How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080): Recommended full GMP evidence

On this page

• Inspection report
• Corrective actions
• Site master file
• Letter of authorization

This section outlines the specific requirements of the recommended GMP evidence that you must submit to support an application that requires a full GMP evidence package. It also describes the GMP evidence you must maintain at your Canadian site for sites listed on your API FB annex.

The GMP evidence can have light redactions to hide confidential business information or trade secrets (for example, customer names, employee names or product information). Redactions of entire paragraphs in the evidence are not acceptable and will result in a deficiency.

The original GMP evidence documents should be available in either of Canada's official languages (English or French). If this is not possible, you should provide:

• a copy of the original information
• a translated copy in English or French and
• an attestation of the accuracy of the translation, signed by the certified translator

Electronic signatures are acceptable for all GMP evidence documents. For information on the appropriate controls for electronic signatures, consult:

• Good manufacturing practices guide for drug products (GUI-0001)

Inspection report

Health Canada will accept the final and most recent inspection report (for example, within the last 3 years or a validity period considered acceptable by us). The inspection report must be signed and issued by the following authorities or partners:

• Health Canada (exit notice)
• regulatory authority
• qualified authority
• qualified bodies such as:
  • World Health Organization (WHO)
    • for foreign buildings listed on API FB annex and FB annex
    • Note: Some authorities may use a template similar to WHO's template. We only accept an inspection report that is signed and issued by WHO. Refer to WHO's Public Inspection Report database to confirm eligibility.
  • European Directorate for the Quality of Medicines and Healthcare (EDQM)
    • for foreign buildings listed on API FB annex or on the FB annex that conduct API related activities (for example, release testing sites)
• corporate or consultant audit
• refer to Corporate or consultant audit reports

The inspection report should:

• be completed against GMP standards or a standard considered acceptable by Health Canada
• cover the foreign building's activities, categories and dosage forms that you are requesting in the DEL application

If the submitted evidence of GMP compliance of a foreign building is a Health Canada inspection report (exit notice), no other recommended evidence needs to be submitted.

We will accept, on a case-by-case basis, inspection reports issued by a regulatory or qualified authority, or a qualified body that conducted a product-specific inspection. For example, we will consider inspection reports that cover the same activities, product categories or dosage forms that you request in your application.

An onsite evaluation (OSE) conducted by Health Canada's Biologic and Radiopharmaceutical Drugs Directorate is not enough to demonstrate the GMP compliance of a foreign building. This type of evaluation does not cover all applicable sections of Part C, Division 2 of the Food and Drug Regulations (FDR).

Note: We may contact the issuing authority of the inspection report for more information if we identify any compliance concerns when reviewing the report. This may impact the timelines of your application.

For more information, consult:

• Applications and service standards for drug establishment licences (GUI-0127)

If you do not have an inspection report from 1 of these authorities and are importing a critical product, email us at foreign.site-etranger@hc-sc.gc.ca to evaluate options. (A real or imminent drug supply shortage of a medically necessary drug as determined by Health Canada is considered a critical product.)

Inspection reports based on remote inspections by a regulatory or qualified authority

Remote inspections have proven invaluable for protecting people's health under extenuating circumstances. However, some critical aspects of an onsite inspection may be missed when remote inspections are conducted.

Onsite components of inspections provide stronger oversight than solely remote inspections due to the challenges and limitations of remote inspections. For this reason, remote inspections from regulatory or qualified authorities or qualified bodies will be considered only for the following low-risk activities:

• packaging and labelling
  • for example, placing a drug in a container, other than its primary container, such as a carton or box, and placing an outer label on the drug's secondary container
• product types and activities that are eligible for a corporate or consultant audit

There may be cases where there is a critical and immediate need for updated GMP evidence and an onsite inspection is not feasible due to extenuating factors (such as travel restrictions, geo-political concerns, time constraints). In these cases, we may accept an inspection report based on a remote inspection by a regulatory or qualified authority, or qualified body.

You may submit the most recently available onsite inspection report to supplement the review of the remote inspection report if you:

• add a new foreign building to your DEL that has not been assessed by Health Canada previously or
• identify any changes in the foreign building's licensable activities since our last assessment

Hybrid inspections that contain an onsite component of the inspection will be considered for review for all product and activity types.

Submitting multiple inspection reports

If you are submitting multiple inspection reports to support different activities, categories and dosage forms, your cover letter should:

• indicate the reason for submitting multiple reports
• include a summary of which report covers which activity, category or dosage form
• explain the reason for not submitting the most recent inspection report

We will accept older GMP evidence (for example, evidence is within 3 years but is not the most recent) if it covers the activities, categories or dosage forms in the scope of the application and the newer evidence does not.

Corporate or consultant audit reports

If there are no inspection reports by a regulatory or qualified authority or qualified body, you may submit an onsite corporate or consultant audit report for the following specific activities and product types only:

• fabricate, package/label or test non-prescription/over-the-counter (OTC) drugs
• fabricate, package/label or test medical gases
• fabricate, package/label or test non-sterile ethical drugs
• sterilize packaging materials for drugs that will be aseptically filled without terminal sterilization

A self-audit report conducted by a member of the foreign building is not considered acceptable GMP evidence to support the building's compliance.

