Document Number: CU/13/HTA 15/1.0 Effective Date:
09 Jan 2013
Version Number & Date: 3.0 & Jan 2013
Superseded Version Number and Date:
Review Date:
09 Jan 2014
HTA 10/32
July 2011
Author:
Carina Hibbs
Sharon Orton
Approved by:
Professor Jonathan Bisson
Position:
HTA Governance
Officer, GOVRN
HTA Co-ordinator,
GOVRN
Position:
DI – Licence No 12422
____________________
____________________
Signature Date
____________________
Signature Date
Disclaimer
When using this document, please ensure that the version you are using is the most up to date either by checking on the GOVRN/HTA website for any new versions or contact the
HTA Governance Officer to confirm the current version.
Out of date documents must not be relied upon and should be destroyed
CU/13/HTA15/1.0 Page 1 of 30

Version
Number
Changes to Document
HTA 10/32 Substantial changes:
Addition of Sections 8 and 9
Alternations of order and text throughout
Update consent information
HTA 10/32 Contact and licensing information updated
Minor updates to text
Document number change from HTA
10/32 to CU/13/HTA15/1.0 to fall in line with numbering of CU HTA SOPs
Changes authored by
Date Approved
Carina Hibbs 14/06/2011
Carina Hibbs 09/01/2013
CU/13/HTA15/1.0 Page 2 of 30

CARDIFF UNIVERSITY HTA COMPLIANCE
QUALITY MANAGEMENT MANUAL
CONTENTS
1 INTRODUCTION ........................................................................................................................................ 4
2 POLICY AND OBJECTIVES .................................................................................................................... 4
3 DEFINITIONS ............................................................................................................................................. 5
4 QUALITY SYSTEM .................................................................................................................................... 6
5 GOVERNANCE ARRANGEMENTS ....................................................................................................... 7
6 ORGANIZATION CHARTS ...................................................................................................................... 9
7 AUTHORITY & RESPONSIBILITIES ................................................................................................... 12
8 KEY AREAS WITHIN THE HUMAN TISSUE ACT 2004 ................................................................... 13
9 EXEMPTIONS FROM THE HTA LICENCE ......................................................................................... 16
10 STANDARD AND LOCAL OPERATING PROCEDURES ................................................................ 18
11 ANNUAL SURVEY OF HOLDINGS AND INTERNAL AUDIT ......................................................... 19
12 RECORDS AND TRACEABILITY ......................................................................................................... 20
13 RISK ASSESSMENTS AND ADVERSE EVENTS ............................................................................. 21
14 MANAGEMENT REVIEW AND DOCUMENTATION & VERSION CONTROL ............................. 22
15 REFERENCES ......................................................................................................................................... 24
16 REFERENCED SOPS ............................................................................................................................. 24
17 CONTACTS .............................................................................................................................................. 25
Appendices
A.
B.
Supplementary List of Relevant Material
Flowcharts: licensing and consent requirements for human tissue for research
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1 INTRODUCTION
The Human Tissue Act 2004 (HT Act) came fully in to force on 1 September 2006.
The aim of the HT Act is to provide a legal framework regulating the storage and use of human tissue from the living and the removal, storage and use of tissue from the deceased. It introduces regulation of activities like post mortem examinations, and the storage of human material for education, training and research. It is intended to achieve a balance between the rights and expectations of individuals and families, and broader considerations, such as the importance of research, education, training, pathology and public health surveillance to the population as a whole.
The Human Tissue Authority (HTA) is the governing body set up to regulate activities that come under the HT Act. The HTA is a watchdog that supports public confidence by licensing organisations that store and use human tissue for purposes such as research, patient treatment, post-mortem examination, teaching, and public exhibitions.
Cardiff University holds four HTA Licences; two for research purposes, one for human application and one for anatomy. The two Research Licences, a hub and a satellite, cover Heath Park and Cathays Campus, respectively. The Heath Park hub
Licence also covers tissue held by Cardiff & Vale University Health Board for research purposes at the Heath Park site. The Human Application and Anatomy
Licences are held in School of Biosciences.
This Quality Management System relates to the compliance with the HT Act and
Human Tissue Authority standards and guidance.
2 POLICY AND OBJECTIVES
Cardiff University’s HTA quality management policy is to ensure compliance with the
HT Act and with the Codes of Practice set by the Human Tissue Authority, specifically Codes of Practice 1, 5, 8 and 9 (Consent, Disposal, Import and Export and Research respectively).
This level of quality is achieved through adoption of a system of procedures that reflect the regulatory standards and guidelines.
Achievement of this policy involves all staff who work with human tissue, who are individually responsible for the quality of their work, and should result in a continually improving working environment for all. This policy will be provided and explained to each employee involved in working with human tissue by the relevant Principal
Investigator, Person Designated under the Licence or Human Tissue Act Compliance
Team .
To achieve and maintain the required level of assurance the Designated Individual
(DI) retains responsibility for the Quality Management System with routine operation controlled by the individual Principal Investigator and/or Person Designated.
The objectives of the Quality Management System are: a) b)
To maintain an effective Quality System complying with the HT Act and the
HTA Codes of Practice.
To ensure compliance with relevant statutory and safety requirements.
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3 c) To achieve and maintain a level of quality which enhances the University's reputation with stakeholders.
DEFINITIONS
Chief Investigator (CI)
–
The individual who takes overall responsibility for the design, conduct and reporting of a study if it is at one site; or if the study involves researchers at more than one site, the Chief Investigator takes responsibility for the design, management and reporting of the study, co-ordinating the investigators who take the lead at each site. A senior individual must be designated as the Chief
Investigator for any research undertaken in or through the NHS or social services, which involves participants or their organs, tissue or data.
Designated Individual (DI)
–
The individual designated in the licence as the person under whose supervision the licensed activity is authorised to be carried on. There is one DI for each licence and they are legally responsible for ensuring compliance with the conditions of the licence. The HTA must be satisfied as to the suitability of this person.
Human Tissue
–
Any and all constituent parts of the human body formed by cells.
Human Tissue Act Compliance Team
–
The team within Governance and
Compliance Division, with a representative from the UHB R&D Office, that ensures compliance with the HTA Licence through audits and maintenance of the Quality
Management System.
Human Tissue Authority (HTA) – The governing body set up to regulate activities that come under the HT Act. The HTA is a watchdog that supports public confidence by licensing organisations that store and use human tissue for purposes such as research, patient treatment, post-mortem examination, teaching, and public exhibitions.
Licence Holder – The person or corporate body responsible for applying for the
Licence and any changes to the Licence. In the case of a corporate body, a named individual acts as its representative. The HTA must be satisfied as to the suitability of this person. The Licence Holder is Cardiff University and the named individual is Dr
Chris Turner, REGOS .
Material Transfer Agreement (MTA) – a contract that governs the transfer of research materials between two organisations when the recipient intends to use the material for their own research.
National Research Ethics Service (NRES) – Oversees and reviews Research
Ethics Committees (REC) who in turn safeguard the rights, safety, dignity and wellbeing of research participants, independently of research sponsors.
Person Designate (PD) – A person to whom the licence applies and to whom the authority conferred by the licence extends. Each School operating under an HTA
Licence should have at least one Person Designate.
Principal Investigator (PI) – The appropriately qualified individual at each project site who has responsibility for the conduct of the project at that site.
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Quality Management System
–
The means by which the processes and procedures used in human tissue research are assured and maintained in compliance with the
HT Act and the standards and guidance set by of the HTA.
Relevant Material
–
Any material, other than gametes, removed from the body that consists of or includes human cells. In the HT Act references to relevant material from a human body do not include:

embryos outside the human body,

hair and nail from the body of a living person,

cell lines or any other human material created outside the human body,

serum, plasma, DNA and RNA.
The HTA has issued a Supplementary List of Materials which contains additional information, see Appendix A.
Researchers/ Hands-on-Staff - Staff who are responsible to the PI and carry out the day to day procedures.
Standard Operating Procedure (SOP)
–
Detailed, written instructions to achieve uniformity of performance of a specific function.
Storage
–
Maintaining the tissue under appropriate controlled conditions.
4 QUALITY SYSTEM
The Quality Management System applies to all activities of the University that involve the removal, storage, use and disposal of human bodies, organs and tissue for research purposes. There are three levels to the system:
4.1 Level 1: Quality Manual
This document details the systems in place to ensure compliance with the HTA
Licence and gives information to researchers whose projects may come under the remit of the Licence. It should be read by anyone at Cardiff University who is involved in research with human tissue.
4.2 Level 2: Standard Operating Procedures
These documents describe the actual processes and controls applied to all activities concerned with the removal, storage, use and disposal of human bodies, organs and tissue for research purposes. They should be consulted and followed for all relevant procedures.
Local Quality Manuals and Standard Operating Procedures have been developed to address specific, local practices. The Local Operating Procedures are approved by the relevant site Working Group and are maintained locally by the responsible PD.
Quality Manuals are developed within Schools and individual laboratories.
4.3 Level 3: Internal Audit
The main aim of the internal audit is to ensure that all activities related to human tissue, including consent, transportation, storage and disposal are conducted in
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accordance with the HTA Codes of Practice and that internal systems for compliance are effectively in place.
5 GOVERNANCE ARRANGEMENTS
The governing body for the University is Council and the chief academic body is the
Senate. The remit for both bodies is described in
Cardiff University’s Charter,
Statutes and Ordinances.
5.1 Governance Committee
In Session 2007-08 a Governance Committee was set up to advise Council on all matters relating to the governance of the University and on the level of compliance with the mandatory requirements of legislation and other regulations. The
Governance Committee is chaired by the Vice-Chair of Council [Mr J Jeans, a lay member] and it has a lay majority. The Committee has a number of sub-committees that report to it, including the Health, Safety and Environment Committee, the
University Research Ethics Committee and the Biological Standards Committee.
5.2 University Research Ethics Committee
The University Research Ethics Committee’s remit is to develop and sustain a
University-wide awareness of ethical issues arising from research involving human participants, human material or human data, which is not covered by ethical considerations associated with clinical research. The Committee’s membership includes two lay members of Council, one of whom is also currently a member of the
Governance Committee.
5.3 The Committee Structure and HTA Matters
Governance Committee receives an annual report on activities and progress in relation to the HT Act across the University. The University Research Ethics
Committee receives a report and update on HTA matters arising from the working groups at every meeting.
5.4 HTA Working Group
The HTA Working Group supports the hub and satellite Research Licences issued for the Heath Park and Cathays Campus, respectively. The group is chaired by the DI and comprise the lead PDs from each licensed area, other PDs, and administrative support staff representing the Governance and Compliance Division, the Research and Commercial Division, the Occupational, Safety Health and Environment Unit and, as appropriate, University Health Board partners. The Wales Cancer Bank DI is also a member.
The remit of the group is to discuss issues relating to the HTA Licence requirements, share examples of good practice, and to facilitate regular communication between the DI and the PDs. The group, via the Governance and Compliance Division, submits regular update reports to the University ’s Research Ethics committee, which in turn reports to the Governance Committee. A formal annual report is made to the
Governance Committee by Governance and Compliance Division.
5.5 Research Governance
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The University’s Research and Commercial Division has a Research Governance team that serves the U niversity’s research community. The team aims to advise on the University’s Research Governance Framework and the conduct of clinical research, as well as provide an effective research governance environment for researchers.
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6 ORGANIZATION CHARTS
6.1 Structure and Organization for the Heath Park Hub Research Licence
Designated Individual: Professor Jonathan Bisson
Persons Designate:
School of Medicine
Lead PD - Prof Bharat Jasani
ICAGE/HAEMY &AML - Dr Paul White
IPCPH - Dr Clive Gregory
IPMCN - Dr Kiran Mantripragada
ICAGE/GYNON (HPV) - Dr Ned Powell ITIME - Prof Nick Topley
ICAGE/MGENE - Mrs Shelley Idziaszczyk ITIME - Mr Karl Hanzel
INIIM (Tenovus) - Dr Eddie Wang MOLEX - Prof Colin Dayan
INIIM (HWB) - Dr Paul Bowden MOLEX/DIABE - Dr Wendy Powell
School of Dentistry
Prof Phil Stephens – Lead PD
Prof Barbara Chadwick
Dr Fiona Gagg
Dr Alan Gilmour
UHB
Institute of Medical Genetics - Dr Ian Frayling – UHB/MGENE
Human Tissue Act Compliance Team:
HTA Co-ordinator - Mrs Sharon Orton
Governance Officer (HTA) - Dr Carina Hibbs
UHB Governance Officer (HTA) - Mrs Patricia Tamplin
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6.2 Structure and Organization for the Cathays Campus Satellite Research Licence
Designated Individual:
Professor Jon Bisson
Persons Designate:
Dr Julie Albon (OPTOM)
Dr James Birchall (PHRMY)
Mr Bill Edwards (BIOSI)
Dr Andrea Longman (ARUK BBC)
Human Tissue Act Compliance Team:
HTA Co-ordinator - Mrs Sharon Orton
Governance Officer (HTA) - Dr Carina Hibbs
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6.3 Structure and Organization for the School of Biosciences Anatomy Licence
Designated Individual:
Dr Tracey Wilkinson
Persons Designate:
Dr Alvin Kwan
Dr Rob Santer
Dr Hannah Shaw
Dr Shiby Stephens
Dr Alan Watson
Mr Bill Edwards (Technical Manager)
Ms Lisa Meads (Anatomy Technician and Assistant Bequeathals Officer)
Mr Swaran Yarnell (Mortician and Bequeathals Officer)
Human Tissue Act Compliance Team:
HTA Co-ordinator - Mrs Sharon Orton
Governance Officer (HTA) - Dr Carina Hibbs
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7 AUTHORITY & RESPONSIBILITIES
7.1 Authority
All staff are delegated authority to perform their allocated responsibilities. Section 7.2 provides a summary of the principal responsibilities of each job role.
All staff share the authority and responsibility of identifying non-compliant practices and recording these instances such that corrective action can be taken, both to rectify the immediate situation and to prevent recurrence.
The Designated Individuals continually review the University's resources to ensure that adequate staff, equipment and materials are available to meet regulatory requirements.
7.2 Responsibilities
Chief Investigator/Principal Investigator (CI/PI)
The CI/PI is the person responsible, individually or as the leader of researchers at a particular site, for the conduct of a study. In terms of complying with the HTA
Licence, the CI/PI is responsible for:

informing the PD and HTA Co-ordinator of any relevant projects;

ensuring that each project is compliant with the HTA Licence;

ensuring that all MTAs are in place for any incoming/outgoing tissue transfers
(see Section 8);

completing the Annual Survey of Holdings (see Section 11);

maintaining relevant and good quality records (see Section 12);

drafting and updating risk assessments (see Section 13);

adverse event reporting (see Section 13);

implementing recommendations made following internal audit or HTA inspections;

ensuring all staff working on projects have relevant training, including HTA and/or consent where necessary.
Designated Individual
Designated Individuals have a key role to play in implementing the requirements of the HT Act. They are the person under whose supervision the licensed activity is authorised to be carried out. They have the primary (legal) responsibility under
Section 18 of the HT Act to secure:

that suitable practices are used in undertaking the licensed activity;

that the other persons who work under the licence are suitable;

and that the conditions of the licence are complied with.
The relevant PI chairs the biannual working group meeting for each site and signs off updated documentation, such as SOPs.
Licence Holder
The Licence Holder has the responsibility to pay for the licence and has the right to apply to the HTA to vary the licence with regard to changing the DI.
Persons Designate
Persons Designate, appointed by the DI, are able to direct in relation to licensable activities. The role of the PD is supplementary to that of the DI in the governance framework, although the DI remains ultimately legally responsible for supervising the
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activities to be authorised by the licence, the PD acts at a local level to support the
DI.
At the Heath Park site, there are lead PDs for the Medical and Dental Schools who co-ordinate and monitor compliance within their School. Additionally, there are PDs for specific areas or projects. The lead PD is first point of contact for the DI to ensure compliance within the School. On the Cathays Campus site, there is a PD for each
School storing human tissue under Licence (currently Schools of Biosciences,
Optometry and Pharmacy) and an additional PD for the ARUK BBC Group in the
School of Biosciences. The responsibilities of the PDs include:

maintaining a list of projects that are storing human tissue in their area and whether they are under Licence or covered by REC/NRES approval;

visiting each project to ensure compliance with documentary and physical requirements;

checking and holding copies of risk assessments and staff training records relating to HTA;

checking storage facilities and their maintenance;

assisting in the internal audit of other Schools;

following up any recommendations made during the internal audit or HTA inspection of their relevant School/Unit;

notifying the Human Tissue Act Compliance Team of any new projects that come under the HTA Licence;

participating in working group meetings.
Human Tissue Act Compliance Team
The Human Tissue Act Compliance Team is responsible for the control and maintenance of the Quality Management System, including drafting and updating documentation and performing internal audits. Other responsibilities include conducting the Annual Survey of Holdings and following-up responses in order to maintain an up-to-date and accurate Register of Holdings.
Researchers/ Hands-on-Staff
Staff who carry out the day to day procedures are responsible for:

ensuring they have the appropriate training (see Section 8);

ensuring that relevant SOPs are followed (see Section 10);

creating/maintaining accurate records of human tissue collection, storage, use and disposal (see Section 12);

their own familiarisation with risk assessments and contingency plans (see
Section 13);

