or application type). Only 1 NON for each submission or application is sent.
If you wish to clarify items in the NON or the reason for it being issued, you should contact the RPM or SRAO.
For an NDS, SNDS, ANDS, SANDS, EUNDS, EUSNDS, EUANDS and EUSANDS, you must submit the solicited response to an NON within 90 calendar days (or the time agreed upon by both parties) from the date the NON was sent.
For applications for a DIN, you must submit the solicited information within 45 calendar days (or the time agreed upon by both parties) from the time the NON was sent.
Response to a notice of non-compliance (NON)
You must submit a response to an NON in the same format as the original submission or application. The response must include a copy of the NON, be submitted in a question-and-answer format and reference the applicable sections in the original submission or application.
If you decide you do not need to file the solicited information, you must provide a sound scientific rationale in order for us to consider the response to be complete.
You should send all the requested information and up-to-date documents, including an updated cover letter, in a single package to OSIP. OSIP will process this information and send it to the appropriate review area within 10 calendar days.
When OSIP begins to process the response to the NON, it will change the status of the submission to “Process”. If OSIP determines that the response is administratively incomplete, it will change the status to “Process Hold”.
Once OSIP verifies that the response is administratively complete, it will notify the appropriate area that the response has been processed.
When the response to the NON is received, the screening 2 period begins. Acknowledgment letters are not sent when responses to NONs are received.
Acceptance of a response to a notice of non-compliance (NON)
When the response to an NON is screened and found to be acceptable for review, we will send a screening acceptance letter (SAL) to the sponsor. A review 2 period begins immediately after we issue the SAL.
The RPM or SRAO is the initial point of contact for the sponsor.
Notice of non-compliance withdrawal letter (NON-W)
An NON-W is sent to the sponsor if the:
- response to an NON contains unsolicited information, is incomplete or is deficient (during the screening process)
- sponsor does not submit the solicited information (the response to an NON) within the assigned time period
- Health Canada interprets this as a request to withdraw the submission or application or
- submission is still non-compliant (during the scientific review of the response to the NON)
Submissions or applications may be withdrawn without having an impact on refiling.
Learn about refiling.
You may file a request for reconsideration after an NON-W has been issued.
Learn about reconsideration of decisions.
Scientific review reports
Sponsors will receive review reports from Health Canada within 7 calendar days after an NOD, NOD/W, NON or NON/W has been issued for all submissions except DINAs/DINBs and DINDs. For DINAs/DINBs and DINDs, sponsors may request reports following receipt of an NOD, NON, NOD/W or NON/W.
Sponsors may also request review reports following receipt of an NOL, NOC or NSN.
Address your requests to the director of the review centre, bureau or office. Health Canada aims to provide requested review reports to the sponsor within 30 calendar days of receiving the request.