We recommend that you use the following template when performing the audit and preparing your application. It will help to reduce or eliminate the number of deficiency notices that we may issue:

• Good manufacturing practices: Audit report form (FRM-0211)

The following information must accompany the corporate or consultant audit report and be part of your application:

• a justification for submitting a consultant or corporate audit report, which clearly states the specific activity and product type that falls within the eligibility criteria for a consultant or corporate audit
  • include in your cover letter or audit report
• the resumé of the persons performing the audit, which should demonstrate that they are qualified to perform audits and have experience in and knowledge of one of the following as per section C.02.006 in Good manufacturing practices guide for drug products (GUI-0001):
  • Canadian GMPs
  • PIC/S GMP guidance documents
• observations noted during the audit that are risk-classified
  • consult Risk classification guide for drug good manufacturing practices observations (GUI-0023)
  • we will review the classification of observations
• audit report signed and dated by the auditor
• inspection report more than 3 years old from a regulatory authority or a qualified authority, if available
  • do not resubmit if the applicable inspection report was already submitted to support your previous application for the foreign building
  • provide the previous application number in your cover letter for us to access

Considerations for foreign building performing sterilization of packaging material

If there are no inspection reports by a regulatory or qualified authority or qualified body, you may submit:

• a corporate or consultant audit report completed against
  • ISO 13485:2016 – Medical devices
  • the ISO standard covering the applicable type of sterilization being performed by the foreign building
    • for example, ISO 11137-3:2017 Sterilization of health care products for foreign buildings performing gamma irradiation
• an ISO certificate, if available, as supplementary information

Along with the full audit report, you must also submit the additional information described in Corporate or consultant audit reports. The auditor's resumé should demonstrate their knowledge and experience in ISO standards and conducting ISO audits.

For foreign buildings responsible for sterilization of packaging material, indicate the activity as "fabricate" and the dosage form as "packaging material (S)" on Drug establishment licence application: Form and instructions (FRM-0033).

For more information on licensing the sterilization of packaging material, consult:

• Guidance on drug establishment licences (GUI-0002)

Considerations for foreign building campuses

When the foreign building is located within a campus, the cover letter should:

• confirm which buildings are conducting licensable activities and the type of activities being conducted at each building and their addresses
• confirm whether the inspection report covers each building conducting licensable activities
• indicate which buildings are covered by the site master file (SMF) and
• indicate whether each building operates under the same quality system

Where this information can be found in the GMP evidence, provide a reference to the page number in the cover letter.

Health Canada will review the campus as a whole if all the individual buildings operate under the same quality system. If this is the case, submit a FRM-0033 listing the address that represents the entire campus. The address should be the same as the address for the campus in the SMF.

Submit your application to us with separate FRM-0033s (or section 5 of FRM-0033) for each foreign building conducting licensable activities if:

• the building is a campus where the individual buildings operate under different quality systems or
• we have previously reviewed the campus by individual building conducting licensable activities

All FRM-0033s may be submitted in a single application. We will assess this information when we review the GMP evidence.

We reserve the right to review a campus as individual buildings, if necessary, regardless of the quality system (for example, if we identify potential GMP concerns for the individual buildings).

Corrective actions

Submit a copy of the corrective actions signed and dated by a person responsible for the foreign building. The corrective actions should correspond to the observations cited in the submitted inspection report, if applicable.

If the corrective actions are contained in the final inspection report issued by the inspecting regulatory authority, a separate corrective action document is not needed. Clearly indicate in your cover letter if this is the case, to facilitate GMP assessment.

For a corporate or consultant audit, you must provide documentation indicating the auditor has reviewed the company's corrective actions and found them acceptable.

Site master file

Submit a copy of the most recent, signed and dated SMF (also known as a site reference file (SRF)).

For information on how to include an SMF, consult:

• Explanatory notes for drug establishments on the preparation of a site master file (GUI-0005)

A quality manual may be submitted for foreign buildings that only test, provide secondary packaging and labelling services or sterilize packaging material.

Letter of authorization

In certain cases, the GMP evidence package required to support your application may have been submitted to Health Canada as part of an application by another importer for the foreign building or by an organization on behalf of the foreign building. We will accept a letter of authorization (LoA) from the party (another importer or the foreign building) that previously submitted these documents to reference the GMP evidence.

DEL holders must maintain a copy of this evidence at their domestic building, even if using an LoA. For more information, refer to Maintaining GMP evidence onsite.

Submitting an LoA allows us to leverage existing GMP compliance, cross-reference this previous review and conduct an abbreviated assessment. If the existing GMP evidence supports your application, including all the requested activities, categories and dosage forms for the foreign building, the application will undergo a shorter review process.

You may submit the LoA with your application (cover letter and FRM-0033) if the LoA is issued either by:

• the foreign building to an importer directly
  • only applies if the foreign building submitted the evidence directly to us
• an importer to another importer
  • only applies if the importer providing the LoA has submitted the evidence directly to us

The LoA should also reference an inspection report that covers the activities, categories and dosage forms that you are requesting on FRM-0033.

If these conditions are met, the LoA must:

• be written on the letterhead of the issuing company
• clearly state that authorization is being provided to Health Canada
• clearly state the name and address of the foreign building
• specify which GMP evidence documents are being referenced
  • for example, authority, date, outcome, rating
• be signed and dated, with complete signature block including email address
• demonstrate the GMP evidence has been previously submitted to us
  • for example, providing the application number or copy of the acknowledgment of application acceptance email or GMP screening acceptance notice email