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Policy and Promotion Division

Date 2005-12-12

Regulatory Impact Analysis Statement

(This statement is not part of the Regulation.)

Department or Agency
Health

Title of Proposal
Project No. 1363
Safety of Human Cells, Tissues and Organs for Transplantation Regulations

Statutory Authority
Food and Drugs Act,
c. F-27, subsection 30(1)

Submitted for Consideration for:
Pre-publication (75 day comment period)

Description

The purpose of this regulatory initiative is to minimize the potential health risks to Canadian recipients of human cells, tissues and organs (CTO). These proposed Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations) will address safety in the processing and handling of these products, resulting in improved protection of the health and safety of Canadian transplant recipients.

It is important to acknowledge the life-saving / life-enhancing gifts that make possible the transplantation of human cells, tissues or organs. Health Canada recognizes this noble sacrifice, which should not be considered diminished in any way by the use of regulatory language, necessary under the constraints imposed by the Food and Drugs Act (F&DA). By regulating all establishments and individuals in Canada that handle, process, distribute or import human CTO, these standards-based regulations for CTO will enable Health Canada to play an active role in realizing the intended benefit of these gifts, and contribute to fulfilling its mandate to maintain and improve the health of Canadians.

The proposed CTO Regulations serve as a model for the Smart Regulations initiative since a combination of instruments has been used to regulate, including safety standards upon which they are based; a risk management approach has been incorporated in their design and enforcement; provinces, territories and transplantation experts have been engaged in extensive consultations during the course of their development; and Canadian standards have been made available as a model for other nations through international regulatory cooperation. These regulations also deliver on the Government's commitment in the Budget for 2005 to continue to invest in health care, through direct support of drug safety.

As the CTO Regulations are implemented, a consequential amendment to Schedule D to the F&DA will also be required. The proposed CTO Regulations will cover cord blood and peripheral blood when used as a source of lymphohematopoietic cells intended for use in transplantation, while cord blood and peripheral blood intended for transfusion will continue to be regulated in Schedule D to the F&DA.

The Medical Devices Regulations (MDR) will also be amended upon implementation of the CTO Regulations. The intention is to limit the scope of the MDR to Medical Devices manufactured from or incorporating animal or human cells or tissues. To allow for an appropriate transition, it is proposed that heart valves and dura mater will remain under the MDR until Phase II, when they will be regulated under the CTO Regulations.

Need for Regulation

Health Canada is the federal authority which regulates the safety, efficacy and quality of therapeutic products used in Canada pursuant to the F&DA. To date, there has been no consistent regulatory approach to maximize the safety of human CTO. Certain CTO are currently regulated under the MDR (e.g. dura mater and heart valves), the FDR (e.g. blood) and Processing and Distribution of Semen for Assisted Conception Regulations (e.g. semen for assisted conception), three separate sets of regulations under the F&DA. For other tissues and for organs, there are currently no specific regulations under the F&DA. In addition, there has been a lack of specific safety standards, compliance monitoring and enforcement activities, and adverse event reporting for most establishments handling/processing CTO that takes into consideration the unique characteristics of these products.

Challenges

Instituting an effective approach, one that is both consistent and comprehensive, has proven challenging for a variety of reasons. Canadian establishments engaged in handling/processing CTO for transplantation currently employ multiple sets of voluntary standards that vary in their level of comprehensiveness. Other issues include overlapping federal/provincial jurisdiction and the various types of and uses for tissues, all of which result in a very complex regulatory environment. For these reasons, federal regulatory intervention in the CTO community has long been recommended by various stakeholders, including industry and government.

Health Canada's Response - National Standards

In 1996, Health Canada began to address the need for regulation, and thereby the concerns of stakeholders, by striking a working group of independent experts to develop safety standards for CTO. In 2000, Health Canada contracted with the Canadian Standards Association (CSA) to facilitate the publication of the resulting National Standards designed to maximize the safety, quality and performance of CTO for transplantation. The Standards Council of Canada has accredited the CSA as the standards development organization in Canada. The CSA Technical Committee, which includes representatives from Health Canada, provincial and territorial governments, health professional groups and CTO stakeholders, was tasked with the development of the standards. Following extensive collaboration with experts in the field, federal and provincial governments and interested stakeholders, the National Standards were published in June 2003. This marked the initiation of the development of the new standards-based regulatory framework for CTO.

The time required to develop the National Standards reflects the wide variety of CTO products as well as the technical complexity of the processes utilized by the CTO industry. The CSA Technical Committee was responsible for the simultaneous development of the general and subset standards, adding to the scope of the project. In addition, members of the CSA Technical Committee volunteer their time rather than work exclusively on the standards, all of which contributed to lengthen the time required for their development.

To meet the requirement for public consultation in the development of National Standards, the CSA posted each of the draft standards on its website for a 60-day comment period, in addition to distributing copies to individuals/organizations that expressed an interest. Over 1,000 comments were received through this public review process, and these comments were referred to the CSA Technical Committee for consideration and possible incorporation into the standards.

As they were drafted through a consensus-development process, the National Standards have now met the requirements of the Standards Council of Canada, having provided multiple opportunities for Canadians to express their points of view and/or concerns about these standards. Extensive consultation with key stakeholders during the drafting process provided transplantation programs with a significant familiarity with the standards' requirements. In fact, during these consultations, it was the CTO community that again identified the need for, and recommended the creation of, a regulatory framework for CTO.

The National Standards formed the basis for the safety requirements that have been incorporated into the CTO regulatory framework. The CTO Regulations directly reference sections of the General Standard CAN/CSA Z900.1-03, entitled Cells, Tissues, and Organs for Transplantation and Assisted Reproduction: General Requirements, along with four of the five subset standards for specific organ and tissue types (i.e. the standards for lymphohematopoietic cells, perfusable organs, tissues, and ocular tissues), thus making them mandatory. [The Z900 package of the National Standards may be obtained by calling 1-800-463-6727 or from the following website: http://www.csa-intl.org/onlinestore/]

Interim Measures

The development and implementation of a standards-based regulatory framework is a long-term initiative and is not yet complete. While the National Standards were being developed, Health Canada recognized the need for interim measures. In January of 2003 Health Canada issued a Directive entitled "Technical Requirements to address the Safety of Human Cells, Tissues and Organs for Transplantation" (Directive) and its corresponding Guidance Document entitled "Basic Safety Requirements for Human Cells, Tissues and Organs for Transplantation" (Guidance Document). The Directive and Guidance Document have been recently updated to reflect CSA changes to the testing requirements. Education and awareness activities are planned regarding the requirements which must be met to comply with the CTO Regulations. [The Directive and Guidance Document are posted on the Health Canada website: http://www.hc-sc.gc.ca/dhp-mps/brgtherap/reg-init/cell/cto_directive-eng.php]

These documents provide guidance for donor screening, donor testing, CTO retrieval/collection, processing, preservation, packaging and labelling, storage, quarantine, record keeping, importation, distribution, transplantation, adverse reaction monitoring and error and accident reporting, investigation and recall. Pursuant to the Directive, CTO which are not processed in accordance with the basic standards of safety will be considered by Health Canada to be "manufactured, prepared, preserved, packaged and stored under unsanitary conditions; to be adulterated; or to have the potential to cause injury under normal conditions of use".

National Review

In March 2003, following the release of the Directive and Guidance Document, Health Canada initiated a National Review of establishments handling and/or processing CTO for transplantation. The objective of the National Review is to assess establishments' adherence to basic safety requirements, as specified in the Directive and Guidance Document.

The National Review consists of two stages: a documentation stage during which Health Canada requests supportive information/documentation from programs involved in the handling and/or processing of CTO; and a compliance monitoring stage, during which Health Canada inspects establishments to assess their adherence to basic safety requirements. The National Review has allowed Health Canada to gain a better understanding of the CTO industry in Canada. It has also provided data that can be used to evaluate the overall risks related to CTO for transplantation and, therefore, can contribute to the institution of the appropriate regulatory adverse reaction reporting and compliance monitoring and enforcement mechanisms. An equally important aspect of the National Review is the opportunity it affords Health Canada to demonstrate to establishments the importance of adhering to basic safety standards. Until these regulations are in place, the Directive and Guidance Document will provide interim guidance to Canadian CTO establishments, while the ongoing National Review (both stages) will continue to monitor the compliance of these establishments with basic safety requirements.

National Review

In March 2003, following the release of the Directive and Guidance Document, Health Canada initiated a National Review of establishments handling and/or processing CTO for transplantation. The objective of the National Review is to assess establishments' adherence to basic safety requirements, as specified in the Directive and Guidance Document.

The National Review consists of two stages: a documentation stage during which Health Canada requests supportive information/documentation from programs involved in the handling and/or processing of CTO; and a compliance monitoring stage, during which Health Canada inspects establishments to assess their adherence to basic safety requirements. The National Review has allowed Health Canada to gain a better understanding of the CTO industry in Canada. It has also provided data that can be used to evaluate the overall risks related to CTO for transplantation and, therefore, can contribute to the institution of the appropriate regulatory adverse reaction reporting and compliance monitoring and enforcement mechanisms. An equally important aspect of the National Review is the opportunity it affords Health Canada to demonstrate to establishments the importance of adhering to basic safety standards. Until these regulations are in place, the Directive and Guidance Document will provide interim guidance to Canadian CTO establishments, while the ongoing National Review (both stages) will continue to monitor the compliance of these establishments with basic safety requirements.

Scope of the CTO Regulations for Phase I

These proposed regulations will apply to human organs and minimally manipulated cells and tissues intended for homologous use in transplantation in another individual.

During Phase I, the regulatory framework will not apply to the following therapeutic products:

• Cells and tissues that are more than minimally manipulated;
• CTO that are for non-homologous use (i.e CTO used for a purpose other than its original function);
• Cells and tissues that are for autologous use (i.e. cells or tissues retrieved, modified and later returned to the same individual);
• tissues and cells, except for lymphohematopoietic cells, that are derived from bone marrow, peripheral blood or cord blood, have a systemic effect and depend on their metabolic activity for their primary function;
• Medical Devices that contain cells or tissues that are used in investigational studies in humans, currently regulated under Part 3 of the MDR;
• CTO that are used in clinical trials in humans, currently regulated under Division 5 of the F&DR;
• whole blood and blood components for transfusion, including cord blood for transfusion currently regulated under the FDR and Schedule D to the F&DA;
• cells and tissues regulated under the Assisted Human Reproduction Act or any of its regulations;
• semen regulated under the Processing and Distribution of Semen for Assisted Conception Regulations; and
• cells and tissues that are currently regulated under the MDR (e.g. heart valves, dura mater, demineralized bone, wound covering containing human cells).

