TCPS 2 (2022) – Chapter 12: Human Biological Materials Including Materials Related to Human Reproduction

Introduction

The use of materials originating from human bodies for research contributes greatly to the advancement of knowledge. The sources of these materials can be from patients following diagnostic or therapeutic procedures, autopsy specimens, donations of organs or tissue from living or dead humans, body wastes (including urine, saliva, sweat) or abandoned tissue. Biological materials may also be sought from individuals for use in a specific research project. Once collected, biological materials may be held in biobanks to serve as a research resource for many years.

Ethical considerations raised by research involving human biological materials centre on acceptable access to, and use of, the materials, potential privacy concerns arising from the handling of information derived from such materials, and the special status some individuals and groups accord to the human body and its parts. Because the significance of biological materials varies among individuals and groups, it is important to assess the ethics of research involving such materials with an awareness of and sensitivity to the known values, beliefs, and attitudes of those from whom the materials originated.

Sections A to D of this chapter provide guidance on research involving human biological materials. For the purposes of this Policy, human biological materials include tissues, organs, blood, plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva, and other body fluids. Section E addresses research involving the subset of biological materials that are related to human reproduction. Section F addresses research involving the subset of human biological materials known as "human pluripotent stem cells."

As noted in Chapter 2, an individual whose data and/or biological materials are used in research becomes a participant. In regard to human biological materials, individuals may become participants by agreeing to provide a biological sample for use in a particular project. Individuals may also choose to donate organs, tissue or their entire body for research that occurs after their death. In this way, they become participants through their donation. Researchers may seek access to human biological materials for secondary use in research, and in accordance with Section C of this chapter, a research ethics board (REB) may waive a requirement for individual consent.

A. Key Concepts

Identifiable Human Biological Materials

Human biological materials that may reasonably be expected to identify an individual, alone or in combination with other available information, are considered identifiable biological materials for the purposes of this Policy. Identifiability of human biological materials must be assessed relative to the current state of science and the availability of other sources of identifying information about participants and increasingly sophisticated methods of re-identification. De-identified human biological materials include those that have been anonymized or coded. The assessment of whether human biological materials are identifiable is made in the context of a specific research project.

Types of Human Biological Materials

The following categories, similar to those found in Chapter 5, provide guidance for assessing the extent to which human biological materials could be used to identify an individual:

Due to continuing technological development in genetics, individuals with access to stored human biological materials are increasingly able to use genetic markers to link a non-identifiable sample with an identified sample. For this reason, genetic analysis has made it more difficult to categorize human biological materials as anonymous or anonymized. The definitions above relate to identification of individuals; however, some research involving human biological materials, especially genetic research, may involve identification of groups, even though the human biological materials are non-identifiable at an individual level. Researchers and REBs should be aware of, and guard against, threats to individual privacy and autonomy that arise from re-identification risks, as well as risks to groups, particularly where sensitive research findings will be linked to specific groups.

To maintain confidentiality, it may seem desirable to use anonymized or anonymous human biological materials. However, the scientific requirements of many studies may necessitate use of identifiable human biological materials, to link materials with information about participants, and to avoid using different samples from the same individual. Use of anonymized or anonymous human biological materials has the disadvantage of making it impossible to offer the benefits of research findings to participants and their families, or to alert them to relevant clinical findings. This is particularly significant when research may disclose a previously undiagnosed condition, such as HIV infection or an inherited predisposition to breast cancer, for which potentially effective treatments are available. Use of non-identifiable human biological materials also precludes withdrawal of a participant's material from research use, even at the participant's request.

B. Collection of Human Biological Materials

Human biological materials may be obtained in different ways:

  1. They may be collected expressly for a specific research purpose.
  2. They may be collected incidentally to medical or diagnostic procedures with no initial intent to be used in research.
  3. They may be collected for research or medical or diagnostic purposes with some expectation that they may, or will, also be used in future research, although the precise research project(s) may not be known at the time.

The first category above refers to the initial collection of human biological materials for research, which is described in this section. The latter two categories are relevant to subsequent, secondary uses of human biological materials for research that may not have been conceived at the time the tissue was taken. Secondary use of biological materials is described in Section C.

Article 12.1

Research involving collection and use of human biological materials requires REB review and:

  1. consent of the participant who will donate biological materials; or
  2. consent of an authorized third party on behalf of a participant who lacks decision-making capacity, taking into account any research directive that applies to the participant; or
  3. consent of a deceased participant through a donation decision made prior to death, or by an authorized third party.

Application

Article 12.1 applies prospectively, that is, prior to the collection of human biological materials for research purposes. It applies the general elements of consent in Chapter 3 to the collection and use of human biological materials. During the consent process, a clear distinction should be made between consent to research participation and consent for any clinical procedure or test. In practice, this may mean separate consent information and forms, but in any event the different uses must be clearly explained. Individuals who do not wish to contribute human biological materials for research are free to withhold consent without penalty, and without prejudicing access to any treatment they would otherwise receive. For individuals who lack decision-making capacity, the guidance developed in Chapter 3 regarding authorized third parties shall be observed.

