Canadian Drug Establishment Licences: GMP Requirements for API foreign building

Author: Madhur Jadawala

Canada's Food and Drug Regulations (FDR) were amended to extend the requirements of Division 1A - Establishment Licensing and Division 2 - Good Manufacturing Practices (GMP) to active ingredients used in pharmaceutical drugs for human use only. The amended Regulations came into force on November 08, 2013. This API program was implemented for 3 years and it came into full effect on November 08, 2016. On July 31, 2016, Health Canada did publish a “Notice to Stakeholders - Updates to drug establishment licence applications and good manufacturing practice evidence requirements for active pharmaceutical ingredients” and it can be found here:

https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/notice-stakeholders-updates-drug-establishment-licence-applications-good-manufacturing-practice-evidence-requirements-active-pharmaceutical.html

WHO DOES THIS APPLY TO?

·         All the Canadian establishments (persons) conducting API related activities for APIs used in the manufacture of drugs listed on the Prescription Drug List, Scheduled under the Controlled Drugs and Substances Act (Schedules I, II, III, IV, or V inclusively), or defined as a “narcotic” under the Narcotic Control Regulations:

o   API importers

o   Finished dosage form (FDF) fabricators who import APIs for use in manufacturing

o   FDF importers

WHAT’S NEW

·         As per section C.02.003.3 of the Food and Drug Regulations (FDR), no person shall use an active ingredient in the fabrication of a drug unless it is fabricated, packaged/labelled, tested and stored in accordance with GMP requirements.

·         Effective November 08, 2016, importers are required to update their API Table-A with Health Canada and ensure to keep it comprehensive and consolidated with all the API foreign sites.

·         Importers, along with their most recent API Table-A must also submit section 5.1 attestation of FORM-0033 attesting to maintain API foreign sites Good Manufacturing Practices (GMP) compliance evidence based on inspections by Health Canada or by one of the following recognised regulatory authorities / organizations:

o   Regulatory partners with whom Health Canada has established equivalence under Mutual Recognition Agreements (MRA);

o   Regulatory partners whose inspection system has been assessed and found comparable under the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/s);

o   Organizations such as the European Directorate for the Quality of Medicines and Healthcare (EDQM) and the World Health Organization (WHO), which inspect against ICH Q7 guidelines.

·         Consultant or corporate audits, and other GMP evidence should not be used to demonstrate the API foreign site’s compliance with GMP for the drugs listed on the Prescription Drug List, Scheduled under the Controlled Drugs and Substances Act (Schedules I, II, III, IV, or V inclusively), or defined as a “narcotic” under the Narcotic Control Regulations.

·         The GMP evidence must be readily available with the importer and must be supplied to Health Canada when requested.

·         Health Canada will continue to seek clarification with respect to Table A, as applicable, and assess the GMP compliance evidence of foreign buildings during the inspection of an importer, during the off-site paper assessment, or during the foreign on-site inspection.

List of GMP evidence documents:

v  Foreign buildings inspected by the above-noted recognised regulatory authorities and organizations

1.       most recent, available, signed inspection report issued by Health Canada or by a recognised regulatory authority;

2.       copy of the GMP certificate issued by the recognised regulatory authority, stating the outcome of the inspection above (if available);

3.       corrective actions taken, signed by the foreign building’s responsible official (if applicable);

4.       copy of the Site Master File, or a similar document (such as a quality manual); and

5.       copy of the quality/written agreement between the foreign building’s responsible official and the Canadian establishment

v  Foreign buildings which have not been inspected by the above-noted recognised regulatory authorities and organizations

1.       most recent (within last 3 years) corporate or consultant audit, signed and dated by the lead auditor;

2.       justification for using a consultant/corporate audit report (e.g. only available GMP evidence);

3.       qualifications and experience of the auditor(s);

4.       scope of the inspection (including activities being performed, drugs/APIs covered, and specific building address);

5.       evidence that the consultant or corporate audit was conducted against all applicable sections of Part C, Division 2 of the Food and Drug Regulations;

6.       corrective actions taken, signed by the foreign building’s responsible official and assessed by the auditor for adequacy (if applicable);

7.       copy of the Site Master File, or a similar document (such as a quality manual); and

8.       copy of the quality/written agreement between the foreign building’s responsible official and the Canadian establishment

·         If the foreign buildings’ GMP evidence is not based on inspections by recognised regulatory authorities or organizations, in order to meet the required GMP evidence by November 8, 2016, importer should:

1.       Source APIs from an alternate supplier that has the required GMP evidence. It is the importer’s responsibility to advise the DIN holder of any change in suppliers, so that the DIN holder may obtain Health Canada approval, as applicable;

2.       Arrange for a corporate or consultant audit to be conducted as noted in the “Next phase – Beginning November 8, 2016” section of the July 2015 Notice; or

3.       Request a Health Canada inspection using Good Manufacturing Practices − Request for Inspection of a Foreign Site Form (FRM-0213).

Health Canada takes a risk-based approach to inspections. An inspection should be requested as soon as possible for API foreign buildings involved in activities related to prescription and controlled drugs that the importer would deem medically necessary and/or for which there are no alternate suppliers.

References:

1.       “Notice to Stakeholders - Updates to drug establishment licence applications and good manufacturing practice evidence requirements for active pharmaceutical ingredients”:

https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/notice-stakeholders-updates-drug-establishment-licence-applications-good-manufacturing-practice-evidence-requirements-active-pharmaceutical.html

2.       Health Canada issued DEL Bulletin #2 dated August 04, 2016.