How does Health Canada conduct regulatory compliance and enforcement? What different offices carry out its compliance and enforcement function?

Health Canada’s Regulatory Operations and Enforcement Branch (ROEB) is responsible for oversight and inspections to ensure compliance with acts and regulations. It conducts inspections, compliance verifications, product sampling, enforcement measures, and investigations.

The Regulatory Operations and Enforcement Branch’s mission is to be:

A compliance and enforcement leader that informs and protects Canadians from health risks associated with products, substances, and their environment.

Organizational Structure of the Regulatory Operations and Enforcement Branch (ROEB)

Health Canada’s Regulatory Operations and Enforcement Branch (ROEB) employs more than 1,000 people. What are the different agencies, offices, or divisions within ROEB? What are its different units?

This diagram from Health Canada’s Acting Associate Director of Health Product Inspection and Licensing Division, Teresa Forlini shows how Health Canada is organized, and how its subunits are structured. She shared the diagram in a presentation at the 48th annual International GMP Conference in March 2024 at the University of Georgia in Athens.

Figure 1 | The organizational chart of the Health Canada Regulatory Operations and Enforcement Branch (ROEB).

What Health Canada agency within ROEB handles drug companies? Regulation compliance and enforcement of drug manufacturing is conducted by the Health Product Compliance Directorate (HPCD).

HPCD: Regulatory Compliance and Enforcement of Drug Manufacturing

The largest of ROEB’s component directories, the Health Product Compliance Directorate (HPCD) has more than 300 employees. View the HPCD’s organizational structure and its major programs, units, and activities in the chart below.

Figure 2 | The organizational chart of the Health Canada Health Product Compliance Directorate (HPCD), within the Regulatory Operations and Enforcement Branch (ROEB).

How are Compliance and Enforcement Responsibilities Distributed in the HPCD?

Within the HPCD, the Health Product Inspection and Licensing Division (HPIL) is broadly responsible for monitoring drug makers, including issuing drug establishment licenses (DELs), conducting Good Manufacturing Process (GMP) inspections, and handling Mutual Recognition Agreements (MRAs).

The Drug Shortages Division, which becomes its own directorate in April 2024, is responsible for alleviating and responding to drug shortages, including supply chain integrity.

The Health Product Compliance and Risk Management Division (HPCRM) is mostly concerned with investigations, compliance verification, and enforcement measures with respect to human and vet drugs.

The HPCRM is also responsible for raising the alarm when a health product may pose a public health risk, using product recalls, stopping sales, and issuing public communication. The HPCRM’s list of duties also includes the Good Pharmacovigilance Inspection Program, as well as ensuring that health products stopped by Canada Border Services as they enter the country are compliant with regulations.

How the Health Product Inspection and Licensing Division (HPIL) Manages Inspection Capabilities

There are between 50 and 60 inspectors conducting Good Manufacturing Process (GMP) inspections in Canada, split among each of the country’s three major regions — East, Central, and West.

The HPIL conducts on-site inspections based on a cyclical inspection model, with approximately four years between inspections, and the division can increase inspections of particular sites based on its estimation of risk.

“We try not to touch any of the firms that are related to fabrication testing or packaging and labeling,” just because that could have a negative impact on our MRAs, HPIL Acting Associate Director Teresa Forlini explained in her International GMP Conference presentation.

HPIL divides its GMP oversight activities into four “pillars”:

Domestic on-site inspections — assess GMP compliance with Part C, Division 2–4 of Canada’s Food and Drug Regulations.
Foreign on-site inspections — a risk-based model guides site selection for assessment. “For cause” inspections determine the acceptability of products imported from specific foreign buildings.
Foreign paper assessments — determine GMP compliance of foreign buildings by assessing inspection reports from foreign regulatory authorities that are partners in the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S). Accept Certificates of Compliance from Mutual Recognition Agreement (MRA) partners as evidence of GMP compliance.
Risk files — assess information related to potential non-compliance identified by inspections by foreign PIC/S-partner regulatory authorities; conduct appropriate compliance and enforcement actions to mitigate risks.

Health Canada Domestic and Foreign On-Site Inspections

Domestic manufacturers operate a total of about 950 buildings with Drug Establishment Licenses (DELs) in Canada, with the following approximate breakdown by manufactured product:

45% Human pharmaceuticals
16% Prescription Drug List, Schedule G, Narcotics, or Drug Containing Cannabis
14% Biological
13% Active Pharmaceutical Ingredient (API) (Includes importers of APIs)
8% Vaccine
3% Radiopharmaceutical
1% List A Active Pharmaceutical Ingredients (APIs) for Veterinary Use

Health Canada generally reports a higher compliance rate for Canadian — as compared to foreign — on-site inspections. For example, in fiscal year 2022–2023 (which began Apr. 1, 2022), the health regulator found 4.7% of domestic sites non-compliant, compared to about 6% of foreign sites HPIL had inspected.

What Trends do HPIL Inspector Observations Reveal?

Most observations during domestic on-site inspections are related to the quality control department, which follows a pattern similar to FDA investigator observations in the United States.

For on-site inspections of foreign manufacturers, observations are split roughly 50-50 between observations related to the quality control department and observations related to the premises themselves. In her presentation on drug manufacturing regulatory compliance and enforcement, HPIL Acting Associate Director Teresa Forlini suggested that on-site inspectors in foreign countries concentrate their attention on these two main areas, but other reasons may explain the 50-50 split.

Figure 3 | Health Canada inspectors’ observations can be categorized into these main areas for domestic (Canadian) and foreign sites.

What are “Paper Inspections”?