Where a participant has expressed preferences for future research participation in a research directive before losing decision-making capacity, researchers and authorized third parties shall take such directives into account during the consent process. Chapter 3 provides guidance on research directives. REBs and researchers should be aware that provincial human tissue gift laws may provide a legal framework for the donation of tissue upon death.

Article 12.2

To seek consent for use of human biological materials in research, researchers shall provide prospective participants or authorized third parties with applicable information as set out in Article 3.2 as well as the following details:

  1. the type and amount of biological materials to be taken;
  2. the manner in which biological materials will be taken, and the safety and invasiveness of the procedures for acquisition;
  3. the intended uses of the biological materials, including any commercial use;
  4. the measures employed to protect the privacy of and minimize risks to participants;
  5. the length of time the biological materials will be kept, how they will be preserved, the location of storage (e.g., in Canada, outside Canada), and the process for disposal, if applicable;
  6. any anticipated linkage of biological materials with information about the participant; and
  7. the researchers' plan for handling results and findings, including clinically relevant information and incidental findings.

Application

Chapter 3, especially Article 3.2, provides detailed guidance on the need for consent to participation in research. Where broad consent is being contemplated, researchers shall refer to Article 3.13. Article 12.2 provides additional guidance on information that prospective participants generally require to make an informed decision to donate biological materials for use in research. While all the basic guidelines of Chapter 3 regarding consent apply to research involving human biological materials, some deserve special attention. For example, explaining the potential for commercialization or financial conflict of interest is important, as some research with human biological materials may involve the possibility of significant commercial gain for researchers or sponsors. The process for requesting withdrawal of human biological materials from research shall also be clearly explained, along with an explanation of the conditions under which researchers would not be able to remove a participant's data from the project. For instance, where participants request the withdrawal of their biological materials, information already derived from the materials and aggregated into findings cannot be withdrawn. Anonymization of human biological materials may also preclude subsequent withdrawal. Chapter 3 provides further guidance on handling incidental findings.Footnote 1

C. Consent and Secondary Use of Human Biological Materials for Research Purposes

Chapter 5 provides detailed guidance on secondary use of information for research purposes (in particular, see Articles 5.5A, 5.5B, and 5.6). The following section adapts the provisions in Chapter 5 to the specific context of research involving secondary use of human biological materials. As researchers who seek to use human biological materials for research will often also seek access to information about individuals from whom the materials originate, this section and Chapter 5 should be read together.

Secondary use refers to the use in research of human biological materials originally collected for a purpose other than the current research purpose. A researcher may seek to use human biological materials left over from a diagnostic examination or surgical procedure, or materials that were collected for an earlier project. Reasons to conduct secondary analyses include: avoidance of duplication in primary collection and the associated reduction of burdens on participants; corroboration or criticism of the conclusions of the original research; comparison of change in a research sample over time; application of new tests of hypotheses that were not available at the time of original collection; and confirmation that the data or materials are authentic. Privacy concerns and questions about the need to seek consent arise, however, when human biological materials provided for secondary use in research can be linked to individuals, and when the possibility exists that individuals can be identified in published reports, or through linkage of human biological materials with other data (Article 5.7).

Article 12.3A

Researchers who have not obtained consent from participants for secondary use of identifiable human biological materials shall only use such material for these purposes if they have satisfied the REB that:

  1. identifiable human biological materials are essential to the research;
  2. the use of identifiable human biological materials without the participant's consent is unlikely to adversely affect the welfare of individuals from whom the materials were collected;
  3. the researchers will take appropriate measures to protect the privacy of individuals and to safeguard the identifiable human biological materials;
  4. the researchers will comply with any known preferences previously expressed by individuals about any use of their biological materials;
  5. it is impossible or impracticable to seek consent from individuals from whom the materials were collected; and
  6. the researchers have obtained any other necessary permission for secondary use of human biological materials for research purposes.

If a researcher satisfies all the conditions in Article 12.3A(a) to (f), the REB may approve the research without requiring consent from the individuals from whom the biological materials were collected.

Application

In the case of the secondary use of identifiable human biological materials, researchers must obtain consent unless the researcher satisfies all the requirements in Article 12.3A.

The exception to the requirement to seek consent in this article is specific to secondary use of identifiable human biological materials. The terms of Article 3.7 address alteration of consent in other circumstances and do not apply here.

Secondary use of human biological materials identifiable as originating from a specific First Nations, Inuit or Métis community, or a segment of the Indigenous community at large, is addressed in Articles 9.20 to 9.22.Footnote 2

"Impracticable" refers to undue hardship or onerousness that jeopardizes the conduct of the research; it does not mean mere inconvenience.Footnote 3 Consent may be impossible or impracticable when the group is very large or when its members are likely to be deceased, geographically dispersed or difficult to track. Attempting to track and contact members of the group may raise additional privacy concerns. Financial, human, and other resources required to contact individuals and seek consent may impose undue hardship on the researcher. In some jurisdictions, privacy laws may preclude researchers from using personal information to contact individuals to seek their consent for secondary use of information.

