Health Canada Application Processing.docx

**9. Submission/application processing** **9.1 Processing of an initial submission/application** All information received by OSIP will be processed and sent to the appropriate review Centre/Bureau/Office within 10 calendar days of receipt. During the 10-day processing period, OSIP performs the fo...

**9. Submission/application processing** **9.1 Processing of an initial submission/application** All information received by OSIP will be processed and sent to the appropriate review Centre/Bureau/Office within 10 calendar days of receipt. During the 10-day processing period, OSIP performs the following activities, depending on the submission/application type: - assigns a control number and Dossier ID (only when applicable) to the submission/application - enters the initial information into the Drug Submission Tracking System (DSTS) (e.g., medicinal ingredient, dosage form, brand name, date received, etc. - verifies that the information submitted is administratively complete (e.g., all necessary forms, including those related to cost-recovery have been submitted) - verifies that the format, structure and attributes of electronic data submitted comply with the CTD format and specifications - for submissions subject to the provisions of the *Patented Medicines (Notice of Compliance) Regulations*, verifies that a Patent Form V has been included in the submission/application and ensures that all relevant patents have been addressed through the filing of the Form V, and - verifies the submission is not subject to data protection under the data protection provisions of section C.08.004.1 of the *Food and Drug Regulations*[^Footnote10^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn10) At this stage in processing, the information package may be placed on the following administrative holds: - Process Hold - Initial - Cost Recovery Hold - Patent Form V Hold, or - Data Protection Refused Hold Refer to [Appendix 5](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a95) for a description of the different types of \"Administrative Holds.\" When the hold is resolved or the initial information package is considered administratively complete, the following occurs: - the information package becomes a submission/application - the filing date is entered into the DSTS (i.e., the date when the submission/application is considered administratively complete) - the remainder of the submission/application information is entered into the DSTS, if applicable, and - the appropriate review Centre/Bureau/Office is notified that the submission/application has been processed and can be assigned to a Regulatory Project Manager (RPM) or a Senior Regulatory Affairs Officer (SRAO) for screening. **9.2 Cancellation or withdrawal letter during the processing period** If a sponsor wishes to cancel their submission/application during the processing period, a signed letter requesting the cancellation should be sent to OSIP in the same format as the original submission/application. The status of the submission/application would be changed to \"Cancelled Admin\" in the DSTS as the scientific review has not started. Submissions/applications that are cancelled/withdrawn by the sponsor may be done so without prejudice to a refiling. Should a sponsor wish to refile a submission/application following a cancellation at any point during the processing, screening, Review 1, or following a NOD, the sponsor will be required to resubmit all information for the submission/application. Referencing to the original submission/application will not be acceptable. For submissions/applications cancelled by the sponsor following the issuance of a NON or NON-W or during Review 2, refer to sections 15.6 and 15.7 for information on the refiling of information. **10. Screening of submissions/applications** **10.1 Screening of a submission/application during the Screening 1 period** For information on the screening process of CTAs and CTA-As, refer to the [Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/clinical-trials/clinical-trial-sponsors-applications.html) (Section 2.5.1). When the submission/application is received in the Centre/Bureau/Office, the Screening 1 period begins. The RPM/SRAO[^Footnote11^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn11) will screen all submissions/applications[^Footnote12^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn12) to: - verify that the type and class of the submission/application has been filed correctly given the intended purpose - ensure requisite information for the type and class of the submission/application has been provided, and - verify the fee is appropriate for the submission/application. Health Canada will screen the original submission/application within the performance standards in [Appendix 3](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a89) for Screening 1 period. **10.1.1 Cancellation letter during the Screening 1 period** If a sponsor wishes to cancel their submission/application during the screening period before it has been accepted into scientific review, a signed letter requesting the cancellation should be sent to OSIP in the same format of the original submission/application. The status of the submission/application would be changed to \"Cancelled Admin\" in the DSTS as the scientific review has not started. The Senior Regulatory Project Manager (SRPM) or Senior Regulatory Affairs Officer (SRAO) will issue a cancellation acknowledgement letter. **10.1.2 Screening Acceptance Letter (SAL)** If the information submitted by the sponsor is acceptable at screening and requests for information/clarification are not required (refer to [Section 10.2.1](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a33) for more information): - the submission/application or response to solicited information is accepted for scientific review and a Screening Acceptance Letter (SAL) is sent to the sponsor - the appropriate databases are updated, and - the relevant review division will be notified that the submission/application has been accepted for review. Once the submission/application is accepted for scientific review, the RPM/SRAO will continue to be the point of contact for communication with the sponsor, unless otherwise indicated. **10.2 Solicited Information** Solicited information is considered any information that is requested by Health Canada during the screening of a submission/application. Examples include but are not limited to: Clarification Requests or Screening Deficiency Notices. **10.2.1 Clarification Requests during the Screening 1 period** For information on the screening requests of CTAs and CTA-As, refer to the Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications (Section 2.5.1). The purpose of a Clarification Request is to expand on, seek clarification on specific information or re-analyze existing information in the submission/application during the screening period. For example, Clarification Request may be used to locate misplaced documents, etc. Clarification Requests should not be used to request missing documents or new data such as, new clinical and/or pre-clinical information, including bioavailability studies or chemistry and manufacturing data not previously submitted. Requests will be solicited by fax or email and must be responded to in writing (for more information, refer to [Section 10.2.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a35)). The screening is not interrupted if a complete response is submitted within the requested timeframe. **10.2.2 Response to a Clarification Request during the Screening 1 period** When responding to a Clarification Request, sponsors should clearly identify the name of the drug, the Dossier ID, the control number of the relevant submission/application and the purpose of the correspondence (i.e. \"Response to a Screening Clarification Request\"). Responses to Clarification Requests should be submitted in a Question and Answer format that is referenced to the applicable section(s) in the submission/application. Sponsors are requested to send their responses to Clarification Requests in accordance with the Guidance Document: Preparation of Drug Regulatory Activities in the Electronic Common Technical Document (eCTD) Format or the [Guidance Document: Preparation of Regulatory Activities in the Non-eCTD Electronic-Only Format](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/filing-submissions-electronically.html), as applicable. For sponsors who filed in the non-eCTD electronic-only format, the response should be submitted to OSIP via electronic media (i.e., USB or CD) via courier mail. For the shorter response times to a Clarification Request, sponsors are reminded to take into account the delivery and processing time. For questions regarding filing submissions/applications electronically, sponsors can contact OSIP. Refer to [Appendix 2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a87) for contact information. The solicited information should be submitted 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 duration that a sponsor has to respond to a clarification request does not include the day that the clarification request is issued. The duration does include all other days, including weekends and statutory holidays. (For example, if a clarification request is issued on April 1 and is given 15 calendar days to respond, the deadline to submit the request would be April 16.) For submissions/applications that are administratively processed, solicited information in a Clarification Request should be submitted within five (5) business days from the date of the request. If a Clarification Request is inquiring about the location of data in the submission/application, the response should only include the location of the data or an explanation as to why the data is missing. To clarify points of the Clarification Request, or the rationale for its issuance, sponsors should contact the RPM/SRAO. There is no limit on the number of Clarification Requests that may be solicited for one submission. However, no particular issue will be addressed more than once. Acknowledgement letters are not sent upon receipt of information received in response to Clarification Requests. During the screening of a submission/application, if a response to a Clarification Request is not satisfactory or is not submitted within the specified time to respond, a Deficiency Notice or Rejection letter will be sent for submissions/applications with administrative processing. For all other submission/application types, a Screening Deficiency Notice is sent. **10.2.3 Screening Deficiency Notice (SDN)** If deficiencies are identified during the screening of material relating to a submission or application, the sponsor will be sent a