Notice to Stakeholders –Release of Guidance Documents for Consultation: Various good manufacturing practices and drug establishment licensing guidance documents

January 18, 2017

Health Canada is pleased to announce the release of the following draft guidance documents for a 90 day stakeholder consultation from January 18, 2017 to April 18, 2017:

• GUI-0001: Good manufacturing practices guide for drug products
• GUI-0023: Risk classification guide for drug good manufacturing practices observations
• GUI-0031: Good manufacturing practices for medical gases
• GUI-0080: How to demonstrate foreign building compliance with drug good manufacturing practices
• GUI-0119: Annex 1 to the Good manufacturing practices guide – Manufacture of sterile drugs

These revised guidance documents contain new information. Plain language principles to make the documents easier to read and understand have been considered in rewriting and formatting the documents. They will continue to support compliance with good manufacturing practices and drug establishment licence requirements prescribed in Part C, Division 1A and Division 2 of the Food and Drug Regulations (FDR).

The key changes to the documents are listed below.

How to participate

1. Obtain documents

Please email HPIL-Consultation-IPSOP@hc-sc.gc.ca to receive copies of:

• each draft guidance document, and
• the comment form for your submission of comments by section number and line number.

2. Submit comments

Please email your comments to HPIL-Consultation-IPSOP@hc-sc.gc.ca using one comment form for each guidance document. All comments will be considered in the finalization of the documents. The 90-day consultation period is from January 18, 2017 to April 18, 2017 inclusive.

Comments can also be mailed to:

Health Product Inspection and Licensing Division
Health Product Compliance Directorate
13th Floor, Jeanne Mance Building
200 Eglantine Driveway, Tunney's Pasture
Address Locator # 1913D
Ottawa Ontario K1A 0K9

Overview of Key Changes

The Health Canada guidance documents have been rewritten and formatted using plain language principles to make the documents easier to read and understand. This is in conformance with requirements for migration of documents to the Canada.ca website. As an exception, international content proposed for direct adoption in GUI-0119: Annex 1 to the Good manufacturing practices guide – Manufacture of sterile drugs has been retained as originally written.

GUI-0001 Good manufacturing practices (GMP) guide for drug products is applicable to all fabricators, packagers/labelers, testers, importers, distributors and wholesalers who work with drugs. Changes include:

• New guidance to address emerging issues such as data integrity, and to address new regulations pertaining to active pharmaceutical ingredients (API).
• Enhanced responsibilities for importers of products from non-MRA countries with new requirement to conduct audits of foreign buildings and increased retesting requirements on imported products.
• Removal of guidance under the sterile products section (C.02.029) and replace it with guidance published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). The documents to be adopted are "Guide to Good Manufacturing Practice for Medicinal Products Annexes - Annex 1 - Manufacture of sterile medicinal products" (PE 009-12 - 1 October 2015) and "GMP Annex 1 Revision 2008, Interpretation of Most Important Changes For The Manufacture of Sterile Medicinal Products" (PI 032-2 – 8 January 2010). Health Canada is proposing to adopt this international guidance to enable easier updating of sterile products guidance and facilitate international harmonization. The adopted sterile products guidance is presented in a new document entitled "Annex 1 to the good manufacturing practices guide – Manufacture of sterile drugs (GUI-0119).
• Incorporation of GMP Questions and Answers into the guidance, where appropriate, and introduction of a Q&A section in the appendices. The content of the guidance document "Validation documentation requirements and responsibilities for Drug Fabricators, Packagers/Labellers, Testers, Distributors and Importers" (GUI-0042) was also incorporated. We propose to remove the existing GMP Q&A document and GUI-0042 from the Health Canada website upon approval of this revised GUI-0001.