reporting any adverse events or near misses to the PI (see Section 13).
8 KEY AREAS WITHIN THE HUMAN TISSUE ACT 2004
There are a number of key areas within the HT Act that need to be considered when using human tissue for research purposes, including what is considered to be relevant material, consent, storage, transportation, disposal and training.
8.1 Relevant Material
Within the HT Act, all human tissue that has come from a human donor, other than gametes and nail/hair from a living person, and contains at least one cell is considered to be relevant material.
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Bodily fluids that are likely to contain cells are considered to be relevant material, e.g. blood, urine, saliva.
Cells in culture are not considered to be relevant material unless they contain cells that were created inside the body. Once a cell has undergone one complete celldivision cycle it is considered to have been created outside the body and does not need to come under an HTA Licence.
Human tissue that has been rendered acellular is not considered to be relevant material under the HT Act.
8.2 Consent
The HT Act makes consent the fundamental principle underpinning the lawful storage and use of human bodies, body parts, organs and tissue and the removal of material from the bodies of deceased persons.
All those involved in seeking consent from patients/research participants for the removal, storage or use of human tissue should receive training in the implications and statutory requirements for consent under the HT Act, see 8.6 below.
Under the HT Act, tissue can be used without consent if more than 100 years has passed since the donors death or if the tissue was held before the HT Act came into force in 2006 (an existing holding). Although, in the latter case, it is considered good practice to obtain consent from the donor or donor’s family if the samples are to be used subsequently for research purposes.
Tissue from the living may be stored for use and/or used without consent for research purposes, provided that:

the research is ethically approved by an NRES research ethics committee; and

the tissue is anonymised such that the researcher is not in possession of the information identifying the person from whose body the material has come and is not likely to come into possession of it. (This does not mean that samples must be permanently and irrevocably unlinked.);
Human tissue obtained from the deceased cannot be stored without consent unless it is for coroner’s or criminal justice purposes.
The consent provisions of the HT Act to not apply to imported material, however it is considered good practice to ensure informed consent has been taken. For further information on the import of human tissue, see Cardiff University HTA Standard
Operating Procedure for Import and Export of Human Tissue.
The Licensing and Consent flowcharts in Appendix B further illustrate when research does and does not require consent.
See HTA Code of Practice 1: Consent and Cardiff University HTA Standard Operating
Procedure for Obtaining Informed Consent for further information.
8.3 DNA Theft
DNA (as opposed to the bodily material from which it originates) is not considered to be relevant material under the HT Act and can be stored without the need for an HTA
Licence. However the HT Act does make it an offense to be in possession of bodily
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material with the intention of analysing its DNA without consent to do so. Bodily material is defined as all material that comes from a human body and contains at least one cell, including gametes and nail and hair from a living person.
It is possible to be in possession of bodily material with the intention to extract DNA without consent provided:

the tissue is from a living person; and

the researcher is not in possession, and not likely to come into possession of information that identifies the person from whom it has come; and

