Compliance with the Human Tissue Act 2004

The Human Tissue Act (2004) (HT Act) is the legislative framework which governs the storage and use of relevant material from the living and the removal, storage and use of relevant material from the deceased, for a scheduled purpose.

The Act focuses on both consent and licensing making consent fundamental to the removal, storage and use of human tissue for certain scheduled purposes.

Relevant material, as defined by the HT Act, is material derived from a human body (other than gametes*) which consists of or includes cells (including bodily waste products).

The following are excluded from the Act:

Hair and nail from the body of a living person
Embryos outside the human body *
Cell lines and other material created outside the human body
Any sample that has been rendered acellular within 7 days of initial sample receipt

*Regulated by Human Fertilisation and Embryology Act 1990

The Human Tissue Authority (HTA)

The Human Tissue Authority regulates activities related to the HT Act and issues codes of practice and practical guidance for the storage and use of human tissue. It acts as the licensing authority and carries out inspections to ensure that licence conditions are met.

The following licences are held by the University:

HTA Research Licence - Designated Individual: Dr Andrew Povey

HTA Anatomy Licence - Designated Individual: Professor Ingrid Gouldsborough

HTA Human Application License- Designated Individual: Professor Sue Kimber

Licensing of human tissue for research

A research licence is required from the HTA in the following circumstances:

For the storage of human tissue samples which consist of or contain whole cells (some exemptions apply) for research where such research is not covered by current project specific NHS research ethics approval.

Existing collections, imported material and tissue held for a project approved by a committee that is not an NHS Research Ethics Committee (e.g. a university ethics committee) must be stored under a licence from the HTA.

A licence is required by tissue banks that distribute tissue to researchers, even though the bank itself may have NHS REC approval.

All staff storing human tissue for research under the above conditions must register their activity with the Research Governance, Ethics and Integrity Team to ensure coverage under the University's HTA Licence for Research.

For information regarding the Human Tissue Act and storage of human tissue please go to the relevant sections.

To whom the act applies

The Human Tissue Act 2004 applies to all persons storing and using relevant material from the living and removing, storing and using relevant material from the deceased, for a scheduled purpose.

The attached flow chart outlines the licensing and consent considerations for persons wishing to use human tissue samples for research. Researchers must ensure that tissue samples are obtained with appropriate consent where relevant and all licensable activities notified to the University Research Governance, Ethics and Integrity Team prior to commencement.

All research involving human tissue requires ethics approval either via the University Ethics Committee or NHS Research Ethics Committee (REC), however, the Human Tissue Authority only recognises ethics approval from an NHS REC. If tissue is being used or stored without NHS ethics approval, it must be stored under the University's HTA licence for research and must, therefore, be registered with the University and have UREC approval.

An HTA licence should not be viewed as an alternative to ethics approval by a recognised research ethics committee (NHS REC).

The HTA considers as best practice to seek ethics approval in all but exceptional circumstances.

All investigators must ensure that a favourable ethical opinion has been granted by a recognised research ethics committee (REC) where required or the University of Manchester Ethics Committee (UREC) for any research project or clinical trials involving the use of human tissue on University of Manchester premises.
Investigators must notify the Research Governance Officer of their project so that it can be registered on the University of Manchester Directorate of Research and Business Engagement Support Services database before any work on their project begins.

All staff working with human tissue under the University's Research Licence and those who may wish to retain tissue at the end of an ethically approved research project must comply with the HTA Codes of Practice and University policies and procedures for the management of human tissue samples for research.

Failure to comply with the Human Tissue Act

The following are classed as offences under the Act and can result in penalties ranging from a fine to up to three years' imprisonment:

Removing, storing or using human tissue for Scheduled Purposes without appropriate consent.
Storing or using human tissue donated for a Scheduled Purpose for another purpose.
Trafficking in human tissue for transplantation purposes.
Carrying out licensable activities without holding a licence from the HTA (with lower penalties for related lesser offences such as failing to produce records or obstructing the HTA in carrying out its power or responsibilities).
Having human tissue, including hair, nail, and gametes, with the intention of its DNA being analysed without the consent of the person from whom the tissue came or of those close to them if they have died. (Medical diagnosis and treatment, criminal investigations, etc., are excluded)

If I am working with/storing human tissue what should I do?