Registration of CTO Establishments

The main compliance monitoring and enforcement feature for Phase I is a registration scheme for establishments that process, distribute or import CTO. All source establishments and establishments that distribute or import will be required to apply for registration with Health Canada. It is also important to note that in order to comply with the CTO Regulations, Canadian establishments can only import cells and tissues from foreign source establishments registered with Health Canada.

The registration application contains a description of the CTO processed, distributed or imported by the establishment and the types of activities it carries out or for which it is responsible. In addition, the registration form contains a certification of compliance with the CTO Regulations that must be signed by the medical or scientific director, depending on the establishment's organizational structure. If it is deemed that the information provided is sufficient and satisfactory, the Minister will issue a registration number to the establishment that is valid for a period of up to 2 years. The registration number is valid until December 31 in the year after the year in which it was issued. [The registration form will be posted on the Health Canada web site: http://www.hc-sc.gc.ca/dhp-mps/compli-conform/info-prod/cell/index-eng.php]

The Minister has the power to refuse to issue a registration number if there is reason to believe that any information provided is false, misleading, inaccurate or incomplete. The Minister also has the power to suspend or revoke a registration number if there is reason to believe that the establishment is not in compliance with the CTO Regulations. Any change in the information provided on the registration application, including addition or cessation of activities listed, must be communicated to the Minister. This registration scheme will provide a comprehensive list of all establishments involved in handling/processing CTO in Canada, the activities they perform and the establishments to whom they distribute.

Source Establishment

The source establishment plays a pivotal role in determining the safety of CTO, through its responsibility for the oversight of donor screening, donor testing, donor suitability assessment, preparation, preservation, packaging and labelling, quarantine, banking, whether it performs these functions or they are performed by another establishment on its behalf. An additional requirement is that establishments must have a quality assurance system in place to control the oversight of all the activities for which it is responsible, including the investigation of all errors, accidents and adverse reactions.

Processing

Processing includes the screening, testing and suitability assessment of donors, as well as the retrieval, preparation and preservation, packaging and labelling, quarantine, and banking of CTO. The regulations reference specific sections of the National Standards which outline the basic requirements for donor screening, serological testing, and bacteriological testing listed in the general standard and/or specific subset standards. The exclusion criteria component of the donor suitability assessment also references the appropriate section of the National Standards, by tissue/organ type. Establishments are also required to have validated written standard operating procedures (SOP) for all activities performed in their establishment.

Packaging and Labelling

Appropriate packaging and labelling are essential components of the safety and accurate identification of CTO. Packaging material must be inspected before use to ensure they are free from damage. The information requirements for interior and exterior labels and package inserts are listed in the tables to the labelling sections of the regulations, and must be in either English or French. These requirements vary according to whether the label is for a cell, tissue or organ and whether cells and tissues are banked. For example, cells or tissues intended for banking must have an expiry date indicated on the label.

Storage

The CTO Regulations specify that storage must be secure against unauthorized access and able to maintain environmental conditions appropriate to the CTO requirements. CTO intended for autologous use (not subject to these regulations) must be segregated from those intended for allogeneic use (subject to these regulations). CTO that are untested or are reactive or positive for transmissible disease agents or markers must be segregated from all other CTO. In addition, establishments must observe the validated maximum storage periods for CTO.

Quarantine

The CTO Regulations stipulate that cells and tissues that have not been tested or have tested positive for applicable infectious disease markers specified in the donor suitability assessment section, must be segregated or quarantined from screened cells and tissues that tested negative. These cells and tissues remain in quarantine until infectious disease and bacteriological testing is completed, the results are negative or non-reactive, and the results have been documented, reviewed and considered acceptable by the medical or scientific director.

Cells and tissues that are the subject of an investigation of any error, accident or adverse reaction must also be segregated from other cells and tissues until such time as the results of the investigation deem the CTO suitable for transplantation. In addition, as new infectious diseases emerge, a source establishment must quarantine all of its banked cells and tissues until they are tested for that disease agent or marker.

Exceptional Distribution

A need was identified for a mechanism to allow for the rare distribution of a CTO that may not meet all of the requirements of these regulations, when no fully compliant CTO is available. Under similarly exceptional circumstances, a source establishment may distribute CTO that have not been processed in accordance with these regulations, provided that the transplant surgeon obtains their medical director's authorization for the distribution. In addition, the medical director of the transplant establishment must authorize the exceptional distribution, and the recipient must have given his/her informed consent. After the exceptional distribution of a CTO, the source establishment must still complete the donor suitability assessment and carry out any appropriate follow-up testing. In most cases, the exceptional distribution criteria can only be met by life-saving / life-enhancing transplantations.

A notice of exceptional distribution must indicate the section of these regulations with which the CTO does not comply (except for imported organs), the medical director's justification for the distribution, the name of the transplanted CTO, the name of the source establishment that distributed the CTO, the name of the transplant establishment, the transplant physician or dentist and medical director who authorized the distribution, the time and date of the authorization for distribution, and a copy of the written authorization signed by the medical director. The notice must be retained in the files of both the source and transplant establishment.

Errors and Accidents

The proposed regulations require that establishments must report to the source establishment all known or suspected errors or accidents that occur during processing that are associated with a CTO. They must identify and quarantine the CTO implicated in the error or accident. Furthermore, establishments must notify all other establishments in the supply chain including any establishment that either supplied, processed, or to which it distributed the implicated CTO. The notice must identify the implicated CTO; describe the error or accident including the name of any suspected transmissible disease agent; and advise that all implicated CTO in their possession be quarantined and not further distributed. A timely written confirmation is required for any verbal notice.

Adverse Reactions

Adverse reaction surveillance is an essential component of a regulatory framework for therapeutic products to help identify risks to the supply chain and to help ensure appropriate action is taken to minimize future risk. The CTO Regulations require that all establishments report adverse reactions to the source establishment that processed the relevant CTO. In their report to the source establishments, all establishments must identify the suspected transmissible disease or disease agent and the implicated CTO. Establishments are required to quarantine all CTO from the same donor in their possession and notify all establishments to which it distributed the CTO in question.

Investigations and Reporting to Health Canada

Due to the source establishment's strategic location in the supply chain, the CTO Regulations place the onus on source establishments to investigate all errors, accidents and adverse reactions. Within 24 hours of the start of an investigation, the source establishment must report to Health Canada the name of the suspected infectious disease/agent, the type of CTO and the number of recipients potentially effected. Nevertheless, this requirement to report to Health Canada does not replace the establishment's requirement to report designated infectious diseases to Provincial/Territorial Health Authorities.

The source establishment is required to notify all establishments to which it distributed the implicated CTO that it has initiated an investigation, as well as the initial results and the final outcome of the investigation. To facilitate this process, establishments must provide the source establishment with any information in their possession that could assist in the investigation. Furthermore, the source establishment must report to Health Canada the progress of the investigation within 30 days of initiating the investigation and every 30 days until the final report is submitted. The final report must describe the results of the investigation, the final disposition of the CTO in question and any corrective action taken.

Records

Establishments are required to have written standard operating procedures for all their critical activities and keep records in locations secure against unauthorized persons. In addition, the source establishment is responsible for assigning a donor identification (ID) code to the CTO when it is retrieved/collected. All subsequent handlers of the CTO, including the transplant establishment, must retain the necessary records to be able to trace a CTO from the donor to the final recipient.

Source establishments must keep records that contain the donor ID code, documentation demonstrating completion of donor suitability assessment; a description of CTO; the name of the retrieval establishment; documentation of all processing steps including equipment and instruments used; documentation of any adverse reaction, error or accident related to the CTO, the results of their investigation and any corrective action taken; and the notice of exceptional distribution, if any.

Transplant establishments must keep records that contain a means to identify the recipient; the donor ID code; a description of CTO transplanted; confirmation that the donor suitability assessment was completed; documentation of any adverse reaction, error or accident related to the CTO, the results of their investigation and any corrective action taken; notice of exceptional distribution, if any; and a copy of the recipient consent.

Retention Period for Records

Records that must be retained indefinitely include the records specified above as being required for the source and transplant establishments (except for records of non-serious error and accident and adverse reactions); distribution records, including records of destruction of CTO; records of the investigation of all serious error and accident and all serious adverse reactions; and every version of the Standard Operating Procedures used in the processing/handling of the CTO. A ten year retention period is required for all records pertaining to the qualifications, training and competency assessment of personnel; internal audits; and reports of investigation into errors, accidents and adverse reactions that are not serious.

Personnel

Establishments are required to have sufficient personnel with the qualifications necessary to perform their assigned duties. Personnel may be qualified by education, training or experience (or a combination thereof). Establishments must have a system in place to provide personnel with initial and ongoing training and to evaluate their competency.

Facilities

Establishments are required to have facilities that are constructed and maintained so as to allow for the performance of all its activities, the efficient cleaning and disinfection to prevent contamination or cross-contamination, environmental and microbiological monitoring and control in all areas and controlled access to all areas where its activities are carried out.

Equipment

All establishments must use equipment that is cleaned and maintained, and where applicable, validated, calibrated, disinfected or sterilized before each use and revalidated or recalibrated after any repair or change that may result in a change to its specification. Any equipment used to store cells, tissues or organs must maintain the validated storage temperature.

Processing Supplies

An establishment that processes CTO must store solutions, reagents and other supplies under appropriate environmental conditions. Establishments must also ensure that supplies used for cleaning, maintenance, disinfection or sterilization do not react with, or are not absorbable by, the CTO.

Quality Assurance System

Establishments are required to have a quality assurance system in place that complies with the requirements of the regulations and enables them to carry out all their activities. An important component of a quality assurance system is the standard operating procedures (SOP), which must be kept current, be approved by the medical or scientific director, be available where relevant activities are carried out and have all changes approved by the medical or scientific director before they are implemented. Establishments are required to review SOP annually and again after any changes to the CTO Regulations.

Transitional Provisions

CTO processed prior to the coming into force of the CTO Regulations must meet the strict safety requirements for donor suitability assessment, testing, packaging, labelling and records listed in this section. Transitional provisions will allow establishments to determine the suitability of banked cells and tissues. These provisions will come into effect on the day the regulations are registered and remain in effect for five years.