Screening Deficiency Notice identifying the deficiencies. This may also include submissions where the drug is filed as a DIN Application but is considered a new drug or where the monograph attestation is found not to reflect the submission content. The status of the submission/application will change to \"inactive 45\" in the DSTS. A SDN can be sent to the sponsor without prior issuance of a Clarification Request. The solicited information is to be submitted within 45 calendar days from the date the SDN was sent. To clarify points of the SDN or the rationale for its issuance, sponsors should contact the RPM/SRAO. **10.2.3.1 Response to Screening Deficiency Notice (SDN)** When responding to a SDN, sponsors should clearly identify the name of the drug, the Dossier ID, the control number of the relevant submission/application and the purpose of the correspondence (i.e. \"Response to SDN\") in the cover letter. The response is to be submitted in a question and answer format, referenced to the applicable section(s) of the submission/application as appropriate. The response to a SDN should not contain unsolicited information (refer to [Section 14.0](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a61)) unless otherwise specified in the SDN. The sponsor should send all requested information along with the up-to-date documents including an updated cover letter in a single package to OSIP for processing. All information received by OSIP will be processed and sent to the appropriate review Centre/Bureau/Office within 10 calendar days. When OSIP begins to process the Response to SDN, the status of the submission would be changed to \"Process\" in the DSTS. Should OSIP determine that the Response to SDN is administratively incomplete; the submission status will be changed to \"Process Hold\". Once OSIP verifies that the \"Response to SDN\" is administratively complete, the RPM/SRAO will be notified that the response has been processed. Acknowledgement letters are not sent upon receipt of responses to SDNs. Upon receipt of the information requested in the Screening Deficiency Notice, a new Screening 1 period will begin (with the associated performance standards), and the requested material and information will be screened for completeness. **10.2.3.2 Acceptance letter following the response to a Screening Deficiency Notice (SDN)** If the response to the SDN is acceptable, a SAL will be sent to the sponsor and the Review 1 Period will begin immediately (refer to [Section 10.1.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a31) - SAL). **10.2.3.3 Screening Rejection Letter (SRL)** A SRL will be sent for by the SRPM/SRAO[^Footnote14^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn14) for all drug submissions/applications if the sponsor fails to provide a response to the SDN within 45 calendar days or if the information submitted is incomplete, deficient or contains unsolicited information. A SRL (instead of a SDN) will be sent for a Notifiable Change (NC) or SNDS/SANDS if the proposed changes are Level III changes only[^Footnote15^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn15). To clarify points of the SRL or the rationale for its issuance, sponsors should contact the RPM or SRAO. If a SRL has been issued, the sponsor may refile the submission/application (refer to [Section 15.1](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a73)). A sponsor may file a Request for Reconsideration following the issuance of a SRL (Refer to [Section 16](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a80) - Reconsideration of Decisions issued for Human Submissions and Applications). **11. Scientific Review of submissions/applications** **11.1 Scientific Review process** For information on the scientific review process of CTAs and CTA-As, refer to the [Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/clinical-trials/clinical-trial-sponsors-applications.html) (Section 2.5.2). The Review 1 period begins immediately after the SAL is issued. Health Canada will evaluate the submission/application within the performance standards in [Appendix 3](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a89). The reviewer will examine and analyse the information submitted to ensure the product meets the requirements set out in the applicable sections of the *Food and Drug Regulations*. The RPM/SRAO is responsible for coordinating review timelines and is the initial point of contact for communication with the sponsor. Refer to [Appendix 2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a87) for contact information. **11.1.1 Screening solicited and unsolicited information submitted during the Scientific Review** For information on what is considered solicited and unsolicited information, refer to [Section 12.0](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a43) and [Section 14.0](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a61) respectively. Solicited and unsolicited information submitted by the sponsor during the scientific review may be screened, where appropriate, to ensure that: - a cover letter is provided with the information that includes the control number of the relevant submission/application - the purpose of the correspondence is clearly stated as solicited or unsolicited, and - the information submitted in an acceptable format (e.g. question and answer, side-by-side comparison), referenced to the