Register your project and forward your survey and any queries to the Research Governance Officer for Human Tissue
Undertake the MRC human tissue e-learning training, once you are on the page choose Research and Human Tissue Legislation - updated. You will need to either login or create a new account.

If you are storing/using tissue under licence, you will need to be covered by a Person Designated (PD) and maintain a laboratory master file. The Research Governance Officer (Human Tissue) will provide you with a template and advise you how to set this up.

You will also need to comply with the University's policies and procedures for storing tissues under the licence.

Register your tissue samples

All planned activity involving the storage and use of human tissue samples under the University's HTA Research Licence must be notified in advance to the Research Governance Officer (Human Tissue).

To register human tissue collections, researchers are required to complete an HTA Survey Form. All completed forms must be returned to the Research Governance Officer (Human Tissue).

Who does this apply to?

The survey is intended to collect information about the relevant activity of individuals (irrespective of whether they are University Staff) involved with use/storage of human biological samples (samples, other than gametes, which consist of or include human cells) on University of Manchester premises. This will ensure coverage under the HTA licence for Research where this is appropriate.

Please note that the HTA does not issue licences for individual collections of relevant material but rather, for the sites on which such material is stored.

At present the following buildings hold collections of tissue under the University’s HTA Licence for Research:

The Core Technology Facility
Manchester Incubator Building
AV Hill Building
Michael Smith Building
Stopford Building

A Satellite licence is also in place for the storage of relevant material for Research at the Manchester Interdisciplinary Biocentre (MIB)

Please also note that the following sites at which relevant material might be stored by University of Manchester staff are covered by licences specific to those sites.

Cancer Research UK Manchester Institute - covered by the Christie NHS Foundation Trust Licence for Research
Local NHS Trust sites – covered by licences held by each individual Trust

Wolfson Molecular Imaging Centre (WMIC) - This site does not currently hold a Licence from the Human Tissue Authority for the storage of relevant material for research.

Who should complete the HTA Survey Form?

The form should be completed by individuals who have the primary responsibility for the use and storage of biological samples. This will include:

Principal Investigators
Custodians of tissue banks/holdings
Other staff (e.g., clinicians) storing tissues for research purposes

Key Contact:

Dr Diane Escott, Research Governance Officer (Human Tissue) diane.escott@manchester.ac.uk

Guidance on ethical approval for human tissue studies

WHEN DO I NEED TO APPLY FOR UREC APPROVAL FOR A HUMAN TISSUE STUDY?

When the Research involves the storage and use of human tissue, on HTA Licensed premises which includes:

Samples imported from outside the UK
Samples collected from Healthy Volunteers
Research limited to secondary use of tissue samples previously collected, in the course of normal care, with consent for research and the patients or service users are not identifiable to the research team (GAfREC)*
Samples held under the HTA licence

In this instance, you may seek NHS/HRA REC approval for your study, but it is not a requirement. If you choose to not seek NHS approval then in addition to seeking UREC approval you will be required to store and use your human tissue under the UoM HTA Licence for Research. The HTA Code of Practice on Research recommends that any research with human tissue is conducted with ethical approval and that a HTA storage licence should not be seen as an alternative to NHS/HRA approval.

*GAfREC. According to the Governance Arrangements for Research Ethics Committees (GAfREC), your research does not require NHS/HRA REC approval if it is research which is limited to previously collected, non-identifiable human tissue samples, consisting of or including cells, in accordance with the terms of donor consent, ie, the donor has consented to their tissue being used for research purposes. In this instance you will be required to store and use your human tissue under the UoM HTA Licence for Research and you will be required to submit an application to the UoM research ethics committee, UREC. In addition, donor consent for use of the samples in research must be demonstrated, and the proposed research must be within the terms of donor consent. The research must not also involve removal, storage or use of new samples from the living or the deceased and the research must not involve use of identifiable information held with the samples.

WHEN DO I NEED TO APPLY FOR NHS/HRA REC ETHICS APPROVAL FOR A HUMAN TISSUE STUDY?