At the time of initial collection, individuals may have had an opportunity to express preferences about future uses of their biological materials, including research uses. See paragraphs (d) and (i) in the Application of Article 3.2. Custodians that hold human biological materials have an obligation to respect the individual's expressed preferences. Where an individual does not want biological materials used for future research, custodians should remove these biological materials from any collections used or made available for research. Alternatively, individuals may have made an express donation of biological materials for research in accordance with human tissue gift legislation.

In cases where the proposed research involves issues of greater sensitivity (e.g., research involving stigmatizing conditions), an REB may require that researchers engage in discussion with people whose perspectives can help identify the ethical implications of the research, and suggest ways to minimize any associated risks. Discussion is not intended to serve as proxy consent. Rather, a goal of discussion is to seek input regarding the proposed research, such as the design of the research, measures for privacy protection, and potential uses of findings. Discussion may also be useful to determine whether the research will adversely affect the welfare of individuals from whom the biological materials were collected. Researchers shall advise the REB of the outcome of such discussions. The REB may require modifications to the research proposal based on these discussions.

Article 12.3B

Researchers shall seek REB review, but are not required to seek participant consent, for research that relies exclusively on the secondary use of non-identifiable human biological materials.

Application

The onus will be on the researcher to establish to the satisfaction of the REB that, in the context of the proposed research, the human biological materials to be used can be considered non-identifiable for all practical purposes. For example, the secondary use of coded human biological materials may identify individuals in research projects where the researcher has access to the key that links the participants' codes with their names. Consent would be required in this situation. However, the same coded human biological materials may be assessed as non-identifiable in research projects where the researcher does not have access to the key. Consent would not be required in this situation.

Article 12.4

When secondary use of identifiable human biological materials without the requirement to seek consent has been approved under Article 12.3A, researchers who propose to contact individuals for additional biological materials or information or for reasons related to the welfare of the participant shall, prior to contact, seek REB approval of the plan for making contact.

Application

In certain cases, a research goal may be achieved only through follow-up contact with individuals to collect additional biological materials or information. In rare cases, during the course of analysis, a researcher may discover a finding that has a potential impact on an individual's welfare. If the researcher suspects that welfare implications to the participant may be significant, the researcher and REB should refer to the guidance in Article 3.4, which addresses material incidental findings. Under Article 12.3A, the REB may have approved secondary use without the requirement to seek consent based, in part, on the impossibility or impracticability of seeking consent from all individuals whose biological materials are proposed for use in research. Where contact with a subgroup is feasible, researchers may subsequently wish to attempt to make contact with some individuals to obtain additional information or biological materials. Contact with individuals whose previously collected biological materials have been approved for secondary use in research raises privacy concerns. Individuals might not want to be contacted by researchers or might be upset that identifiable biological materials were disclosed to researchers without their consent. The potential benefits of follow-up contact must clearly outweigh the risks to individuals of follow-up contact, and the REB must be satisfied that the proposed manner of follow-up contact minimizes risks to individuals. The proposed plan should explain who will contact individuals to invite their participation in the research (e.g., a representative of the organization that holds the individual's biological materials) and the nature of their relationship with those individuals. Researchers must also ensure that a plan for follow-up contact complies with applicable privacy legislation; for example, some privacy laws prohibit researchers from contacting individuals unless the custodian of the information has first obtained individuals' consent to be contacted. Whenever possible, it is preferable that re-contact with participants be carried out by the organization or the custodian holding the biological materials. Researchers will need to seek consent from individual participants for any new collection of data or biological materials. Article 3.1 provides further guidance on consent and approaches to recruitment.

D. Storage and Banking of Human Biological Materials

The collection and retention of human biological materials in biobanks creates an ongoing resource for research. Biobanks vary widely in their characteristics: some are very small, while others hold biological materials from thousands of individuals; they may be disease-specific or contain materials from a wide population base. Different types of human biological materials may be stored in biobanks, such as blood, tumour or tissue samples. Biobanks may include, or be linked with, databases of identifiable or non-identifiable information. Materials held in a biobank may be intended only for use in a specific project, or a biobank may be established to provide access to biological materials for numerous projects over many years. Researchers engaged in multi-site research may seek access to materials held in biobanks in different jurisdictions (see Chapter 8 for additional guidance).

Biobanking facilitates research with human biological materials and offers potential benefits to society. Access to stored human biological materials – and associated information about individuals whose materials are banked – can be particularly useful in helping researchers understand diseases that result from complex interactions between our genetic makeup, environmental exposure, and lifestyles. Banking of human biological materials may also present risks to individuals whose biological materials and other personal information are stored, accessed, used, retained, and disclosed through a biobank. Research involving such materials may also implicate the interests of biological relatives and others with shared genetic characteristics.

