Notice - Draft 2nd Edition "Guidance Document for Cell, Tissue and Organ Establishments: Safety of Human Cells, Tissues and Organs for Transplantation" for consultation

October 2, 2012

Health Canada is pleased to share with you a revised Draft 2^nd Edition Guidance Document for Cell, Tissue and Organ Establishments: Safety of Human Cells, Tissues and Organs for Transplantation (CTO Guidance document) for consultation. It is important that you know what has changed, how these changes will be implemented, and that you have an opportunity to comment on these changes.

What has changed?

This CTO Guidance document provides clarification and interpretation of the regulatory requirements contained in the Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations). This Draft 2^nd Edition has been revised to reflect imminent updates to the Canadian Standards Association (CSA) standards, to improve the clarity in certain areas of the document, and to introduce new nucleic acid testing (NAT) requirements for certain tissues and cord blood.

Changes to reflect CSA Standard updates

The CTO Regulations make ambulatory references to the following Canadian Standards Association (CSA) documents:

• Z900.1 Cells, Tissues, and Organs for Transplantation: General Requirements
• Z900.2.2 Tissues for Transplantation;
• Z900.2.3 Perfusable Organs for Transplantation;
• Z900.2.4 Ocular Tissues for Transplantation; and
• Z900.2.5 Lymphohematopoietic Cells for Transplantation.

New editions of these CSA standards are now in the final stages of approval and will soon be published by the CSA. Any update to the referenced content of the CSA standards will have force of law once the new editions are published. The CTO Guidance document has been revised accordingly. The Annex to this notice provides a few noteworthy examples of CSA changes that will require establishments to update their donor screening and testing procedures.

Changes to improve content

The guidance document has also been amended to address certain issues that required clarification. These changes result from regulatory experience and stakeholder inquiries and feedback received since April 16, 2009.

Changes to introduce NAT

The CTO Regulations require "appropriate and effective" tests for specific disease agents. Mandatory and recommended tests are described in the CTO Guidance document, and Health Canada has taken this opportunity to propose new transmissible disease testing requirements that would be considered mandatory for tissue donation and cord blood donation.

Health Canada proposes to make NAT a requirement instead of a recommendation for the detection of human immunodeficiency virus type 1 (HIV-1) and Hepatitis C (HCV) for tissue donation from deceased donors, as well as for cord blood donation. This proposal has been informed by results of a survey that was sent on April 10, 2012, to all Establishments in Canada that are Registered under the CTO Regulations.

How will these changes be implemented?

This Draft 2^nd Edition of the CTO Guidance document is intended for comment only. It will be revised based on your feedback (see below), and then finalised for implementation. After the 2^nd Edition CTO Guidance document is revised and published, CTO establishments will have a reasonable period of time to implement newly introduced testing requirements (i.e., 6 months to introduce HIV-1 and HCV NAT for tissues and cord blood).

Changes to sections of the CSA standards that are referenced in the CTO Regulations shall have the immediate force of law once they are published by the CSA (regardless of the status of the 2^nd Edition CTO Guidance document). Establishments are responsible for obtaining these documents and shall be required by Health Canada to comply with any updates.

Health Canada will attempt to minimize any delay between the publication of the new editions of the CSA standards and the release of a final version of the 2^nd Edition CTO Guidance document so that additional guidance is available to CTO establishments.

How can I provide input?

Please note that this Draft 2^nd Edition CTO Guidance document has been color coded in order to highlight sections that have been amended. The color coding consists of the following:

• Red font identifies text that has been added or modified since the last edition of the document
• Yellow shading indicates areas in which text has been removed from sections that remain otherwise unmodified.

To request the Draft Guidance document: Interested stakeholders who wish to provide comments may send a request for an electronic copy to bgtd.opic@hc-sc.gc.ca.

Please include in the subject line the title and the preferred language of the draft Guidance Document you wish to receive.