Researchers are legally required, under the HT Act, to seek NHS/HRA REC approval if they wish to carry out the following activities:

To store or use the tissue of a living or deceased person for a research project on premises without a licence from the HTA
To store or use tissue from the living for a research project without consent where the samples are anonymised to the researcher
To analyse human DNA in material from the body of a living person (or using the results of DNA analysis) without consent, in circumstances where the researcher is unable to identify the tissue donor and not likely to be able to do so in the future
To store or use tissue for a research project where consent is required and the tissue is from adults unable to consent for themselves
To export tissue from the living and there is no consent in place for use in future research

In addition, applications for NHS/HRA REC approval are required where the research involves:

The collection of the tissues from NHS patients or
The use of previously collected tissue from which past or present NHS patients could be identified

Please note: If you are carrying out research using tissue from a Research Tissue Bank which has NHS REC approval, you will not be required to seek project-specific NHS ethics approval for your study, nor will you require a licence from the HTA to store your samples, if the tissue bank has as a condition of their REC approval the ability to confer ethical approval to your study. Please check the tissue banks conditions of ethical approval.

There are two different types of application to NHS/HRA REC researchers using human tissue can make; project specific approval or research tissue bank approval.

1. Project-Specific Approval – the approval lasts only for the duration of the project as defined in the study protocol and application form. The duration can be extended if necessary. Use this route for the following:

CTIMPS involving storage and use of human tissue
Research involving removal of human tissue or other bodily material from the living as part of the protocol (ie, primarily for research purposes)
Research involving the use of stored tissue or data in circumstances where the researcher is able, or could be able, to identify the donors
Research involving any contact with donors or relatives to seek consent, obtain further data or undertake any other research procedure
Research involving use of stored tissue from a research tissue bank which does not have ethical approval from an NHS REC
Research involving use of stored tissue from a research tissue bank, which has ethical approval from an NHS REC, but (a) the terms of the approval do not extend to generic approval for projects receiving tissue from the bank, or (b) the tissue bank manager requires the researcher to obtain project-specific approval before agreeing to release tissue
Research involving stored tissue from a clinical diagnostic archive that is not licensed to store tissue for use in research and is not ethically approved

The ethical approval given for a project-specific application is confined to that project only, as described in the protocol and the application form. The project can be divided into separate stages but approval for each stage is only given if it is in the protocol and application form and relates to the same set of research questions. NHS/HRA REC states that it is not acceptable to use the project-specific application form to seek open-ended approval for use of stored tissue in future research programmes (although the terms of consent itself may be generic and open-ended, allowing for future approved research using the same samples). Nor is it acceptable to submit substantial amendments to approved projects in order to use tissue for another project with a different set of research questions.

2. Research Tissue Bank Approval (RTB) – An HTA licence is necessary to establish a tissue bank.

Researchers may also make an application to NHS/HRA REC so as to confer generic ethical approval prospectively for a range of research to be carried out by the research establishment. Or, to other researchers external to the bank, with the conditions of ethical approval.

The definition of a RTB or Biobank is “A collection of human tissue or other biological material, which is stored for potential research use beyond the life of a specific project with ethical approval or for which ethical approval is pending.” RTB, storing human tissue for in as yet unspecified research must obtain a storage licence from the HTA. There is no requirement for RTB to obtain ethical approval, unless you want to be able to facilitate research programmes without project-specific ethics approval.

Research conducted using tissue provided by RTB under approval conditions will be considered to have ethical approval from the NHS/HRA REC under the terms of the ethical approval for the RTB. This means that the end user researcher will not require a licence from the HTA for storage of the tissue for use in relation to that research project.

WHAT IF I WANT TO USE MY SAMPLES IN FUTURE RESEARCH?