Article 12.5

Institutions and researchers that maintain biobanks:

  1. shall ensure that they have or use appropriate facilities, equipment, policies, and procedures to store human biological materials safely, and in accordance with applicable standards; and
  2. shall establish appropriate physical, administrative and technical safeguards to protect human biological materials and any information about participants from unauthorized handling.

Application

Safe storage of human biological materials is important to maintain their scientific value, and to protect materials and associated information about participants. Procedures for storage and record keeping shall include effective measures to ensure that participants' identities are protected. Such measures include the security of facilities and effective procedures for data handling, record keeping and regulating access to human biological materials and information. Appropriate governance of biobanks is also important for managing access to and use of stored biological materials. The appropriate governance structure and management of a biobank will vary depending on its size and usage.

Organizations that maintain biobanks may have their own policies on privacy of, confidentiality of and access to materials. Researchers should be aware of requirements for compliance with such policies. For example, researchers may be required to apply to the organization for permission to access biological samples, and they may be required to enter into an agreement with the organization that sets out conditions for research access to and use of materials in the biobank.

Identifiable data derived from human biological materials may be linked to other research or public databases. Such data linking can be a powerful research tool and a valuable resource for monitoring the health of populations, understanding factors influencing disease, and evaluating health services and interventions. However, data linkage also raises separate privacy issues, discussed in Chapter 5, Section E.

E. Research Involving Materials Related to Human Reproduction

Researchers who conduct research involving human biological materials related to human reproduction shall follow applicable guidance expressed in other chapters of this Policy. This section provides further guidance for research involving embryos, fetuses, fetal tissue, and reproductive materials. For the purposes of this Policy, the following definitions apply:Footnote 4

While research involving materials related to human reproduction has great promise for assisting the development of healthy pregnancies, curing illness, and repairing or rebuilding tissue, it raises special ethical considerations. Accordingly, this research has provoked vigorous debate. Discussion and reflection should continue as our scientific understanding develops.

Significant ethical issues include consent to research involving materials related to human reproduction, privacy concerns, the risk of harm to those who provide reproductive materials, an embryo or fetus, and potential commodification of reproductive capabilities and materials related to reproduction. Researchers and REBs have a continuing duty to remain mindful of the public interest in these issues, and to respect policy, legal and regulatory requirements. In particular, researchers and REBs shall be aware of the detailed requirements and prohibitions set out in the Assisted Human Reproduction Act.

Article 12.6

In addition to requirements in this chapter that apply to all research involving human biological materials, the following guidelines apply to research involving materials related to human reproduction:

  1. Research using materials related to human reproduction in the context of an anticipated or ongoing pregnancy shall not be undertaken if the knowledge sought can reasonably be obtained by alternative methods.
  2. Materials related to human reproduction for research use shall not be obtained through commercial transaction, including exchange for services.

Application

Because of the risk of harm to the woman or the fetus, Article 12.6(a) requires that the use of these materials be avoided where pregnancy is anticipated or ongoing, if research goals may be accomplished in some other way.

Article 12.6(b) reflects concerns about the commercialization or commodification of human reproduction. Exchange for services refers, for instance, to trading a service, such as a medical treatment, for an in vitro embryo or gamete.

Research Involving Human Embryos

Article 12.7

Research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if:

  1. the research is intended to benefit the embryo;
  2. research interventions will not compromise the care of the woman, or the subsequent fetus;
  3. researchers closely monitor the safety and comfort of the woman and the safety of the embryo; and
  4. consent was provided by the gamete donors.
Application

Research potentially altering the embryo by chemical or physical manipulation shall be distinguished from research directed at ensuring normal fetal development. For example, the evaluation of potential teratogens and their effects on certain cell lineages may use early embryos, but those embryos must not be implanted for an ongoing pregnancy.

The Assisted Human Reproduction Act prohibits the creation of a human embryo specifically for research purposes, with the limited exception of creating an embryo for the purpose of improving, or providing instruction in, assisted reproduction procedures.

Article 12.8

Research involving embryos that have been created for reproductive or other purposes permitted under the Assisted Human Reproduction Act, but are no longer required for these purposes, may be ethically acceptable if:

  1. the ova and sperm from which they are formed were obtained in accordance with Article 12.7;
  2. consent was provided by the gamete donors;
  3. embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy; and
  4. research involving embryos will take place only during the first 14 days after their formation by combination of the gametes, excluding any time during which embryonic development has been suspended.
Application

Research on embryos requires the consent of the gamete donors. The REB may not waive the requirement for such consent. In particular, researchers and REBs should be aware of the Assisted Human Reproduction (Section 8 Consent) Regulations under the Assisted Human Reproduction Act.Footnote 5

Research Involving Fetuses and Fetal Tissue

Article 12.9

Research involving a fetus or fetal tissue:

  1. requires the consent of the woman; and
  2. shall not compromise the woman's ability to make decisions regarding continuation of her pregnancy.
Application

Research may be undertaken on methods to treat, in utero, a fetus with genetic or congenital disorders. Because the fetus and the woman cannot be treated separately, any intervention to one involves an intervention to the other. Research involving a fetus or fetal tissue shall be guided by respect for the woman's autonomy and physical integrity. Guidance provided in other chapters of this Policy (e.g., consent, privacy and confidentiality, inclusion, and exclusion) will also apply. Researchers should ensure that a clear distinction is made between consent to research and consent for any clinical procedures or testing. In practice, this may mean separate consent information and documents, but regardless of the process employed, the differences between research and clinical procedures must be clearly explained.

Where the fetus has been born alive and viable, research involving human biological materials associated with the child must meet the conditions of Article 3.9. A fetus that has been born alive and viable is a child with its own independent interests.

F. Research Involving Human Pluripotent Stem Cells

Guidance regarding a proportionate approach to research ethics review, consent, privacy, confidentiality, and research with human biological materials and other ethical guidance described in earlier chapters of this Policy apply equally to research involving human pluripotent or human totipotent stem cells. This section provides further guidance for research involving human pluripotent or human totipotent stem cells. In addition to following the guidance provided in this Policy, researchers are responsible for compliance with all applicable legal and regulatory requirements (e.g., the Assisted Human Reproduction Act and its Regulations and the Food and Drugs Act and its Regulations).

Stem Cell Oversight Committee (SCOC)

In recognition of the complex ethical issues associated with research involving pluripotent stem cells, a Stem Cell Oversight Committee (SCOC) was created by CIHR in 2003.

To ensure compliance with Chapter 12, Section F of this Policy, SCOC reviews research involving human pluripotent and human totipotent stem cells that:

Applications that receive SCOC approval shall then be submitted to local REBs as part of the local research ethics review process. SCOC does not review research involving human pluripotent stem cells that come from somatic (non-embryonic) tissue and that are not going to be transferred into humans or non-human animals.

Article 12.10

Research involving human pluripotent or human totipotent stem cells that have been derived from an embryonic source, and/or that will be grafted or transferred in any other form into humans or non-human animals requires review and approval by SCOC and an REB. The researcher shall provide evidence of SCOC approval to the REB.

Application

  1. Types of stem cell research that comply with this Policy and require SCOC review include:

    1. Research for the purpose of deriving or studying human embryonic stem cell lines or other cell lines of a pluripotent or totipotent nature from human embryos, provided that:
      1. the embryos used, whether fresh or frozen, were originally created for reproductive purposes and are no longer required for such purposes; and
      2. consent was provided by the persons for whom the embryos were originally created for reproductive purposes. Where third party donor gametes were used to create the embryo, the third party gamete donor(s) shall have given, at the time of donation, consent to the unrestricted research use of any embryos created, when these embryos are no longer required for reproductive purposes. Where the third party gamete donors referred to in this paragraph are anonymous, it is not possible to seek their consent for embryo use. In such cases, the responsibility of consent for embryo use has, in effect, been transferred to the persons for whom the embryos were created for reproductive purposes; and
      3. neither the ova nor the sperm from which the embryos were created, nor the embryos themselves, were obtained through commercial transactions (i.e., were acquired by payment of money in excess of costs actually incurred, or in exchange for services).
    2. Research on anonymized or coded human embryonic stem cell lines that have been created in Canada, or created elsewhere and imported for research purposes, provided that:
      1. those created in Canada were developed in compliance with this Policy or, prior to December 9, 2014, the Guidelines for Human Pluripotent Stem Cell Research. It is incumbent on the recipient of such cell lines to ensure that this is the case. The recipient shall provide satisfactory evidence to SCOC and the local REB that the cell lines fulfill the consent provisions before research can begin;
      2. the recipient of stem cell lines created in a country other than Canada provides SCOC with satisfactory evidence that the manner in which the stem cell lines were created in the country of origin, including the embryo donors' consent, satisfies the laws and policies of that country. Should SCOC find that the manner of creation of these stem cell lines and the consent provisions vary significantly from the principles of this Policy, or, prior to December 9, 2014, the Guidelines for Human Pluripotent Stem Cell Research, it may not approve the use of these cell lines in stem cell research in Canada.
    3. Research involving the grafting or any other form of transfer of human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, cells derived from those cells, or other human cells that are likely to be pluripotent into non-human animals, from birth to adulthood, provided that:
      1. the research is designed to reconstitute a specific tissue or organ to derive a pre-clinical model or to demonstrate that the cells are pluripotent (e.g., teratoma formation); and
      2. these non-human animals grafted with human stem cells will not be used for reproductive purposes.
    4. Research involving the grafting or any other form of transfer of human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, cells derived from those cells, or other human cells that are likely to be pluripotent into humans with legal capacity shall be in compliance with the Food and Drugs Act and its Regulations, including the Safety of Human Cells, Tissues and Organs for Transplantation Regulations.