GUI-0023: Risk classification guide for drug good manufacturing practices observations is applicable to all fabricators, packagers/labelers, testers, importers, distributors and wholesalers who work with drugs. Changes include:

• Expanded scope to include on site inspections of domestic and foreign buildings (finished dosage form as well as API sites). It also includes Health Canada's assessment of GMP evidence to ensure the information submitted by importers demonstrates the foreign building's compliance with Division 2 of the FDR.
• New sample observations to reflect updated additional requirements introduced into two guidance documents being posted for consultation at the same time – Good manufacturing practices guide for drug products (GUI-0001) and Annex 1 to the good manufacturing practices guide – Manufacture of sterile drug products (GUI-0119). The new observations cover new regulatory requirements such as for APIs, and emerging issues such as data integrity.

GUI-0031: Good manufacturing practices for medical gases is applicable to all fabricators, packagers/labelers, testers, importers, distributors, wholesalers and home care providers who work with medical gases. Changes include:

• Questions and answers (Q&As) from Medical Gas - Good Manufacturing Practices (GMP) Questions and Answers were incorporated into the main guidance, where appropriate. Specific Q&As are listed as an appendix. In future, it is proposed that Q&As be maintained as an appendix to this document.
• New regulations and revised definition for wholesaler was included to reflect changes to the FDR resulting from the coming into force of regulations pertaining to APIs.
• Chapter 4 on quality management was updated to reflect changes made to GUI-0001 (to harmonize internationally). Changes include reference to concepts of quality risk management and quality management throughout product lifecycle, with reference to ICH Q10.
• New or expanded rationale and interpretations in chapter 5 respecting senior management responsibilities, deviations and non-conformances, accuracy and reliability of data and records, and records expectations.

GUI-0080: How to demonstrate foreign building compliance with drug good manufacturing practices is applicable to all Canadian importers who work with drugs. Changes include:

• Incorporation of information with respect to foreign buildings that fabricate, package, label or test non-sterile APIs.
• Incorporation of the new evidence required by date to replace the expiry date on a drug establishment license and details on the implications.
• Clarification on filing requirements, processing and Health Canada's assessment.
• Revised evidence requirements for foreign buildings that fabricate, package, label or test finished dosage forms or APIs.
• Incorporation of Questions and Answers into the guidance, where appropriate, and introduction of a Q&A section in the appendices.

GUI-0119: Annex 1 to the Good manufacturing practices guide – Manufacture of sterile drugs is applicable to all fabricators, packagers/labelers, testers, importers, and distributors who work with sterile drugs.

Health Canada is seeking feedback on a proposal to adopt the international GMP guidance published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S) as described in the proposed Health Canada guide.

• The PIC/S documents proposed to be adopted by Health Canada in GUI-0119 are "Guide to Good Manufacturing Practice for Medicinal Products Annexes - Annex 1 -Manufacture of sterile medicinal products" (PE 009-12 - 1 October 2015) and "GMP Annex 1 Revision 2008, Interpretation of Most Important Changes For The Manufacture of Sterile Medicinal Products" (PI 032-2 – 8 January 2010).
• The PIC/S documents are currently being revised under a joint initiative that includes Health Canada.
• A consultation with Canadian stakeholders on the content of the upcoming revision to the PIC/S GMP Annex 1 is anticipated in the first half of 2017.
• Under this proposal, Health Canada will remove guidance currently published under the sterile products section (C.02.029) of "Good Manufacturing Practices (GMP) Guidelines – 2009 Edition, Version 2 (GUI-0001)" and replace it with guidance published by the PIC/S as Health Canada GUI-0119.
• The adoption of these PIC/S documents for the manufacture of sterile drugs is intended to facilitate increased international harmonization. The interpretations in the PIC/S documents are to be adopted verbatim in this guide.
• Health Canada's GMP Questions and Answers pertaining to sterile drugs will be incorporated in a Q&A section in the appendices of GUI-0119. We propose to remove the existing document entitled "Good Manufacturing Practices Questions and Answers" from the Health Canada website upon approval of the revised GUI-0001 and GUI-0119.
• Health Canada plans to rename the current "Annex 1 to the Current Edition of the Good Manufacturing Practices Guidelines - Selected Category IV Monograph Drugs" (GUI-0066) to an alternate Annex number upon its next revision.