NHS/HRA REC PROJECT-SPECIFIC ETHICS APPROVAL

In all instances researchers must consider whether they have donor consent for use of samples in future research. For an NHS/HRA REC approved study, Researchers should apply for further NHS/HRA ethics approval, no later than the date on which the first project ends – as defined in the research protocol. Or apply for review of a RTB with plans for further research. If these options are not followed then researchers should dispose of their samples in accordance with HT Act and donor consent for the project. If donor consent allows, researchers could transfer the samples for storage to a licensed tissue bank; usage will require further NHS/HRA approval. Or, store the samples on HTA licensed premises in accordance with donor consent; usage will require further NHS/HRA approval.

UREC PROJECT SPECIFIC ETHICS APPROVAL

In this instance the researcher should check that donor consent allows for use of the samples in future research and apply for further UREC approval to use the samples in a different research study. Or researchers can continue to store the samples, on HTA licensed premises, in line with donor consent; further use in research will require UREC approval. Or researchers should dispose of their samples in accordance with HT Act and donor consent.

Policies and procedures

All staff working with human tissue stored under the University's HTA Research Licence and those who may wish to retain tissue at the end of an ethically approved research project must comply with the HTA Codes of Practice and University policies and procedures for the management of human tissue samples for research.

Policies

Standard Operating Procedures and Guidance Documents

HTA Forms

Frequently asked questions

The University Research Governance, Ethics and Integrity Team receives frequent queries from researchers who wish to determine whether specific tissue types are considered "relevant" and/or licensable under the Human Tissue Act.

Several examples follow with specific guidance intended to provide clarity in the areas highlighted:

Teeth
Bone
Cultured Cells
Human Tissue Xenografts
Semen
Archival Tissue
Tissue with current project specific NHS research ethics approval

1) What is relevant material?

For the purpose of the Human Tissue Act, "relevant material" means material, other than gametes, which consists of or includes human cells. References to relevant material from a human body do not include:

(a) embryos outside the human body, or
(b) hair and nail from the body of a living person.

A Supplementary List of materials is also available from the HTA and provides further clarification on what is considered relevant material under the Act.

2) Are teeth & bones relevant material?

Teeth

Where the cellular component of teeth (pulp) is allowed to degrade by just letting them dry out or washing them in hypotonic solution (which would lyse the cellular material in the pulp) - would the dried teeth still be considered relevant material?

The HTA considers that the aging processes would not make all the tissue fully acellular and therefore it would still be considered "relevant material" under the Act.

Bones

Are bones that have been bleached and dried over time still considered relevant material?

The HTA Code of Practice for processed material suggests that:

"Where a processed material is generally agreed - as a result of the process - to leave it always either cellular or acellular, then the presumption should be that all examples should be regarded as such. The HTA would rely on an assurance that the process in question had been carried out. Under this category plastinated tissue and plastinated body parts (where the cellular structure is retained by the plastination process) are to be regarded generically as relevant material; while plasma or serum, for example, will be regarded as not. The two latter processed materials, widely produced from blood taken for diagnostic investigations, are however examples of where 'normal expectations' may well need to be exercised."

The HTA's Supplementary list of material includes skeletons, which are often bleached in hydrogen peroxide as part of the cleaning process. The HTA considers that the bleaching/aging processes would not make all the tissue fully acellular and therefore it would still be considered "relevant material" under the Act.

3. Are cells extracted from tissue and then passaged considered relevant material?

Following consultation with the HTA, the University has determined that one passage is sufficient for a cell culture to fall outside of the HT Act. Consequently, the storage of such material is not licensable by the HTA.

4. Do human tissue xenografts fall under the HT Act as relevant material?

The HTA policy on human tissue xenografts as relevant material is as follows:

"Human tissue xenografts are classed as relevant material as the sample will contain cells that have come from a human body. If a sample is known to contain even a single cell that has come from a human body, the sample should be classified as relevant material."

The HTA further advises, however, that human tissue xenografts are not considered a method of storing human cells and therefore do not require a licence for their storage. Furthermore, once the human tissue is implanted into the recipient species, it loses its "identity" as human tissue as it will inevitably be modified by the surrounding environment, hence, it does not fall under HTA licence.

5. Is semen covered by the Human Tissue Act?

The storage and use of gametes (comprising cells connected with sexual reproduction) and embryos are governed by the Human Fertilisation and Embryology Act 1990 and regulated accordingly by the Human Fertilisation and Embryology Authority (HFEA).

