5.4 Compliance with national legislation regarding Human Tissue

Introduction

Different national legislation applies across the UK in relation to the arrangements for the use of Human Tissue in research. The main relevant differences in legislation across the UK are detailed below:

England, Northern Ireland and Wales

• The Human Tissue Act 2004 applies

Scotland

• The Human Tissue (Scotland) Act 2006 applies to tissue from the deceased
• The HTA’s remit in relation to research does not extend to Scotland except in the case of DNA

The Human Tissue Act 2004 sets out a legal framework for regulating the storage and use of human tissue from the living, and removal, storage and use of human tissue from the deceased, for purposes including ‘research in connection with disorders, or the functioning, of the human body’. Where biological material is to be rendered acellular (and is thereby no longer considered to be relevant material for the purposes of the Human Tissue Act), it should be clear when and where this will occur.

The Human Tissue (Scotland) Act 2006 sets out provisions for the removal, retention and use of ‘organs, tissue and tissue samples’ from the deceased, i.e. body parts or bodily fluids (including any derivative of skin) removed post mortem, and subsequently used for research. It does not regulate the use of tissue from the living for research.

The study-wide reviewer will be responsible for considering the study according to the national legislation of their nation alone. However, the study-wide reviewer must highlight to the other participating UK nations where there are differences in legislation that will need to be considered. Study wide reviewers should be clear, when considering the arrangements for collection and use of human tissue, how information governance requirements and expectations will be met (e.g. how and when will biological material be pseudonymised or anonymised?) (see section 5.1 for further details).

Consent

Consent (or Authorisation) is a fundamental principle of both the Human Tissue Act 2004 and the Human Tissue (Scotland) Act 2006. Please see sections 2.1 and 5.1 for further details regarding the requirements for the purposes of obtaining this.

Consent can be specific to the project itself, or more generic to include storage and future use. If the sponsor is seeking generic consent then they should consider how much information should be provide to potential participants to help them understand the scope of future use and what this might mean for them balancing the need to ensure informed consent with the uncertainty of what research requirements may arise in the future.

It should be made clear at the outset, when consent, or authorisation is being sought, that it can be withdrawn at any time. The practical implications of withdrawing consent should be discussed to help participants, or their representatives, understand what is realistic in terms of withdrawal and to manage expectations.

In England, Wales and Northern Ireland

Consent is always required under common law to remove biological material from a human and is legally required to store and use ‘relevant material’ from the living or deceased for a ‘scheduled purpose’ such as research (unless one of the exemptions below applies). Relevant material is defined as ‘material, other than gametes, which consists of or includes human cells’ and a full list of the materials considered to be ‘relevant’ is provided by the HTA.

In relation to the living consent should be obtained from the person concerned, assuming they have the capacity to consent for themselves. Where they do not then, where tissues are being used as part of a clinical trial of an investigational medicinal product (CTIMP), the UK Medicines for Human Use (Clinical Trials) Regulations 2004 apply (see section 5.2 for details). Where the tissue will be used in non-CTIMP research, in England and Wales, the Mental Capacity Act 2005 applies and in Northern Ireland the Mental Capacity Act (Northern Ireland) 2016 applies (see section 5.3 for details).

In relation to children, if a child is considered competent, then consent should be sought from the child. If a child is not competent, or not willing to make a decision, consent should be obtained from a person with parental responsibility. Even when a child is competent to consent, it is good practice to consult those with parental responsibility and involve them in the process of the child making the decision. Where tissues are being used as part of a CTIMP a child (under 16) cannot legally provide consent for themselves and consent should be sought from a person with parental responsibility.