the material is used for a specific research project with NRES approval.
Although no offence will be committed in this situation, the HTA recommends that, where practical, consent is obtained.
An offence will be committed where somebody has bodily material intending to analyse its DNA and use the results for research without consent for non-excepted purposes (see HTA Code of Practice 1: Consent).
8.4 Storage
The HTA does not define storage, it can mean hours, days, weeks or longer. Being in possession of human tissue for a scheduled purpose is deemed to be ‘storage’.
Human tissue must be stored securely, in line with health and safety guidelines, and appropriate records kept. University and local SOPs must be followed. Risk assessments of storage provision should be made and contingency plans put in place to manage breakdowns and adverse events.
Long-term storage is acceptable where consent is in place or one of the above exemptions applies. Holdings must be reviewed on an annual basis.
See Cardiff University HTA Standard Operating Procedure for Storage of Human
Tissue for further information.
8.5 Transport and Export
Consent must be in place to transport or export human tissue, unless the tissue is from the living, anonymised and NRES approval is in place to transport/export without consent.
No human tissue may be transported from one establishment to another within
England, Wales or Northern Ireland unless both establishments have an HTA
Licence or the tissue is covered for transportation under NRES approval.
A Material Transfer Agreement (MTA) must be in place for all incoming and outgoing tissue transfers. From an HTA perspective, an MTA should define how the human tissue will be preserved, any potential contamination risks associated with it and who will be responsible for disposal if applicable. For incoming tissue, the supplier will usually provide the MTA. For outgoing transfers, the University will provide the MTA.
MTAs must not be signed by individual researchers and must go through Cardiff
University Research and Commercial Division.
Appropriate modes of transport, suitable routes and arrangements with people involved must be planned and arranged in advance and records kept of all tissue movements
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Risk Assessments of the transportation of human tissue must be made and regularly reviewed.
The Cardiff University HTA Standard Operating Procedures for Transportation of
Human Tissue and Import and Export of Human Tissue must be followed.
8.6 Disposal
Human tissue must be disposed of with respect. As an absolute minimum tissue identified for disposal should be bagged separately from other clinical waste.
Appropriate methods of destruction, storage and arrangements with people involved must be planned and arranged in advance. Risk Assessments of the disposal of human tissue must be made and regularly reviewed.
Records of disposal must be maintained even if this is to record that the tissue was
‘used up’ in processing. This is still deemed to be disposal as there is no longer any relevant material remaining.
9
The Cardiff University HTA Standard Operating Procedure for Disposal of Human
Tissue must be followed for the disposal of human tissue. For further information see
HTA Code of Practice 5: Disposal of Human Tissue.
8.7 Training
The policy of the University is to ensure that all personnel are trained and experienced to the extent necessary to undertake their assigned activities and responsibilities effectively.
Under the HT Act, anyone taking consent for the collection of human tissue must be trained to do so. Cardiff University Research and Commercial Division and UHB jointly run a Good Clinical Practice training course; one of the modules on this covers consent.
Anyone who holds tissue under the HTA Licence must be trained in the HT Act. A training course covering the requirements of the HTA is run through the University’s
Staff Development Programme, which includes information on how to comply with the HTA Licence and licence exemptions. The MRC also have an on-line course related to HTA activities, which would satisfy the terms of the HTA Licence.
Certificates of completion of any on-line courses must be retained as proof of completion.
Line managers are responsible for identifying and making recommendations on the training needs of their staff and for ensuring that all employ ees’ allocated specific tasks are suitably qualified and experienced to execute those tasks.
Full records should be maintained of all training undertaken by employees. The relevant PD should be notified of any training in relation to HTA.
See the Cardiff University HTA Standard Operating Procedure for Staff Training for more information.
EXEMPTIONS FROM THE HTA LICENCE
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The two Research Licences held by Cardiff University allow for the storage, use and disposal of human tissue from the living and the deceased, and the removal of human tissue from the living for the purposes of research. All research projects that come under the Licence must adhere to the regulations set out by the HTA and covered in the Quality Management System.
There are several exemptions from the Licence, these are detailed below and highlighted in the Licensing and Consent flowcharts in Appendix B.
Note: even if project is exempt from the Licence, if it involves the removal, use or storage of human tissue the relevant PD and Human Tissue Act Compliance
Team must be informed.
9.1 REC/NRES Approval
If a specific research project has REC/NRES approval, or approval is pending, it will not need to come under the HTA Licence. However if the tissue is to be retained following the end date of the ethics approval, it will need come under the University’s
HTA Licence and the PI must adhere to the regulations set out by the HTA and covered in the Quality Management System. This is the case even if the retention of the tissue was reviewed and approved by NRES
– once the project itself ceases so too does the approval and any subsequent tissue storage must be under the HTA
Licence unless further NRES approval is in place or pending. As such it is advisable that all projects with NRES approval adhere to the processes detailed in the Quality
Management System.
All research tissue banks must be held on HTA Licensed premises, even if REC approval is in place.
Note: Ethical approval from committees within the University does not constitute
NRES approval and therefore any projects with University ethical approval will need to come under the licence and comply with the regulations set out by the HTA and covered in the Quality Management System.
9.2 Tissue from Tissue Bank with Generic Ethical Approval
If the tissue comes from a REC-approved tissue bank with generic ethical approval and an HTA Licence, the recipients of the tissue do not need to store it under an HTA
Licence during the period of the research project, subject to certain requirements. At the end of the project any residual tissue must be returned to the tissue bank or be disposed of. If the researcher wishes to retain the tissue they must apply for their own NRES ethical approval or store the tissue under the HTA Licence.
Note: If the research tissue bank stores the tissue on HTA-licensed premises but does not have generic ethics approval, each researcher acquiring human tissue from the bank must store it under an HTA Licence, or apply for their own specific project
NRES approval.
9.3 Storage is Incidental to Transportation
Under the HT Act, where human tissue is in storage pending transfer elsewhere, providing it is held for a matter of hours or days and certainly no longer than a week, the HTA takes the view that the storage is incidental to transportation and an HTA licence is not required.
9.4 Intention to Extract DNA/RNA
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Where human tissue is being held whilst it is processed with the intention to extract
DNA or RNA, or other subcellular components that are not relevant material (i.e. rendering the tissue acellular), the HTA views this as analogous to the incidental to transportation exception. A licence is not therefore required, providing the processing takes a matter of hours or days and certainly no longer than a week.
Note: Where a researcher holds tissue for a short period for the purpose of a project
(e.g. to conduct analysis prior to discarding the tissue), and the tissue is not rendered acellular this is storage for a scheduled purpose (i.e. research). Such storage requires either a licence from the HTA or NRES approval for the project.
9.5 Cell Cultures
For the purpose of research that does not involve any application of tissues or cells into humans, material that is created outside the human body does not fall under the remit of the HTA.
Note: Cell cultures are relevant material if they contain cells that were created inside the human body e.g. if the culture contains original cells from a biopsy or blood sample. Once cells in culture have undergone one full cell-division cycle, the culture no longer contains original cells and the tissue does not have to be held under
Licence. However the tissue will need to come under the HTA Licence until the researcher is satisfied that no original cells remain.
9.6 Acellular Material
The HT Act only applies to tissue that contains human cells; once the tissue has been rendered acellular it no longer comes under the HTA Licence.
9.7 Deceased for more than 100 years
If the tissue comes from someone who has been dead for more than 100 years, it does not need to be held under an HTA Licence.
10 STANDARD AND LOCAL OPERATING PROCEDURES
10.1 Standard Operating Procedures
Cardiff University HTA Standard Operating Procedures have been developed and agreed by the HTA Working Group. SOPs have been generated, and must be consulted, for the following procedures:

preparation, review and issue/approval of SOPs;

obtaining informed consent;

disposal of human tissue;

transportation of human tissue;

management of records;

staff training;

adverse event reporting;

internal audit;

risk management and contingency planning;

maintenance of temperature controlled storage facilities

setting up a research tissue bank;

import and export of human tissue.
CU/13/HTA15/1.0 Page 18 of 30

The latest version of the SOPs can be found on the University HTA website.
10.2 Local Operating Procedures
Local Operating Procedures have been developed and approved for certain Schools and are available on the appropriate School web-page. The Local Operating
Procedures are based on the principles outlined in the University Standard Operating
Procedures, adapted to suit local practices.
11 ANNUAL SURVEY OF HOLDINGS AND INTERNAL AUDIT
11.1 Annual Survey of Holdings
The Human Tissue Act Compliance Team conducts an Annual Survey of Holdings to assess how much human tissue is held for research, who holds it and where. Prior to the survey being conducted, each Head of School is required to sign a form stating whether or not human tissue is held within their School. The survey is then completed by PIs in each School that has acknowledged storing human tissue.
The survey includes the following questions:

how many samples are held;

where they are held;

the purpose of tissue storage;

whether there is NRES/REC approval for the project;

whether the tissue is stored as part of a tissue bank;

whether consent was taken;

