Validation Documentation Requirements and Responsibilities for Drug Fabricators, Packagers / Labellers, Testers, Distributors and Importers

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Table of Contents

Scope

Introduction

Information Required

1. For distributors of drugs fabricated, packaged/labelled and tested in Canada:
2. For importers of drugs fabricated, packaged/labelled and tested in countries having a signed Mutual Recognition Agreement (MRA) with Canada:
3. For importers of drugs fabricated, packaged/labelled and tested in non-MRA Countries:

Responsibilities

4. For Canadian fabricators, packagers/labellers or testers of drugs:
5. For distributors of drugs fabricated, packaged/labelled and tested in Canada:
6. For importers of drugs from MRA Countries:
7. For importers of drugs from non-MRA Countries:
8. For all drug establishments:

Reference Documents

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Scope

This guidance has been prepared to specify what documented evidence the Health Products and Food Branch Inspectorate (HPFBI) considers acceptable during an inspection, from drug establishments, to demonstrate compliance with validation requirements. Parties responsible for validation activities are also identified.

Introduction

As specified in the Scope section of the Validation Guidelines for Pharmaceutical Dosage Forms, it is expected that importers and distributors of drugs have documented evidence, as outlined below, that the fabricators and packagers of these drugs meet the validation requirements. The availability of information respecting the validation is a shared responsibility between the fabricator and the distributor.

At the site of fabricators, packagers/labellers and testers, inspectors will evaluate the validation master plan, the qualification of systems and equipment and the validation of cleaning and test methods, as applicable. In cases where the product specific process validation studies have not been submitted as part of a drug submission, assessment of process validation will be verified by the inspector.

Information Required

The following information should be available for the purpose of inspection and evaluation:

1. For distributors of drugs fabricated, packaged/labelled and tested in Canada:

1.1 a certificate of manufacture with a certificate of analysis or a fabricator's batch certificate

1.2 a copy of the fabricator's valid Establishment Licence

1.3 complete process validation information, on an individual product basis, when not available at the fabricator's site.

2. For importers of drugs fabricated, packaged/labelled and tested in countries having a signed Mutual Recognition Agreement (MRA) with Canada:

2.1 a fabricator's batch certificate

2.2 the valid importer's Establishment Licence identifying the foreign site.

3. For importers of drugs fabricated, packaged/labelled and tested in non-MRA Countries:

3.1 a certificate of manufacture with a certificate of analysis

3.2 the valid importer's Establishment Licence identifying the foreign site

3.3 product specific process validation documentation showing:

3.3.1 the validation approach utilized by the fabricator (prospective, concurrent or retrospective)

3.3.2 the reference numbers and dates of approval for:

• the master formula including packaging
• the process validation protocol
• the process validation studies
• the validation of the test methods

3.3.3 the lot numbers involved and the dates of completion of these studies

3.3.4. a certified copy of the approved conclusions of the product validation studies

Upon request, copies of complete protocols and related studies for all validation activities must be made available for review on the premises of the importer within 72 hours.

Responsibilities:

4. For Canadian fabricators, packagers/labellers or testers of drugs:

4.1 validation master plan, cleaning validation, test method validation and qualification of utilities, supports systems and equipment are the responsibility of the fabricator; these elements will be verified by the inspector at the fabricator's site;

4.2 for marketed drugs, when process validation data have not been submitted as part of a submission application, these data will be verified by the inspector at the fabricator's site.

5. For distributors of drugs fabricated, packaged/labelled and tested in Canada:

5.1 the inspector will verify, at the distributor's site, the availability and the completeness of the information referred to in Section 1

6. For importers of drugs from MRA Countries:

6.1 the inspector will verify, at the importer's site, the availability and the completeness of the information referred to in Section 2

7. For importers of drugs from non-MRA Countries:

7.1 for marketed drugs, the inspector will verify, at the importer's site, the availability and the completeness of the information referred to in Section 3.

8. For all drug establishments:

8.1 for New Drugs¹, the relevant evaluation units within the Therapeutic Products Directorate (TPD), Biologics and Genetic Therapies Directorate (BGTD) or Veterinary Drugs Directorate (VDD) will evaluate the process validation and test method validation specific to the product.

Where documented arrangements are made, responsibilities for validation can be assumed by another party (e.g. in the case of testing facilities). It is ultimately the responsibility of the importer or distributor to assure that the required validation has been conducted.

Reference Documents

Validation Guidelines for Pharmaceutical Dosage Forms
http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/validation/gui_29_tc-tm-eng.php

¹ In section C.08.001 of the Food and Drug Regulations, "new drug" means

(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;

(b) a drug that is a combination of two or more drugs, with or without other ingredients, and that has not been sold in that combination or in the proportion in which those drugs are combined in that drug, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that combination and proportion for use as a drug; or

(c) a drug, with respect to which the manufacturer prescribes, recommends, proposes or claims a use as a drug, or a condition of use as a drug, including dosage, route of administration, or duration of action and that has not been sold for that use or condition of use in Canada, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that use or condition of use of that drug.