International Perspective

Other international regulatory agencies have similar regulations and/or guidelines for cells and tissues. Health Canada's proposed CTO Regulations harmonizes well with other nations' policies to protect the health of recipients through oversight of the assessment of donor suitability, procurement, and processing of CTO for transplantation. For example, the United States' phased-in implementation and the use of a registration scheme, coupled with an adverse reaction reporting requirement, is similar to the proposed Canadian CTO Regulations. International harmonization provides confidence that CTO obtained from these countries should meet the same high safety standards set by the CTO Regulations, and enables an uninterrupted supply of safe CTO for transplantation.

Due to our development of the National Standards for CTO, Canada is perceived as a regulatory leader in the field of transplantation safety. This was demonstrated by the World Health Organization (WHO)'s request for Canada to host the First Global Consultation on Regulatory Requirements for Human Cells and Tissues for Transplantation in Ottawa, November 29 to December 1, 2004. In addition, Australia has requested permission to use our National Standards in the development of their regulations for cells and tissues, furthering both our image as leaders in the regulation of CTO as well as international harmonization.

Alternatives

Both regulatory and non-regulatory options were explored, including: 1-the status quo; 2-voluntary standards; 3- waiting until all elements of the full framework could be implemented at the same time; and the chosen alternative 4-implementing a safety standards-based framework in two phases.

Alternative 1

The status quo option was quickly rejected. The current F&DA and associated regulations treat CTO in an inconsistent manner. Some human tissue-derived products are classified as Medical Devices under the MDR. However, organs and minimally manipulated tissue products have never been treated as Medical Devices, neither by the transplantation industry nor by Health Canada. While CTO are currently regulated as drugs under the general provisions of the F&DA and are subject to the FDR, it is recognized that many of the regulations that apply to drugs cannot apply to organs or minimally manipulated cells and tissues.

For the above reasons, it was determined that Canada needs a framework that will encompass organs and minimally manipulated cells and tissues intended for transplantation. This decision recognized that human CTO products are therapeutic products distinguished from traditional pharmaceutical products or Medical Devices. Also, stakeholders' expectations of a standards-based regulatory framework for CTO would not be met with this alternative.

Alternative 2

The option of voluntary standards was also rejected. In a 2001 survey of all facilities handling and/or processing CTO intended for transplantation in Canada, nearly one third of all the establishments admitted to not following any recognized standards, (e.g. American Association of Tissue Banks, Eye Bank Association of America, European Association of Tissue Banks, etc.). Moreover, although the majority of facilities use some standards to maximize safety, it was not easy to verify to what extent they complied with the standards they claimed to follow. Therefore, adding new voluntary national standards would not provide the necessary assurance that the establishments meet all the requirements listed in the standards, and would not maximize the safety of CTO available to Canadians. In this regard, Health Canada could not fulfill its mandate by implementing voluntary standards. In addition, stakeholders' expectations of a standards-based regulatory framework would once again not be met with this alternative.

Alternative 3

The third option, which advocated waiting until a complete regulatory framework was ready for implementation, was also rejected. Although early in the developmental process, implementation of a full regulatory framework was intended, Health Canada changed its strategy to a two-phased approach, thus allowing the specific safety regulations to be given priority. The need was recognized for a registration (or similar) scheme to enhance the picture of handling and processing of CTO in Canada before deciding on a full compliance monitoring and enforcement regime. A further consideration was the fact that the CTO community consists of many varying establishments never before regulated, indicating that a step-wise approach to regulation was preferable.

Alternative 4 [Proposed Solution]

The fourth and chosen option was to develop regulations that incorporate the basic safety requirements for CTO by direct reference to the National Standards and implement these regulations in two phases. Phase I consists of standards-based safety requirements for CTO, coupled with the reporting of errors, accidents and adverse reactions known to have resulted or with the potential to result in infectious disease transmission, and a registration/certification of compliance for establishments that process, distribute or import CTO; Phase II will add a more comprehensive compliance monitoring and enforcement, error, accident and adverse reaction monitoring and reporting schemes. This two-phased approach was considered the best option because it allows the more critical safety components of the regulations to be implemented more quickly, thus enabling Health Canada in its mandate of safeguarding CTO products available for transplantation in Canada. It also allows sufficient time to consult with stakeholders on compliance monitoring and enforcement options available for Phase II, to incorporate their comments, and to address their concerns in the final regulations. Consultations provide an additional opportunity to identify any regional issues that should be addressed by the new regulatory framework.

Standards-based regulations specific for CTO meets the definition of Smart Regulations, being more intelligible and meeting current standards of practice in the field of transplantation. This alternative is consistent with the phased-in regulatory framework implemented in the United States (US) by the Food and Drug Administration. Since some of the establishments that supply Canada with CTO are located in the US, having compatible regulatory systems enables an uninterrupted supply of safe CTO for transplantation.

Benefits and Costs

This option will result in the following benefits and costs. They have been presented below according to sector.

Establishments involved in the transplantation of CTO

To determine the estimated costs to establishments, Health Canada contracted Goss Gilroy Inc (GGI) in 2003 to conduct a benefit-cost analysis of the National Standards for CTO and the National Standards for Blood and Blood Components. For the purposes of this RIAS, the results presented will only pertain to the analysis conducted for CTO. The GGI survey was to determine the incremental costs that establishments would incur to bring their establishments into compliance with the standards and to maintain them at that level for the next 20 years.

Costs

Since the proposed regulations are based on the National Standards, the results of the benefit-cost analysis conducted by GGI provide a good estimate of the costs required by the establishments to meet the safety-based requirements of the regulations. However, since some of the requirements in the National Standards are not covered in the proposed CTO Regulations, it is fair to conclude that the cost estimate of the National Standards provide a higher estimate than the actual costs of the proposed CTO Regulations. In addition, some of the sections in the National Standards overlap between federal and provincial jurisdiction and it was unrealistic to ask respondents to distinguish between federal or provincial jurisdiction. For example, one respondent could be aware that to meet the standards he would require one additional staff. That person may work on many activities covered by the National Standards, making it difficult to determine the exact percentage of time the person may work to meet the requirements that fall under federal jurisdiction.

Also, since 2003, it is expected that many establishments will have already invested resources in order to come into compliance with the National Standards and Health Canada's Directive and Guidance Document. The National Review of establishments that handle/process CTO for transplantation has further emphasized the need for establishments to follow the National Standards and comply with the Directive and Guidance Document. Some establishments have achieved voluntary accreditation with the Eye Bank Association of America (EBAA), the American Association of Tissue Banks (AATB), the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT), and the American Society for Histocompatibility and Immunogenetics (ASHI), which have similar safety requirements for cell and tissue processing. Thus, for the purpose of this study we anticipate some of the initial costs presented in this section may already have been addressed by some establishments. It is therefore fair to conclude that the overall cost estimates provided in this RIAS overestimate the real costs related to these proposed CTO Regulations as these costs may have already been incurred by these establishments in an effort to achieve compliance.

Methodology

A survey of the entire CTO Community population was used to quantify the incremental benefits and costs of implementing the standards. This methodology was seen as the most reliable given the fact that every identified establishment across Canada would be given an opportunity to state how they were following the standards and identify the area of potential financial burden for their establishment. It was also felt that establishments were in the best position to identify the gaps within their own facilities. The number and type of establishments surveyed in the study, as well as the response rate, is identified in Table 1.

To capture the varying information related to establishment type, six different questionnaires were developed based on the National Standards. The respondents were asked to identify their level of compliance with the requirements of the relevant standards and estimate the additional costs necessary to bridge the gaps in their compliance.

Table 1: Type and Number of Establishments and Response Rate to the Survey

Compliance Level

Respondents answered questions regarding different sections of the National Standards. The overall results demonstrate a relatively high level of self-reported compliance with all standards across establishment types (See Table 2). Clearly, a higher level of compliance will diminish an establishment's incremental cost of meeting the standards, and therefore the proposed CTO Regulations. It is anticipated that since 2003, this compliance level has increased with the National Standards and Health Canada's Directive and Guidance Document.

Table 2: Percentage of Compliance by Type of Establishment

Note : Totals for each establishment type equals 100%, representing all respondents in each category.

Estimated Costs

To determine the financial impacts, establishments were asked to quantify the gaps between their current practices and what the National Standards prescribe. Due to the relative size of the National Standards, it was deemed impossible to ask each establishment to cost each section of the standards. Therefore, cost estimates were provided in the following categories: Building, Testing, Personnel, Equipment, Computerization/Record Keeping/Reporting, and Other (which included a combination of activities like audits, training and developing SOP.

The costs were broken down according to these 6 different categories and were designated as initial (first year only) or ongoing costs (20 year period at a 5% discount rate) to recognize that some costs would be recurring and some would not. For example, hiring one staff would have cost implications for this year and upcoming years. On the other hand, adding building space would have cost implications for the construction year. The total costs (including initial costs) per establishment type and per cost category are shown in Table 3.

Table 3: Total (and Initial) Costs of Meeting the Standards by Type of Establishment and by Cost Category, ongoing costs discounted at 5%, all costs represented in millions of dollars.

Note : Initial costs are included in the Total costs per establishment type and per cost category. Discounted ongoing costs can be determined by subtracting Initial costs from Total costs.

Benefits

The objective of introducing National Standards and regulations is to ensure all required procedures related to retrieval, processing, testing, labelling, storage and distribution of CTO for transplantation are met, to reduce the incidence of adverse reactions and errors and accidents in CTO recipients. Benefits from implementing the National Standards would accrue from:

• improved handling procedures in the period predating the implementation of the standards, resulting from establishments updating their infrastructure and staff in anticipation of the new standards;
• greater consistency in handling procedures that would result from the adoption and implementation of the National Standards across all establishments; and,
• reduced costs to healthcare institutions and individuals from fewer adverse medical reactions, shorter hospital stays, etc.

GGI's benefit-cost analysis demonstrated that the minimum level of benefits for meeting the requirements of the National Standards over the next 20 years (discounted at 5%) is estimated at over $1 billion. This greatly exceeds the total costs estimated at $244 million over the same time period, identified in Table 3.

Other Costs and Benefits to Establishments - Registration

In addition to adhering to the National Standards, some establishments, such as source establishments, distributors and importers, will be required to register with Health Canada and declare their compliance with the proposed CTO Regulations. Although registration with Health Canada will be free of charge, minimal costs will be incurred by each registering establishment to prepare registration documentation. They will also have to attest to compliance with the regulations. From a trade perspective, distributors who import tissues could determine that the cost of registering does not justify remaining in this business. However, since registering with Health Canada has no attached fee, it is not anticipated that this will be an issue.