  2. Types of stem cell research that are not permitted under Canadian legislation and shall not be conducted at all include:

    1. Research involving the creation of human embryos specifically to derive stem cell lines or other cell lines of a pluripotent or totipotent nature;
    2. Research involving the creation of blastocysts from cells derived from pre-blastocyst stage human embryos;
    3. Research involving somatic cell nuclear transfer into human oocytes (cloning) or involving stimulation of an unfertilized egg to produce a human embryo (parthenogenesis) for the purposes of developing human embryonic stem cell lines or other cell lines of a pluripotent or totipotent nature;
    4. Research involving the directed donation of human embryos or human embryonic stem cell lines to particular individuals;
    5. Research in which human or non-human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, or other cells that are likely to be pluripotent or totipotent are combined with a human embryo;
    6. Research in which human or non-human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, or other cells that are likely to be pluripotent or totipotent are grafted or transferred in any other form to a human fetus;
    7. Research in which human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, or other cells that are likely to be pluripotent or totipotent are combined with a non-human embryo; or
    8. Research in which human embryonic stem cells, embryonic germ cells, induced pluripotent stem cells, or other cells that are likely to be pluripotent or totipotent are grafted or transferred in any other form to a non-human fetus.

Consent

Chapter 3, especially Articles 3.1 to 3.5, provides detailed guidance on the need to seek consent for participation in research. The following articles provide additional guidance for situations that are unique to stem cell research.

Article 12.11

Embryos no longer needed for reproductive purposes may be donated for use in research (including research to derive and study human embryonic stem cells). Embryo donors and gamete donors, if these are different individuals, shall be advised of all available options in respect of the use of the embryos and their consent sought prior to the use.

Article 12.12

At the time when the embryos are to be used for research to derive and study embryonic stem cells (including other human cells or cell lines of a pluripotent or totipotent nature), consent of the embryo donors shall be sought again if this constitutes a substantive deviation from the original terms of consent. Research shall not proceed unless consent is obtained.

Application

This requirement affirms the right of the donors to withdraw consent and is necessary because of the possible lengthy delay between the time at which the original consent is given and the time at which the embryos are utilized for research purposes. Members of the health care team treating and/or counselling prospective participants should not be the persons to seek consent from the embryo donors at the time of re-consent. If the gamete donors are not the same individuals as the embryo donors, and appropriate consent for the unrestricted research use of the embryos was given at the time of gamete donation, then a renewal of the consent provided by the gamete donors is not required.

Article 12.13

When seeking consent for human embryonic stem cell research, in addition to the information outlined in Article 3.2, researchers shall provide to prospective research participants the following. An:

  1. explanation that the cell line(s) will be anonymized or coded;
  2. assurance that prospective research participants are free to not participate and have the right to withdraw at any time until it becomes impossible or impracticable to do so;
  3. explanation that the research could result in the production of a stem cell line that could be maintained for many years, distributed to other parts of the world, and used for various research purposes;
  4. explanation that the research participants will not directly benefit financially from any future commercialization of cell lines; nor will there be any personal benefit in terms of dispositional authority over any embryonic cell lines created (i.e., there will be no directed donation of the cells or cell lines to particular individuals).
Application

Article 12.13(b) refers to the withdrawal of both consent and human biological materials. The process for requesting withdrawal of human biological materials from research shall be clearly explained, along with an explanation of the conditions under which withdrawal may become impossible or impracticable. For instance, where participants request the withdrawal of their biological materials, information already derived from the materials and aggregated into findings cannot be withdrawn. Anonymization of human biological materials may also preclude subsequent withdrawal. Once an anonymized or coded cell line is created, it may have a wide distribution, making withdrawal of materials almost impossible.

Creation of Excess Embryos

Article 12.14

Researchers shall not ask, encourage, induce or coerce members of the health care team to generate more embryos than necessary for the optimum chance of reproductive success. This is tantamount to creating embryos for research, which is prohibited under the Assisted Human Reproduction Act.

National Registry

SCOC maintains an electronically accessible national registry of human pluripotent stem cell lines and human totipotent stem cell lines derived from an embryonic source, generated in Canada. Induced human pluripotent stem cell lines are not listed with the registry, as they are not derived from embryonic sources.

Article 12.15

All human pluripotent stem cell lines or human totipotent stem cell lines derived directly from embryos under the auspices of an institution that is eligible to receive Agency funds shall be listed with the national registry of human embryonic stem cell lines and made available by the researcher to other researchers, subject to reasonable cost-recovery charges.