applicable section in the electronic submission/application, as appropriate, and the information is complete for the intended purpose **11.1.2 Cancellation letter during the Scientific Review** If a sponsor wishes to cancel their submission/application during the scientific review, but before a decision is made to issue an NOC, NOD, NON, Notice of Compliance with Conditions Qualifying Notice (NOC/c-QN), NOD-Withdrawal (NOD-W) or NON-Withdrawal (NON-W), a signed letter requesting the cancellation should be sent to OSIP in the same format as the original submission/application. The status of the submission/application would be changed to \"Cancelled Science\" as the scientific review has started. The SRPM/SRAO will issue a cancellation acknowledgement letter. Submissions/applications may be cancelled by the sponsor without prejudice to a refiling (refer to [Section 15.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a74) for information on refiling). **11.1.3 Pause the Clock during the Scientific Review** Pause the clock is a tool that allows the review clock to be paused under specified 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 (e.g., Review 1 and Review 2) for cost-recovered submissions/applications. Administrative submissions/applications are excluded from this mechanism. Pauses can occur with these submissions/applications in the following instances: a. Sponsor request for an extension to respond to a Clarification Request A sponsor may request an extension to respond to a Clarification Request. The extension request should be submitted as soon as possible in the form of a letter and written rationale. The clock would pause if the following criteria are met: - the extension request is beyond the number of days allocated to respond to a Clarification Request as indicated in [Section 12.1.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/a46) of this guidance document, (i.e., 15 days for submissions with a 180 - 300 day performance standard; 10 days for submission/application with a 91-179 day performance standard; 5 days for submissions/applications with a 0 - 90 day performance standard), - the extension request is a minimum of 5 days but not beyond 90 days per Clarification Request, and - Health Canada approves the extension in writing to the sponsor. Following Health Canada\'s approval of the extension and after the standard clarification response time has elapsed, the review clock pauses. The sponsor has the additional time approved by Health Canada to respond to the request, and the target date is changed. Note that there may be situations where Health Canada would not approve an extension or grant an extension to an existing pause. The review clock would resume 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, a NOD or NON will be issued (refer to [Section 12.1.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/a46)). For example, if Health Canada issues a Clarification Request with a 10 day response time for a submission with a 91-179 day performance standard: - if an 8 day extension is requested beyond the standard 10 day response time and the extension request is approved, the review clock would pause for 8 days beginning on day 11, and the response would be 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 would not pause. b. Seeking Advice from an External Advisory Committee[^Footnote16^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn16) Health Canada will inform the sponsor if an External Advisory Committee is required during the review period. Health Canada will strive to identify the need for an External Advisory Committee as early as possible in the review. If a pause is required, the sponsor will be notified of this by Health Canada. The nature of the questions for the External Advisory Committee will be included in the notification. Health Canada\'s review clock would resume upon receipt of the final recommendation(s) from the committee, at which point the revised performance standard date will be confirmed. **12. Solicited information during the Scientific Review** **12.1 Solicited information** Solicited information is any information requested by Health Canada during the scientific review. Examples include but are not limited to: Clarification Requests, a Notice of Deficiency (NOD) or a Notice of Non-Compliance (NON). **12.1.1 Clarification Request during the Scientific Review** Refer to [Section 10.2.1](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a33) for information regarding Clarification Requests as the information in this section is also applicable to Clarification Requests solicited during the scientific review. Examples of solicited information during the scientific review may include clarification on a statistical analyses package, the rationale for interim pivotal trials, or changes to proposed labelling material. **12.1.2 Response to a Clarification Request during the Scientific Review** Refer to [Section 10.2.