Annex 7 to the Good manufacturing practices guide for drug products - Selected non-prescription drugs

(PDF Version, 998 KB)

Date issued: August 2020

Date implemented: August 2020

Replaces: Annex 1 to the Current Edition of the Good Manufacturing Practices Guidelines – Selected Category IV Monograph Drugs (GUI-0066) June 10 2011

Health Canada is the federal department responsible for helping the people of Canada to maintain and improve their health. We assess the safety of drugs and many consumer products, help improve the safety of food, and provide information to Canadians to help them make healthy decisions. We provide health services to First Nations people and to Inuit communities. We work with the provinces to ensure our health care system serves the needs of Canadians.

Également disponible en français sous le titre:
Annexe 7 du Guide sur les bonnes pratiques de fabrication – Lignes directrices sur certaines drogues en vente libre

For more information, please contact:

Health Canada
Address Locator 0900C2, Ottawa, ON K1A 0K9
Tel.: 613-957-2991
Toll free: 1-866-225-0709
Fax: 613-941-5366
TTY: 1-800-465-7735
Email: publications@hc-sc.gc.ca

This publication can be made available in alternative formats upon request.

© Her Majesty the Queen in Right of Canada, as represented by the Minister of Health, 2020

Publication date: August 2020

This publication may be reproduced for personal or internal use only without permission provided the source is fully acknowledged.

Cat.: H139-17/2020E-PDF
ISBN: 978-0-660-35117-9
Pub.: 200065

Disclaimer

This document does not constitute part of the Food and Drugs Act (the Act) or its regulations and in the event of any inconsistency or conflict between the Act or regulations and this document, the Act or the regulations take precedence. This document is an administrative document that is intended to facilitate compliance by the regulated party with the Act, the regulations and the applicable administrative policies.

Table of contents

The following table shows the types of icons used in this document, and the way they are intended to be used.

Important: Key or cautionary information for people to know.

Information: Supplementary information like quotes and legal references.

About this document

Purpose

This guide is for people who work with selected non-prescription drugs as:

This document is an annex to the Good manufacturing practices guide for drug products (GUI-0001). You must read the two documents together to understand all relevant guidelines. These guides will help you understand and comply with Part C, Division 2 of the Food and Drug Regulations (the Regulations), which is about Good Manufacturing Practices (GMP). You can find definitions to terms used in this guide under Appendix A - Glossary.

Note: The previous version of this document focused solely on Category IV Monograph products. This document applies to an expanded list of drugs and, as such, the title has been changed to refer to “selected non-prescription drugs.”

Scope

This annex applies to the non-sterile, selected non-prescription drugs that are subject to Part C, Division 2 of the Food and Drug Regulations and have a Drug Identification Number (DIN):

Many of the products listed above are considered as Category IV monographs, please see Non-prescription drugs: Category IV monographs. For each monograph, the following are specified: ingredients, strengths indications, directions for use, and warnings.

For imported products, the exemptions granted under the scope of a mutual recognition agreement (MRA) are limited to products that are considered drugs/medicinal products in their country of origin. If you are an importer, it is your responsibility to determine the classification of the product in the country of origin.

The scope of this document does not include products regulated by the Natural Health Products Regulations. For more information, please see the Good Manufacturing Practices Guidance Document for natural health products.

Introduction

The Food and Drug Regulations and Good manufacturing practices guide for drug products (GUI-0001) apply to all drugs. However, some interpretations in GUI-0001 may not apply in all situations such as with some personal care products. This annex to the current edition of GUI-0001 clarifies those aspects of GMP that are relevant to the fabrication, packaging/labelling, testing, importation and distribution of selected non-prescription drugs.

To avoid repetition, only those interpretations that are different from the ones in GUI-0001 are included in this annex. The numbering of each interpretation used in this annex corresponds to the numbering of the interpretation being modified from GUI-0001.

Unless otherwise stated in this annex, all interpretations included in the Good manufacturing practices guide for drug products (GUI-0001)also apply to selected Non-prescription drugs.

Guidance documents like this one are meant to help industry and health care professionals understand how to comply with regulations. They also provide guidance to Health Canada staff, ensuring that the rules are enforced in a fair, consistent and effective way across Canada.