Privacy and Confidentiality

The secondary use of human biological materials for research purposes must meet the requirements of Articles 12.3A and 12.4, which provide detailed guidance on protecting personal information of participants. The following articles provide additional guidance for situations that are unique to stem cell research. In these cases, all human cells or cell lines should be delivered in an anonymized or coded form, and, if coded, the key code should be accessible only to a custodian or trusted third party who is independent of the researcher who receives the cells (Chapter 5, Section A, Types of Information).

Article 12.16

All human pluripotent stem cell lines or human totipotent stem cell lines shall be anonymized or coded unless the research only involves the directed donation of induced pluripotent stem cells.

Application

While research involving the directed donation of human embryonic stem cell lines is not permitted under this Policy (Article 12.10.2[c]), research involving the directed donation of induced pluripotent stem cells is permitted, as induced pluripotent stem cells are not derived from human embryos.

Article 12.17

All researchers who make stem cell lines available to other academics shall ensure that the cell lines are anonymized or coded.

Conflicts of Interest

Chapter 7 (in particular Articles 7.2 and 7.4) provides guidance on conflicts of interest. The following articles provide additional guidance for situations that are unique to stem cell research.

Article 12.18

Stem cell research teams shall not include members of the health care team treating and/or counselling prospective participants who could influence the prospective participants' decisions to donate their embryos.

Application

This article seeks to minimize the risk that, for the purposes of stem cell research, prospective participants will feel pressured to create more embryos than needed for reproductive purposes or be pressured to donate embryos no longer needed for reproductive purposes. There may be a risk of undue influence where health care team members are also members of the stem cell research team (Article 3.1).

Article 12.19

When researchers or their institutions have, or acquire, financial interests in the outcome of the stem cell research, including but not limited to income from commercial firms supporting their research, stock holdings in corporations supporting their research, or patents in products produced through their research, they shall disclose this information to SCOC, the REB and current and prospective research participants (see Articles 7.2 and 7.4 regarding institution and researcher conflicts of interest). In some instances, disclosure may not be a sufficient response to concerns about actual, perceived or potential conflicts of interest. Researchers and/or their institutions may be asked to remedy any possible distortion of proper procedures attributable to such conflicts.

Article 12.20

Copies of contracts between researchers, institutions and industry sponsors and any relevant budgetary information shall be provided to SCOC and the REB to examine and evaluate any potential or actual conflicts of interest and to ensure the right to publish in a timely manner without undue restriction.

G. Cell Line Exemptions

Exemption from REB review for de-identified cell lines

The following article exempts from REB review research that relies exclusively on the re-use of human somatic cell lines where privacy concerns are low and where REB review would not add any further protections for research participants beyond those already provided by the source of the cell lines. "Relies exclusively" means that, from a human participation perspective, the research only involves the human cell line. Research that involves the donor or other human participants in conjunction with the cell line requires REB review.

While this exemption may eventually be applied to other types of data and human biological materials as well, at present it is limited to a narrow exemption.

Article 12.21

REB review is not required for research that relies exclusively on the re-use of de-identified human somatic cell lines where:

  1. the researcher will comply with known consent terms;
  2. the researcher does not know or have access to the identity of the participant;
  3. the researcher will not take any steps to identify the participant; and
  4. the research is unlikely to reveal the identity of the participant.
Application

REB review of research involving the re-use of an existing de-identified cell line (e.g., research involving a cell line that has been purchased from a commercial biobank) may not increase protection for participants and may unnecessarily burden researchers and REBs. Risks to privacy are low if the researcher does not know or have access to the identity of the participant (b). Risks are even lower if the research is unlikely to reveal the identity of the participant (d) and the researcher will not take any steps to identify the participant (c). Moreover, if consent terms are known to the researcher, they must comply with them to ensure respect for participant autonomy (a).

All members of the research team must comply with the conditions in Article 12.21 for the exemption to apply. Researchers must consider all stages of the research when determining whether it meets the conditions of the exemption, including, for example, analysis and dissemination of results. When in doubt about the applicability of this exemption, researchers should consult their REBs.

Should any of the conditions described in Article 12.21 change during the conduct of the research, researchers must inform their REB prior to conducting further research with the cell line, because the risks to the participant may have increased if the terms of the exemption are not fulfilled. The urgency of informing the REB after it has been determined that a condition of Article 12.21 has changed is commensurate with the level of risk that the change presents to participant welfare. The REB has the discretion to determine the appropriate course of action (e.g., pause the study and wait for REB approval). In determining the appropriate course of action, the REB should consider the issues relevant to participant protection such as how the participant identity was revealed, to whom, and how participant privacy will be protected going forward. Consideration should be given as to whether consent can and should be sought from the participant for the research to continue.

Ongoing research having received REB approval and that complies with the exemption criteria outlined in Article 12.21 would no longer require continuing research ethics review. Researchers are responsible for reporting such a change to their REB (Article 6.16).