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a34) for information regarding the response to a Clarification Request during the screening period. This information is also applicable to a response to a Clarification Request submitted during the scientific review. Sponsors are to send their responses to Clarification Requests in accordance with the Guidance Document: Preparation of Drug Regulatory Activities in the Electronic Common Technical Document Format or the [Guidance Document: Preparation of Regulatory Activities in the Non-eCTD Electronic-Only \[1\] Format](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/filing-submissions-electronically.html). The timeline to respond should be between 2 and 15 calendar days and will be based on the type and the performance standard of the submission/application (see Table 1 below). While the type of submission/application should guide response times, these are guidelines and can be adjusted. Where warranted, Health Canada can adjust the timelines to be longer or shorter based on the complexity of the request, dialogue with the sponsor and/or circumstances of the review. Table 1: Time to Respond to a Clarification Request during Scientific Review 180-300 day performance standard 15 days ---------------------------------- --------- 91-179 day performance standard 10 days 0-90 day performance standard 5 days CTAs and CTA-As 2 days Note: During the review of a Clinical Assessment Package to request Priority Review status, the solicited information in a Clarification Request should be submitted within two (2) business days from the date of the request. Refer to the [Guidance for Industry: Priority Review of Drug Submissions](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/priority-review/drug-submissions.html). The review of the submission/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 to respond, the following may be sent to the sponsor: - a Notice of Deficiency (NOD) (refer to [Section 12.1.3](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a47)) - a Not Satisfactory Notice (NSN) (refer to [Section 13.4](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a55)), or - a Notice of Non-Compliance (NON) (refer to [Section 13.6](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a57)) **12.1.3 Notice of Deficiency (NOD) - NDS, SNDS, ANDS, SANDS or an Application for a DIN (DINA, DINB, DIND)** A NOD will be sent to the sponsor when: - during the scientific review of a submission/application[^Footnote17^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn17), deficiencies and/or significant omissions that preclude continuing the review are identified, or - during the scientific review of an Application for a DIN (DINA, DINB, DIND), the product is identified as a New Drug and the sponsor is requested to file a NDS, or an ANDS. At the time of the NOD issuance, all scientific review streams will stop and the submission/application status will change to \"Inactive 45\" or \"Inactive 90\" in the DSTS (depending on the submission/application type) even if the review in the other streams has not been completed. Deficiencies identified to date from all review streams will be included in the NOD. Only one NOD is sent per submission/application. The difference between a NOD and a Notice of Non-Compliance (NON) is that the review of the submission/application is not complete when a NOD is issued. To clarify points of the NOD or the rationale for its issuance, sponsors should contact the RPM/SRAO. For NDSs, SNDSs, ANDSs and SANDSs, the Response to a Notice of Deficiency is to be submitted within 90 calendar days (or such time as the Centre/Bureau/Office and sponsor may agree upon) from the date the NOD was sent. For Applications for a DIN, the Response to a Notice of Deficiency is to be sent within 45 calendar days (or such time as the Centre/Bureau/Office and sponsor may agree upon) from the date the NOD was sent. If a NOD was issued during an early review, and after a subsequent review, the sponsor may be sent a: - Notice of Deficiency Withdrawal (NOD-W) (refer to [Section 12.1.3.3](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a50)) - Notice of Compliance (NOC) (refer to [Section 13.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a53)), or - Notice of Non-Compliance (NON) (refer to [Section 13.6](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a57)). **12.1.3.1 Response to Notice of Deficiency (NOD) - NDS, SNDS, ANDS, SANDS or an Application for a DIN (DINA, DINB, DIND)** A Response to NOD is to be submitted in the same format as the original submission/application. The solicited information is to include a copy of the NOD and should be submitted in a question and answer format and referenced to the applicable section(s) of the submission/application. Should a sponsor decide it is not necessary to file the solicited information; a sound scientific rationale for this position must be presented in order for the response to be considered complete. The sponsor should send all of the requested information along with up-to-date documents including an updated cover letter in a single package to OSIP for processing. All information received by OSIP will be processed and sent to the appropriate review Centre/Bureau/ Office within 10 calendar days. When OSIP begins to process the Response to NOD, the status of the submission would be changed to \"Process\". Should OSIP determine that the Response to NOD is administratively incomplete; the submission status will be changed to \"Process Hold\". Once OSIP verifies that the Response to a NOD is administratively complete, the appropriate Centre/Bureau/Office is notified that the response has been processed. When the response to the NOD is received, a new Screening 1 period begins (refer to [Section 11.1.1](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a41) - Screening of Solicited and Unsolicited Information Submitted during the Scientific Review). Acknowledgement letters are not sent upon receipt of Responses to NODs. **12.1.3.2 Acceptance of a response to a Notice of Deficiency (NOD)** When the Response to a NOD is screened and found acceptable for scientific review, a SAL will be sent to the sponsor (refer to [Section 10.1.