With regards to the benefits, registration of establishments will provide the regulator with a tool with which to act in the event of an infectious disease transmission. The registration will provide a known point of contact from which to trace all the effected CTO products for transplantation. Better record keeping and communication of errors, accidents and adverse reactions between all establishments will further benefit the system with improved traceability of product from donor to recipient. Therefore, the costs associated with registration activities will be outweighted by having a safer supply of CTO and will provide the regulator with a clear composition of the current Canadian industry.

Manufacturers of Medical Device Containing CTO

There is no immediate impact for manufacturers of CTO that are currently classified as Medical Devices (i.e. heart valves, dura mater, demineralized bone, wound covering containing non-viable human cells, etc.) since for Phase I, they will continue to be regulated as Medical Devices. However, this advanced notice of Health Canada's intention to regulate these products under the CTO Regulations in Phase II will give these manufacturers more time to adapt to this proposed change.

Donors and Donor Families

It is anticipated that donors and their families will not be financially affected by these regulations. However, donors and their families will benefit from increased confidence in a transplantation system that uses basic safety requirements for CTO formalized in regulations, with a long term potential of further increasing the number of donations of CTO. Requiring that CTO be handled in a safe manner emphasises the value donors place on the gift itself and reaffirms improved health benefits to the recipient.

Transplant Recipients

It is anticipated that recipients of transplanted CTO will not be financially affected by the proposed CTO Regulations. Nevertheless, it is possible that some establishments will prefer to discontinue the distribution of CTO or that foreign CTO may be lost due to a supplier's decision not to register with Health Canada. This would ultimately reduce the supply of CTO available for transplantation in the short term, while the system adjusts in the long term.

However, the benefits of transplantation are significant for recipients. This includes the increased confidence that the transplanted CTO has met basic safety requirements in its processing and handling, thus greatly reducing the possibility of an adverse reaction such as the transmission of an infectious disease. Greater consistency in processing and handling procedures by all establishments will also increase the likelihood of a successful transplantation, and a healthy recovery for the patient.

Hospitals and Transplant Programs, Provincial and Territorial Governments

While hospitals and transplant establishments may require additional staff to fulfill the new requirements for record keeping, and error, accident and adverse reaction monitoring and reporting, they will benefit from the knowledge that the CTO products available are safer for therapeutic use. Having safer CTO products will result in fewer costs to these establishments related to follow-up and treatment of recipients.

Due to the nature of the system, it is anticipated that the provincial and territorial governments will be required to fund the gap between current practice in all establishments and the requirements prescribed in the regulations. However, provincial and territorial governments have called on Health Canada to develop this regulatory framework, have participated in the development of the National Standards and were informed of the release of the Directive and Guidance Document.

Provincial and territorial governments will benefit in the long term through reduced costs to establishments, healthcare institutions and individuals from fewer adverse medical events and shorter hospital stays. These results of the benefit-cost analysis were circulated extensively among provincial/territorial governments and key stakeholders.

Public

The public will not pay a direct cost for the investments some establishments will be required to make in order to comply with the proposed CTO Regulations. Potential recipients of CTO will benefit from the peace of mind of knowing that the safety of available CTO for transplantation is maximized by the proposed regulations. Public confidence in the safety of transplantation procedures themselves may ultimately increase the number of those willing to become future CTO donors.

Evaluation

A two-staged comprehensive evaluation of the regulatory framework for CTO for transplantation is planned. A formative study to assess the extent to which the framework has been implemented as planned, and to identify areas for adjustment, will be conducted one year after implementation of the framework. A summative study of outcomes and objectives achieved will be carried out within five years of the formative study. In addition, ongoing monitoring will occur throughout the life cycle of the framework to provide Health Canada with information on the performance of the framework vis-à-vis intended objectives. This information will also be used to support the formative and summative evaluations.

Evaluation will address questions concerning: rationale and continuing need for the regulatory framework; whether the framework is being implemented as planned and is progressing towards achievement of intended outcomes; success in relation to intended outcomes; cost effectiveness relative to other potential design and delivery approaches; and lessons learned for the future. In addition to assessing the extent to which the framework has made progress towards maximizing the safety and quality of CTO for transplantation, evaluation will assess whether the standards-based approach to regulation is working as intended.

Consultation

Over the past decade, stakeholders have been given the opportunity to provide input on these developing regulations through a series of public consultations and communication activities across Canada.

In November 1986, the Health Services and Promotion Branch of Health Canada published Guidelines for Establishing Standards for Special Services in Hospitals - Organ and Tissue Donation Services in Hospitals. This was one of the first comprehensive documents to emphasize the importance of minimizing the risk of disease transmission through CTO transplantation.

One of the first external reports to recommend regulatory intervention by Health Canada, published in December 1994, was entitled "Safety of Human Organ and Tissue Transplantation in Canada". The working group for this report was assembled through Organ Sharing Canada, which was established in 1992 by a joint initiative of the executives of the Canadian Association of Transplantation and the Canadian Transplantation Society. Among the recommendations made were that "National Standards for organs and tissue transplantation be established, that a process be developed for the mandatory certification and accreditation of all organ and tissue transplant programs and that the standards established by a national agency be used for accreditation and inspection programs".

On October 29-31, 1995, Health Canada sponsored the National Consensus Conference on the Safety of Organs and Tissues for Transplantation. Participating stakeholders included representatives from the Canadian Red Cross Society, the Canadian Organ Replacement Registry, Québec-Transplant, the Eye Bank of Canada, the Ontario Ministry of Health, the Canadian Transplant Society and the British Columbia Transplant Society. These participants proposed that the Canadian General Standard on Safety of Organs and Tissues for transplantation be revised to incorporate input from experts at the conference (this standard was the very first draft version of what would become the National Standard). They further recommended that the revised Canadian General Standard on Safety on Organ and Tissues for Transplantation be accepted as a template for the development of subsets of specific standards for individual organ and tissue types. Both these recommendations have been incorporated in the development of the National Standards.

In September 1996, the interprovincial working group created by the Advisory Committee on Health Services (ACHS) produced a report entitled "Organ and Tissue Donation and Distribution in Canada: A Discussion Document". This early consultation with the provinces produced a resounding support for Health Canada's initiatives in the development of National Standards for donor screening, serological testing, record-keeping, packaging and labelling and storage, including the safety aspects of laboratory testing and transportation.

In April 1999, the report entitled "Organ and Tissue Donation and Transplantation: A Canadian Approach" was published by the House of Commons Standing Committee on Health. The Committee gave all stakeholders and the general public an opportunity to express their views on CTO. To achieve this, the Committee held public hearings over the course of two months, during which it heard from over 100 individuals. In addition, it accepted written briefs from other individuals and organizations. The Committee recommended that the Minister of Health ensure that the Canadian General Standard for Safety of Organs and Tissues for Transplantation and its subsets be approved and made mandatory through incorporation by reference into regulations made under the F&DA as soon as possible.

A report entitled "A Coordinated and Comprehensive Donation and Transplantation Strategy for Canada" was published in November 1999 by the National Coordinating Committee (NCC) for Organ and Tissue Donation, Distribution and Transplantation for the Federal / Provincial / Territorial Advisory Committee on Health Services (ACHS). The Committee recommended that "the safety standards for perfusable organs, ocular and other tissues, sperm, bone marrow and xenotransplantation be referenced in the F&DA", thus making them mandatory.

In November 2001, Health Canada published an Information Kit entitled "Towards Renewed Regulatory Frameworks for Whole Blood and Blood Components Intended for Transfusion and Cells, Tissues and Organs Intended for Transplantation and Assisted Reproduction" (Info Kit). In the Info Kit, Health Canada clearly detailed its proposals for new CTO Regulations under the F&DA. It stated that the proposed regulations would be based on the safety requirements listed in the National Standards, and that other key elements of the regulatory framework would include surveillance and adverse reaction reporting, and a compliance monitoring and enforcement strategy.

The Info Kit also explained that the CSA's process for developing National Standards requires public review of the standards. To fulfill this requirement, copies of the draft Standards were sent to provincial/territorial representatives, CTO programs and all individuals who had expressed a desire to comment on the draft. The over 1,000 comments received through the public review process were referred to the CSA Technical Committee for consideration. The National Standards have now met the requirements of the Standards Council of Canada. Namely, they were drafted through a consensus-development process, and an extensive opportunity for Canadians to express their opinions or concerns about these new National Standards has also been afforded.

The Info Kit has been updated and re-printed twice (in 2003 and 2004) in order to update the community with information regarding the regulatory framework for CTO. The Kit has been sent to all known establishments and individuals that handle and/or process CTO for transplantation, providing information on the progress of the developmental process, as well as inviting stakeholders to the many consultations and public information sessions offered over that same period. The extensive public consultation process on the new National Standards offered an opportunity for Canadians to express their opinions or concerns and was considered sufficient to move forward with regulations.

A series of one-on-one meetings with provincial/territorial representatives have provided periodic progress reports on the developing CTO Regulations and solicited feedback and collaboration in areas of overlapping jurisdiction, with a view to maximizing the safety of Canadian transplant recipients. Presentations on the CTO regulatory framework made to the Canadian Council for Donation and Transplantation (CCDT), which includes representation from the provinces and territories, has further ensured the provinces' awareness of the requirements and impact of the proposed regulations. In addition, the results of the benefit-cost analysis of the National Standards conducted by Goss Gilroy Inc in 2003 were circulated extensively among provincial/territorial governments and other key stakeholders. Consultations were held in October 2005 with provincial and territorial representatives to examine compliance monitoring and enforcement and error, accident and adverse reaction reporting options for Phase II, which provided yet another opportunity to update our partners on the CTO Regulations.

Since 2001, Health Canada has further promoted the creation of the regulatory framework for CTO by making several (greater than 50) presentations to professional associations, and provincial governments. Stakeholder input on the more comprehensive adverse reaction reporting and compliance monitoring and enforcement options for Phase II of the CTO Regulations was initiated with four regional consultations in March 2005, held in Toronto, Edmonton, Halifax and Montreal. The feedback obtained from those consultations will be considered in the development of the Phase II Regulations, and the final report has been posted on the Health Canada web site.