‘Appropriate consent’ is required to obtain relevant material from the deceased (unless the person died more than 100 years ago). Appropriate consent means

• the consent of the deceased person given before death
• if there was no prior consent by the deceased person, the consent of a nominated representative
• if no representative was appointed, a person in a ‘qualifying relationship’ [23]
• for a deceased child, the person who had parental responsibility immediately prior to the child’s death or another person in a qualifying relationship

In Scotland

In terms of research, the Human Tissue (Scotland) Act 2006 does not regulate the use of tissue from the living for research. Instead this is governed by the requirements of the common law, NHS Research Scotland Human Tissue Accreditation Scheme, and other related legislation (such as the Adults with Incapacity Act 2000). Informed consent is legally required for research if the tissue is from a living person and the samples are identifiable (or are anonymised but there is no approval from a Research Ethics Committee).

The Human Tissue (Scotland) Act 2006 does set out provisions for the removal, retention and use of ‘organs, tissue and tissue samples’ from the deceased, i.e. body parts or bodily fluids (including any derivative of skin) removed post mortem, and subsequently used for research. Authorisation is legally required for research if the issue is collected after 01 September 2006 (for both anonymous and identifiable samples). Authorisation can be provided by individuals themselves before death, a ‘nominee’ [24] or ‘nearest relative’ (in order of priority) [25]. It should be noted that a Welfare Attorney or Welfare Guardian cannot give authorisation on behalf of an incapacitated adult for activities post-mortem unless they are a ‘nominee’ or a ‘nearest relative’ of the deceased.

In relation to the collection of tissue from children after death authorisation should be provided by

• for a child 12 years of age and over
  • themselves before death if deemed competent or, if not deemed competent, a person with parental rights and responsibilities.
  • after death a ‘nominee’ or person with parental responsibility
• for a child under 12 years of age
  • a person with parental rights and responsibilities only

Material is exempted from the requirements of the Act and can legally be used for research without Authorisation if it is an existing sample, obtained before 01 September 2006, (including any identifiable or anonymous material from the living or deceased).

Collection of Human Tissue from Adults unable to Consent for themselves

Where the study will involve the collection of tissue samples from adults that are unable to consent for themselves the sponsor should ensure that arrangements are in place to follow the provisions the relevant, nation specific legislation.

In CTIMPs

In CTIMPs, in accordance with the Medicines for Human Use Act 2004, which apply UK wide, a Legal Representative should be appointed who will be asked to provide consent on behalf of the individual be recruited. This consent fulfils the consent requirements of the nation specific Human Tissue legislation. Please see section 5.2 for further details.

In non-CTIMPs

In Scotland, the Adults with Incapacity (Scotland) Act 2000 allows legal representative to give consent on behalf of an adult who lacks the capacity to do so. This consent fulfils the consent requirements of the nation specific Human Tissue legislation.

In England, Wales and Northern Ireland, The Human Tissue Act 2004 (Persons who Lack Capacity to Consent and Transplants) Regulations 2006, provides for this situation. This Regulation provides that where activities which fall under the Human Tissue Act 2004 are being undertaken with adults lack the capacity to consent, the Mental Capacity Act 2005, and therefore advice should be sought from consultees.

Please see section 5.3 for further details.

Consent exemptions

Consent is required to use and store relevant material for research, unless one of the following legal exemptions applies

• the relevant material is classed as an existing holding i.e. held prior to 1st September 2006
• the relevant material is imported
• the relevant material has been taken from a living person AND the researcher is not able to identify the person AND the research project is ethically approved by an NHS REC
• the relevant material is to be received from an HTA-licensed RTB with generic ethical approval from recognised REC and the biological samples are non-identifiable to the researcher
• the relevant material is from a person who died more than 100 years ago

The sponsor should state whether they intend to obtain consent for the use of relevant material for research purposes and, where they do not, provide a justification explaining why this is not required. It should be noted that the HTA code of practice on research confirms that Although there are legal exemptions from the need for consent under the HT Act (‘consent exceptions’), it is good practice to obtain consent wherever it is practical to do so, considering ethical issues such as the feasibility of identifying and re contacting tissue donors, any distress that may be caused through reminding donors/relatives of serious illness or injury and any potential health related findings that the research may uncover for the donor. For existing holdings, it is good practice to consider the ethical issues involved in their potential use, balancing this against the issues involved in obtaining new samples. For imported tissues it is good practice to get assurance that samples have been obtained with valid consent in the country of origin.

