Inspection Strategy for Post-Market Surveillance (POL-0041)

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Table of Contents:

1. Purpose
2. Background
3. Scope
4. Definitions

5. Compliance and Monitoring Activities

5.1 Inspections
5.1.1 Inspection activities
5.1.2 Duration of inspections
5.2 Inspection Rating and Reporting

6. Response to Non-Compliance
7. Responsibilities
8. Procedures
9. Effective Date
10. References

1. Purpose

The purpose of this document is to detail the strategy for the effective and uniform implementation of a national inspection programme to assess compliance of manufacturers with the Food and Drugs Act (Act) and the Food and Drug Regulations (Regulations) with regards to reporting of adverse drug reactions and reporting of unusual failure in efficacy of new drugs to Health Canada.

2. Background

The Regulations set forth requirements for manufacturers regarding reporting of adverse drug reactions and the reporting of unusual failure in efficacy of new drugs to Health Canada. Currently, there is no formal inspection programme in place to assess industry's compliance with these regulations. However, as part of its mandate to maximize the safety and efficacy of drugs, Health Canada is implementing an inspection programme for Post-Market Surveillance.

Inspections will be conducted by Health Canada under the authority of sections 23 and 24 of the Act. These activities will be conducted by the Health Products and Food Branch Inspectorate (Inspectorate).

3. Scope

This inspection programme applies to:

• Manufacturers of pharmaceutical and biological drugs

Blood products and therapeutic and diagnostic vaccines are included in the scope of this programme. However, radiopharmaceuticals, veterinary drugs, natural health products and preventative vaccines, including immunization schedule vaccines, influenza vaccines and vaccines for travel, whole blood and blood components are excluded. In addition, this inspection programme does not apply to drugs for which a Clinical Trial Application has been submitted to Health Canada.

4. Definitions

Adverse drug reaction: a noxious and unintended response to a drug, which occurs at doses normally used or tested for the diagnosis, treatment or prevention of a disease or the modification of an organic function; (réaction indésirable à une drogue) (C.01.001 (1)).

HPFB: The mandate of the Health Products and Food Branch of Health Canada is to take an integrated approach to the management of the risks and benefits to health related to health products and food by minimizing health risk factors to Canadians while maximizing the safety provided by the regulatory system for health products and food; and, promoting conditions that enable Canadians to make healthy choices and providing information so that they can make informed decisions about their health. (DGPSA)

Importer: A person who imports into Canada a drug for the purpose of sale. (importateur)

Inspection: an independent evaluation, conducted by an objective, unbiased inspector, or inspection team, to assess an establishment's compliance against set standards or Regulations. Inspections are normally conducted on a multi-year cycle or as required. (inspection)

Inspector: Any person designated as an inspector for the purpose of the enforcement of the Food and Drugs Act under subsection 22(1) or the Controlled Drugs and Substances Act under section 30. (inspecteur)

Inspectorate: The Directorate of the HPFB whose primary role is to deliver a national compliance and enforcement program for all products under the mandate of the HPFB, with the exception of products regulated as foods. (Inspectorat)

Manufacturer: "manufacturer" or "distributor" means a person, including an association or partnership, who under their own name, or under a trade-, design or word mark, trade name or other name, word or mark controlled by them, sells a food or drug (fabricant or distributeur) (A.01.010)

MHPD: The Marketed Health Products Directorate of HPFB is responsible for coordination of consistency of post-approval surveillance and assessment of signals and safety trends concerning all marketed health products. (DPSC)

New Drug: "(a) a drug that contains or consists of a substance, whether as an active or inactive ingredient, carrier, coating, excipient, menstruum or other component, that has not been sold as a drug in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that substance for use as a drug..." (Drogue nouvelle) ©.08.001)

The Therapeutic Products Directorate, HPFB policy issue, New Drug - Sufficient Time (August 21, 1991), interprets the phrase "sufficient time" as a minimum of seven years from the initial date of marketing in Canada.

Serious adverse drug reaction: a noxious and unintended response to a drug that occurs at any dose and that requires in-patient hospitalization or prolongation of existing hospitalization, causes congenital malformation, results in persistent or significant disability or incapacity, is life-threatening or results in death; (réaction indésirable grave à une drogue) (C.01.001 (1))

Serious unexpected adverse drug reaction: a serious adverse drug reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the drug; (réaction indésirable grave et imprévue à une drogue) (C.01.001 (1))

For additional definitions, consult the documents listed as references at the end of this strategy.

5. Compliance and Monitoring Activities

The Inspectorate will provide information and encourage voluntary compliance with Canadian regulatory requirements. Compliance will be assessed through inspections conducted by the Inspectorate.

5.1 Inspections

Within the scope of the Post-Market Surveillance Drug Inspection programme, manufacturers of pharmaceutical and biological drugs will be inspected by the Inspectorate. The Inspectorate will assess the compliance of manufacturers with the Regulations pertaining to adverse drug reaction reporting, specifically, sections C.01.016, C.01.017 of the Regulations. The compliance of establishments with regards to requirements for reporting failure in efficacy of new drugs, as set forth in sections C.08.007 and C.08.008 of the Regulations will also be assessed.

The Post-Market Surveillance inspection cycles will begin in 2004. Up to twenty-five percent of the establishments under the scope of this strategy will be inspected in the first year. The inspection programme will be assessed after the first year of operation in order to determine whether modifications are required.

5.1.1 Inspection activities

The assessment for post-market surveillance will be conducted in conjunction with the assessment of establishments for compliance with Part C, Division 2, Good Manufacturing Practices (GMP) of the Regulations. Therefore, the inspection cycles for the Post-Market Surveillance Drug Inspection programme will be integrated into the inspection cycles for the GMP inspections. Additional time will be allocated for the overall visit to accommodate both types of inspections. Not all firms inspected for compliance with Division 2 will be inspected for compliance with post-market surveillance activities in a given inspection cycle.

5.1.2 Duration of inspections

The average duration of the inspection will vary depending on the type of activities and the size of the establishment, in addition to the volume of adverse drug reactions recorded by the firm, but is estimated at 1 day. The average time for an inspection will be re-assessed after the first year of operation of the inspection programme.

5.2 Inspection Rating and Reporting:

Rating:

• Two ratings will be used:
  C - No objectionable conditions or practices were observed with regards to regulatory requirements pertaining to reporting of adverse drug reactions and/or reporting of unusual failure in efficacy of new drugs
• NC - Objectionable conditions or practices were observed with regards to regulatory requirements pertaining to reporting of adverse drug reactions and/or reporting of unusual failure in efficacy of new drugs

Reporting:

• An Inspection report will be issued to the inspected establishment in a timely manner. The Inspection Report will contain observations noted during the inspection. An Exit Notice will be issued to the establishment.
• Responses to observations noted in the Inspection Report (Inspection Exit Notice) will be required from the inspected establishment within a specified period of time. Responses should outline corrective actions to any deficiencies recorded.

6. Response to Non-Compliance

Where non-conformity to the Act and/or Regulations is identified, the inspected establishment will have the opportunity to correct identified deficiencies. Where necessary, the Inspectorate will consider enforcement actions in accordance with the HPFB Compliance and Enforcement Policy (POL-0001).

7. Responsibilities

It is the responsibility of the Inspectorate and the Marketed Health Products Directorate (MHPD) to collaborate and act in partnership in the application of this Inspection Strategy. It is the Inspectorate's responsibility to perform inspections and the responsibility of MHPD to analyze the data provided by the Inspectorate in conjunction with their objectives.

8. Procedures

Specific inspection activities will be documented and supported by detailed standard operating procedures.

9. Effective Date

The implementation date of this Inspection Strategy is August 1^st, 2004.

10. References

1. Food and Drugs Act
2. Food and Drug Regulations
3. Health Products and Food Branch Compliance and Enforcement Policy, No. POL-0001
4. Health Canada, Guidelines for Reporting Adverse Reactions to Marketed Drugs, Guidelines for the Canadian Pharmaceutical Industry on Reporting Adverse Reactions to Marketed Drugs (Vaccines Excluded), Revised July 2001
5. Health Products and Food Branch, Therapeutic Products Directorate, New Drug - Sufficient Time (August 21, 1991)