Apart from sperm cells, normal semen contains other cells and can therefore be considered as relevant material for the purposes of the HT Act.

6. I have archival tissue taken before September 2006. Does this come under the Act?

Yes. You will need to register your collection with University Research Governance, Ethics and Integrity Team and store it under the HTA licence for research. You are not legally required to prove consent has been taken.

7. I have ethics approval for my tissue samples. Does my tissue come under the Act?

If you have current project specific ethics approval from a recognised NHS REC, then you will still need to register your study with the University Research Office but your samples will not be stored under the licence.

If you intend to retain your tissue for future research once your ethics approval lapses, you should contact the Research Policy Officer (Human Tissue) to discuss preparing your holdings for storage under the licence.

8. Additional Frequently Asked Questions

If you have additional queries that have not been answered by the guidance above, please see the FAQ's on the HTA website.

Human application license guidance

Compliance with the Q&S Regulations

The European Union Tissue and Cells Directives (EUTCD) set the standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissue and cells intended for human application and were transposed into UK law via the Human Tissue (Quality and Safety for Human Application) Regulations 2007 - The Q&S Regulations.

A fundamental principle of the EUTCD is the requirement to ensure that adequate systems are in place for the traceability of all tissues and cells from donor to recipient.

Any human tissue used in patient treatment (human application), even where this is for research, must comply with the requirements of the EUTCD.

The Human Tissue Authority (HTA)

The Human Tissue Authority (HTA) is one of the Competent Authorities in the UK for the implementation of the EUTCD and has responsibility for regulating tissues and cells (other than gametes and embryos) intended for human application.

The HTA enforces the standards of quality and safety, carries out inspections to ensure that all applicable compliance standards and licence conditions are met and issues practical guidance for the conduct of any activity involving tissues and cells for human application.

Licensing for Human Application

A licence is required from the HTA in the following circumstances:

Storage for more than 48 hours for the purposes of human application
Procurement
Testing
Processing
Distribution
Import / export

The University, via the North West Embryonic Stem Cell Centre, currently holds a licence for the testing, processing, storage and distribution of tissues and cells for human application.

HTA Licence for Human Application:

Corporate Licence Holder Representative: Professor Nalin Thakker

Designated Individual: Professor Sue Kimber

All University Tissue Facilities (UTFs) wishing to engage in licensable activities, as described above, must notify the Research Governance Officer (Human Tissue) in the Directorate of Research and Business Engagement to ensure appropriate coverage under the HTA Licence for Human Application.

Material regulated by the HTA for the Human Application Sector

The following material when used for human application is governed by the Q&S Regulations and regulated by the HTA:

Cells - ‘individual human cells or a collection of human cells when not bound by any form of connective tissue, including cell lines grown outside the human body but not including: gametes; blood and blood components’
Cell Lines - Cell lines created with the intention of being used in patient treatment are regulated by the HTA and must also be shown to comply with the EUTCD. Failure to do so could adversely affect any future application for authorisation of a medicinal product.
Tissue - “All constituent parts of the human body formed by cells, but not including:
- Gametes; or
- Embryos outside the human body; or
- Organs or parts of organs if it is their function to be used for the same purpose as the entire organ in the human body

Supplementary list of materials

A supplementary list which further clarifies material regulated for the human application sector under the Q&S Regulations is available on the Human Tissue Authority webpage.

The Human Fertilisation and Embryology Authority (HFEA)

The Human Fertilisation and Embryology Authority (HFEA) is the other Competent Authority in the UK and delivers the requirements of the EUTCD by regulating the procurement, storage and use of reproductive cells (sperm, eggs) and embryos for human application.

Compliance

All staff working with human tissue obtained for storage and use under the University's HTA Licence for Human Application must comply with the Q&S Regulations, the HTA Codes of Practice, the HFEA Code of Practice where relevant, and the University’s policies and procedures for the management of tissue and cells for human application.

Key Contacts:

Sue Kimber, Designated Individual sue.kimber@manchester.ac.uk

Diane Escott, Research Governance Officer (Human Tissue) diane.escott@manchester.ac.uk