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a31) - SAL). A new Review 1 period begins immediately after the issuance of the SAL. The RPM/SRAO will serve as the initial point of contact for communication with the sponsor. **12.1.3.3 Notice of Deficiency Withdrawal letter (NOD-W[^Footnote18^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn18))** A NOD-W will be sent to the sponsor if: - during the screening process the Response to a NOD is found to contain unsolicited information, is incomplete, or is deficient - the sponsor fails to submit the solicited information (i.e. the Response to the NOD) within the assigned time period. Health Canada will interpret this as a request to withdraw the submission/application, or - during the scientific review of the Response to a NOD, it is determined that the submission/application remains deficient. Submissions/applications may be withdrawn without prejudice to a refiling (refer to [Section 15.4](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a76) for information on refiling). A sponsor may file a Request for Reconsideration following the issuance of a NOD-Withdrawal Letter (refer to [Section 16](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a80) - Reconsideration of Decisions Issued for Human Submissions and Applications). **13. Completion of the Scientific Review of a submission/application** **13.1 Processing of the submission/application following completion of the review** Upon completion of a review where a decision has been recommended (either negative or positive), one of the following decision documents is prepared. **13.2 Notice of Compliance (NOC) - NDS, SNDS, ANDS, SANDS, EUNDS, EUSNDS, EUANDS, AEUSNDS, NDS-D, SNDS-D, SNDS-c, SANDS-c** When the scientific review of a submission for a Division 8 product is completed and the submission complies with the *Food and Drug Regulations*, the sponsor may receive the following: - a Drug Identification Number, in the form of a Drug Notification Form (DNF), in accordance to sub-section C.01.014.2(1) of the *Food and Drug Regulations*, and - either a 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 (IP Hold) until the requirements of the *Patented Medicines (Notice of Compliance) Regulations* have been met and/or until 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. Prior to receiving a NOC, submissions may also be placed on a Switch Hold or a Regulatory Hold. For a description of the types of holds mentioned in this section, refer to [Appendix 5](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a95). **13.3 No Objection Letter (NOL) - Application for a DIN (DINA, DINB, DIND), NC, PDC-prescription, PDC-non-prescription, PDC-disinfectant, 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 the sponsor will receive: - a Drug Identification Number, via a Drug Notification Form (DNF), in accordance to sub-section C.01.014.2(1) of the *Food and Drug Regulations*, or - a NOL for PDC-prescription, PDC-non-prescription, PDC-disinfectants and PDC-Bs - an Approval Letter for DIN-Bs A NOL will also be sent by the responsible review Centre/Bureau/Office for NCs, CTAs or CTA-As when the scientific review of the submission/application has been completed and found to be in compliance. **13.4 Not Satisfactory Notice (NSN) - NC, PDC-prescription, PDC-non-prescription, PDC-disinfectant, PDC-B, CTA, CTA-A** When deficiencies are identified during the review of a NC, PDC-prescription, PDC-non-prescription, PDC-disinfectant, PDC-B, or CTA, CTA-A, a NSN will be sent to the sponsor by the responsible review Centre/Bureau/Office specifying the deficiencies. The review of the submission will stop on the date the NSN is sent. If a NSN has been issued, the sponsor may refile the submission/application (refer to [Section 15.5](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a77) for information on refiling). A sponsor may file a Request for Reconsideration following the issuance of a NSN (refer to [Section 16](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a80) - Reconsideration of Decisions issued for Human Submissions and Applications). **13.5 Notice of Compliance with Conditions Qualifying Notice (NOC/c-QN)** This section is not applicable to CTAs and CTA-As When data submitted has undergone a scientific review and has been determined to qualify under the NOC/c policy, the appropriate Directorate of Health Canada will contact the sponsor to discuss the details of the submission, commitments, and its potential consideration under the NOC/c policy. Following discussions with the sponsor, Health Canada will issue a NOC/c - QN if appropriate. The NOC/c - QN indicates that the submission qualifies for a NOC under the NOC/c policy and 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. The sponsor should submit the appropriate information within 30 calendar days of receipt of the NOC/c-QN. Responses to a NOC/c-QN should reference the submission control number and be sent to OSIP. Upon receipt of the sponsor\'s response