Reviewing DEL applications : Applications and service standards for drug establishment licences (GUI-0127)

On this page

• DEL application review process
• Intake
• DEL screening
• GMP compliance review: Domestic inspections
• GMP compliance review: Full GMP evidence paper assessments
• GMP compliance review: CoC request and review
• Licensing decision

DEL application review process

The following table (Table 3) shows the review steps, timelines and documents received for each drug establishment licence (DEL) application stream. For information on streams, refer to the section on How we manage DEL applications.

Table 3: DEL application reviews

Stream	Review step	Timeline (calendar days)	Document issued by Health Canada
n/a	Application receipt	n/a	System-generated email auto-response
1	Intake	20	Application completion notice or revised DEL Annex as applicable
	Total review time	20	n/a
2	Intake	20	Acknowledgement of application acceptance
	DEL screening	45-55	DEL screening completion notice and stream assignment
	Licensing decision	45	Application completion notice, DEL or DEL Annex
	Total review time	120	n/a
3A – Abbreviated assessment	Intake	20	Acknowledgement of application acceptance
	DEL screening	45	DEL screening completion notice
	GMP screening	30	GMP screening acceptance notice and stream assignment
	Abbreviated assessment, including NERBY extension requests not requiring in-depth review	45	GMP compliance notification or GMP compliance notification of NERBY extension granted
	Licensing decision	45	Application completion notice, DEL or DEL Annex
	Total review time	185	n/a
3B – CoC retrieved from available database	Intake	20	Acknowledgement of application acceptance
	DEL screening	45	DEL screening completion notice
	Notification of CoC availability	30	Notification of CoC availability and stream assignment
	CoC request and review	40	n/a
	Licensing decision	45	Application completion notice, DEL or DEL Annex
	Total review time	185	n/a
4A – Full assessment	Intake	20	Acknowledgement of application acceptance
	DEL screening	45	DEL screening completion notice
	GMP screening	50	GMP screening acceptance notice and stream assignment
	Full assessment, including NERBY extension requests requiring in-depth review	90	GMP compliance notification or GMP compliance notification of NERBY extension granted
	Licensing decision	45	Application completion notice, DEL or DEL Annex
	Total review time	250	n/a
4B – CoC requested from MRA partner	Intake	20	Acknowledgement of application acceptance
	DEL screening	45	DEL screening completion notice
	Notification of CoC availability	30	Notification of CoC request to MRA partner and stream assignment
	CoC request and review	110	n/a
	Licensing decision	45	Application completion notice, DEL or DEL Annex
	Total review time	250	n/a
4C – Domestic inspection	Intake	20	Acknowledgement of application acceptance
	DEL screening	45	DEL screening completion notice and stream assignment
	Domestic inspection	140	Issuance of inspection rating
	Licensing decision	45	Application completion notice, DEL or DEL annex
	Total review time	250	n/a
n/a: not applicable

Intake

At the intake step, Health Canada reviews all DEL applications to verify they are administratively complete. We encourage you to use the following criteria to ensure your application is complete.

1) For DEL application form (FRM-0033)

• most current version of FRM-0033 is used
• document is not corrupt
• if locked, a password is provided
• form is complete and signed
• all indicated documents and emails are included
• for foreign building and address changes, additional information is provided, if applicable
• if Table A was submitted, Active Pharmaceutical Ingredient (API) foreign building attestation of FRM-0033 is complete

For more information on what is required for foreign building name and address changes, consult:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

2) For Table A

• correct version of Table A is used
• Table A is for 1 Canadian drug establishment building
• all mandatory fields of Table A are complete
• no non-compliant foreign buildings are listed
• if Table A indicates the APIs will be imported in the form of a Finished Dosage Form (FDF), the foreign building that manufactures the FDF is already listed on the DEL or its addition has been requested as part of the application (section 5.0 of FRM-0033)

Note: Good manufacturing practices (GMP) evidence does not need to be submitted for foreign buildings included on Table A. However, you must ensure that GMP evidence is available for API foreign buildings to demonstrate they are in compliance with Division 2 of the Food and Drug Regulations (regulations).

