Annex 3A to the Good manufacturing practices guide - Schedule C drugs (GUI-0026): Overview

Date implemented: July 04, 2024
Replaces: Guidance Document Annex 3 to the Current Edition of the Good Manufacturing Practices Guidelines - Schedule C Drugs (GUI-0026), November 19, 2010

Disclaimer: This document does not constitute legislation. If there is any inconsistency or conflict between the legislation and this document, the legislation takes precedence. This is an administrative document intended to facilitate compliance by the regulated party with the legislation and the applicable administrative policies.

On this page

• Purpose
• Scope
• Introduction
• Note about guidance documents in general

Purpose

This document is for people who work with Schedule C drugs (radiopharmaceuticals) as:

• fabricators
• packagers
• labellers
• testers
• distributors
• importers

It is an annex to the latest version of 2 guidance documents:

• Good manufacturing practices guide for drug products (GUI-0001)
• Good manufacturing practices guidelines for active pharmaceutical ingredients (GUI-0104)

The annex will help you understand and comply with Part C, Division 2 of the Food and Drug Regulations. For definitions to terms used in this guide, please refer to the glossary.

Scope

This annex provides additional guidance for the manufacture and control of bulk intermediates and finished Schedule C drugs. To understand all relevant guidelines, you must read the annex together with the Good manufacturing practices guide for drug products (GUI-0001).

Note: The scope does not include establishment licensing. To understand how to comply with Good Manufacturing Practices (GMP) requirements to get an establishment licence, please refer to the Guidance on drug establishment licences (GUI-0002).

Health Canada took into account the GMP principles and concepts adopted internationally for radiopharmaceuticals when developing this annex. For related international GMP guidance documents for radiopharmaceuticals, refer to the reference section.

Note: The fabricator of the radiopharmaceutical should describe and justify which GMP guidance is appropriate for specific process/manufacturing steps that define the manufacture of the:

• active ingredient (GUI-0104)
• finished dosage form (GUI-0001)

Note also that radiation safety requirements are also not within the scope of this annex. For more information on radiation safety, consult the Canadian Nuclear Safety Commission's (CNSC) web site and review its regulations, policies and guidance documents.

Specifically, CNSC's GD-52: Design guide for nuclear substance laboratories and nuclear medicine rooms applies to the following sections of GUI-0001:

• premises
• equipment
  • fume hood, plumbing, storage and security
• sanitation
  • handling and storage of radioactive wastes and personnel behaviour
• manufacturing control
  • procedure writing for managing rejected materials

The raw material testing section of GUI-0001 provides information on standard operating procedures for conditions of transportation. The transportation conditions should follow the recommendations of CNSC's Packaging and Transport Licensing Division.

Positron-emitting radioisotopes and radiopharmaceuticals (PERs) are beyond the scope of this annex. Because of their extremely short radioisotope half-life and shelf life, these drugs have unique manufacture and quality control requirements.

For guidance on this class of Schedule C drugs, consult:

• Annex 3B to the Good manufacturing practices guide – Positron-emitting radiopharmaceuticals (GUI-0071)

Introduction

Radiopharmaceuticals, kits and generators are listed in Schedule C to the Food and Drugs Act (act) and are regulated under the Food and Drug Regulations. The following 2 guidance documents apply to these drugs:

• Good manufacturing practices guide for drug products (GUI-0001)
• Good manufacturing practices guidelines for active pharmaceutical ingredients (GUI-0104)

Some drugs have unique properties that require additional guidelines. This annex to GUI-0001 clarifies the good manufacturing practices (GMP) that concern the manufacture of finished Schedule C drugs and bulk intermediates.

Most radiopharmaceuticals are used as diagnostic agents and contain minute quantities of radionuclides (on a weight basis) in the final drug product. In addition to chemical and biological impurities, radiopharmaceuticals may also contain radioactive (radionuclidic and radiochemical) impurities. These impurities may have a detrimental effect on the usefulness and reliability of the drug as a diagnostic agent as well as the radiation dose given to the patient.

Radiopharmaceuticals used as therapeutic agents require additional consideration. They contain high energy and long-lived radionuclides, which present greater radiation doses to the patient.

Since most radiopharmaceuticals have a short shelf life, they are often administered to patients within a short time after fabrication or reconstitution. In these situations, the product may need to be released before certain quality control tests are completed. For these reasons, it is important to continually assess the effectiveness of the quality assurance program for radiopharmaceuticals.

Note about guidance documents in general

Guidance documents like this one help industry and health care professionals understand how to comply with regulations. They also provide guidance to Health Canada staff so that the regulations are enforced fairly, consistently and effectively across Canada.

Health Canada inspects establishments to assess their compliance with the Food and Drug Act and associated regulations. Our inspectors will use this document as a guide to assess your compliance with GMP requirements for sterile drugs.

These guidelines are not the only way to interpret GMP regulations and do not cover every possible case. Other ways of complying with GMP regulations will be considered with proper scientific justification. Also, as new technologies emerge, different approaches may be called for.

Guidance documents are administrative and do not have the force of law. Because of this, they allow for a flexible approach. Use this guide to help you develop specific approaches to meet your unique needs.