DNA Analysis

Under Section 45 of the Human Tissue Act it is an offence to hold ‘bodily material’ with the intent to analyse its DNA and use the results for research without ‘qualifying consent.’ This guidance also applies to RNA analysis when used to provide information about DNA for research). There are some exceptions when obtaining consent is not practicable. Unlike the rest of the Human Tissue Act, Section 45 applies across the whole of the UK, including in Scotland.

The term ‘qualifying consent’ is only used within Section 45 of the HT Act. In practice, obtaining qualifying consent is fundamentally the same as obtaining any other consent for research except that

• in relation to deceased adults if the deceased has appointed a ‘nominated representative’ then their consent will only be valid for DNA analysis if that person was also in a ‘qualifying relationship’ with the deceased (as there is no provision for consent provided by a nominated representative under Section 45 of the HT Act)

The HTA Code of practice on Research states that if consent for research has previously been obtained and it is later decided to include DNA analysis in the research, as long as the consent does not rule-out DNA analysis, then the original consent will suffice as ‘qualifying’ consent for use in England, Wales and Northern Ireland. However, where the sponsor knows, when seeking consent, that they intend to conduct DNA analysis, then the HTA expects this to be made clear to donors during the consent process.

Licencing requirements

In England, Wales, and Northern Ireland

Under the Human Tissue Act 2004, a license is required to store ‘relevant material’ for research in connection with disorders, or the functioning of, the human body (unless an exemption applies). The HTA additionally license premises, such as Research Tissue Banks, which store tissue from the living and deceased for research. The HTA expects licensed establishments to meet the HTA’s Research Standards. The HT Act requires that removal of tissue from the deceased for research within the scope of the HT Act must always take place under the authority of an HTA license. In other words, the specific removal premises must be licensed and a Designated Individual (DI) will be responsible for the removal activity.

A list of licensed research establishments is given on the HTA’s website; Find an establishment | Human Tissue Authority

A license is required to store relevant material from the living or deceased for research in connection with disorders or the functioning of the human body unless:

• it is for a specific project approved, or pending approval, by a Research Ethics Committee or where storage after a specific project is deemed essential as a record of the completed research project, for example to verify or quality check the research data. Storage for this purpose without an HTA License should be for a defined period as set out in the protocol and should be for no longer than 12 months. For studies involving human tissue, the analysis of the samples should be undertaken as part of the data collection before the end of study is declared
• storage, up to a maximum of 7 days, is incidental to transportation
• it is stored, for up to a maximum of 7 days, with the intent to render the sample acellular
• it is obtained from an HTA-licensed research tissue bank
• (in relation to the deceased) It is from a person who died prior to 01 September 2006 and at least 100 years have elapsed since their death

The sponsor should be clear on its arrangements for obtaining relevant licenses (where applicable). For studies involving human tissue, the analysis of the samples should be undertaken as part of the data collection before the end of study is declared. If researchers wish to store tissue for other purposes, for example for future research, or for longer than 12 months the tissue should be transferred to an existing licensed research establishment.

In Scotland

The storage of tissue within Scotland does not require licencing. On behalf of the Chief Scientist Office, NHS Research Scotland carry out the Scottish Human Tissue Accreditation Scheme for the collection and storage of tissue under the guardianship of NHS Scotland Research Tissue Banks / Biorepositories based on criteria that are equivalent to the standards expected within the UK. Sponsor & NHS REC delegate approval to their nodal biorepositories so that at the end of a study if there is surplus tissue this will either be stored within the NRS Biorepository or can be registered with the nodal biorepository who will ensure that this tissue meets accreditation standards.