For more information, consult:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

For more information on how to complete Table A, follow the Table A instructions. To ask for a copy of the most recent version of Table A and instructions, email us at del.questions-leppp@hc-sc.gc.ca.

Once intake is completed, you will receive an “acknowledgement of application acceptance notice” within 20 days following application receipt.

DEL screening

At the DEL screening step, Health Canada reviews the application and cover letter to make sure they are complete and that the scope of the application is identified. We use the following criteria, among others:

• FRM-0033 is complete and includes all required sections

For an application to amend a DEL where the amendment is specific to a foreign building, we verify that the:

• change is consistent with the authorized drug category, dosage form or sterility status under the activity of import or
• application includes a request to amend the activity of import
  • for example, if a foreign building is added that fabricates sterile pharmaceuticals:
    • the domestic building must be licensed to import sterile pharmaceuticals or
    • the application must include a request to add the activity of import for sterile pharmaceuticals to the domestic building for the dosage forms to be imported

If Health Canada identifies a deficiency, we will issue a “deficiency notice” outlining the deficiency that must be addressed. The application clock will be paused.

The applicant is responsible for providing a complete, clear and accurate application. If the applicant asks to change the scope of an application after the DEL screening step is completed, we may refuse to accept changes to the scope. Refer to the section on Rejecting applications for more information.

For applications to amend the domestic building information:

• During the DEL screening step, we will decide if a domestic inspection is needed in order to issue the DEL.
  • If an inspection is not required, the application is considered a Stream 2 application and proceeds directly to a licensing decision.
  • If an inspection is required, the application is considered a Stream 4 application and you will be informed in the “DEL screening completion notice”. For more information on domestic inspections, refer to the section on GMP compliance review: Domestic inspection. 
• Health Canada will issue a “DEL screening completion notice” within 75 days following application receipt.

For new DEL applications, including reinstatements, reactivations and reapplications:

• An inspection is required before we issue the DEL. The application is considered a Stream 4 application and you will be informed in the “DEL screening completion notice”. For more information on domestic inspections, refer to the section on GMP compliance review: Domestic inspection. 
• Health Canada will issue a “DEL screening completion notice” within 65 days following application receipt.  

For applications that include a foreign building for which the supporting GMP evidence is a certificate of compliance (CoC) and Health Canada has already reviewed the CoC:

• If the requested activities, categories and dosage forms are covered by the CoC, the application is considered a Stream 2 application and proceeds directly to licensing decision without undergoing further GMP compliance review.
• Health Canada will issue a “DEL screening completion notice” within 65 days following application receipt. 

To find out if Health Canada has received and reviewed the CoC, visit the Drug and Health Products Inspections Database (DHPID):

• search the foreign building name and address
• confirm if the inspection start date matches the date on the CoC

Note: If Health Canada needs to confirm with a regulatory partner with whom there is a mutual recognition agreement (MRA) whether the requested activities, categories and dosage forms are in scope of the CoC already on file, the application’s service standard will be affected as described in the section on service standards.

The following remaining applications will undergo GMP compliance review:

• applications related to foreign buildings for which full GMP evidence is used as supporting evidence, including requests for the extension of a NERBY date (full GMP evidence paper assessment)
• applications related to foreign buildings for which a CoC, including applicable EJ CoCs, is available as supporting evidence and Health Canada does not have the CoC on file (CoC request and review)

Health Canada will issue a “DEL screening completion notice” within 65 days following application receipt. 

GMP compliance review: Domestic inspection

A GMP inspection may be required after DEL screening of an application for a new domestic building, reinstatement of a DEL, reapplication of a DEL or an amendment to a domestic building. If so, the application will be in Stream 4. To prepare for a GMP inspection, refer to the drug GMP documents listed on the references page.

If you have submitted a reinstatement application, during this step, Health Canada will also:

• review the information submitted, as per C.01A.018 of the Food and Drug Regulations (regulations)
• confirm the company has adequately addressed our concerns before scheduling the inspection

You must be ready and available for a GMP inspection at the time of application. Health Canada has the authority to inspect any building in Canada subject to an application where the applicant proposes to conduct a licensable activity, store drugs or maintain records.

A request by a company to delay the proposed date of inspection is subject to approval by Health Canada inspectors. If approved, we will pause the application. Refer to the sections on calculating the clock and pause-the-clock triggers. If your request to delay the inspection is not approved by Health Canada, we will conduct an inspection.

If you are not ready for an inspection when an inspector contacts you, the inspector may recommend that you withdraw your application by emailing us at del.questions-leppp@hc-sc.gc.ca. The request must come from an authorized contact on file for the DEL or include an authorized contact on the request.

If you do not withdraw the application, we will conduct an inspection. Lack of readiness may result in a non-compliant (NC) rating. Inspection ratings are posted on the following database:

• Drug and Health Products Inspections Database (DHPID)

Once the inspection is completed, Health Canada will issue the “exit notice” within 205 days following application receipt.

Then, the following information will be posted on the DHPID:

• inspection rating
• summary of observations made during the inspection
• inspection outcome and measures taken by Health Canada

Following these steps, the application moves to the licensing decision step.

GMP compliance review: Full GMP evidence paper assessments

GMP screening

During the GMP screening step, Health Canada verifies the evidence submitted against the requirements, which are outlined in the following guidance document:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

We also make sure the name and address of the foreign building on the FRM-0033 and on the site master file (SMF) match. If they don’t match and you would like to provide an explanation, we encourage you to include additional details in the cover letter. If we identify any deficiency during the GMP screening process, we will indicate this in a “deficiency notice”.

Note: Before you submit a DEL application, make sure the GMP evidence demonstrates that the foreign building is compliant to conduct the requested activities, categories and dosage forms. Otherwise, you will receive a “deficiency notice”.

If we don’t identify a deficiency or the identified deficiencies are resolved, we will:

• accept GMP evidence for assessment
• send a “GMP screening acceptance notice” for the foreign building within 95 days following application receipt

We will then process the application through 1 of 3 pathways (whichever applies):

1. full assessment
2. abbreviated assessment
3. NERBY extension request

Full assessment

We will conduct a complete assessment to verify that the GMP evidence demonstrates the foreign building’s compliance with Divisions 2 to 4 of the regulations if:

• we have not yet reviewed the inspection report or
• the application was submitted to request the review of new evidence following a non-compliant rating for an FDF or API foreign building

In this case, the application will be in Stream 4.

Learn more:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

You can visit the DHPID to find out if your inspection report has been reviewed by:

• searching the foreign building name and address
• verifying if the inspection start date matches the date in your GMP evidence package

If required, Health Canada will issue a “deficiency notice” to request additional evidence during the assessment. This evidence must be submitted within the time period that we specify.

After we have completed our review, we will issue a “GMP compliance notification” within 205 days following application receipt.

Applications for foreign buildings listed on the Foreign Building Annex move to the licensing decision step once all foreign buildings have been deemed compliant.

Applications requesting the review of new evidence of API foreign buildings following a previous NC rating will be deemed completed once we issue a “GMP compliance notification”. To add the site to your DEL, you must submit a subsequent amendment to the API Foreign Building Annex after receiving the “GMP compliance notification”.

For more information on whether the foreign building is listed on the Foreign Building Annex or API Foreign Building Annex, consult:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

Abbreviated assessment

If we have already reviewed an inspection report that supports the application, including all of the requested activities, categories and dosage forms for the building, the application will undergo a shorter review process. In this case, the application will be in Stream 3.

If required, we may issue a “deficiency notice” to request additional evidence during the assessment. This evidence must be provided within the time period that we specify.

You can visit the DHPID to find out if your inspection report has been reviewed by:

• searching the foreign building name and address
• verifying if the inspection start date matches the date in your GMP evidence package

After we have completed our review, we will issue a “GMP compliance notification” within 140 days following application receipt. The application then moves to the licensing decision step.

New Evidence Required By (NERBY) extension request

Health Canada will review the information and, if required, may issue a “deficiency notice” to request additional evidence during the assessment. This evidence must be provided within the time period that we specify.

Our assessment will result in 1 of 2 outcomes:

1. Extension granted
   • the information provided supports an extension of the NERBY date
   • the applicant is informed of this outcome by email via a “GMP compliance notification of extension granted”
     • you may continue to import from the foreign building for the period of the extension
     • you should submit an application to Health Canada as soon as a new inspection report becomes available, regardless of the revised NERBY date
   • the application moves to the licensing decision step
2. Extension not granted
   • the information provided does not support an extension of the NERBY date
   • the applicant is informed of this outcome and the reasons for not granting an extension by email
   • the application may be rejected and further communication will be sent regarding importation authority from that foreign building

Sometimes a more in-depth review of the application may be required to evaluate changes that occurred at the foreign building since the last inspection:

• If this is the case for your application, your application will be in Stream 4 and Health Canada will inform you of the outcome within 205 days following application receipt.
• If not, your application will be in Stream 3 and we will inform you of the outcome within 140 days following application receipt.

In either case, the stream assigned will be confirmed in the “GMP screening acceptance notice” within 95 days following application receipt.

For more information on NERBY extensions, consult:

• How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080)

GMP compliance review: CoC request and review

This review is for applications supported by CoCs issued by an MRA partner for a building located within their jurisdiction or outside of their jurisdiction (extra-jurisdictional CoCs) where Health Canada needs to retrieve or request the CoC.

If Health Canada already has a CoC on file and does not need to retrieve a new one, the application will be in Stream 2. For more information, refer to the section on DEL screening.

Health Canada receives the CoC from either:

• an available database, such as:
  • EudraGMDP database
  • MHRA-GMDP database
  • Register of veterinary-only GMP sites or
• the MRA partner directly

If the CoC is in an available database, the application will be in Stream 3. If Health Canada needs to request it from an MRA partner, the application will be in Stream 4.

You will be informed within 95 days following application receipt whether the CoC was retrieved or a request has been sent to the MRA partner.

A Health Canada request and review of a CoC results in 3 possible outcomes:

1. MRA partner provides the CoC and indicates that the product category, dosage forms and activities requested are covered 
   • the application proceeds to the licensing decision step
   • the foreign building is added to the Foreign Building Annex of the DEL or an amendment to the Foreign Building Annex is made for all requested activities and categories of drugs (and sterility) that are covered by the CoC
     • for EJ CoCs, these buildings will be assigned a NERBY date
2. MRA partner provides the CoC but indicates that the product category, dosage form or activity is not covered 
   • the application is deficient and a “deficiency notice” is issued
   • an opportunity is given to the applicant to either provide a CoC, explain how the existing CoC covers the requested activities, categories and dosage forms or withdraw their application
     • submitting alternate GMP evidence would be considered a change in scope and would lead to full or partial rejection of the application
   • if you have not corrected the deficiency after 2 chances to provide the information, the application will be fully or partially rejected
     • a new application must be submitted with alternate supporting GMP evidence
3. MRA partner indicates that there is no valid CoC
   • the application is deficient and a “deficiency notice” is issued
   • an opportunity is given to the applicant to provide a CoC or withdraw their application as it is not acceptable to submit alternate GMP evidence
     • submitting alternate GMP evidence would be considered a change in scope and would lead to full or partial rejection of the application
   • if you have not corrected the deficiency after 2 chances to provide the information, the application will be fully or partially rejected
   • a new application must be submitted with alternate supporting GMP evidence

For more information on deficiency notices, refer to the section on calculating the clock.

Licensing decision

Applications must meet the requirements outlined in the regulations and Guidance on drug establishment licences (GUI-0002).

Health Canada:

• reviews the application and ensures that discrepancies and deficiencies are addressed
• reviews the GMP inspection report rating, scope and recommendations
• makes sure the application, assessment recommendation and regulations align
• identifies if terms and conditions are recommended

Health Canada will inform you of a final licensing decision by email. The email may include the DEL or DEL Annex as a portable document format (PDF) attachment.

For more information, refer to the section on communicating with applicants.