Health Canada inspects establishments to assess their compliance with the (the Act) and associated regulations. When we conduct an inspection, we will use this document as a guide in assessing your compliance with GMP requirements.

These guidelines are not the only way GMP regulations can be interpreted, and are not intended to 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 flexibility in approach. So use this document to help you develop specific approaches that meet your unique needs.

Modified interpretations

Personnel

C.02.006

Interpretation 1 in GUI-0001 associated with requirements for education and experience of personnel is replaced with the following to provide clarity in expectations for select non-prescription drugs.

  1. The person in charge of your quality control department (if you are a fabricator, packager/labeller, tester, importer or distributor) and the person in charge of your manufacturing department (if you are a fabricator or packager/labeller):
    1. must hold:
      1. in the case of a fabricator, packager/labeller, or tester — a Canadian university degree or a degree recognized as equivalent by a Canadian university or Canadian accreditation body in a science related to the work being carried out
      2. in the case of an importer or distributor — a diploma, certificate or other evidence of formal qualifications awarded on completion of a course of study from a university, college or technical institute in a science related to the work being carried out
    2. must have two years of practical experience in their area of responsibility
    3. may delegate duties and responsibility (for example, to cover all shifts) to a person who is qualified, while remaining accountable for those duties and responsibility:
      1. in the case of a fabricator, packager/labeller, or tester — the person must have a diploma, certificate or other evidence of formal qualifications awarded after completion of a course of study at a university, college or technical institute in a science related to the work being carried out, combined with at least two years of relevant practical experience.
      2. in the case of an importer or distributor — the person must have necessary academic training and experience.

Sanitation

C.02.007

Interpretations 3.a and 3.e in GUI-0001 associated with cleaning validation requirements are replaced with the following:

Raw material testing

C.02.009

Interpretation 3 in GUI-0001 associated with specifications of raw materials is replaced with the following:

Interpretation 4 in GUI-0001 associated with requirements for purified water is replaced with the following:

Interpretation 7 in GUI-0001 associated with requirements to validate test methods is replaced with the following:

Interpretation 11 in GUI-0001 associated with requirements to test each container of a lot of raw material is replaced with the following:

Manufacturing control

C.02.011

Interpretation 13.b in GUI-0001 associated with validation of changeover procedures for fabrication or packaging/labelling of non-medicinal products is replaced with the following:

Interpretations 22 to 24 in GUI-0001 associated with validation of critical production processes requirement is replaced with the following:

Process consistency
C.02.012

Interpretation 12.b.i in GUI-0001 associated with validation responsibilities for analytical methods and production processes in written agreements is replaced with the following:

Quality control department

C.02.015

Interpretation 8.e and 8.l.iv in GUI-0001 concerned with validation of test methods is replaced with the following:

Finished product testing

C.02.018

Interpretation 2 in GUI-0001 associated with requirements to validate test methods is replaced with the following:

C.02.019

In addition to Interpretation 4 in GUI-0001:

Document review must allow the importer to be able to determine that the products meet their specifications. Examples include Certificate of Analysis (CoA), batch records and any other relevant documents.

C.02.020

Importers of drug products in the List of Non-prescription Drug for which the testing requirements set out in subsections C.02.019 (1) and (2) of the Food and Drug Regulations Do Not Apply must ensure that the drugs were manufactured in accordance with the Master Production Documents (MPD) prior to releasing for sale. Certificate of manufacture is considered an acceptable evidence (please refer to the Good manufacturing practices guide for drug products (GUI-0001) for additional information).

Stability

C.02.027
  1. Interpretation 1 in GUI-0001 associated with requirements to make stability determinations in accordance to Health Canada and International Council on Harmonisation (ICH) guidelines is replaced with the following:

Determine the stability of a drug before any marketing takes place. Its stability should also be determined before making any significant changes to formulation, fabrication procedures or packaging materials that may affect the drug’s shelf life. You should make this determination according to Health Canada and ICH guidelines.