In summary, the consultation mechanisms employed in the creation of the proposed regulations have permitted extensive opportunity for stakeholder feedback. During the consultations, no group or association expressed concerns about the new standards-based regulations. In fact, as shown above, Health Canada has reacted to the needs expressed by the CTO community by initiating the regulatory process to maximize the safety of transplantation products across Canada. As the development of the regulatory framework continues, Health Canada continues to communicate, both in writing and in face to face meetings, with provincial/territorial governments to discuss the impact of the CTO Regulations on their jurisdictions.

A 75-day comment period will follow publication in Canada Gazette, Part I. Stakeholders, including the following, will be notified directly of the pre-publication: CTO programs identified in the National Review; the pharmaceutical industry and associations, Deans and Registrars of Pharmacy, Medicine and Dentistry, Provincial and Territorial Ministries of Health, professional associations of physicians and dentists, hospitals and other CTO stakeholders.

The results of all consultations will be analysed and all recommendations, including comments received following the pre-publication of the CTO Regulations in the Canada Gazette, Part I, will be considered for incorporation into the final version of the Safety of Human Cells, Tissues and Organs for Transplantation Regulations.

Compliance and Enforcement

The compliance monitoring and enforcement scheme that accompanies the CTO Regulations provides Health Canada with a means of staying abreast of existing CTO establishments, the types of CTO being processed, the activities in which they are engaged, and their level of compliance with the regulations. Establishment registration will provide Health Canada with information that can be used to assess the risks associated with establishments' activities related to the handling/processing of CTO, as well as provide an enabling mechanism to assess compliance.

Prior to the enactment of the CTO Regulations, compliance will continue to be monitored through the ongoing National Review of establishments handling and/or processing CTO for transplantation. In the interim, establishments must adhere to the basic safety requirements specified in Health Canada's Directive and Guidance Document.

Contact

Liz Anne Gillham-Eisen
Cells, Tissues and Organs Unit
Policy and Promotion Division
Biologics and Genetic Therapies Directorate
Health Canada
Address Locator 0702A
2nd Floor, Health Protection Building
Tunney's Pasture
Ottawa, Ontario
K1A 0K9
FAX: (613) 952-5364
E-mail: BGTD_PPD_DPP@hc-sc.gc.ca

Notice is hereby given that the Governor in Council, pursuant to section 30^a of the Food and Drugs Act, proposes to make the annexed Safety of Human Cells, Tissues and Organs for Transplantation Regulations.

Interested persons may make representations with respect to the proposed Regulations within 75 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice and be addressed to Liz Anne Gillham-Eisen, Unit Manager, Cells, Tissues and Organs, Policy and Promotion Division, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Department of Health, Postal Locator 0702A, Health Protection Building, Tunney's Pasture, Ottawa, Ontario K1A 0L2 (fax: (613) 952-5364; e-mail: BGTD_PPD_DPP@hc-sc.gc.ca).

Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act.

Ottawa, , 2005

Diane Labelle
Acting Assistant Clerk of the Privy Council

^a S.C. 2004, c. 23, s. 2

(SOR/DORS)

Safety of Human Cells, Tissues and Organs for Transplantation Regulations

Interpretation

Definitions

1. The following definitions apply in these Regulations.

"accident"

"accident" means an unexpected event that is not attributable to a deviation from the standard operating procedures or applicable laws and that could adversely affect a transplant recipient or establishment personnel or the safety, efficacy or quality of cells, tissues or organs.

"Act"

"Act" means the Food and Drugs Act.

"adverse reaction"

"adverse reaction" means an undesirable response in the recipient to transplanted cells, tissues or organs, including the transmission of a disease or disease agent.

"banked"

"banked", with respect to cells and tissues, means processed cells and tissues that have been determined safe for transplantation and that are stored by the source establishment in its inventory and available for distribution or transplantation.

"cell"

"cell" means the fundamental biological unit of a human organism that is for use in transplantation.

"distribute"

"distribute" does not include to transplant.

"donor"

"donor" means a living or deceased person from whom cells, tissues or organs are retrieved.

"donor assessment record"

"donor assessment record" includes the donor screening, any available donor testing results, information obtained from the donor's medical records and a copy of the donor consent.

"donor identification code"

"donor identification code" means the unique numeric or alphanumeric designation that is assigned by the source establishment to a donor under section 48 and that associates each cell, tissue and organ, or part of one, to that donor.

donor screening"

"donor screening" means an evaluation based on the donor's medical and social history and physical examination, the results of any diagnostic procedures performed, and, if applicable, the autopsy.

"donor suitability assessment"

"donor suitability assessment" means an evaluation based on the donor screening and

1. in the case of cells and tissues and of organs retrieved from live donors, all donor testing results; and
   
2. in the case of organs retrieved from deceased donors, the donor testing results that are necessary at the time of transplantation.

"donor testing"

"donor testing" means the laboratory tests and measurements done on a donor or donor specimen to determine all of the following:

1. whether the donor has or ever had a transmissible disease or is or ever was infected with a transmissible disease agent;
   
2. donor compatibility information; and
   
3. the degree of functionality of the cell, tissue or organ that is to be retrieved.

"error"

"error" means a deviation, whether intentional or not, from the standard operating procedures or applicable laws and that could adversely affect a transplant recipient or establishment personnel or the safety, efficacy or quality of cells, tissues or organs.

"establishment"

"establishment" means a person, a partnership or an unincorporated entity, or a part of any of them, that carries out any of the following activities in respect of cells, tissues or organs:

1. importation;
   
2. processing;
   
3. distribution; and
   
4. transplantation.

"exceptional distribution"

"exceptional distribution" means the distribution under sections 36 to 38 of cells, tissues or organs that have not been processed under these Regulations.

"exterior label"

"exterior label" means the label that is affixed to the exterior package.

"exterior package"

"exterior package" means the outermost package in which a cell, tissue or organ is delivered, transported or shipped.

"general standard"

"general standard" means National Standard of Canada CAN/CSA-Z900.1-03 entitled Cells, Tissues, and Organs for Transplantation and Assisted Reproduction: General Requirements, as amended from time to time.

"homologous"

"homologous", in respect of a cell, tissue or organ, means that the cell, tissue or organ performs the same basic function after transplantation.

"interior label"

"interior label" means the label that is affixed to the interior package.

"interior package"

"interior package" means the innermost package of a cell, tissue or organ that has a non-sterile exterior.

"lymphohematopoietic standard"

"lymphohematopoietic standard" means National Standard of Canada CAN/CSA-Z900.2.5-03 entitled Lymphohematopoietic Cells for Transplantation, as amended from time to time.

"medical director"

"medical director", in respect of an establishment, means a physician or dentist who is licensed under the laws of the jurisdiction in which the establishment is situated to provide health care or dental care and who is responsible for the application of the standard operating procedures and for all medical or dental procedures carried out there, as the case may be.

"minimally manipulated"

"minimally manipulated" means

1. in respect of a structural tissue, that the processing does not alter the original characteristics that are relevant to its claimed utility for reconstruction, repair or replacement; and
   
2. in respect of cells and nonstructural tissue, that the processing does not alter the biological characteristics that are relevant to their claimed utility.

"ocular standard"

"ocular standard" means National Standard of Canada CAN/CSA-Z900.2.4-03 entitled Ocular Tissues for Transplantation, as amended from time to time.

"organ"

"organ" means a perfusable human organ for use in transplantation, whether whole or in parts, and whose specific function is intended to return after revascularization and reperfusion.

"organ standard"

"organ standard" means National Standard of Canada CAN/CSA-Z900.2.3-03 entitled Perfusable Organs for Transplantation, as amended from time to time.

"package insert"

"package insert" means the document that is prepared by the source establishment to accompany a cell, tissue or organ.

"processing"

"processing", in respect of cells, tissues and organs, means any of the following activities:

1. donor screening;
   
2. donor testing;
   
3. donor suitability assessment;
   
4. retrieval, except for organs;
   
5. post-retrieval testing;
   
6. preparation for use in transplantation, except for organs;
   
7. preservation;
   
8. quarantine;
   
9. banking; and
   
10. packaging and labelling.

"quality assurance system"

"quality assurance system" means the co-ordinated activities of an establishment that relate to the safety of cells, tissues and organs. It includes

1. the standard operating procedures;
   
2. records to demonstrate that the standard operating procedures have been implemented; and
   
3. internal audit processes to verify that the standard operating procedures are being implemented.

"scientific director"

"scientific director", in respect of an establishment, means an individual who is responsible for the application of the standard operating procedures and for all technical procedures carried out there.

"serious adverse reaction"

"serious adverse reaction" means an adverse reaction that results in any of the following consequences to the recipient:

1. their in-patient hospitalization or its prolongation;
   
2. their persistent or significant disability or incapacity;
   
3. the need for medical, dental or surgical intervention to preclude permanent damage or the permanent impairment of a body function;
   
4. a life-threatening condition; and
   
5. their death.

"source establishment"

"source establishment" means

1. in the case of an organ from a deceased donor, the relevant organ donation organization;
   
2. in the case of an organ from a living donor or lymphohematopoietic cells that are not banked, the relevant transplant establishment; and
   
3. in the case of tissues or banked lymphohematopoietic cells, the relevant cell or tissue bank.

"standard operating procedures"

"standard operating procedures" means the component of the quality assurance system that comprises instructions that set out the processes and procedures to follow in carrying out the activities of an establishment.

"tissue"

"tissue" means a functional group of human cells for use in transplantation. It includes the cells and tissues set out in the definition "tissue" in section 3.1 of the general standard, except for paragraph (l).

"tissue standard"

"tissue standard" means National Standard of Canada CAN/CSA-Z900.2.2-03 entitled Tissues for Transplantation, as amended from time to time.

"transplant"

"transplant" means to implant cells, tissues or organs into a recipient.

"validation"

"validation" means the documented process of demonstrating that a system, activity, process, technical procedure or piece of equipment will consistently lead to the expected results.

