Notice - Submission Filing Requirements - Good Manufacturing Practices (GMP)/Establishment Licences (EL)

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January 22, 2010

Notice

Our file number: 09-112079-974

Submission Filing Requirements - Good Manufacturing Practices (GMP)/Establishment Licences (EL)

The Therapeutic Products Directorate (TPD) of the Health Products and Food Branch (HPFB) of Health Canada announces the requirements for evidence of Good Manufacturing Practices (GMP) for Drug Submissions. This is to support TPD's on going effort to improve the efficiency of the drug submission review process and thus increase the percentage of submissions reviewed within the targeted timeframe. This will also allow the Inspectorate to manage its resources efficiently to ensure there is no delay in issuing Establishment Licences (EL).

Pursuant to Sections C.08.002(2)(e) and C.08.002.1(2)(a) of the Food and Drug Regulations a new drug submission shall contain "details of the method of manufacture and the controls to be used in the manufacture, preparation and packaging of the new drug". These "controls" include those which ensure GMP and which are required in order to be in compliance with Divisions 1A (Establishment Licences) and 2 (Good Manufacturing Practices, C.02.003, C.02.009, C.02.016, C.02.018, and C.02.028) of the Regulations.

Drug submissions that have been accepted for review by TPD and for which compliance with Divisions 1A and 2 has yet to be confirmed by the Inspectorate typically result in extended review periods. As GMP is an important measure of an establishment's commitment to quality, a valid Canadian GMP compliance rating is required by TPD at the time of submitting for pre-market approval.

For drug submission purposes, "evidence of GMP compliance" would include a:

• Valid Health Canada EL, or
• Current GMP compliance rating issued by the HPFB Inspectorate.

This requirement will be applicable to all New Drug Submissions (NDS), Abbreviated New Drug Submissions (ANDS), Supplemental New Drug Submissions (SNDS), Supplemental Abbreviated New Drug Submissions (SANDS), Notifiable Changes (NC) submitted for review by TPD. Manufacturers would need to have a satisfactory rating for their site for the particular dosage form (for example sterile product).

Sponsors should submit the applicable GMP documentation to the Inspectorate in advance of any regulatory filing to ensure that the Canadian GMP compliance rating is included in the drug submission. Refer to GUI-0080 "Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites" for additional information. In the absence of satisfactory evidence of GMP compliance submissions will not be accepted into review.

The table below provides a summary of facilities that would require evidence of GMP compliance in order to be accepted for review.

Contact Information:

Therapeutic Products Directorate
Director, Bureau of Pharmaceutical Sciences
Health Canada
Finance Building, 101 Tunney's Pasture Dr.
Ottawa, Ontario
K1A 0K9
Email: BPS_enquiries@hc-sc.gc.ca

Inspectorate
Manager, Drug Good Manufacturing Practices Unit
Health Products and Food Branch Inspectorate
Health Canada
250 Lanark Avenue, Address Locator 2007B
Ottawa, Ontario
K1A 0K9
E-mail: Foreign_Site_Etranger@hc-sc.gc.ca

Summary of Good Manufacturing Practices (GMP) Requirements for Drug Submission Purposes

Activity	Evidence of Good Manufacturing Practices (GMP)
	Included in the drug submission (yes/no)?
Drug Substance
Research and Development Testing	no
Manufacture (fabrication)	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
Drug Product
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
Lyophilization	yes
Packaging	yes
Labelling	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