Interpretation 9 in GUI-0001 associated with the requirement for validation of analytical test procedures in accordance with ICH guidelines is replaced with the following:

Interpretations 10 and 12 in GUI-0001, associated with the requirement for evaluation of stability data in accordance with ICH guidelines, is replaced with the following:

C.02.028

Interpretation 3 in GUI-0001 associated with bracketing and matrixing in accordance with ICH for the continuing stability program is replaced with:

Minor changes to the formulations (e.g. addition, deletion or substitution of a fragrance, flavour or colour) may be acceptable without new stability data. However, you must conduct ongoing stability studies on the revised formulation to show that the proposed change does not affect the quality of the drug product. You may conduct these studies while you market the modified product.

Appendix A – Glossary

Acronyms

API
Active pharmaceutical ingredient
cfu
colony forming units
CoA
Certificate of Analysis
DEL
Drug Establishment Licence
DIN
Drug Identification Number
DIN-HM
Homeopathic DIN
GMP
Good manufacturing practices
ICH
International Council for Harmonisation
MPD
Master Production Documents
MRA
Mutual Recognition Agreement
NOC
Notice of Compliance
NPN
Natural Product Number
WHO
World Health Organisation

Terms

These definitions explain how terms are used in this document. They supplement the definitions provided in the Good manufacturing practices guide for drug products (GUI-0001).

If there is a conflict with a definition in the or the Food and Drug Regulations, the definition in the Act/Regulations prevails.

Active ingredient – A drug that, when used as a raw material in the fabrication of a drug in dosage form, provides its intended effect. (C.01A.001(1))

Active pharmaceutical ingredient - An active ingredient that is used in the fabrication of a pharmaceutical. (C.01A.001 (1))

Note: For the purpose of these guidelines, this definition also includes: an active ingredient that is used in the fabrication of a drug that is of non-biological origin and that is listed in Schedule C to the Act.

Batch (or lot) - A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continuous production, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount produced in a fixed time interval. (ICH Q7

Batch certificate – Means a certificate issued by the fabricator of a lot or batch of a drug that is either imported within the framework of a mutual recognition agreement or referred to on the List of Non-prescription Drugs Not Subject to Certain Testing Requirements, and in which the fabricator

An example of a batch certificate's content is also described in Health Canada's International Harmonized Requirements for Batch Certification which was developed with our MRA partners but is still relevant for products covered in Annex 7.

Batch number – (See lot number)

Bracketing - The design of a stability schedule such that only samples on the extremes of certain design factors (e.g. strength, package size) are tested at all-time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. Where a range of strengths is to be tested, bracketing is applicable if the strengths are identical or very closely related in composition (e.g. for a tablet range made with different compression weights of a similar basic granulation, or a capsule range made by filling different plug fill weights of the same basic composition into different sized capsule shells). Bracketing can be applied to different container sizes or to different fills in the same container closure system. (ICH Q1A)

Certificate of analysis (CoA) - A document containing the name and address of the lab performing the test(s), name and specifications of the material(s), test(s) performed, test method(s) used, actual numerical results, approval date(s), signature of approver, and any other technical information deemed necessary for its proper use.

Certificate of manufacture – A document issued by a vendor to a distributor or importer that attests that a specific lot or batch of drug has been produced in accordance with its master production documents. Such certificates include a detailed summary of current batch documentation, with reference to respective dates of revision, manufacture, and packaging, and are signed and dated by the vendor’s quality control department. For drugs that are fabricated, packaged/labelled and tested in MRA countries, the batch certificate is considered to be equivalent.

Change control – A written procedure that describes the action to be taken if a change is proposed (a) to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and testing of drugs, or (b) that may affect the operation of the quality or support system.

Changeover procedure - A logical series of validated steps that ensure the proper cleaning of suites and equipment before the processing of a different product begins.

Critical process - A process that if not properly controlled may cause significant variation in the quality of the finished product.