Import and export of human tissue

In England, Wales and Northern Ireland

The Human Tissue Act 2004 covers the import and export of relevant material to and from England, Wales and Northern Ireland. When ‘relevant material’ is coming into England, Wales or Northern Ireland from Scotland it is considered an import and vice versa an export.

Although consent is a fundamental principle of the HT Act, the consent provisions do not apply to imported material. However it is good practice to gain assurance that consent has been obtained in the source country and, where it has not been, the sponsor should provide a justification for this including (where applicable) assurance that appropriate ethical approval, or equivalent, has been obtained in the host country which will judge ethical acceptance of the research in line with local customs and traditions. MRC provides guidance on the considerations for low and middle income countries and the UK REC may wish to take a view when reviewing the study before issuing a favourable opinion for the research to be conducted in the UK.

Relevant material must not be imported and exported solely to avoid the consent requirements.

Where relevant material will be imported then the sponsor should put in place a Material Transfer Agreement to provide assurances to the importer that this tissue has been collected in line with local legal requirements.

Following the withdrawal of the UK from the European Union the implementation of the Northern Ireland Protocol has had an impact on the import and export of Human Tissue to and from Northern Ireland. If the sponsor anticipates that this will be required as a part of the research protocol, then they should seek advice from the Human Tissue Authority and the Northern Ireland Coordinating Centre.

In Scotland

Similar standards are expected for the import and export of human tissue into/out of Scotland. Where this is anticipated advice should be sought from the Scottish National Coordinating Centre and/or the relevant Biorepository. An NHS National Research Scotland Material Transfer Agreement should be in place for all tissue involving a designated Biorepository. There are three available material transfer agreements. These are for

1. material only
2. consented tissue and associated data
3. unconsented tissue and associated data

The sponsor should ensure that they execute the correct agreement depending on their proposed study arrangements. Study wide reviewers should be clear on the proposed arrangements and should seek clarification from the sponsor if required.

Analysis of samples

The sponsor should be clear what arrangements have been made for the analysis of samples and clarify how this information will be provided to participating NHS/HSC organisations to enable them to understand their responsibilities (usually in the study protocol or another related document, such as a laboratory manual. It should be noted that there is no requirement that a laboratory manual be provided for the purposes of study wide review as, at that time, it may not have been written

The main analysis of the samples for the purposes of answering the research question should be undertaken as part of the data collection before the end of study is declared. Study wide reviewers should ensure that relevant information will be provided to participating NHS/HSC organisations to enable them to understand their responsibilities. Such information should include

1. if samples will be analysed locally then the sponsor should explain to participating NHS/HSC organisations. whether, and if so in what respects, this differs from standard of care arrangements
2. if samples will be transferred to a central lab then the sponsor should explain the arrangements for such transfer including whether the sponsor or the participating NHS/HSC organisation will be responsible for arranging the courier to transport the samples and whether a separate Material Transfer Agreement is required

Where the sponsor considers that the analysis of samples may produce potential health related findings the provisions in section 2.1 should be referred to and relevant information provided.

Storage arrangements for samples (where applicable)

The sponsor should be clear whether any samples will be stored during or after the research study and whether such storage will take place locally at the participating NHS/HSC organisation or at a central facility. It should be clear how long samples will be stored for, whether they will be stored in an identifiable or anonymised format, for what purposes they will be stored, and what will happen to the samples at the end of this time. Study wide reviewers should ensure that it is clear how this information will be provided to participating NHS/HSC organisations to enable them to understand their responsibilities and confirm that relevant information regarding retention is included in the Participant Information Sheet(s).

Disposal arrangements for samples

The sponsor should explain their arrangements for the handling of Human Tissue following the end of the study.

Before disposing of human tissue, the sponsor should consider options for maximising use, in line with donors’ expectations. Where the sponsor proposed to destroy samples, rather than retain them for use in future research a justification should be provided, particularly in the case of rare or potentially valuable samples or samples obtained from pre-existing collections, such as pathology departments.