In Canada, in order to import a drug product, the importer’s license must list every building playing a part in the whole supply chain. A GMP inspector must review the paperwork concerning foreign buildings before they can be listed on a license, so importing firms submit GMP evidence for inspectors to compare with information from guidelines.

Based on inspections by PIC/S-partner, trusted foreign regulatory agencies, Health Canada inspectors develop risk estimates covering previous observations. Based on internal guidelines, inspectors then use this information to decide whether each foreign building qualifies as compliant and can therefore be listed on the license by the importing drug firm.

In general, if an importing drug firm does not have a Health Canada Exit Notice for a foreign building, it must submit GMP evidence that includes:

Certificates of Compliance issued by the local authority
A qualified Inspection Report
Evidence of any corrective action
The site Master File or Quality Manual

Health Canada assigns a New Evidence Required BY (NERBY) date when the foreign site is located in a country whose regulator does not have a Mutual Recognition Agreement (MRA) with Health Canada — or the site’s product or activities are not covered by an MRA in an otherwise MRA country.

NERBY dates are risk-based, but usually fall on a date four years from a qualified inspection.

The following figure illustrates the process that guides Health Canada’s paper assessment process, according to Appendix D of GUI-0080 (pdf), “How to demonstrate foreign building compliance with drug good manufacturing practices.”

Figure 4 | An overview of Health Canada’s process for paper assessments. Note: “FB” is an abbreviation of “foreign building.”

Foreign Risk Files

According to Health Canada’s Forlini, of the 4,000 foreign buildings involved in the drug supply—including fabrication, packaging, labeling, and testing—that Health Canada licenses, 23% are located in non-MRA, non-PIC/S-partner countries. These are the agency’s highest-risk concern among foreign buildings.

To watch for risk triggers in foreign buildings, a small team of Health Canada employees pays attention to information from other regulatory agencies, such as FDA warning letters and 483s, Canadian firms’ compliance submissions, importers and foreign buildings themselves, as well as from international coordination and planning committees, newspapers, and other sources.

How Health Canada Handles Risk Triggers

Health Canada opens a risk file in response to a risk trigger, and when it verifies an impact on the Canadian drug market, it requests GMP information from importers. This includes:

Identification of the affected products and quantity
Medical necessity of the products
Information about the foreign building’s corrective actions
The importer’s risk assessment

When a product meets the standard of medical necessity, Health Canada inspector determines the risk trigger’s risk rating and whether a Health Canada compliance or enforcement action is warranted, based on observations from previous inspections and guidelines in GUI-0023, “Risk classification guide for drug good manufacturing practices observations.”

“Commonly encountered GMP issues with respect to risk files are ‘integrity’ and ‘cleaning validation,’” says Forlini. This is followed by “‘process validation,’ then ‘lack of quality oversight,’ ‘lack of scientific rationale,’ and’ deviations and investigations are not thoroughly investigated,’” she says. “I think those are common trends everywhere.

Health Canada then uses POL-0001, “Compliance and enforcement policy for health products,” to determine the appropriate C&E action.

Health Canada can take compliance and enforcement actions when:

A firm is importing from a foreign building not in the firm’s DEL
A foreign on-site inspection results in a non-compliant finding
A risk is detected with a foreign building
A paper assessment results in a non-compliance rating
There is no current GMP evidence for a foreign building on an importer’s DEL

What Enforcement Actions Can Health Canada Take?

“We can suspend the DEL,” says Forlini. “We can also add terms and conditions — we don’t necessarily want to suspend the entire DEL because that does have an impact on the supply chain.” The agency might instead assign terms and conditions that an importer cannot import from a certain building, she says.

Of course, Health Canada can impose a regulatory stop sale, conduct a product recall, or issue a public warning.

The following figure shows how many inspections and other activities Health Canada undertook from Apr. 1, 2022, to Dec. 31, 2023.

Figure 5 | Number of Health Canada inspections and other activities carried out in fiscal year 2022-2023 and a portion of fiscal year 2023-2024.

Health Canada’s Mutual Recognition Agreements

Health Canada is increasingly recognizing MRA-partner regulatory agencies’ GMP outcomes for buildings within that agency’s home country, as well as for buildings within third-party countries.

The following figure shows when Health Canada and the regulatory authority of other countries initiated a Mutual Recognition Agreement (MRA).

Figure 6 | Date of initiation of Mutual Recognition Agreements between Health Canada and other countries’ drug regulatory authorities.

Health Canada is currently working on an enhanced confidentiality agreement with the U.S. FDA, and with Switzerland’s SwissMedic. Health Canada is holding discussions to expand the operational scope of the existing MRA.

Also, Health Canada recently expanded the acceptance of certificates of compliance for extra-jurisdictional inspections conducted by Australia’s Therapeutic Goods Administration (TGA).

See this Redica Systems article to read about the expansion of Mutual Recognition Agreements between the European Union and the United States.

Health Canada’s Regulation of Foreign and Domestic Drug Firms

Several offices within Health Canada are responsible for regulating drug firms, with HPIL and HPCRM performing major compliance and enforcement roles within Health Canada’s Regulatory Operations and Enforcement Branch.

HPIL classifies its activities into four major pillars: domestic on-site inspections, foreign on-site inspections, foreign paper assessments, and risk files.

Health Canada inspectors develop risk estimates based on information from multiple sources, including inspections by PIC/S-partner, trusted foreign regulatory agencies. When a foreign building is determined to have a risk trigger, an inspector creates a risk file and determines whether compliance and enforcement action is warranted.

Health Canada and foreign drug regulatory agencies rely on each other’s assessments of foreign buildings through Mutual Recognition Agreements, which they are expanding and clarifying.