what IT systems are in place for record keeping.
Based on the information given in the Annual Survey, an accurate Register of
Holdings is compiled and used to determine which projects come under the HTA
Licences. The Register of Holdings is also used to select projects/groups that will undergo internal audit.
11.2 Internal Audit
Internal audits of Schools/research projects are undertaken to confirm that the area concerned is adhering to the University's Procedures and is compliant with HTA requirements and regulations. The audit programme operates on a two-year cycle. In the first year there is a face-to-face physical audit; in the second year a paper-based audit return is made.
The face to face audit schedule comprises a records audit, to ensure records are accurate, complete and legible; a process audit to ensure staff are adhering to SOPs; and a traceability audit to ensure that the establishment can trace specimens from donors consent, or point of receipt if supplied by a third party, to storage, use or disposal. Following the inspection, a report is produced highlighting any issues that need to be addressed to ensure compliance with the HTA Licence. Evidence that these have been addressed will be followed up within three months of the audit and during the paper based audit the following year.
Once a School/Unit has had a face to face audit, the second year in the audit process is a paper based audit return. If this identifies any areas of concern, an
CU/13/HTA15/1.0 Page 19 of 30

inspection visit will be made. Should particular needs be identified, the frequency of audit may be increased at the discretion of the Human Tissue Act Compliance Team.
Audits are undertaken by the University’s Governance and Compliance Division, together with a PD from another School/Unit. Non-compliance issues will be brought to the attention of the person responsible, and will be recorded, documented and subject to timely corrective action to ensure full rectification.
See Cardiff University HTA Standard Operating Procedure for Internal Audit for more information.
12 RECORDS AND TRACEABILITY
12.1 Records
Each project or person storing tissue should ensure that their holdings are fully documented. As a minimum, the following information should be kept for each sample:

sample ID reference. This should be unique and be anonymised and should not include patient details;

tissue type (if more than one stored/used);

date of receipt and details of where it came from;

consent details and where the consent form is held;

storage location, including room, unit, shelf, box and position;

details and dates of processing of sample;

if relevant, details and dates of any transfers out to and back from other locations on a temporary basis;

date and method of disposal. This could be transfer to another location or destruction using approved procedures;

reason for disposal;

name of researcher/PI
The system for recording this information should be proportionate to the activity being carried out. Ideally, the information should be in electronic format (spreadsheet or database) but if the collection is small, a paper-based system would be acceptable. A template spreadsheet and database can be found on the University HTA website.
Principal investigators and custodians of human tissue collections must ensure that the following records are captured/created and maintained where required (this list is indicative and not exhaustive):

consent (where required), detailing:
who gave consent;
what the consent related to;
whether consent is related to a specific project or for wider use in research;
any restrictions on the use stipulated during the consent;
if the consent records are in the custody of another organisation, the
Principal Investigator or custodian of human tissue collections must ensure that they have documentation that contains assurances of compliance with Human Tissue Act requirements,

ethics approval,

human tissue use and movement, e.g. receipts, transfer documentation,
MTAs, laboratory log books,
CU/13/HTA15/1.0 Page 20 of 30


maintenance, cleaning and calibration of equipment,

risk assessment,

tissue destruction, e.g. receipts, laboratory log books,

adverse events
, including ‘near misses’,

local Standard Operating Procedures and quality management documentation,

staff training,

system for labelling human tissue.
Records stored on electronic media should comply with best practice and University guidance in respect of security, access and back-up of the records. Any supporting documentation (such as receipts, log books of processing, disposal registers or receipts, consent documentation) should be kept separately.
For further information see Cardiff University HTA Standard Operating Procedure for
Management of Records.
12.2 Audit Trail
One of the requirements of the HTA Licence is that institutions ensure a full traceability trail is maintained and documented for the storage and movement of all licensable material from receipt to end use, disposal or distribution.
12.3 Labelling
Tissue samples should be individually labelled. The information on the label should be sufficient to identify the sample and would normally include a unique ID reference and the date of receipt. The label should not include any patient/participant details.
13 RISK ASSESSMENTS AND ADVERSE EVENTS
13.1 Risk Assessments
Risk assessments should be carried out for all procedures relating to the storage, use, transportation and disposal of human tissue. Risks to the tissue, in addition to the handlers, should be assessed. Such risk assessments should be recorded using the appropriate Cardiff University HTA Risk Assessment form and should be reviewed on a regular basis. Risk assessments must be kept by the PI and copies sent to the HTA Co-ordinator and relevant PD.
Things to consider when completing a risk assessment for the tissue include package failure, delay or loss in transit, malfunction of storage facilities, unauthorised access to tissue samples, incorrect procedures being carried out, untrained personnel handling the tissue and any other hazards that result in tissue loss.
For further information see Cardiff University HTA Standard Operating Procedure for
Risk Management and Contingency Planning.
13.2 Adverse Events
If an adverse event occurs, a report of the incident and any corrective action taken should be generated and recorded. As much relevant detail as possible should be included on the accident report; it is essential that the exact location of the
CU/13/HTA15/1.0 Page 21 of 30

accident/incident is clearly identified, using the correct school/division address. The staff/student number is also essential for the reporting of accidents.
Any accidents or incidents involving human tissue stored by the University should be recorded on the appropriate HTA adverse incident reporting form and reported to the
School PD and to the HTA Co-ordinator. All procedures laid out in the Cardiff
University HTA Standard Operating Procedure for Adverse Event Reporting must be followed.
The corrective action required to prevent recurrence will be evaluated, documented, and its effective implementation monitored. All rectification is subsequently reinspected to ensure that it is satisfactory. All employees are encouraged to suggest improvements in methods, materials, suppliers.
All accidents and incidents involving individuals must be reported within the
School/Unit and also to Occupational Safety Health and Environment Unit (OSHEU).
Accident forms are available for downloading from the OSHEU website (or in hardcopy from School / division administrators).
14 MANAGEMENT REVIEW AND DOCUMENTATION & VERSION CONTROL
14.1 Management Review
Review of the suitability and effectiveness of the Quality Management System will take place annually at the HTA Working Group.
The objectives of Management Review are:

to establish whether the Quality Management System is achieving the expected results in ensuring that the University is conforming to regulatory standards, and is functioning in accordance with the established Operating
Procedures;

to expose irregularities or defects in the System, identify weaknesses and evaluate possible improvements;

to review the effectiveness of previous corrective actions, and to review the adequacy and suitability of the management system for current and future operations of the University;

to review any complaints received, identify the cause and recommend corrective action if required;

to review the findings of internal/ external audits and identify any areas of recurring problems or potential improvements;

to review the reports of nonconforming items and trend information to identify possible improvements;

to review any Quality System documentation that has reached its review date.
14.2 Documentation & Version Control
All documentation relating to the Quality Management System is revised and reissued as necessary, and all obsolete versions are removed from the point of use.
All changes to documents are reviewed by the person responsible for the original issue and, where appropriate, the nature of the change is indicated on the document.
Responsibility for the control of local documentation lies with the relevant PD.
CU/13/HTA15/1.0 Page 22 of 30

Master copies of the revised documents are retained as records of the changes and renewed as necessary to ensure clarity. Revisions to documents will be approved by both Working Groups, usually at a joint annual meeting.
CU/13/HTA15/1.0 Page 23 of 30

15 REFERENCES

Cardiff University HTA Website: http://www.cardiff.ac.uk/govrn/cocom/humantissueact/index.html

Cardiff University Human Resources
– Training and Development web pages: http://www.cardiff.ac.uk/humrs/training/index.html

Cardiff University Research and Commercial Division GCP Training http://www.cardiff.ac.uk/racdv/resgov/training/index.html

Cardiff University Research Governance Framework: http://www.cf.ac.uk/racdv/resgov/index.html
 Cardiff University Staff Development Programme ‘An Introduction to the
Human Tissue Act’ http://www.cardiff.ac.uk/humrs/training/programme/All%20Workshops%20A-
Z/an-introduction-to-the-tissue-act.html

HTA Code of Practice 1: Consent http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/c ode1consent.cfm

HTA Code of Practice 5: Disposal of Human Tissue http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/c ode5disposal.cfm

HTA Code of Practice 8: Import and Export of Human Bodies, Body Parts and
Tissue http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/c ode8importandexport.cfm

HTA Code of Practice 9: Research http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/c ode9research.cfm

Medical Research Council elearning ‘Research and Human Tissue
Legislation’: http://www.rsclearn.mrc.ac.uk/
16 REFERENCED SOPS
All Cardiff University HTA Standard Operating Procedures:

Preparation, Review and Approval of SOPS [CU/09/HTA01/3.0]

Obtaining Informed Consent [CU/09/HTA02/3.0]

Storage of Human Tissue [CU/09/HTA03/3.0]

Disposal of Human Tissue [CU/09/HTA04/3.0]

Transportation of Human Tissue [CU/09/HTA05/3.0]

Management of Records [CU/09/HTA06/3.0]

Staff Training [CU/09/HTA07/3.0]

Adverse Event Reporting [CU/11/HTA08/3.0]

Internal Audit [CU/11/HTA09/3.0]

Risk Management and Contingency Planning [CU/11/HTA10/3.0]

Maintenance and Upkeep of Constant Temperature Storage Facilities
[CU/11/HTA11/3.0]

Import and Export of Human Tissue [CU/13/HTA12/1.0]

Running a Research Tissue Bank [CU/13/HTA13/1.0]
CU/13/HTA15/1.0 Page 24 of 30

17 CONTACTS
17.1 DI and PDs
Name
Prof Jonathan Bisson
School/
UHB
DI
CU/UHB
Coverage Email
All areas BissonJI@cf.ac.uk
Tel
(207)43742
Dr Andrea Longman
Mr Bill Edwards
Prof Phil Stephens
BIOSI PD
ARUK
BBC
BIOSI PD BIOSI
DENTL
Lead PD DENTL
Prof Barbara Chadwick DENTL PD DENTL
Dr Fiona Gagg DENTL PD DENTL
Dr Alan Gilmour
Prof Bharat Jasani
Dr Paul White
DENTL PD DENTL
MEDIC
Lead PD PATHY
MEDIC PD
AML and
HAEMY
LongmanAJ1@cf.ac.uk
EdwardsWD@cf.ac.uk
StephensP@cf.ac.uk
ChadwickBL@cf.ac.uk
WhiteFS@cf.ac.uk
Gilmour@cf.ac.uk
Jasani@cf.ac.uk
(208)75419
(208)75136
(207)42529
(207)46569
(207)42546
(207)42617
(207)42700
WhitePC@cf.ac.uk
(207)44524
Dr Ned Powell
Dr Paul Bowden
Dr Clive Gregory
MEDIC PD
Mrs Shelley Idziaszczyk MEDIC PD
MEDIC PD
ICAGE/
GYNON PowellNG@cf.ac.uk
ICAGE/
MGENE IdziaszczykSA1@cf.ac.uk
INIIM in
HWB
MEDIC PD IPCPH
Bowden@cf.ac.uk
GregoryC1@cf.ac.uk
(207)44742
(206)87859
(206)87302
(206)87221
Dr Kiran Mantripragada MEDIC PD IPMCN
Prof Nick Topley
Mr Karl Hanzel
MEDIC PD ITIME
MEDIC PD
(assistant) ITIME
Prof Colin Dayan
Dr Wendy Powell
MantripragadaKK@cf.ac.uk
Topley@cf.ac.uk
HanzelK@cf.ac.uk
MEDIC PD MOLEX DayanCM@cf.ac.uk
MEDIC PD
(assistant) MOLEX PowellW1@cf.ac.uk
(206)87063
(207)43770
(207)42050
(207)42182
(207)48497
Dr Tracey Martin
Dr Eddie Wang
Dr Julie Albon
MEDIC
MEDIC PD
SURGY
Tenovus
Building
MartinTA1@cf.ac.uk
WangEC@cf.ac.uk
OPTOM PD OPTOM AlbonJ@cf.ac.uk
(207)46536
(206)87318
(208)75427
Dr James Birchall PHRMY PD PHRMY BirchallJC@cf.ac.uk
(208)75815
Dr Ian Frayling UHB Med Gen Ian.Frayling@wales.nhs.uk
(207) 44203
17.2 Human Tissue Act Compliance Team
Name Division Position Email
Mrs Sharon Orton GOVRN HTA Co-ordinator HTA@cf.ac.uk
Tel
(208)74888
Dr Carina Hibbs GOVRN Governance Officer HTA@cf.ac.uk
Mrs Pat Tamplin UHB Governance Officer Pat.Tamplin@wales.nhs.uk
(208)70231
(207)45879
CU/13/HTA15/1.0 Page 25 of 30