The exemption in Article 12.21 does not invalidate other TCPS articles that may apply to the research being considered. The following are two examples. Research involving the derivation of induced pluripotent stem cells that will be transferred into humans or animals requires REB review (Article 12.10). Research involving the re-use of human biological materials (including cell lines), identifiable as originating from an Indigenous community, within Canada or internationally, requires REB review (Article 9.20). Note that the TCPS definition of "human biological materials" includes cell lines (Article 2.1).

Research involving the creation of a cell line requires REB review and approval. Researchers should therefore consider at the outset whether they plan to re-use these cell lines, and if so, seek REB approval (and participant consent, where applicable) for re-use at the time of the initial ethics review.

Researchers are also responsible for ascertaining and complying with all applicable legal and regulatory requirements with respect to consent and the protection of privacy of participants (Chapter 5). These legal and regulatory requirements may vary depending on the jurisdiction in Canada in which the research is being conducted, and who is funding and/or conducting the research. They may comprise constitutional, statutory, regulatory, common law, and/or international or legal requirements of jurisdictions outside of Canada (Chapter 1, Section C).

Exemption from REB review for identified cell lines in the public domain

In general, REB review is required for research involving the re-use of identified cell lines (Article 12.3A). However, if the cell line and the participant's identity are already in the public domain, REB review would not address provenance or privacy issues in any meaningful way. If it is impossible or impracticable to seek consent, there is no consent process that can be reviewed by an REB. If the research is unlikely to cause new harm to the participant, the research-attributable risk is minimal. If the research complies with consent terms, then REB review offers them little additional protection.

The following article exempts from REB review research that relies exclusively on the re-use of identified somatic cell lines that are already available and identified in the public domain. "Relies exclusively" means that, from a human participation perspective, the research only involves the human cell line.

Article 12.22

REB review is not required for research that relies exclusively on the re-use of identified human somatic cell lines where:

  1. the cell line is already available and identified in the public domain;
  2. it is impossible or impracticable to seek participant consent;
  3. the researcher will comply with known consent terms; and
  4. the research is unlikely to harm the participant.
Application

An example to which this article applies is the HeLa cell line.Footnote 6 The HeLa cell line was derived in the early 1950s, in Baltimore, from tissue that was obtained without consent from Henrietta Lacks. Because of its ability to replicate itself, the HeLa cell line was and is widely used in research. The scientific knowledge it helped acquire became the basis for many health-related products that proved to be lucrative to the companies that developed them.

Identified cell lines are those labelled with a direct identifier such as a name (Chapter 12, Section A). Cell lines in the public domain are those available from public catalogues such as one would find at a commercial biobank. Availability can range from freely available with no barrier at all, to accessible if a researcher formally requests and is granted access in accordance with established criteria, e.g., a materials transfer agreement.

"Impracticable" means incapable of being put into practice due to a degree of hardship or onerousness that jeopardizes the conduct of the research; it does not mean mere inconvenience (see Glossary).

When considering whether research may harm participants, researchers must consider whether anything about the research will have a negative effect on participants' welfare, broadly construed. The nature of the harm may be social, behavioural, psychological, physical or economic (see Glossary). The specific nature and context of the research may also require researchers to make reasonable efforts to identify and mitigate potential harms to participants' relatives and community. This is the case, for example, when the research may reveal sensitive information about them.

When in doubt about the applicability of this exemption, researchers should consult their REBs. The exemption in Article 12.22 does not invalidate other TCPS articles that may apply to the research being considered.

References

Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Health-Related Research Involving Humans, 2016. Retrieved on August 11, 2022.

Fonds de la recherche en santé du Québec, Rapport final du groupe-conseil sur l'encadrement des banques de données et des banques de matériel biologique à des fins de recherche en santé (only in French) [ PDF (342 KB) - external link ], 2006. Retrieved on August 11, 2022.

Health Canada, Notice – Release of ICH E6(R2): Good Clinical Practice. April 2019. Retrieved on November 16, 2022.

International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH). Definitions for genomic biomarkers, pharmacogenomics, pharmacogenetics, genomic data and sample coding categories E15 [ PDF (142 KB) - external link ]. 2007. Retrieved on August 11, 2022.

International Society for Biological and Environmental Repositories, Best Practices: Recommendations for Repositories, 4th Edition, 2022. Retrieved on August 11, 2022.

Ministère de la Santé et des Services Sociaux, Guide d'élaboration des cadres de gestion des banques de données et de matériel biologique constituées à des fins de recherche (only in French) [ PDF (751 KB) - external link ], 2012. Retrieved on August 11, 2022.

Organisation for Economic Co-operation and Development, OECD Guidelines on Human Biobanks and Genetic Research Databases [ PDF (319 KB) - external link ], 2009. Retrieved on August 11, 2022.

Stem Cell Oversight Committee (SCOC). Human Pluripotent Stem Cell Research: Frequently Asked Questions, 2022. Retrieved on September 8, 2022.

World Medical Association, Declaration of Taipei on Ethical Considerations Regarding Health Databases and Biobanks, 2016. Retrieved on August 11, 2022.

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