Comments should be submitted to Health Canada, preferably in electronic format using the attached template, within 75 days of the publication of this notice. All comments will be considered in the finalization of the draft guidance.

Template for comments

Comments should be directed to:

Office of Policy and International Collaboration
Biologics and Genetic Therapies Directorate
Health Canada
Address locator: 0702A
Tunney's Pasture, Ottawa, Ontario, K1A 0K9
Fax: (613) 952-5364
E-mail: bgtd.opic@hc-sc.gc.ca

Annex

Examples of amended CSA provisions that will require Establishments to update their Donor Screening and Testing Procedures

Please note that the examples provided below do not represent a comprehensive set of all of the amendments that will appear in the second edition of the CSA Z900 standards package. Establishments are encouraged to cross reference the second edition of the CSA Z900 standards with the most recently updated first edition in order to identify all of the relevant changes.

The following noteworthy changes all impact donor screening and testing requirements under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations). As mentioned in the accompanying notice, all of the CSA sections that are referenced by the CTO Regulations have force of law. Amendments to these referenced sections come into force beginning on the day of publication of the new CSA standards. Therefore, establishments are encouraged to review and update their procedures as soon as possible in order to ensure compliance with the CTO Regulations.

Z900.2.3 Perfusable organs for transplantation

1. Section 12.2.2.3 now requires that a donor history include a history of allergies.

This information should be communicated to the transplant establishment if the allergies are considered clinically relevant. For example, providing information on the presence of a life-threatening allergy in the donor, with potential to be transferred to the recipient, would allow transplant establishments to alert the recipient to avoid the allergen(s) in question and/or seek appropriate testing.

2. Section 14.2.6.3 now makes cytomegalovirus (CMV) and Epstein-Barr virus (EBV) testing mandatory.

Z900.2.5 Lymphohematopoietic cells for transplantation

1. Under section 14.2.3 West Nile Virus Nucleic Acid Testing (NAT) is now a requirement for all lymphohematopoietic cells. Active West Nile Virus is also a contraindication to donation under section 13.1.3.1.

WNV NAT is necessary for:

1. all donors, during times in the year when West Nile virus is potentially transmissible to humans in Canada; and
2. any donor who in the preceding 56 days has travelled in areas where West Nile virus is endemic

2. Section 12.2.2.3.1 now requires a donor history include transmissible genetic diseases in the donor's family;
3. Section 12.2.2.3.1 also requires a donor history include a history of known allergies, except in the case of cord blood donors.
4. Section 12.2.2.4 contains two additional testing requirements for cord blood.

Testing is now required for the purposes of ABO and Rh typing of the cord blood unit. Testing is also now required for the purposes of identifying hemoglobinopathies.

5. HLA typing requirements are now more specific.

HLA typing of the cord blood unit must be performed:

1. at the time of banking for unrelated allogeneic donors; or
2. at the time of release for related allogeneic donors;

Confirmatory HLA typing of the cord blood prior to release using a contiguous segment must also be performed.

6. "Persons previously diagnosed with melanoma" is now specifically mentioned as a contraindication to donation under section 13.1.3.1 in addition to persons previously diagnosed with a hematologic malignancy (e.g., leukemia or lymphoma).

Donors previously diagnosed with other types of cancer shall be deferred, unless they have been evaluated and deemed suitable to donate by a blood centre physician, in accordance with operating procedures.

7. There is a new contraindication under section 13.1.3.3 regarding "a family history of a genetic disease that could affect the recipient" for unrelated allogeneic cord blood donations.

A cord blood unit shall not be accepted for unrelated allogeneic use if there is a family history of a genetic disease that could affect the recipient, and either of the following applies:

1. the risk of transmission of the genetic disease cannot be determined (e.g. there is no available test); or
2. it will not be possible to monitor and follow up with the donor prior to use of the cord blood unit.

Note: Family history includes

1. parents (including egg, sperm, or embryo donor, if applicable);
2. grandparents;
3. siblings as of the time of donation; and
4. parents' siblings.