Health Products and Food Branch

Inspectorate
Graham Spry Building, 2nd Floor
250 Lanark Avenue
Address Locator # 2002B
Ottawa, Ontario
K1A 0K9

November 28, 2005

05-123206-811

To: Associations

I am pleased to inform you that a new version of the document entitled "Validation
Documentation Requirements and Responsibilities for Drug Fabricators, Packagers / Labellers,
Testers, Distributors and Importers" is now available on the Compliance and Enforcement
section of the Health Canada’s website at:
http://www.hc-sc.gc.ca/dhp-mps/compli-conform/index_e.html

This document has been reviewed as part of the Inspectorate's quality management
process and has been amended to further clarify issues brought to the attention of the
Inspectorate. Please note that no changes to the requirements were made, therefore, consultation
is not deemed necessary.

Inquiries about this document can be addressed to the Manager, Drugs GMP Inspection
Unit by telephone at (613) 957-1492, by fax at (613) 957-6709, or by e-mail at
GMP_questions_BPF@hc-sc.gc.ca.

Original signed by
Diana Dowthwaite (for)

Jean Lambert
Director General
 Health Canada
Health Products and Food Branch

OUR MANDATE:

To promote good nutrition and informed use of drugs, food, medical devices and natural health products, and to maximize the safety
and efficacy of drugs, food, natural health products, medical devices, biologics and related biotechnology products in the Canadian
marketplace and health system.

Health Products and Food Branch Inspectorate

Guideline

Validation Documentation Requirements and

Responsibilities for Drug Fabricators, Packagers /
Labellers, Testers, Distributors and Importers
(GUIDE-0042)

Supersedes:
July 10, 2001

Date issued:
September 1, 2005

Date of implementation:
October 1, 2005

Ce document est aussi disponible en français.

Health Canada / Health Products and Food Branch Inspectorate

TABLE OF CONTENTS

SCOPE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

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

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

REFERENCE DOCUMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Validation Documentation Requirements and Responsibilities for Drug

Fabricators, Packagers / Labellers, Testers, Distributors and Importers (Guide-0042) / October 2005 2
Health Canada / Health Products and Food Branch Inspectorate

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

Validation Documentation Requirements and Responsibilities for Drug

Fabricators, Packagers / Labellers, Testers, Distributors and Importers (Guide-0042) / October 2005 3
Health Canada / Health Products and Food Branch Inspectorate

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

Validation Documentation Requirements and Responsibilities for Drug

Fabricators, Packagers / Labellers, Testers, Distributors and Importers (Guide-0042) / October 2005 4
Health Canada / Health Products and Food Branch Inspectorate

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_e.html

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.

Validation Documentation Requirements and Responsibilities for Drug

Fabricators, Packagers / Labellers, Testers, Distributors and Importers (Guide-0042) / October 2005 5