Data - Means all original records and certified true copies of original records, including source data and metadata and all subsequent transformations and reports of this data, which are recorded at the time of the activity and allow full and complete reconstruction and evaluation of the activity. (Adapted from WHO draft)

Distributor or manufacturer - 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. (A.01.010)

Divisions 1A and 2 to 4 apply to the following distributors:

  1. a distributor of an active ingredient or a drug in dosage form that is listed in Schedule C to the Act; and
  2. a distributor of a drug for which that distributor holds the drug identification number. (C.01A.003)

Dosage form – A drug product that has been processed to the point where it is now in a form in which it may be administered in individual doses, unless otherwise defined in the Food and Drug Regulations.

Drug - "drug" includes any substance or mixture of substances manufactured, sold or represented for use in:

  1. the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animals,
  2. restoring, correcting or modifying organic functions in human beings or animals, or
  3. disinfection in premises in which food is manufactured, prepared or kept;

(Section 2 of the Food and Drugs Act)

In Division 1A and Division 2 of the Food and Drug Regulations, “drug” does not include a dilute drug premix; a medicated feed as defined in subsection 2(1) of the Feeds Regulations, 1983; an active ingredient that is for veterinary use and that is not an active pharmaceutical ingredient; an active pharmaceutical ingredient for veterinary use that is not required to be sold pursuant to a prescription and that is also a natural health product as defined in subsection 1(1) of the Natural Health Products Regulations; a drug that is used only for the purposes of an experimental study in accordance with a certificate issued under section C.08.015.. (C.01A.001 (2))

Drug establishment licence - A licence issued to a person in Canada to conduct licensable activities in a building which has been inspected and assessed as being in compliance with the requirements of Divisions 2 to 4 of the Food and Drug Regulations.

Drug identification number - A drug identification number (DIN) is an eight (8)-digit numerical code assigned by Health Canada to each drug product marketed under the Food and Drugs Act and Regulations. A DIN uniquely identifies the following product characteristics: manufacturer, brand name, medicinal ingredient(s), strength of medicinal ingredients(s), pharmaceutical form, route of administration.

Fabricate – To prepare and preserve a drug for the purpose of sale. (C.01A.001(1))

Finished product – A product that has undergone all stages of production, including packaging in its final container and labelling.

Import – To import into Canada a drug for the purpose of sale. (C.01A.001(1))

Label – Includes any legend, word, or mark attached to, included in, belonging to, or accompanying any food, drug, cosmetic, device, or package (section 2 of the Act). As described in package/label, the action of labelling refers to affixing the inner or outer label to the drug. (C.01A.001)

List of Non-prescription Drugs Not Subject to Certain Testing Requirements – Means the document entitled List of Non-prescription Drugs for Which the Testing Requirements Set Out in Subsections C.02.019(1) and (2)of the Food and Drug Regulations Do Not Apply that is published by the Government of Canada on its website, as amended from time to time. (C.01A.001(1))

Lot – See Batch.

Lot number – Any combination of letters, figures, or both, by which any food or drug can be traced in manufacture and identified in distribution. (A.01.010)

Manufacturing batch record – Records demonstrating that the batch of a drug was fabricated in accordance with the approved master production documents.

Marketing authorization – A legal document issued by Health Canada, authorizing the sale of a drug or a device based on the health and safety requirements of the Food and Drugs Act and its associated Regulations. The marketing authorization may be in the form of a Notice of Compliance (NOC), Drug Identification Number (DIN), a device licence for classes II, III and IV medical devices, or a natural product number (NPN) or homeopathic DIN- HM (DIN-HM).

Master production documents (MPD) – Documents that include specifications for raw material, for packaging material and for packaged dosage form; master formula, sampling procedures, and critical processing related standard operating procedures (SOPs), whether or not these SOPs are specifically referenced in the master formula.

Matrixing – The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point. The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same container closure system, and possibly in some cases, different container closure systems. (ICH Q1A) The concept of matrixing may also apply in other areas such as validation.

MRA country – A country that is a participant to a mutual recognition agreement with Canada. (C.01A.001(1))

Mutual recognition agreement (MRA) – An international agreement that provides for the mutual recognition of compliance certification for Good Manufacturing Practices for drugs. (C.01A.001)

Original record – Data as the file or format in which it was originally generated, preserving the integrity (accuracy, completeness, content and meaning) of the record, e.g. original paper record of manual observation, or electronic raw data file from a computerised system. (MHRA GMP Data Integrity Definitions and Guidance for Industry March 2015)

Package – As described in ‘package/label,’ the action of packaging refers to putting a drug in its immediate container. (Adapted from C.01A.001(1))

Package/label – To put a drug in its immediate container or to affix the inner or outer label to the drug. (C.01.A.001(1)) This includes the repackaging and relabeling of previously packaged and labelled drugs.

