February 10, 2017
Our file number: 17-101644-531
The Therapeutic Products Directorate (TPD) of the Health Products and Food Branch (HPFB) of Health Canada is revising the process related to the requirements for evidence of Good Manufacturing Practices (GMP) for drug submissions. The goal of this revision is to better align the drug submission screening and review process with the Drug Establishment Licence (DEL) process. This should allow sponsors to make timely drug submissions while still providing adequate assurance of an establishment’s commitment to quality.
Pursuant to Sections C.08.002(2)(e ), C.08.002.01(2)(b), C.08.002.1(2)(a) and C.08.003(2)(e) of the Food and Drug Regulations a new drug submission (NDS), an extraordinary use new drug submission (EUNDS), an abbreviated new drug submission (ANDS), an abbreviated extraordinary use new drug submission (AEUNDS), or a supplement to any of these submissions, shall contain “details of the method of manufacture and the controls to be used in the manufacture, preparation and packaging of the new drug ”. The “controls ” include those which ensure GMP, and which are required in order to be in compliance with Division 1A (Establishment Licences) and Division 2 to 4 (Good Manufacturing Practices ) of the Regulations.
In order to ensure that submission review resources are dedicated to the assessment of drug submissions for products that can be sold in Canada, and as evidence of an establishment’s commitment to quality, TPD has historically required that buildings performing licensable activities to be GMP compliant. As of the date of this Notice, and as detailed below, TPD will also accept submissions where a complete application to amend the DEL pursuant to C.01A.006 of the FDR for new buildings and activities not currently listed on the drug submission sponsor’s DEL has been filed with the Minister at least 90 days prior to the time of filing a drug submission.
This requirement will be applicable to all NDS, EUNDS, ANDS, AEUNDS, Supplements, and DIN applications, thereto, submitted to the TPD for review. Eligible submissions are those where (1) all required buildings and activities are listed on the current DEL, (2) a site has a GMP compliance rating in Canada for the required activities and dosage form(s), and/or (3) a complete DEL application has been filed with the Minister for any new buildings and activities. Where a DEL application was needed, the sponsor may file the drug submission 90 days after the Acknowledgment of Application Acceptance for the DEL application is issued by the Minister. Drug submissions which do not meet the requirements listed above will be issued a screening rejection letter.
In addition, where any site listed in a drug submission is considered by Health Canada to be non-compliant for GMP, a screening rejection letter will be issued.
The table below provides a summary of activities that require documentation of a valid DEL and/or DEL application.
This revised process will come into effect for drug submissions filed after the date of this notice.
Health Products and Food Branch
Therapeutic Products Directorate
Bureau of Pharmaceutical Sciences
Regulatory Operations and Regions Branch
Health Product Compliance Directorate
Health Product Inspection and Licensing Bureau
|Activity||Evidence of Good Manufacturing Practices (GMP)|
|Included in the drug submission (yes/no)?|
|Research and Development Testing||no|
|Milling or Micronization||no|
|Sterilization* (including the sterilization of packaging components)||yes|
|Lyophilization for non-sterile drug substances||no|
|Lyophilization for sterile drug substances*||yes|
|Testing (drug substance release) for the drug product manufacturer||yes|
|Research and Development Testing||no|
|Manufacture (fabrication) - drug product intermediate||yes|
|Manufacture (fabrication) - final drug product||yes|
|Sterilization (including the sterilization of packaging components)||yes|
|Testing (drug substance release, drug product release, and drug product ongoing stability)||yes|
|Storage and Distribution (Canadian sites only)||on a case by case basis|
Sterilization of a drug substance is considered to be a component of the drug product manufacturing where the final sterile drug product is not subject to filtration or terminal sterilization.