Where biological material has been transported outside of the participating organisation, it should be clear whether and how the biological material will be returned, retained or destroyed and the agreement/arrangements (e.g. model agreement material transfer clauses) for this.

There will be times when disposal is the most appropriate option i.e. following the terms of consent or where samples are no longer fit for purpose. In this case study wide reviewers should ensure that the sponsor has explained the arrangements for sample destruction, including when and how the samples will be destroyed and how this destruction will be recorded in line with the MRC guidance, including how samples will be handled for destruction in a sensitive and respectful manner (particularly in relation to the destruction of samples from the deceased). Within Scotland the NRS Biorepositories can help to support researchers and sponsors in the disposal of tissue whilst providing relevant policies and documentation.

The sponsor should explain how they will manage a situation where a donor revokes consent for use of their samples (may be some/all) for research and requests destruction including how the sponsor/central facilities will be made aware of this request if the samples have already been shipped and when this will not be possible (i.e. if samples have been fully anonymised).

Study-wide considerations

• it should be clear what Human Biological materials the study will make use of and whether any collection or analysis of such material is optional
• it should be clear, of the Human Biological materials to be collected, what is ‘relevant material’ and what is not. In relation to relevant material it should be clear at what point that will be rendered a-cellular (if applicable)
• has the sponsor explained, and detailed in the PIS, how information governance requirements and expectations will be met in relation to any data associated with human tissue samples (e.g. if, and if so how and when biological material will be pseudonymised or anonymised?)
• has the sponsor described, and detailed in the PIS, their arrangements for ensuring informed consent is in place for the purposes of the collection, storage and use of new, or existing, Human Tissue samples from the living, as appropriate, and do these comply with the relevant national legislative requirements?
• has the sponsor described, and detailed in the PIS, their arrangements for ensuring informed consent (or Authorisation) is in place, as appropriate, for the purposes of the collection, storage and use, of new, or existing, tissue samples from the deceased as appropriate, and do these comply with the relevant national legislative requirements
• has the sponsor explained how they will manage a situation where a donor revokes consent for use of their samples (may be some/all) for research and requests destruction including how the sponsor/central facilities will be made aware of this request if the samples have already been shipped and when this will not be possible (i.e. if samples have been fully anonymised). Has relevant information been provided in the PIS regarding the participants right to withdraw their consent and samples from the study (including where any limitations may apply to this)?
• where the sponsor is seeking generic consent for future storage and use of samples have they provided appropriate information in the PIS to potential participants to help them understand the scope of future use and what this might mean for them balancing the need to ensure informed consent with the uncertainty of what research requirements may arise in the future
• has the sponsor made arrangements to comply with the relevant licencing requirements of the Human Tissue Act, and/or, in Scotland, made arrangements to transfer any surplus tissue to an NHS Scotland Research Tissue Banks / Biorepositories at the end of the study?
• where tissue will be imported and exported (including between Scotland and the rest of the UK)
  • has the sponsor clarified whether consent will be sought in the source country and, where it not be, has the sponsor provided an appropriate justification for this?
  • has the sponsor put in place appropriate contractual arrangements will be in place to cover this activity?
• where the study will involve DNA analysis (RNA analysis when used to provide information about DNA for research) has the sponsor made arrangements to obtain appropriate ‘qualifying consent’ and has this intended analysis been detailed in the PIS
• has the sponsor confirmed what arrangements have been made for the analysis of samples and clarified how this information will be provided to participating NHS/HSC organisations to enable them to understand their responsibilities?
• has the sponsor confirmed, and detailed in the PIS, what arrangements have been made for the storage of samples following the end of the study and clarified how relevant information will be provided to participating NHS/HSC organisations to enable them to understand their responsibilities?
• has the sponsor confirmed, and detailed in the PIS, what arrangements have been made for the handling of Human Tissue following the end of the study in relation to, as applicable, retention for use in future research, return of material to the original holders and disposal in accordance with the HTA code of practise