APPENDIX A
Supplementary list of materials
This list is intended to provide supplementary guidance to the HTA’s broader policy framework on ‘relevant material’.
The list is not intended as exhaustive or exclusive, but is intended to provide guidance to stakeholders in respect of a number of materials that guidance on the status of, as relevant material or otherwise, has previously been sought. The HTA will review and update the list periodically.
The list currently refers solely to which human body parts, tissues and cells are defined as
‘relevant materials’ for the purposes of the Human Tissue Act 2004, in line with the statutory definition above. The HTA intends to expand the list in the future to also provide guidance to the human application sector on which ‘tissues and cells’ are regulated under the Human
Tissue (Quality and Safety for Human Application) Regulations 2007.
Where a material is not included within the following list stakeholders should refer to the policy framework to formulate their own assessment of the material’s status in line with the guidance provided in the framework.
Materials classified in the following list as relevant material are done so subject to the following general caveat that they are relevant material except where:

They have divided or been created outside the human body

They have been treated, processed or lysed through a process intended to render them acellular. This would include the freezing or thawing of cells only where that process is intended to render the material acellular.
Material
Antibodies
Artificially created stem cells*
Bile
Relevant materials for the purposes of the Human
Tissue Act 2004?
No
No
Yes
Blood
Bone Marrow
Bones/Skeletons
Brain
Breast Milk***
Breath Condensates and exhaled gases
Buffy coat layer (interface layer between plasma and blood cells when blood is separated)
Cell lines**
Yes
Yes
Yes
Yes
Yes
No
Yes
No
CU/13/HTA15/1.0 Page 26 of 30

Cells that have divided in culture
CSF (Cerebrospinal fluid)
Cystic fluid
DNA
Eggs*
Embryonic stem cells (cells derived from an embryo)**
Embryos (outside the body)*
Extracted material from cells, e.g. nucleic acids, cytoplasmic fraction, cell lysates, organelles, proteins, carbohydrates and lipids.
Faeces
Fetal tissue
Fluid from Cystic lesions
Gametes*
Hair (from deceased person)
Hair (from living person)
Joint Aspirates
Lysed Cells
Mucus
Nail (from deceased person)
Nail (from living person)
Nasal and Bronchial Lavage
Non blood derived stem cells (i.e. derived from the body)
Non fetal products of conception (i.e. the amniotic fluid, umbilical cord, placenta and membranes)
Organs
Pericardial fluid
Plasma
(Please note: Depending on how plasma is prepared and processed, it may contain small numbers of platelets and other blood cells. If any of the se cells are present then the plasma must be regarded as relevant material).
Platelets
Pieural fluid
Primary cell cultures (whole explant/biopsy present)
Pus
RNA
Saliva
Serum
Skin
Sperm*
Sputum (or Phlegm)
Stomach contents
Teeth
Tumour tissue samples
Umbilical cord blood stem cells
Urine
CU/13/HTA15/1.0
No
Yes
Yes
No
No
No
No
No
Yes
Yes
Yes
No
Yes
No
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
No
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Page 27 of 30

* While outside the definition of relevant material for the purposes of the HT Act, these materials fall under the remit of the Human Fertilisation and Embryology Act 1990, and are regulated by the Human Fertilisation and Embryology Authority (HFEA).
** Cell lines and embryonic stem cell lines fall within the regulatory remit of the HTA by virtue of the Human Tissue (Quality and Safety for Human Application) Regulations 2007, which regulates the processing, storage and distribution of stem cell lines for human application. Both the HFEA and the Medicines and Healthcare products Regulatory Agency
(MHRA) also have a regulatory remit in respect of cell lines and embryonic stem cells lines.
A joint position statement issued by the HTA, HFEA and MHRA provides guidance on the relevant regulatory remits.
*** Breast milk does not constitute tissue or cells for human application under the (Quality and Safety for Human Application) Regulations 2007, but is classified as relevant material for the purposes of the Human Tissue Act 2004 where stored or used for a scheduled purposes.
CU/13/HTA15/1.0 Page 28 of 30

APPENDIX B
LICENSING AND CONSENT REQUIREMENTS FOR HUMAN TISSUE FOR RESEARCH
FROM THE LIVING
Storage of human tissue from the living
Consent required?
Licence required?
Yes, unless:

It is obtained before 1
September 2006
OR
 it is from the living and is non-identifiable to the researcher
AND
 is for a specific project approved by a recognised research ethics committee
Yes, unless:
 it is for a specific project approved by a recognised research ethics committee (or pending approval)
OR
 storage is incidental to transportation
OR
 it is stored with intent to render acellular
REC- Research Ethics Committee
HTA 10/32 Page 29 of 30

LICENSING AND CONSENT REQUIREMENTS FOR HUMAN TISSUE
FOR RESEARCH FROM THE DECEASED
Storage of human tissue from the deceased
Consent required?
Licence required?
Yes, unless obtained before 1
September 2006
Yes, unless:
 it is more than 100 years old
OR
 it is for a specific project approved by a recognised research ethics committee (or pending approval)
OR
 storage is incidental to transportation
OR
 it is stored with intent to render acellular
REC- Research Ethics Committee
HTA 10/32 Page 30 of 30