Application

Scope of Regulations

2. These Regulations apply only to organs and minimally manipulated cells and tissues.

Non-application -- various

3. (1) These Regulations do not apply to any of the following therapeutic products:

1. cells, tissues and organs that are for non-homologous use;
   
2. cells, tissues and organs that are for autologous use;
   
3. heart valves and dura mater;
   
4. tissues and cells that, except for lymphohematopoietic cells that are derived from bone marrow, peripheral blood or cord blood, have a systemic effect and depend on their metabolic activity for their primary function;
   
5. medical devices that contain cells or tissues and that are used in investigational testing involving human subjects under Part 3 of the Medical Devices Regulations;
   
6. cells, tissues and organs that are used in clinical trials under Division 5 of Part C of the Food and Drug Regulations;
   
7. Class IV medical devices that are regulated under the Medical Devices Regulations;
   
8. blood components, blood products and whole blood, except for cord blood for use in lymphohematopoietic cell transplantation;
   
9. cells and tissues that are regulated under the Assisted Human Reproduction Act or any of its regulations; and
   
10. semen that is regulated under the Processing and Distribution of Semen for Assisted Conception Regulations.

Non-application -- regulations made under the Act

(2) No other regulation made under the Act applies to cells, tissues or organs that are the subject of these Regulations.

Prohibition

Distribution and importation

4. (1) Subject to subsection (2) and sections 36 to 38, no establishment shall distribute or import a cell, tissue or organ unless it is processed by a registered establishment under these Regulations and determined safe for transplantation.

Exception -- importation of organs

(2) An establishment may import an organ from an establishment that is not registered if the conditions set out in section 36 are met.

Registration

Requirement to register -- source establishments

5. (1) Every source establishment must be registered under these Regulations.

Requirement to register -- distribution and importation

(2) An establishment, except a retrieval establishment and a transplant establishment, that distributes or imports cells, tissues or organs must be registered under these Regulations.

Application

6. (1) An application for registration of an establishment must be made in the form established by the Minister, be dated and signed by the medical director or scientific director, and contain all of the following information:

1. the establishment's name and civic address, and its postal address if different, and the name and telephone number of a person to contact for further information with respect to the application;
   
2. a detailed description of the types of cells, tissues and organs that the establishment processes, distributes or imports;
   
3. a description of the types of processing, distribution or transplantation activities that the establishment carries out or for which it is responsible;
   
4. the period during which the establishment has been in operation; and
   
5. a statement dated and signed by the medical director or scientific director that certifies that the establishment is in compliance with these Regulations.

Information on request

(2) An establishment must provide the Minister, on written request, with any relevant information necessary to complete the application, by the date specified in the Minister's request.

Registration number

7. (1) On review of an application for registration, if the Minister determines that the information provided in the application is complete, the Minister must issue a registration number to the establishment.

Validity

(2) Subject to section 9, a registration number is valid until December 31 in the year after the year in which it is issued.

Refusal

8. The Minister may refuse to issue a registration number to an establishment if he or she has reason to believe that any of the information provided by the establishment in its application is false, misleading, inaccurate or incomplete.

Suspension or revocation

9. The Minister may suspend or revoke a registration number if he or she receives a notice under section 10 or has reason to believe that any of the following circumstances exists:

1. a serious adverse reaction has occurred that is attributable to the establishment;
   
2. information provided by the establishment under section 6 is false, misleading, inaccurate or incomplete;
   
3. the establishment has failed to notify the Minister in accordance with section 10; or
   
4. the establishment is not in compliance with these Regulations.

Ongoing requirement to notify Minister

10. (1) Subject to subsection (2), an establishment must notify the Minister in writing of any change in the information provided in its application for registration, within 30 days after the change is made.

Cessation of activity

(2) If an establishment ceases to process, distribute or import cells, tissues or organs, it must notify the Minister in writing of that fact, within 90 days after it ceases that activity.

Contents of notice

(3) The notice must be dated and signed by the medical director or scientific director and include all of the following information:

1. the establishment's name and civic address, and its postal address if different;
   
2. the establishment's registration number;
   
3. the date on which the change or cessation became effective; and
   
4. in the case of the cessation of an activity, the disposition of the cells, tissues and organs in the establishment's possession.

Additional information

11. An establishment must provide the Minister, on written request, with any additional relevant information to demonstrate that the activities it carries out are in compliance with these Regulations, by the date specified in the Minister's request.

Source Establishment

Responsibility

12. A source establishment is responsible for the processing of cells, tissues and organs, whether the processing is carried out by the source establishment itself or by another establishment, and for determining whether the cells, tissues and organs are safe for transplantation.

Processing

General

Validation

13. An establishment must use validated processes, systems, equipment and supplies to process cells, tissues and organs.

When pooling permitted

14. An establishment may only pool cells, tissues or organs from different donors during processing to create a therapeutic dose for a single recipient.

Donor Suitability Assessment

Requirements -- cell, tissue and organ donors

15. In assessing the suitability of a donor of cells, except lymphohematopoietic cells, or of tissues or organs, an establishment must perform all of the following steps:

1. obtain the donor information and history in accordance with sections 12.2 and 12.3 of the general standard;
   
2. determine that the donor is not unsuitable to donate on the basis of the contraindications or exclusion criteria set out in section 13.1.3 of the general standard and in Annex E to that standard; and
   
3. perform the donor serological testing specified in section 14.2.6 of the general standard, except paragraph 14.2.6.1d) in the case of ocular tissue and except paragraph 14.2.6.1e) in the case of ocular tissue and organs.

Hemodilution algorithm

16. In determining whether to reject a donor, an establishment must apply a hemodilution algorithm if a donor pretransfusion blood sample is unavailable.

Additional exclusion criteria -- tissue donors

17. In assessing the suitability of a tissue donor, except an ocular tissue donor, an establishment must perform both of the following steps:

1. determine that the donor is not unsuitable to donate on the basis of the contraindications or exclusion criteria set out in section 13.1.2 of the tissue standard; and
   
2. perform any tests specified in section 14.2.6 of the tissue standard.

Additional exclusion criteria -- ocular tissue donors

18. In assessing the suitability of an ocular tissue donor, an establishment must determine that the donor is not unsuitable to donate on the basis of the contraindications or exclusion criteria set out in sections 13.1.3 to 13.1.6 of the ocular standard.

Additional requirements -- organ donors

19. In assessing the suitability of an organ donor, an establishment must perform all of the following steps:

1. obtain the donor information and history in accordance with sections 12.2.2.3, 12.2.2.4, 12.2.3.4 and 12.2.3.7 of the organ standard;
   
2. determine that the donor is not unsuitable to donate on the basis of the contraindications or exclusion criteria set out in section 13.2.2 of the organ standard; and
   
3. perform the tests specified in sections 14.1.2, 14.2.6.3, 14.2.6.6 and 14.3.2 of the organ standard.

Requirements -- lymphohematopoietic cells

20. In assessing the suitability of a donor of lymphohematopoietic cells, an establishment must perform all of the following steps:

1. obtain the donor information and history in accordance with sections 12.2.2.2 and 12.2.2.3 of the lymphohematopoietic standard;
   
2. perform a physical examination of the donor;
   
3. determine that the donor is not unsuitable to donate on the basis of the contraindications or exclusion criteria set out in section 13.1.3 of the lymphohematopoietic standard; and
   
4. perform the tests specified in sections 12.2.2.4 and 14.2.3 of the lymphohematopoietic standard.

Retrieval

Retrieval interval -- tissues

21. An establishment that retrieves tissue from a deceased donor must carry out the retrieval within the validated maximum interval between the cardiac asystole of the donor and the retrieval of the tissue.

Testing

Licensed diagnostic devices

22. (1) In vitro diagnostic devices that are used by an establishment in the testing of donor blood for transmissible disease agents or markers under these Regulations must be licensed, for screening donors, either

1. in Canada, if the testing is performed in Canada; or
   
2. in Canada or the United States, if the testing is performed outside Canada.

Exception

(2) Despite paragraph (1)(b), in the case of lymphohematopoietic cells that are imported into Canada for transplantation into a specific recipient, the in vitro diagnostic devices may be licensed in Canada or any other jurisdiction.

Bacteriological testing -- tissues

23. An establishment that retrieves tissue, except ocular tissue, must perform bacteriological testing in accordance with section 14.3 of the tissue standard, except for section 14.3.2.8.

Packaging and Labelling

Packaging

Packaging materials

24. An establishment that packages cells, tissues or organs must inspect all packaging materials before use to ensure that they are free from damage.

Labelling

Language requirement

25. All of the information that is required by these Regulations to appear on a label or package insert must be in either English or French.

Cells

26. An establishment that distributes cells must ensure that all of the applicable information, as indicated by an "X", set out in the table to this section is provided on the interior label, in the package insert and on the exterior label.

Table to Section 26

Labelling Requirements for Cells

Tissues

27. An establishment that distributes tissues must ensure that all of the applicable information, as indicated by an "X", set out in the table to this section is provided on the interior label, in the package insert and on the exterior label.

Table to Section 27

Organs

28. An establishment that distributes organs must ensure that all of the applicable information, as indicated by an "X", set out in the table to this section is provided on the interior label, in the package insert and on the exterior label.

Table to Section 28

Additional information required

29. An establishment that imports and distributes, or that only distributes, a cell or tissue must add the following information to that required by sections 26 and 27:

1. on the exterior label and package insert, the name of the establishment, its civic address and the name and telephone number of a contact person; and
   
2. on the interior and exterior labels and package insert, the establishment's registration number.

Storage and Quarantine

Storage limits

30. An establishment that stores cells, tissues or organs must observe their validated maximum storage periods.

Storage location

31. An establishment must store cells, tissues and organs in a location that has appropriate environmental conditions that maintain the safety of the cells, tissues and organs and that is secure against the entry of unauthorized persons.

Segregation -- autologous and allogeneic uses

32. An establishment that stores cells, tissues or organs must ensure that those that are intended for autologous use are segregated from those intended for allogeneic use.

Segregation -- transmissible disease agents and markers

33. An establishment that stores cells, tissues or organs must ensure that any of them that are untested or for which the results of tests on donor blood samples are positive or reactive for transmissible disease agents or markers or unavailable are segregated from all other cells, tissues and organs.

Quarantine -- cells and tissues

34. (1) A source establishment must ensure that cells and tissues are quarantined until all of the following processing activities are completed:

1. the donor is found to be suitable after completion of the donor suitability assessment;
   
2. bacteriological test results are reviewed and found to be acceptable, if applicable; and
   
3. all processing records are reviewed for completeness and compliance with the standard operating procedures.

Additional requirement -- live donors of tissue

(2) In addition to the requirements set out in subsection (1), the source establishment must quarantine tissues that are retrieved from live donors in accordance with section 17.2 of the general standard.

Quarantine -- new transmissible diseases

35. (1) Whenever a new transmissible disease agent or marker is added to section 14.2.6 of the general standard, to section 12.2.2.4 or 14.2.3 of the lymphohematopoietic standard or to section 14.2.6 of the tissue standard, a source establishment must quarantine all of its banked cells and tissues until they are tested for that disease agent or marker.

Untested cells and tissues

(2) Any cell or tissue in respect of which testing is not carried out in accordance with subsection (1) may not be determined safe for transplantation.

Exceptional Distribution

Conditions

36. A source establishment may distribute cells, tissues or organs that have not been determined safe for transplantation if all of the following conditions are met:

1. a cell, tissue or organ that has been determined safe for transplantation is not immediately available;
   
2. the transplant physician or dentist, based on their clinical judgement, requests their medical director to authorize the exceptional distribution;
   
3. the medical director of the transplant establishment authorizes the exceptional distribution; and
   
4. the transplant establishment obtains the informed consent of the recipient.

Notice in donor record

37. (1) A source establishment that distributes cells, tissues or organs under section 36 must put a notice of exceptional distribution in the donor record.

Notice in recipient record

(2) A transplant establishment that authorizes the exceptional distribution of cells, tissues or organs under section 36 must put a notice of exceptional distribution in the recipient record.

Contents of notice

(3) A notice of exceptional distribution must contain all of the following information:

1. the name of the transplanted cell, tissue or organ;
   
2. except in the case of an organ that is the subject of an importation, the provisions of these Regulations with which the cell, tissue or organ is not in compliance at the time of its distribution;
   
3. the justification for the distribution that formed the basis for the medical director's decision to authorize it;
   
4. the name of the source establishment that distributed the cell, tissue or organ;
   
5. the name of the transplant establishment, of the transplant physician or dentist and of the medical director who authorized the distribution; and
   
6. the time and date of the written authorization of the distribution and a copy of the authorization signed by the medical director.

Follow-up

38. A source establishment that distributes a cell, tissue or organ under section 36 before the donor suitability assessment is complete must, after the distribution, complete the assessment, carry out any other appropriate follow-up testing and notify the relevant transplant establishment of the results.

Error, Accident and Adverse Reaction Investigation

Errors and Accidents

Required action by establishments

39. (1) An establishment that has reasonable grounds to believe that an error or accident has occurred during the processing of cells, tissues or organs must take all of the following steps without delay:

1. determine the nature and scope of the error or accident;
   
2. determine the donor identification codes of all implicated cells, tissues and organs;
   
3. identify and quarantine any other implicated cells, tissues and organs in its possession; and
   
4. notify all of the following establishments:
   
   
   1. the source establishment,
      
   2. the establishment from which it received the implicated cells, tissues and organs, and
      
   3. any establishment to which it distributed implicated cells, tissues or organs.

Contents of notice

(2) The notice must include all of the following information:

1. a description of the error or accident;
   
2. the donor identification codes of all implicated cells, tissues and organs;
   
3. the name of any suspected transmissible disease or disease agent or a description of how the integrity of the implicated cells, tissues or organs may have been compromised; and
   
4. a statement that all implicated cells, tissues and organs are to be quarantined immediately and until the source establishment completes an investigation.

Written notice

(3) If the notice is given verbally, a confirmatory written notice must be sent as soon as possible afterwards.

Further action by source establishment

40. On receipt of a notice under section 39, or after having complied with the requirements of that section, the source establishment must take both of the following actions:

1. initiate an investigation into the suspected error or accident without delay; and
   
2. notify the Minister in writing that an investigation has been initiated with respect to an error or accident that could lead to a serious adverse reaction involving the transmission of an infectious disease or disease agent.

Adverse Reactions

Required action by establishments

41. (1) An establishment that has reasonable grounds to believe that an unexpected adverse reaction has occurred must take all of the following steps without delay:

1. determine the donor identification code of the transplanted cell, tissue or organ;
   
2. identify and quarantine any other cells, tissues and organs in the establishment's possession that could potentially cause an adverse reaction in the same way as the transplanted cell, tissue or organ; and
   
3. notify all of the following establishments:
   
   
   1. the source establishment,
      
   2. the establishment from which it received the implicated cells, tissues and organs, and
      
   3. any establishment to which it distributed implicated cells, tissues or organs.

Contents of notice

(2) The notice must include all of the following information:

1. a description of the adverse reaction;
   
2. the donor identification code of all implicated cells, tissues and organs;
   
3. the name of any suspected transmissible disease or disease agent or a description of how the integrity of the implicated cells, tissues or organs may have been compromised; and
   
4. a statement that any implicated cells, tissues and organs are to be quarantined immediately and until the source establishment completes an investigation.

Written notice

(3) If the notice is given verbally, a confirmatory written notice must be sent as soon as possible afterwards.

Further action by source establishment

42. On receipt of a notice under section 41, or after having complied with the requirements of that section, the source establishment must take both of the following actions:

1. initiate an investigation into the adverse reaction without delay; and
   
2. in the case of an unexpected serious adverse reaction, notify the Minister in writing that an investigation has been initiated with respect to an unexpected serious adverse reaction that is thought to involve the transmission of an infectious disease or disease agent.

Investigations

Requirement to cooperate

43. An establishment must provide the source establishment that is conducting an investigation with any relevant information in its possession with respect to cells, tissues or organs that it distributed or transplanted.

Notice to Minister and timing of notice

44. The notice under section 40 or 42 must be given at the following times and include the following information:

1. within 24 hours after the start of the investigation, a preliminary report that includes the name of the suspected infectious disease or disease agent involved; and
   
2. within 30 days after the start of the investigation and every 30 days after that until the final report is made, an update on the steps taken in the investigation during those 30 days.

When investigation shows no contamination or compromise

45. If the results of the investigation show that the implicated cells, tissues or organs are not contaminated or compromised, the source establishment must notify every establishment that was notified under paragraph 39(1)(d) or 41(1)(c) to that effect in writing.

When investigation inconclusive or shows contamination or compromise

46. If the results of the investigation show that some or all of the implicated cells, tissues or organs are contaminated or compromised, or the results are inconclusive, the source establishment must notify every establishment that was notified under paragraph 39(1)(d) or 41(1)(c) to that effect in writing.

Final report to Minister

47. On completion of an investigation described in paragraph 40(b) or 42(b), the source establishment must submit a final report to the Minister that contains all of the following information:

1. the results of the investigation;
   
2. the final disposition of the cells, tissues and organs that were the subject of the investigation and the reasons for that disposition; and
   
3. any corrective actions taken.

Records

Donor identification code -- source establishment

48. (1) A source establishment must assign a donor identification code to each donor of a cell, tissue or organ for which it has responsibility.

Donor identification code -- all establishments

(2) Every establishment must ensure that the donor identification code is a component of its records system.

Requirement

49. An establishment's records must contain information with respect to all cells, tissues and organs that it processes, distributes, imports or transplants that identifies

1. the establishment from which it receives the cells, tissues and organs; and
   
2. all establishments to which it distributes the cells, tissues and organs.

Record quality

50. Records kept by an establishment must be accurate, complete, legible and indelible.

Source establishment records

51. The source establishment must keep records with respect to cells, tissues and organs that it processes that contain at least all of the following information:

1. the donor identification code;
   
2. documentation showing completion of the donor suitability assessment;
   
3. a description of the cells, tissues and organs retrieved from the donor;
   
4. the name of the retrieval establishment;
   
5. documentation of all processing activities;
   
6. all technical information related to the equipment and instruments used during processing;
   
7. the notice of exceptional distribution, if any; and
   
8. documentation of any errors, accidents and adverse reactions in connection with cells, tissues or organs retrieved from the donor that it banked or distributed, their investigation, assessment and monitoring and any corrective action taken.

Transplant establishment records

52. The transplant establishment must keep records with respect to cells, tissues and organs that it transplants that contain at least all of the following information:

1. a description of the transplanted cells, tissues or organs;
   
2. the donor identification code;
   
3. the notice of exceptional distribution, if any, and confirmation that the donor suitability assessment was completed as required by section 38;
   
4. information that allows the identification of the recipient;
   
5. a copy of the recipient consent; and
   
6. documentation of any errors, accidents and adverse reactions in connection with those cells, tissues or organs, their investigation, assessment and monitoring and any corrective action taken.

Establishments to cooperate

53. An establishment must provide the source establishment and the transplant establishment with all of the information described in sections 51 and 52 that it possesses to complete the establishment's records.

Retention -- indefinite

54. (1) An establishment must keep the following records indefinitely:

1. the records described in section 49;
   
2. the records described in section 51, except paragraph (f), and except paragraph (h) in the case of errors and accidents and adverse reactions that are not serious;
   
3. the records described in section 52, except paragraph (f) in the case of errors and accidents and adverse reactions that are not serious;
   
4. the record of destruction or other disposition of cells, tissues and organs, if applicable;
   
5. investigation reports of serious adverse reactions; and
   
6. every version of the standard operating procedures.

Retention -- 10 years

(2) An establishment must keep the following records for 10 years:

1. from the time an individual ceases to be an employee of the establishment, documentation of the qualifications, training and competency of that employee;
   
2. reports of internal audits conducted under section 67; and
   
3. investigation reports of errors and accidents and adverse reactions that are not serious.

Storage of records

55. An establishment must keep records in a location that has appropriate environmental conditions and that is secure against the entry of unauthorized persons.

Personnel, Facilities, Equipment And Supplies

Personnel

Sufficient number and qualifications

56. (1) An establishment must have sufficient personnel who are qualified by education, training or experience to perform their respective tasks to carry out its activities.

Competency

(2) An establishment must have a system for the orientation and training, both initial and ongoing, of personnel and for the evaluation of their competency.

Facilities

Requirements

57. An establishment's facilities must be constructed and maintained to permit all of the following:

1. the carrying out of all of its activities;
   
2. the efficient cleaning, maintenance and disinfection of the facilities in a way that prevents contamination and cross-contamination;
   
3. environmental and microbiological monitoring and control appropriate to the areas where its activities are carried out; and
   
4. controlled access to all areas where its activities are carried out.

Equipment and Supplies

Requirements -- equipment

58. All equipment used by an establishment in carrying out its activities must be cleaned and maintained and, whenever applicable,

1. validated for its intended purpose;
   
2. calibrated;
   
3. disinfected or sterilized before each use; and
   
4. revalidated or recalibrated, as appropriate, after any repair or change is made to it that results in a change to its specifications.

Requirements -- storage equipment

59. An establishment that uses equipment to store cells, tissues or organs must ensure that the equipment maintains the validated storage temperature.

Processing supplies

60. An establishment that processes cells, tissues or organs must store solutions, reagents and other supplies under appropriate environmental conditions.

Cleaning supplies

61. An establishment that processes cells, tissues or organs must ensure that it uses supplies for cleaning, maintenance, disinfection or sterilization that do not react with, or that are not absorbable by, the cells, tissues or organs.

Quality Assurance System

General

Quality assurance system required

62. An establishment must ensure that it has a quality assurance system in place that complies with the requirements of these Regulations for all activities that it carries out.

Standard Operating Procedures

Standard operating procedures required

63. An establishment must have standard operating procedures with respect to the safety of cells, tissues and organs for all activities that it carries out.

Requirements

64. The standard operating procedures of an establishment must meet all of the following requirements:

1. be in a standardized format;
   
2. be approved by the medical director or scientific director;
   
3. be available for use at all locations where the relevant activities are carried out;
   
4. have any changes to the procedures approved by the medical director or scientific director before being implemented; and
   
5. be kept up-to-date.

Routine review

65. (1) An establishment must review its standard operating procedures annually and again after any amendment to these Regulations.

Supplementary review

(2) When the report of an investigation of an error, accident or adverse reaction under section 47 or of an internal audit reveals a deficiency in a standard operating procedure, the establishment must review that procedure.

Records of compliance

66. An establishment must keep records that demonstrate that it has implemented the standard operating procedures.

Internal audit

67. An establishment must have annual internal audits conducted to verify that its activities comply with these Regulations and with its standard operating procedures, by personnel who do not have direct responsibility for the activities being audited.

Powers of Inspectors

Certificate of designation

68. The certificate of designation given under subsection 22(2) of the Act must

1. certify that the person named in it is an inspector for the purposes of the Act; and
   
2. be signed by the Minister and by the person named in it.

Taking photographs

69. An inspector may, in the administration of these Regulations, take photographs of any of the following:

1. any article that is referred to in subsection 23(2) of the Act;
   
2. any place where the inspector believes on reasonable grounds that any article referred to in paragraph (a) is processed; and
   
3. anything that the inspector believes on reasonable grounds is used or is capable of being used in the processing of any article referred to in paragraph (a).

Transitional Provisions

General

Application of sections 71 to 82

70. Cells and tissues that were processed before the coming into force of these Regulations and that do not meet the requirements of these Regulations may be imported or distributed if they are processed in accordance with sections 71 to 82.

Prohibition

71. Despite section 70, cells and tissues described in that section may not be imported or distributed unless the requirements of subsection 48(2) and section 49 are met.

Processing

General

Validation and pooling

72. Sections 13 and 14 apply to cells and tissues described in section 70.

Donor Suitability Assessment

When source establishment in possession of cells or tissues

73. The source establishment that is in possession of cells or tissues described in section 70 must ensure that the requirements of sections 71, 72 and 74 to 79 are met in order to determine that they are safe for transplantation.

When transplant establishment in possession of cells or tissues

74. The transplant establishment that is in possession of cells or tissues described in section 70 must ensure that they have been determined safe for transplantation by the source establishment.

Review of documentation

75. (1) In determining the safety of cells and tissues for the purpose of sections 73 and 74, the source establishment must review the donor screening documentation to verify that both of the following conditions are met:

1. the donor screening was based on all of the information set out in section 12.2 of the general standard; and
   
2. subject to subsections (2) and (3), the contraindications or exclusion criteria described in the following provisions were applied:
   
   
   1. paragraph 15(b) and sections 17 and 18 in the case of tissues, and
      
   2. paragraph 20(c) in the case of lymphohematopoietic cells.

Exceptions

(2) If the donor screening documentation indicates that specific questions were not asked to elicit signs, symptoms and risk factors regarding the contraindications and exclusion criteria specified in paragraph (1)(b), the source establishment may nevertheless distribute the cells and tissues if the documentation indicates both of the following:

1. that general questions were asked about the donor's medical history and that either
   
   
   1. the following specific questions were asked:
      
      
      1. subject to subsection (3), those regarding high-risk behaviours as set out in Annex E to the general standard, except question E.1e) in the case of a deceased donor, and
         
      2. in the case of ocular tissue, those regarding the donor's family history of Creutzfeldt-Jakob disease, or
         
   2. the donor is requalified by asking the specific questions omitted on the donor screening; and
      
2. the testing requirements of sections 76 and 77 are met.

Exception -- exclusion criteria requiring temporary deferral

(3) If the donor screening documentation indicates that the specific questions referred to in clause (2)(a)(i)(A) were not asked, in the case of those of the exclusion criteria for high-risk behaviours set out in Annex E to the general standard that require a temporary deferral of up to 12 months, the source establishment may nevertheless distribute the cells and tissues if the donor is retested for the antibodies to the transmissible disease agent after the cells or tissues have been quarantined for at least six months.

Testing

Serological testing

76. (1) The source establishment in respect of cells or tissues described in section 70 must verify that the serological testing specified in paragraphs 14.2.6.1a) to e) and section 14.2.6.2 of the general standard was carried out, except paragraphs 14.2.6.1d) and e) in the case of ocular tissues.

When serological testing not done -- all diseases

(2) If any of the serological testing was not done, the source establishment may nevertheless distribute the cells and tissues if any of the following circumstances applies:

1. serum samples from the donor exist and serological tests are done on them in accordance with paragraphs 15(c) and 20(d);
   
2. there are no serum samples from the donor, but validated procedures for the detection of the relevant disease agent or marker are used and the disease agent or marker is not present; or
   
3. in the case of a living donor, the donor is retested in accordance with paragraphs 15(c) and 20(d).

When serological testing not done -- HTLV and syphilis

(3) If the serological testing did not include HTLV-I and -II and syphilis testing, the source establishment may nevertheless distribute the cells and tissues distributed if any of the following circumstances applies:

1. the cells and tissues are leukocyte-rich, serological tests for anti-HTLV-I and -II were not done, but a validated method that inactivates HTLV-I and -II was used during the processing of the cells and tissues;
   
2. serological tests for anti-HTLV-I and -II were not done and the cells and tissues are leukocyte-poor; or
   
3. serological tests for syphilis were not done but a validated method that inactivates syphilis was used during the processing of the cells and tissues.

Living donors -- banked tissues

77. In the case of banked tissues described in section 70 that are from living donors, the source establishment must take all of the following steps:

1. quarantine the tissues for at least 180 days;
   
2. retest the donor for transmissible disease agents or markers in accordance with paragraph 15(c); and
   
3. ensure that the tissues conform with section 17.2 of the general standard.

Bacteriological testing -- tissues

78. (1) The source establishment in respect of tissues described in section 70, except ocular tissues, must verify that the bacteriological testing was carried out in accordance with section 14.3 of the tissue standard, except for section 14.3.2.8.

When no records of bacteriological testing

(2) The source establishment may distribute tissues described in section 70, except ocular tissues, for which there are no records of bacteriological testing if a sample of the banked tissue is tested as described in subsection (1).

Blood typing

79. The source establishment in respect of cells or tissues described in section 70 must verify that the cells and tissues comply with section 14.2.7 of the general standard.

Packaging and Labelling

Packaging

80. Section 24 applies to cells and tissues described in section 70.

Minimum information on interior label

81. (1) The following information must appear on the interior label of a cell or tissue described in section 70:

1. the donor identification code; and
   
2. the name of the cell or tissue.

Information to be added to package insert

(2) A source establishment that is in possession of cells or tissues described in section 70 must ensure that any of the information required by sections 26 and 27 that is not already on the interior label is added to the package insert.

Exception

82. Sections 26 and 27 do not apply to cells and tissues that are in the possession of a transplant establishment for transplant at that establishment.

Coming Into Force

Coming into force

83. (1) These Regulations come into force on the day on which they are registered.

Transitional provisions

(2) Sections 70 to 82 cease to be in force five years after the day referred to in subsection (1).

Notice is hereby given that the Governor in Council, pursuant to section 30^a of the Food and Drugs Act, proposes to make the annexed Regulations Amending Schedule D to the Food and Drugs Act (Blood and Blood Derivatives).

Interested persons may make representations with respect to the proposed Regulations within 75 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice, and be addressed to Liz Anne Gillham-Eisen, Unit Manager -- Cells, Tissues and Organs, Policy and Promotion Division, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Department of Health, Postal Locator 0702A, Health Protection Building, Tunney's Pasture, Ottawa, Ontario K1A 0L2 (fax: (613) 952-5364; e-mail: BGTD_PPD_DPP@hc-sc.gc.ca).

Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act.

Ottawa, 2005

Diane Labelle
Acting Assistant Clerk of the Privy Council

^a S.C. 2004, c. 23, s. 2

(SOR/DORS)

Regulations Amending Schedule D to the Food and Drugs Act (Blood and Blood Derivatives)

Amendment

1. The reference to

Blood and blood derivatives

in Schedule D to the Food and Drugs Act^a is replaced by the following:

Blood and blood derivatives, except cord blood and peripheral blood that are a source of lymphohematopoietic cells for transplantation

Coming Into Force

2. These Regulations come into force on the day on which they are registered.

^a R.S., c. F-27

Notice is hereby given that the Governor in Council, pursuant to section 30^a of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Medical Devices Regulations.

Interested persons may make representations with respect to the proposed Regulations within 75 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice, and be addressed to Liz Anne Gillham-Eisen, Unit Manager -- Cells, Tissues and Organs, Policy and Promotion Division, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Department of Health, Postal Locator 0702A, Health Protection Building, Tunney's Pasture, Ottawa, Ontario K1A 0L2 (fax: (613) 952-5364; e-mail: BGTD_PPD_DPP@hc-sc.gc.ca).

Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act.

Ottawa, , 2005

Diane Labelle
Acting Assistant Clerk of the Privy Council

^a S.C. 2004, c. 23, s. 2

(SOR/DORS)

Regulations Amending the Medical Devices Regulations

Amendment

1. Subrule 14(1) of Part 1 of Schedule 1 to the Medical Devices Regulations^a is replaced by the following: (1) Subject to subrule (2), the following medical devices are classified as Class IV:

1. a medical device that is manufactured from or that incorporates human or animal cells or tissues or their derivatives; and
   
2. a medical device that is manufactured from or that incorporates a product produced through the use of recombinant DNA technology.

Coming Into Force

2. These Regulations come into force on the day on which they are registered.

^a SOR/98-282