to the NOC/c - QN, Health Canada will commence a scientific review of the additional information provided, which is subject to a 30 calendar day performance standard. Should the information be considered acceptable, Health Canada will finalize, with the sponsor, the conditions associated with issuance of the NOC under the NOC/c policy as well as the Letter of Undertaking (LOU). For more information, consult the [Guidance Document: Notice of Compliance with Conditions](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/notice-compliance-conditions.html) (NOC/c) available on the Health Canada website. If the information is not considered acceptable, a NON may be issued (refer to [Section 13.6](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a57)). Acknowledgement letters are not sent upon receipt of information received in response to NOC/c-QNs. **13.6 Notice of Non-Compliance (NON) - NDS, SNDS, ANDS, SANDS, or an Application for a DIN (DINA, DINB, DIND)** This section is not applicable for CTAs and CTA-As. If the scientific review of a submission/application has been completed and is found to be incomplete or non-compliant with the requirements outlined in the *Food and Drugs Act* and its Regulations, a NON will be sent to the sponsor.[^Footnote19^](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#fn19) The NON will specify the issues from all of the scientific review streams that render the submission as non-compliant. At the time of the NON issuance, the scientific review is completed and the submission/application status will change to \"Inactive 45\" or \"Inactive 90\" in the DSTS (depending on the submission/application type). Only one NON per submission/application will be sent. To clarify points of the NON or the rationale for its issuance, sponsors should contact the RPM/SRAO. For NDSs, SNDSs, ANDSs and SANDSs, the sponsor must submit the solicited Response to a Notice of Non-Compliance within 90 calendar days (or such time as the Centre/Bureau/Office and sponsor may agree upon) from the date the NON was sent. For Applications for a DIN, the sponsor is required to submit the solicited information within 45 calendar days (or such time as the Centre/Bureau/Office and sponsor may agree upon) from the time the NON was sent. **13.6.1 Response to a Notice of Non-Compliance (NON)** A Response to a NON is to be submitted in the same format as the original submission/application. The Response to a NON is to include a copy of the NON and should be submitted in a question and answer format which references the applicable section(s) in the original submission/application. Should a sponsor decide it is not necessary to file the solicited information; a sound scientific rationale for this position must be presented in order for the response to be considered complete. The sponsor should send all the requested information along with up-to-date documents including an updated cover letter in a single package to OSIP for processing. All information received by OSIP will be processed and sent to the appropriate review Centre/Bureau/ Office within 10 calendar days. When OSIP begins to process the Response to NON, the status of the submission would be changed to \"Process\". Should OSIP determine that the Response to NOD is administratively incomplete; the submission status will be changed to \"Process Hold\". Once OSIP verifies that the Response to a NON is administratively complete, the appropriate Centre/Bureau/Office is notified that the response has been processed. When the Response to the NON is received, the Screening 2 period begins (refer to [Section 11.1.1](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a41) - Screening of Solicited and Acceptable Unsolicited Information Submitted during the Scientific Review). Acknowledgement letters are not sent upon receipt of responses to NONs. **13.6.2 Acceptance of a response to a Notice of Non-Compliance (NON)** When the response to a NON is screened and found to be acceptable for review, a SAL will be sent to the sponsor (refer to [Section 10.1.2](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a31) - SAL). A Review 2 period begins immediately after the issuance of the SAL. The RPM/SRAO will serve as the initial point of contact for communication with the sponsor. **13.6.3 Notice of Non-Compliance Withdrawal letter (NON-W)** A NON-W is sent to the sponsor if: - during the screening process, the Response to a NON is found to contain unsolicited information that is incomplete or deficient - the sponsor fails to submit the solicited information (i.e. the \"Response to a NON\") within the assigned time period. Health Canada will interpret this as a request to withdraw the submission/application, or - during the scientific review of the Response to a NON, it is determined that the submission remains non-compliant Submissions/applications may be withdrawn without prejudice to a refiling (refer to [Section 15.6](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a78) and [Section 15.7](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a79) for information on refiling). A sponsor may file a Request for Reconsideration following the issuance of a NON-W (refer to [Section 16](https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/management-drug-submissions/industry/document.html#a80) - Reconsideration of Decisions Issued for Human Submissions and Applications).