Personal care products - a substance or mixture of substances which is generally recognized by the public for use in daily cleansing or grooming. Personal care products may fall into one of three regulatory categories in Canada: cosmetics, drugs or natural health products.

Person - Anyone other than an importer, e.g. Retailer.

Quarantine – The status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection. (ICH Q7)

Recognized country or region - means a country that is set out on the List of Foreign Countries and their Regulatory Authorities for the Application of Subsection C.02.019(5) of theFood and Drug Regulationsthat is published by the Government of Canada on its website, as amended from time to time.

Raw data – Original records and documentation, retained in the format in which they were originally generated (i.e. paper or electronic), or as a ‘true copy.’ Raw data must be contemporaneously and accurately recorded by permanent means. In the case of basic electronic equipment which does not store electronic data, or provides only a printed data output (e.g. balance or pH meter), the printout constitutes raw data. (MHRA GMP Data Integrity Definitions and Guidance for Industry March 2015)

Raw material – Any substance other than packaging material or an in-process drug that is intended for use in drug manufacture, including substances that appear in the master formula but not in the drug, such as solvents and processing aids.

Shelf life – The time interval during which a drug product is expected to remain within the approved specification provided that it is stored under the conditions defined on the label and in the proposed containers and closure.

Specifications – Means a detailed description of a drug, the raw material used in a drug, or the packaging material for a drug and includes:

  1. a statement of all properties and qualities of the drug, raw material or packaging material that are relevant to the manufacture, packaging, and use of the drug, including the identity, potency, and purity of the drug, raw material, or packaging material,
  2. a detailed description of the methods used for testing and examining the drug, raw material, or packaging material, and
  3. a statement of tolerances for the properties and qualities of the drug, raw material, or packaging material. (C.02.002)

Standard operating procedure (SOP) – A written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (e.g. equipment operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documents.

Test – To perform the tests, including any examinations, evaluations and assessments, as specified in the Division 2 of the Food and Drug Regulations.

Validation – A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria. (ICH Q7)

Wholesaler – means a person who is not a distributor described in section C.01A.003 and who sells any of the following drugs other than at retail sale: (a) a drug in dosage form that is listed in Schedule C or D to the Act, a drug that is a prescription drug or a controlled drug as defined in section G.01.001; (b) an active ingredient; (c) a narcotic as defined in the Narcotic Control Regulations; or (d) a drug containing cannabis as defined in subsection 2(1) of the Cannabis Act. (C.01A.001(1))

Appendix B - References

Laws and regulations

Food and Drugs Act
https://laws-lois.justice.gc.ca/eng/acts/f-27/

Food and Drug Regulation
http://laws-lois.justice.gc.ca/eng/regulations/C.R.C.%2C_c._870/

Natural Health Product Regulations
http://laws-lois.justice.gc.ca/eng/regulations/sor-2003-196/

Non-prescription drugs: Category IV monographs
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/non-prescription-drugs-category-iv-monographs.html

Good Manufacturing Practices

Good manufacturing practices guide for drug products (GUI-0001)
https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-manufacturing-practices/guidance-documents/gmp-guidelines-0001.html

Good manufacturing practices for active pharmaceutical ingredients (GUI-0104)
https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/guidelines-active-pharmaceutical-ingredients-0104.html

International Guidance Documents

ICH Q1A-E: Stability Testing of New Drug Substances and Products
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/international-conference-harmonisation/quality.html

International Harmonized Requirements for Batch Certification
https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/international/mutual-recognition-agreements/international-harmonized-requirements-batch-certification.html

Mutual recognition agreements
https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/international/mutual-recognition-agreements.html

Report a problem or mistake on this page
Please select all that apply:

Thank you for your help!

You will not receive a reply. For enquiries, contact us.

Date modified: