1 Quality Manual The collection, storage and use of tissue in research in accordance with Newcastle University’s research sector Human Tissue Act Licence (No. 12534) Mhairi Anderson Quality Assurance and Development Manager Effective: 9th March 2015 Review due: 9th March 2016 HTA-QUAL-01 Edition 3 The Quality Manual has been designed to give researchers advice on obtaining, storing and using Human Tissue for Research, both under the HTA Licence and for specific projects. Last printed 08/02/2016 20:04 Page 1 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 APPROVAL Last printed 08/02/2016 20:04 Page 2 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Table of Contents Table of Contents .................................................................................................................................... 3 Table of Figures ....................................................................................................................................... 5 1. INTRODUCTION ............................................................................................................................... 6 2. POLICY AND OBJECTIVES ................................................................................................................. 6 3. STRUCTURE OF THE MANUAL ......................................................................................................... 7 5. THE HUMAN TISSUE ACT................................................................................................................. 9 5.1. 5.1.1. Who regulates compliance with the Human Tissue Act? ............................................... 9 5.1.2. Which materials are covered by The Act? .................................................................... 10 5.2. 7. LICENSING ............................................................................................................................. 14 5.2.1. Which sectors does the Human Tissue Act regulate? ................................................... 14 5.2.2. How are licenses assigned?........................................................................................... 17 5.2.3. What activities are permitted under a Human Tissue Act licence? .............................. 18 5.2.4. Roles and responsibilities under a Human Tissue Act licence ...................................... 19 5.2.5. Licensing exemptions .................................................................................................... 20 5.3. 6. WHAT IS THE HUMAN TISSUE ACT? ........................................................................................ 9 CONSEQUENCES OF NON-COMPLIANCE WITH THE ACT ...................................................... 21 THE NEWCASTLE UNIVERSITY RESEARCH HTA LICENCE ............................................................... 22 6.1. What is covered by the Newcastle University research sector HTA licence? ....................... 22 6.2. Licensed Premises ................................................................................................................. 24 6.3. Roles and responsibilities under the Newcastle University research sector HTA licence .... 25 6.3.1. Licence Holder and Designated Individual .................................................................... 25 6.3.2. Persons Designate ......................................................................................................... 25 6.3.3. Additional assigned roles .............................................................................................. 26 6.3.4. Responsibilities of all other staff working under the licence........................................ 26 OBTAINING TISSUE ........................................................................................................................ 28 7.1. HOW DO I OBTAIN TISSUE?................................................................................................... 28 7.1.1. OPTION 1 – 0BTAIN PRE-EXISTING TISSUE FROM A BIOBANK ...................................... 29 7.1.2. OPTION 2 – COLLECT NEW TISSUE ................................................................................ 33 7.1.3. OPTION 3 – PURCHASING MATERIAL FROM A COMMERCIAL SUPPLIER...................... 35 7.2. CONSENT ............................................................................................................................... 37 7.2.1. Which activities require consent?................................................................................. 37 7.2.2. Who can give consent? ................................................................................................. 39 Last printed 08/02/2016 20:04 Page 3 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 8. 7.2.3. How is consent taken? .................................................................................................. 40 7.2.4. Are there different types of consent?........................................................................... 42 7.2.5. Can consent be withdrawn? ......................................................................................... 42 STORAGE ....................................................................................................................................... 44 8.1. Sample storage requirements............................................................................................... 44 8.2. Data storage and protection ................................................................................................. 46 8.3. What are the storage options at Newcastle University? ...................................................... 47 8.4. Subcontracting storage ......................................................................................................... 49 8.5. Appropriate storage period .................................................................................................. 49 9. SAMPLE TRACKING........................................................................................................................ 50 9.1. Key Principles of sample tracking ......................................................................................... 50 9.1.1. Assigning unique sample numbers ............................................................................... 50 9.1.2. Sample Tracking Records .............................................................................................. 51 9.1.3. Material and data tracking during transfer................................................................... 52 9.1.4. Safety during transportation......................................................................................... 53 10. SAMPLE USE .............................................................................................................................. 54 11. SAMPLE DISPOSAL..................................................................................................................... 55 11.1. Key considerations in sample disposal.............................................................................. 55 11.2. Disposal options ................................................................................................................ 56 11.3. Maintaining proper documentation ................................................................................. 57 11.4. Preventing unnecessary waste of human tissue ........................................................... 57 12. THE QUALITY MANAGEMENT SYSTEM (QMS) .......................................................................... 58 12.1. The Quality Manual ........................................................................................................... 58 12.2. Document Management ................................................................................................... 58 12.3. Document Control............................................................................................................. 59 1.3.1 Document Management System ................................................................................. 59 1.3.2 Newcastle Joint Research Office (NJRO) Website......................................................... 59 1.3.3 The Virtual Research Environment (VRE)...................................................................... 60 1.3.4 The HTA Master File .................................................................................................... 60 1.4 Documentation supporting the QMS.................................................................................... 61 1.5 Adverse events ...................................................................................................................... 63 1.6 Complaints ............................................................................................................................ 63 1.7 Validation and change control .............................................................................................. 64 1.8 Audit ...................................................................................................................................... 64 Last printed 08/02/2016 20:04 Page 4 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 2. 1.9 Training ................................................................................................................................. 65 1.10 Communication with stakeholders ....................................................................................... 66 1.11 Governance ........................................................................................................................... 67 1.11.1 Management commitments ......................................................................................... 67 1.11.2 Access and governance committee .............................................................................. 68 1.11.3 Laypersons .................................................................................................................... 69 APPENDICES .................................................................................................................................. 70 2.3 APPENDIX A - Minimum and best practice standards for the use of human samples in research ............................................................................................................................................ 70 2.4 APPENDIX B – Glossary ......................................................................................................... 80 2.5 APPENDIX C– List of “Relevant Materials” under the HTA ................................................... 84 2.6 APPENDIX D –Copy of the Newcastle University Research HTA Licence .............................. 88 2.6.1 Hub Licence ................................................................................................................... 88 2.6.2 Satellite licences ............................................................................................................ 89 2.7 APPENDIX E – Document Revision History............................................................................ 93 Table of Figures Figure 1 - Structure of Quality Manual ................................................................................................ 8 Figure 2- Human Tissue Authority categories of relevant material ................................................ 13 Figure 3 - Summary of licensing requirements................................................................................. 15 Figure 4 - The Human Tissue Authority licensing process .............................................................. 16 Figure 5 - Licensing Premises............................................................................................................. 17 Figure 6 - Roles and responsibilities required under a HTA research licence ............................... 19 Figure 7 – Roles and Responsibilities Overview ............................................................................... 27 Figure 8 - Obtaining tissue for use in research ................................................................................. 28 Figure 9 - The Integrated Research Application System (IRAS) process ........................................ 32 Figure 10 - Requirements for consent under the Human Tissue Act .............................................. 38 Figure 11 - Qualifying relationships to provide appropriate consent ............................................ 39 Figure 12 - Storage options for relevant materials at Newcastle University ................................. 48 Figure 13 - Sample disposal options .................................................................................................. 56 Last printed 08/02/2016 20:04 Page 5 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 1. INTRODUCTION The Human Tissue Act (2004) was set up to regulate the removal, storage, use and disposal of human bodies, organs and tissue for a number of Scheduled Purposes – such as research, transplantation, and education and training. The Act, which covers England, Wales and Northern Ireland, came into force on 1 September 2006. As human tissue is widely used across Newcastle University, the University holds a Research licence under the Act (Licence no. 12534) –which governs the management of human tissue across the University. This licence, and its requirements, must be understood and respected by all employees who work with human tissues. This Quality Manual has been produced to provide a comprehensive guide for the use of human tissues to help all those collecting and using human samples at Newcastle University. 2. POLICY AND OBJECTIVES Human tissue is considered to be a precious gift. Therefore, in order to demonstrate respect for this gift, and ensure high quality research, it is paramount that all human samples are acquired lawfully, with appropriate consent, and are stored, handled, used and disposed of respectfully, sensitively and responsibly. As such, the University requires that all researchers working with human samples, from the living or deceased, strictly abide by the procedures and standards set out in this Quality Manual. For a summary of minimum and best practice, refer to Appendix A. The objectives of the Quality Manual are therefore: a) To maintain an effective Quality Management System in compliance with the Human Tissue Act and the standards and guidance issued by the Human Tissue Authority. b) To provide a robust, but practical framework for employees to follow to ensure compliance with licensing obligations of the HTA c) To enhance the University’s reputation for the delivery of research of the highest quality and ethical standards and ensure public confidence in the ethics of scientific research d) To demonstrate the University’s commitment to defining the quality of its products and services, and ensuring the continuous review and improvement of quality standards to promote process excellence and good ethical practice. To achieve this policy, it is imperative that all staff working under the Newcastle University research sector HTA licence understand their responsibilities under the Human Tissue Act, and are accountable for the quality of their work. This Quality Manual provides researchers with a comprehensive summary of the Human Tissue Act regulations, providing a clear description of the range of processes that must be conducted in order to organise, conduct, and document research using human tissue. Last printed 08/02/2016 20:04 Page 6 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Each employee or student working under the University’s Human Tissue Act licence must therefore abide by this manual. Additional Quality Policies may also exist within each academic unit detailing how the quality standards set out in this manual are applied in that environment. This policy, and appropriate training, will be made available to all employees and students working with human tissue. 3. STRUCTURE OF THE MANUAL This manual has been compiled to provide researchers with guidance on the full range of processes required when working with human tissues, from study start, to sample disposal. The structure of this manual is described in figure 1. Advice for researchers on minimum and best practice is provided in Appendix A. A glossary on all the terms used in this manual is also provided in Appendix B. Further appendices include a list of relevant material as provided by the Human Tissue Authority (Appendix C), and a copy of the University’s research Human Tissue Act licensing documentation (Appendix D). 4. SCOPE This Quality Manual applies to all individuals operating under the Newcastle University Research Sector Human Tissue Act Licence (Ref. 12534). It should be noted that this manual relates only to the Research Sector Licence held by the University, and not to any other sectors, or organisations licences. For information related to the Newcastle University HTA Anatomy licence, Newcastle upon Tyne NHS Foundation Trust (NUTH) Research, Post Mortem or Human Application licences, please refer to the contacts in table 1 below. Table 1- HTA licences held by Newcastle University and NUTH Organisation Newcastle University Newcastle upon Tyne NHS Foundation Trust 1 HTA Sector Licence Designated Individual named on licence1 Research Professor Andy Hall (andy.hall@ncl.ac.uk) Anatomy Dr Debra Patten (debra.patten@ncl.ac.uk) Research Professor Phil Sloan (Philip.sloan@nuth.nhs.uk) Post Mortem Dr Nigel Cooper (nigel.cooper@nuth.nhs.uk) Human Application Dr Andy Gennery (andy.gennery@nuth.nhs.uk) Subject to change. Please refer to the Human Tissue Authority website for the most up to date names. Last printed 08/02/2016 20:04 Page 7 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 The Human Tissue Act The Newcastle University Research HTA licence Obtaining tissue for use in research Sample storage, use and tracking Disposal The Quality Management System How do I obtain tissue? - Samples from biobanks - Collecting new tissue - Commercial availability Storage - Requirements, data protection, storage options, subcontracting and storage period Disposal - Key considerations - Options - Documentation - Avoiding waste The Quality Manual What is the Human Tissue Act? - Who regulates compliance - Which materials are covered by the Act? Licensing - Sectors, assigning licences, activities, roles and licences exemptions What is covered under the University’s research HTA licence? Licensed premises Roles and responsibilities - Licence Holder and Designated Individual - Person Designate - Additional roles - All other staff Consent - Consequences of non-compliance - - When is consent required? Who can give consent? Types of consent How is consent taken? Withdrawal of consent Tracking - Key principles, assigning unique numbers, records, transfers and safety Document Control - NJRO website, VRE, HTA Master File Documents supporting the QMS Adverse Events Complaints Validation Audit Training Governance Sample use Figure 1 - Structure of Quality Manual Last printed 08/02/2016 20:04 Document Management Page 8 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 5. THE HUMAN TISSUE ACT 5.1. WHAT IS THE HUMAN TISSUE ACT? The Human Tissue Act 2004 (The Act) is a legal framework which regulates the removal, storage, use and disposal of human bodies, organs and tissues. The Act, which came in to full effect on the 1st September 2006 and applies to England, Wales and Northern Ireland, was enforced as a direct response to the findings of the Redfern report2 in which the unauthorised removal, retention, and disposal of human tissue was found at the Alder Hey Children’s Hospital, Bristol Royal Infirmary and many other NHS Trusts. With consent as its fundamental underlying principal, the Act aims to ensure that all human tissues are now managed in an ethical and sensitive manner, by providing a consistent legislative framework for matters relating to body donation and the removal, storage and use of human organs and tissue The following sections detail the regulatory oversight of the Act, which materials are classed as “human tissues”, and the licensing requirements. 5.1.1. Who regulates compliance with the Human Tissue Act? To ensure compliance with the Act, "The Human Tissue Authority” (HTA) was established. Acting as an independent government watchdog, the HTA has the following objectives: 2 To ensure that clear standards are in place for the use of human tissues To inspire public and professional confidence in medical research by ensuring that human tissue is used safely and ethically, and with proper consent To provide researchers with support and guidance to ensure best practice. www.official-documents.gov.uk/document/hc1011/hc05/0571/0571_i.pdf redfern report Last printed 08/02/2016 20:04 Page 9 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 To achieve these objectives the HTA has created a number of codes of practice. The codes of practice provide guidance for researchers and lay down expected standards for each of the sectors the HTA regulates. The codes are designed to support professionals by giving advice and guidance based on real-life experience. There are now 9 Codes of Practice, as described below: These can be accessed from the HTA website: http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice.cfm Code 1 Code 2 Code 3 Code 4 Code 5 Code 6 Code 7 Code 8 Code 9 - Consent Donation of solid organs for transplantation Post-mortem examination Anatomical examination Disposal of human tissue Donation of allogeneic bone marrow and peripheral blood stem cells for transplantation Public display Import and export of human bodies, body parts and tissue Research 5.1.2. Which materials are covered by The Act? Importantly, “human tissue” defined in The Act, is not restricted to organs. According to The Act, a Human Tissue Act licence is required for any material which is deemed to be “Relevant Material” under Section 53 of The Act. A definition of a relevant material is provided below: RELEVANT MATERIAL “Material, other than gametes, which consists of, or includes human cells” The fundamental principle underpinning The Act is therefore that if a sample is known to contain even a single cell that has come from a human body (e.g. blood cells), then the sample should be classified as relevant material. However, this does not include: (a) embryos outside the human body - this is covered by the Human Fertilisation & Embryology Act 20083) (b) hair and nail from the body of a living person. 3 www.legislation.gov.uk/ukpga/2008/22/contents Last printed 08/02/2016 20:04 Page 10 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Although DNA is not HTA relevant material, the HT Act has now created a new offence of DNA ‘theft’ – which is the criminal act of holding human tissue with the intention of analysing its DNA, without the consent of the person from whom the tissue came from (see section7.2). For a comprehensive list of materials included in the Human Tissue Act, researchers may refer to the Human Tissue Authority website: http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/definitionofrelevantmaterial.cfm Advice on how to identify a “Relevant Material” under the Human Tissue Act is provided below. 5.1.2.1. Categories of “Relevant Material” As a Human Tissue Act licence is only required for material which is determined to be a “Relevant Material” under the act, to determine if a researcher needs a Human Tissue Act licence, they must first establish - Is the material I wish to use classed as a “Relevant Material”? (See section 5.1.2) To help researchers to answer this question, the Human Tissue Authority has divided potentially relevant material into four categories. The categories of relevant material are: 1. Specifically identified - This includes material like bodily organs and tissues, consisting largely or entirely of cells, and clearly identifiable and regarded as such. This category of relevant material includes human bodies, internal organs and tissues, skin and bone. 2. Processed material: Where a process has been conducted which results in the cells being removed from the tissue (i.e. the material is rendered “acellular” – does not consist of cells). Importantly: Human Tissue Act licence is only required to store cells. If the cellular component is removed, or disrupted, a HTA licence is not required to store the material To aid researchers to conduct their work: Last printed 08/02/2016 20:04 Page 11 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 The Human Tissue Authority grants researchers up to 7 days to remove the cellular component of a relevant material. During this time, the material can be stored without a HTA licence. However, after 7 days, if the material has not been processed to remove the cells, and no further exemption applies then the material must be stored under a HTA licence. Where it is believed that the processing has rendered the material acellular, the HTA may seek assurance that the processing has 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. 3. Bodily waste: Bodily waste is a less well characterised group of material. Nevertheless the Authority considers that bodily waste is a relevant material as it may contain human cells. In cases where a researcher believes that material, intended for a scheduled purpose, is actually acellular the researcher would need to consult the Authority for advice. 4. Cell deposits and tissues on microscope slides: In general cell deposits or tissue sections on microscope slides are considered to constitute relevant material. This is because such deposits or sections are likely to contain whole cells or are intended to be representative of whole cells. These categories are summarised in Figure 2. However, the fundamental principle remains that if a sample is known to contain even a single cell that has come from a human body, then the sample should be classified as relevant material. The Human Tissue Authority has also produced a supplementary list of materials to provide stakeholders with guidance on whether specific materials fall within the definition of a relevant material under The Act. A copy of this list is also provided in Appendix C and on the HTA website: http://www.hta.gov.uk/ Last printed 08/02/2016 20:04 Page 12 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 • Type 4: Cell deposits & tissues on microscope slides Type 1: SPECIFICALLY IDENTIFIED Consist largely or entirely of human cells & easily distinguished as such e.g. Human bodies, skin, bone, bodily organs RELEVANT MATERIAL NONRELEVANT MATERIAL Licence required unless exemption applies (see section 4.2.4) NO e.g. plastinated tissue/ body parts which retain cellular structure YES e.g. plasma, serum Has the material been rendered acellular? N.B. This must be conducted within 7 days Type 2: Processed Material Licence not required UNSURE Consult the Biobank Quality Assurance Manager or HTA Type 3: Bodily waste (including excretions & secretions) Figure 2- Human Tissue Authority categories of relevant material If a researcher determines that the material they wish to use is a “relevant material” under the act, the material must be stored under a Human Tissue Act licence. However, a number of exemptions in which a licence is not required to store a relevant material are described below in section 5.2.4. Last printed 08/02/2016 20:04 Page 13 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 5.2. LICENSING 5.2.1. Which sectors does the Human Tissue Act regulate? To reflect the fact that human tissue may be used in a number of different environments, The Human Tissue Authority licenses and inspects a number of different sectors. These are summarised in Table 2 below. For full information, refer to the Human Tissue Authority website: http://www.hta.gov.uk/ Table 2- Sectors licensed and inspected by the Human Tissue Authority Sector Activity Anatomy For establishments carrying out anatomical examinations or storing anatomical specimens. For example, where human bodies are used to teach students and to train surgeons and other healthcare professionals Human application For organisations that use human tissue and cells to treat patients. For example, stem cells, skin and heart valves, eye banks and organisations that store skin and bone Post mortem for establishments carrying out post mortems, storing human bodies or organs, tissues or cells from a deceased person and/or removing relevant material from a deceased person other than in the course of a post mortem Public Display Research For establishments wishing to put human bodies, body parts and specimens on public display, e.g. as part of an exhibition in a gallery or museum. This is only applicable if material is taken from the body of a deceased person who died less than 100 years ago. for establishments storing human organs, tissues and cells for research purposes other than for a specific research project approved by a recognised NHS Research Ethics Committee (see section 7.1.2) It should be noted that this Quality Manual relates to the Research Sector only. Staff or students requiring information relating to other sectors should consult the appropriate Designated Individual (see Table 1). Researchers wishing to store material for use in future research must determine if they need to store this material under a HTA licence. A decision tree for determining if a HTA licence is required is provided in Figure 3. The process to apply for a new or adapted Human Tissue Act licence is provided in Figure 4. NOTE: As Newcastle University already holds a research sector Human Tissue Act licence (see section 6), any requests to update this licences or to apply for a new licence must be made to the Quality Assurance Manager or associated Designated Individual. Applications will be reviewed by the Licence Holder in discussion with the Access and Governance committee. For contact details, see section 6.3. Last printed 08/02/2016 20:04 Page 14 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 I want to work with human tissue – Do I need a Human Tissue Act Licence? HTA licence not required Is your material classed as a “Relevant Material” under the Human Tissue Act? no unsure Consult the HTA or the NBB QA Manager yes yes Is the tissue stored with the intent of rendering it acellular within 7 days? no See guidance on obtaining a licence for • carrying out a post mortem • public display or • anatomy What is the primary purpose you store organs, tissue or cells for? Diagnostic purposes (taken from living only) Is the tissue storage incidental to transportation? Yes HTA licence not required No For research purposes (living or deceased) Is the material received from an Research Ethics Committee (REC) approved tissue bank with permission to authorise research? No Is the material more than 100 years old? No Other purposes Is storage for a specific research project with Research Ethics approval? No Are you storing organs, tissue or cells to distribute to other researchers? Yes HTA licence not required however, if researchers retain tissue for future, unspecified research after the expiry of the approval, a HTA licence will be required Yes No Are you storing organs, tissue or cells for a future undefined project or a project without ethical approval? Yes Yes Yes HTA licence not required HTA licence not required HTA Licence required HTA Licence required Figure 3 - Summary of licensing requirements4 4 It should be noted that to be exempt from requiring a HTA licence to store relevant material, ethical approval must be in place from a recognised NHS Research Ethics Committee. Ethical approval from a University ethics committee is not sufficient, and a HTA licence would be required to store material in this case. Last printed 08/02/2016 20:04 Page 15 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 TO REQUEST A NEW HUMAN TISSUE ACT LICENCE Proposed Licence Holder to submit a Research Compliance Report Application (CRA) -Access CRA via HTA website & submit at least 3 months before required commencement date of work HTA log the application on the licencing data base and send the applicant an invoice Licence Holder (LH) must pay fees within 28 days of application (Designated Individual (DI) to ensure payment) DI/LH have 10 days to provide requested material Notification of intention to make a representation within 28 days to: 1. Director of Regulation 2. Head of Regulation 3. Regulation Manager Phase I – Desk Review Suitability of DI, LH, Premises and practices assessed against codes of practice Additional information sought where required Denied Licencing decision Approved Draft licence issued to DI & LH including any additional conditions DI & LH wish to appeal DI & LH happy to continue LH/DI to respond within 28 days - Substantive licence issued To be displayed in licenced premises, including at satellite sites Accepted 1 month later Denied Yes New licence required NEED TO ADAPT THE EXISTING LICENCE? Contact the DI and NBB QA Manager Is the change required a major change? e.g. new sector licence/ new activity required Licence holder sends a request to the HTA to edit the existing licence e.g. add satellite site No Figure 4 - The Human Tissue Authority licensing process Last printed 08/02/2016 20:04 Page 16 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 5.2.2. How are licenses assigned? The HTA licenses premises not people. Licences are assigned in three ways Standalone premises, 1. Hub premises 2. Satellite premises. 3. Standalone premises are where an HTA licence covers a single premise only. Where licensable activities are at different locations, such as a university carrying out research on human tissues and/or cells on two different campuses (like Newcastle University), one location (e.g. the main campus) can become the hub premises and the second location (e.g. the International Centre for Life) can become a satellite of the hub. Hub and satellite arrangement may be a useful licensing solution for large or complex establishments, where the same type of activity is carried out under a single governance system across multiple locations This is summarised in Figure 5. “Satellite Site” “Satellite Site” “Hub Site” Main licence “Satellite Site” “Satellite Site” Figure 5 - Licensing Premises Satellite premises must be under the same governance as the hub premises, including supervision by the Designated Individual (DI). The DI is responsible for ensuring that suitable practices are carried out at any licensed premises under their governance, and for ensuring compliance with the HTA’s licensing conditions and standards. Management of a hub and satellite premises requires the DI to put robust systems in place to ensure that the same governance systems are implemented across all licensed premises. The HTA expects the DI to make regular visits to any and all satellite premises to verify that the governance systems are working in practice. Additionally, the HTA requires the DI to nominate, and inform the HTA, of appropriate individuals named “Person Designate” based Last printed 08/02/2016 20:04 Page 17 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 at each of the satellite premises to oversee the activities taking place under the licence. For further information refer to section 5.2.4 5.2.3. What activities are permitted under a Human Tissue Act licence? Each Human Tissue Act licence clearly sets out the activities which may be conducted under that licence. These activities, called ““Licensable activities”, fall into the following categories: 1. 2. 3. 4. 5. 6. Carrying out an anatomical examination Making of a post mortem exam Removal of relevant material from a deceased person Storage of a relevant material for a number of scheduled purposes Storage of anatomical specimens Public display of relevant material from deceased persons. Where a relevant material is to be stored for a number of “scheduled purposes” a scheduled purposes are defined as the activities relating to the removal, storage and use of human organs and other tissue that require consent. A list of scheduled purposes is provided in Table 3 overleaf (taken from HTA Code of Practice 1 – Consent). Table 3 – Consent requirements under the Human Tissue Act for scheduled purposes Last printed 08/02/2016 20:04 Page 18 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 5.2.4. Roles and responsibilities under a Human Tissue Act licence The HTA prescribe that three key roles are required under The Act. These are: 1. Licence Holder (LH) 2. Designated Individual (DI) 3. Persons Designate (PD) These roles and the associated responsibilities as summarised in Figure 6 and explained in full in the Human Tissue Act Standard Operating Procedure 2 (HTA-SOP-2). Although the PD role imposes no legal responsibility, it is a licence requirement that the Designated Individual has documented evidence of the PD’s acceptance of the PD role. The individuals assigned these roles on the Newcastle University research HTA licence are set out in section 6.3. LICENCE HOLDER (LH) LICENCE HOLDER (LH) • A corporate body, or named person, responsible for applying for the Licence • May apply to change the licence & substitute the DI DESIGNATED INDIVIDUAL (DI) DESIGNATED INDIVIDUAL (DI) • Named on the licence as the person under whose supervision the licensed activity is authorised to be carried on • In a position to ensure that activities are conducted properly, by people who are suitable to carry out those activities, and that all the necessary requirements are complied with • Has primary (legal) responsibility under Section 18 of the Human Tissue Act to secure: o that suitable practices are used in undertaking the licensed activity o that other persons working under the licence are suitable o that the conditions of the licence are complied with PERSON DESIGNATE (PD) PERSON DESIGNATE (PD) PERSON DESIGNATE (PD) PERSON DESIGNATE (PD) • A person to whom the Licence applies, and who is named on the licence. • The PD assists the DI in supervising the licensable activities within their groups. • May be located within a central hub, or at a satellite site, covered by the same licence • Multiple PDs may exist under the same licence Figure 6 - Roles and responsibilities required under a HTA research licence Last printed 08/02/2016 20:04 Page 19 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 5.2.5. Licensing exemptions A number of exemptions exist in which a HTA licence is not required to store a relevant material. Exemptions include: If the material is to be rendered acellular (i.e. cells removed, or disrupted) or transported to another establishment within 7 days If the material is to be stored for diagnostic or other purposes If the material has NHS Research Ethics Committee (REC) approval in place to use it. This approval must come from a recognised NHS REC. o Ethical approval can only be given by a recognised research ethics committee which is either: A Research Ethics Committee (REC) established under and operating to the standards set out in the governance arrangements issued by the UK Health Departments An ethics committee recognised by United Kingdom Ethics Committee Authority (UKECA), to review clinical trials of investigational medicinal o Ethical approval from a University ethics committee does not constitute a recognised NHS REC and therefore a HTA licence is required to store material which only has University ethics approval. If the material is greater than 100 years old If the material has come from an NHS Research Ethics Committee (REC) approved research tissue bank where there is permission in place to use the material Licensing requirements, including exemptions, are summarised in section 5.2. If a researcher is ever in doubt if a Human Tissue Act licence is required, please contact the Quality Assurance and Development Manager (contact details in section 6.3). Last printed 08/02/2016 20:04 Page 20 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 5.3. CONSEQUENCES OF NON-COMPLIANCE WITH THE ACT It is a licence requirement that no person shall conduct a licensed activity other than under the authority of the licence granted. The offences recognised under The Human Tissue Act are summarised as follows Offences under The Human Tissue Act: 1. Removal, storage or use of human tissue for Scheduled Purposes (see section 5.2.3) without appropriate consent 2. Storage or use of human tissue donated for a Scheduled Purpose but used for another purpose 3. Trafficking of human tissue for transplantation purposes 4. Carrying out licensable activities without holding a licence from the HTA 5. Having human tissue, including hair, nail, and gametes (i.e. cells connected with sexual reproduction), 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). A person who contravenes this is seen to have committed an offence unless he/she reasonably believes: That what he/she does is not an activity to which the licensed activities applies That he/she acts under the authority of a licence. Institutions which fail to comply with The Act face a number of enforceable penalties which range from a fine, to up to three years’, imprisonment - or both. As the responsibility for ensuring compliance rests with the Designated Individual, it is the DI who faces prosecution. Non-conformance with the Act also has number of other significant implications for researchers: May invalidate any research conducted using the tissue Risks the reputation of Newcastle University as a centre for excellence in translational research Risks the University’s reputation as an ethical research establishment May result in a loss of public confidence in the ethics of medical research, limiting the provision of future samples Ultimately, removal of the University’s licence would remove the ability to store human tissue for use in research, with significant consequences on the future of research at Newcastle University It is therefore of fundamental importance that all researchers work together with the DI, PDs and Quality Assurance & Development Manager to ensure high quality, ethical research across the University. Last printed 08/02/2016 20:04 Page 21 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 6. THE NEWCASTLE UNIVERSITY RESEARCH HTA LICENCE Newcastle University holds a Research sector Human Tissue Act licence (No. 12534) which licenses the storage of human organs, tissues and cells for research purposes other than for a specific ethically approved research project. i.e. the licence covers human tissue samples held in storage for future, yet unspecified, research purposes. A summary of this licence, including which activities are covered, the premises which are licensed and the roles and responsibilities assigned to this licence are provided below. 6.1. What is covered by the Newcastle University research sector HTA licence? The licensed activity named on the Newcastle University research HTA licence (ref. 12534) is: “Storage of a relevant material for a number of scheduled purposes” (Licensable activity 4, listed in section 5.2.3). The licence does not cover any of the other licensable activities named in section 5.2.3, for example public display or anatomical examination. Should a researcher wish to conduct these activities, a separate or adapted licence would be required. The licence lists a number of “scheduled purposes” (activities which require consent) for which a material can be stored for. These are: Determining the cause of death Establishing after a person’s death the efficacy of any drug or other treatment administered to him Obtaining scientific or medical information about a living or deceased person which may be relevant to any other person (including a future person) Public display Research in connection with disorders, or the functioning of the human body Clinical audit Education or training related to human health Performance Assessment Public Health monitoring Quality Assurance Last printed 08/02/2016 20:04 Page 22 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 It should therefore be noted that: This licence is for the “Storage” of relevant material for research, and does not license the research itself. For researchers to use the tissue stored at Newcastle University, NHS Research Ethics Committee (REC) approval is required. For information on how to request REC approval, see section 7.1.3. Material may be stored for a range of purposes, such as, public display or determining the cause of death (“scheduled purposes”). However, this licence only covers the storage for these purposes. Should an individual want to actually perform these activities, the appropriate licence would be required (e.g. public display, or post mortem – see section 5.2.1). For any researcher who wishes to store a tissue for a purpose not listed on the licence, please contact the DI or Quality Assurance & Development Manager for advice (see section 6.3 for contact details). In this case it may be possible to: Determine if the activity is covered by another sector licence held at the University Apply to vary the existing licence – see section 5.2 Apply for a new Human Tissue Act licence – see section 5.2 Last printed 08/02/2016 20:04 Page 23 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 6.2. Licensed Premises At Newcastle University, The Medical School, including the Paul O’Gorman building is considered to be the “hub” with 4 satellite sites. Each of these premises must display a copy of its associated HTA licence. The addresses of each of these sites are provided below: Licensed premises (Hub site): Newcastle University Named individual for correspondence: Chris Day Newcastle University The Medical School Framlington Place Newcastle Upon Tyne, NE2 4H Tel: +44 (0) 191 222 6000 (switchboard) Satellite Premises: Campus for Ageing and Vitality Freeman Hospital Respiratory Institute of Genetic Medicine Edwardson Building Newcastle University Freeman Road High Heaton Newcastle Upon Tyne NE7 7DN Human Developmental Biology Resource & Cytogenetics Newcastle upon Tyne NE4 5PL United Kingdom Tel: +44 (0) 191 248 1300 Fax : +44 (0) 191 248 1301 Tel: +44 (0)191 233 6161 (Switchboard) Last printed 08/02/2016 20:04 Newcastle University International Centre for Life Central Parkway Newcastle upon Tyne NE1 3BZ Tel: +44 (0)191 241 8616 Fax: +44 (0)191 241 8666 School of Agriculture, Food and Rural Development, Nutrition Agriculture Building Newcastle University Newcastle upon Tyne NE1 7RU Tel: +44 (0)191 222 6900 Fax: +44 (0)191 222 6720 Page 24 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 6.3. Roles and responsibilities under the Newcastle University research sector HTA licence As required by the terms and conditions of the Human Tissue Act licence (see section 5.2.4), Newcastle University has assigned a number of different roles and responsibilities to oversee compliance with the HTA licence (Ref. 12534). These individuals are set-out below, and summarised in Figure 7. For full role For full descriptions, please refer to HTA-SOP-02. The organisational structure adopted under the Newcastle University Research Sector HTA Licence is provided in the HTA Master File and on the Newcastle Joint Research Office (NJRO) website). 6.3.1. Licence Holder and Designated Individual The details of the Licence Holder and Designated Individual named on the Newcastle University research sector HTA licence are provided below. Licence Holder: Newcastle University - Professor Chris Day, PVC for Medical Faculty, named for correspondence Medical Sciences Faculty Office, Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH Email: chris.day@ncl.ac.uk , Telephone: +44 (0) 191 222 7003 Designated Individual: Professor Andrew Hall Clinical Academic Office, M3.100, 3rd Floor, William Leech Building, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle. NE2 4HH Email: andy.hall@ncl.ac.uk , Telephone: +44 (0) 191 208 7161 6.3.2. Persons Designate As the University is spread over a wide campus, the DI has gained the support of a number of Persons Designate (PDs) to oversee compliance with the Act in their local area. All PDs have confirmed their acceptance of this role by signing a PD role description. An up-to-date list of the Person’s designate named on the Newcastle University research sector HTA licence can be found on the Newcastle Joint Research Office website on the human tissue pages, and in the Human Tissue Act Virtual Research Environment (see section 1.3.3). Last printed 08/02/2016 20:04 Page 25 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 A signed role acceptance has been retained by the Quality Assurance and Development Manager – see section 6.3.3. 6.3.3. Additional assigned roles In addition, to the Licence Holder, Designated Individual and Persons Designate, Newcastle University has assigned the following roles: Research Tissue Bank Managers – Under the National Research Ethics Service (NRES) researchers may establish Research Tissue Banks, and become “Research Tissue Bank Managers” (also referred to as Chief Investigators). This role is distinct from the HTA; however as research tissue banks storing relevant material must be stored under a HTA licence, Research Tissue Bank Managers may only store their tissue banks under the jurisdiction of a local Person Designate. A list of the approved Research Tissue Banks and their associated Managers is provided in the HTA Master File. This can also be found in the HTA Virtual Research Environment and on the Newcastle Joint Research Office website (www.newcastlejro.org.uk). Quality Assurance & Development Manager – to conduct internal inspections, training and develop and maintain the quality management system. Human Tissue Act Coordinator - Assigned at the discretion of the PD to support the PD to ensure compliance in their local environment. This is not a requirement of the HTA and bears no legal responsibilities; however it plays a vital support function. A role description for a HTAC is provided in the HTA Master File and on the Virtual Research Environment. An organogram is provided in Figure 7. These roles and the associated responsibilities are described in full in HTA-SOP-02. 6.3.4. Responsibilities of all other staff working under the licence In addition to the formal roles set out in sections 6.3.1 to 6.3.3, it is the responsibility of all staff operating under the University’s HTA licence to know their responsibilities under the Act, to treat donated material with dignity and respect, and to protect the privacy of donors and maintain data confidentiality. Researchers should be aware of cases in which material has to be stored under the licence, must disclose this material to the Person Designate or Designated Individual, and must store the material appropriately in a suitable designated storage location. In accordance with the terms and conditions of the University’s research HTA licence, the Designated Individual (DI) must be aware of all relevant material stored at the University. Last printed 08/02/2016 20:04 Page 26 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 This includes all relevant material stored for research ethics committee approved research where a Human Tissue Act licence is not required for the storage of the material. Therefore, regardless of the method of obtaining tissue, all researchers storing relevant material at the University have a responsibility to disclose this material to the DI. Guidance on how researchers can obtain, store, track and dispose of material is contained in sections 7 to 11. Information on the Quality Management System adopted under the licence is provided in Section 12. LICENCE HOLDER (LH) DESIGNATED INDIVIDUAL (DI) QUALITY ASSURANCE & DEVELOPMENT MANAGER (QAM)* PERSON DESIGNATE (PD) PERSON DESIGNATE (PD) PERSON DESIGNATE (PD) Human Tissue Act Coordinator (HTAC)* – Research Tissue Bank Curators** Voluntary role introduced by Newcastle University * These roles are non-compulsory roles under the HTA but have been established at Newcastle University to support regulatory compliance. ** Research Tissue Bank Curators are approved by Research Ethics Committees under NRES which is distinct from the HTA Figure 7 – Roles and Responsibilities Overview . Last printed 08/02/2016 20:04 Page 27 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 7. OBTAINING TISSUE A number of different options are available for researchers to obtain tissue, either for immediate use in a research project, or for storage for future, yet unspecified research. These methods are summarised in section 7.1. Regardless of the method of obtaining tissue, all researchers have a responsibility to ensure that all human tissue is obtained ethically, and the researcher must be satisfied that appropriate consent is in place for the samples that have been obtained. The consent requirements under the Human Tissue Act are therefore set out in section 7.2 7.1. HOW DO I OBTAIN TISSUE? There are three main options available for researchers for obtaining tissues: 1. Obtaining pre-existing tissue from a biobank 2. Collect new tissue 3. Purchase material from a commercial supplier These options are summarised in Figure 8 below, and described in full in sections 7.1.1, to 7.1.3. Denied Tissue (Relevant material) required Is tissue available/ eligible from a preexisting Biobank? yes OPTION 1: Discuss access with tissue custodian yes no OPTION 3: Purchase material from a commercial supplier Is appropriate consent in place to conduct the research? yes Complete application form and provide supporting evidence for use Custodial review by Access & Governance Committee Apply for research approval to use the tissue through IRAS Tissue released for use using an MTA for external organisations Approved Approval granted Regular declaration of compliance with terms of access required until return/disposal Is the biobank a REC approved biobank? no no OPTION 2: Arrange new tissue collection Approval denied Apply for Research Ethics Committee (REC) approval to collect new tissue through • IRAS – For NHS Patients • University REC– For non-NHS Patients Approval granted Ensure appropriate consent is in place Approval denied Collect tissue yes BIOBANK Samples collected under non-recognised Ethics Committee (e.g. University REC) - Material must be stored under HTA in an approved location Samples collected under recognised Ethics Committee Human tissue act licence not required for duration of NHS REC approval Approval granted Tissue transferred into biobank REC approval expires Has sample been destroyed/used up? yes Email DI to confirm that no sample is remaining no Approval denied Apply for extension of REC approval yes Do you wish to extend the REC approval? no Residual tissue must be transferred to a biobank. Apply to the DI , or set up a new REC approved biobank Figure 8 - Obtaining tissue for use in research Last printed 08/02/2016 20:04 Page 28 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 7.1.1. OPTION 1 – 0BTAIN PRE-EXISTING TISSUE FROM A BIOBANK A “Biobank”, also known as a Research Tissue Bank, is a collection of human tissues, cells and blood that can be used for medical research, or for other purposes. It can contain many different types of biological samples (e.g. tissue samples, DNA and blood) and information (e.g. health records, diet and lifestyle information, and family history of disease, gender, age, and ethnicity) The samples held in biobanks enable researchers to generate data sets large enough to ensure statistical significance, thus aiding data comparability and strengthening scientific data. Researchers may apply to access human tissue stored in biobanks to use in their research. There are many biobanks located at Newcastle University (see section 6.3) throughout the United Kingdom and internationally. If a material is available, to use material stored as part of a biobank researchers must: Submit an access request to the tissue bank custodian for review, and, Obtain Research Ethics Committee (REC) approval to use the material – where appropriate. Step 1: Submit an access request to the tissue custodian Once it has been identified that a tissue of interest is stored in a biobank, a researcher must contact the tissue custodian to discuss access. A formal application to access samples must then be submitted by the researcher specifying the proposed use of the sample. Tissue collections should have a formal access policy with clear steps to be followed. Access requests will be reviewed by an Access Committee based on scientific merit, sample availability and consent in place, other research proposals and the ethics of the proposed research. Often laypersons are asked to sit on access committees to review the use of human tissue in research from a public perspective and enhance public engagement. Details on the membership & terms of reference of this committee are provided in section 1.11.2 The researcher will be informed of the outcome of the application and inform the applicant if they need to obtain ethical approval to use the samples (step 2). The provision of tissue may incur some handling costs. Last printed 08/02/2016 20:04 Page 29 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 As the Human Tissue Act licenses only the storage of material in biobank, to use the material stored in biobanks, researchers must apply for Research Ethics Committee approval to use the material. However, some tissue collections may already have ethical approval in place to use the samples in research. These banks are called Research Ethics Committee approved, “Research Tissue Banks”. What is a REC approved Research Tissue Bank? Research Ethics Committee (REC) approved Research Tissue Banks (RTBs) are tissue collections that have prospectively gained approval for a broad range of future research to be carried out by the establishment responsible for the bank and/or by other researchers to whom tissue is released by the bank within the conditions of the ethical approval. These Research Tissue Banks are not restricted to human tissue within the definition of “Relevant material” under the Human Tissue Act 2004, and may store non-relevant material such as DNA, plasma, cell lines, and/or clinical data. As a condition of approval, research tissue banks must create access policies which document the procedures for processing applications to use the bank, the conditions of access and any governance requirements. Researchers must then apply to use the bank, and requests are reviewed by an access committee in line with the banks access policy. A significant advantage of gaining REC approval as a research tissue bank is that this negates the need for researchers to obtain separate REC approval for every item of research they wish to conduct using tissue - providing that the research to be conducted falls within the scope of the ethical approval that has been granted. Applications for tissue banks to become research tissue banks is not a legal requirement, however, ethical approval for an RTB may have benefits by facilitating programmes of research without a need for individual project-based ethical approval. Such approval may be given for a period of up to five years and may be renewed What does this mean for researchers? If the required tissue is stored as part of a Research Tissue Bank and the proposed research falls within the scope of the ethical approval that has been granted, provided the Access Committee approve the request, the researcher can use the tissue without the need to seek any further REC approval. However, the custodian reserves the right to audit the recipient’s use of samples if this is considered necessary, and regular progress reports on the research project must be provided to the tissue custodian as part of an annual submission to the REC Last printed 08/02/2016 20:04 Page 30 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 that approved the tissue bank. This may include study progress, sample quality, findings and publications. Researchers may also be requested to acknowledge the biobank as the source of samples used in their research If the tissue is not stored as part of a research tissue bank and ethics is not in place to use the material, researchers must obtain REC approval to use the material (step 2). Step 2: Obtain Research Ethics Committee (REC) approval to use the material – where appropriate. Where REC approval is not already in place to use samples obtained from a Biobank, researchers can apply to use the material using the Integrated Research Application System (IRAS) accessed by https://www.myresearchproject.org.uk/. The application process is summarised in Figure 9. For full information refer to the NRES website: http://www.nres.nhs.uk/applications/. For any advice/support in completing this process, please refer to the Newcastle Joint Research Office Website: www.newcastlejro.org.uk/ . NOTE: Possession of current or pending NHS research ethics committee approval for a specific research project from a recognised REC negates the need for a Human Tissue Act licence to store the material for the duration of the ethical approval. However, on expiry of the ethical approval, a Human Tissue Act licence is required to govern the storage of any residual material. The researcher then has the following options: Apply to extend the REC approval and continue the project Transfer of the material to HTA licensed premises Dispose of the tissue (see section 11). Last printed 08/02/2016 20:04 Page 31 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 Complete on-line IRAS APPLICATION FORM from the IRAS website to collect new tissue or gain approval for a new Research Tissue Bank https://myresearchproject.org.uk/Signin.aspx Applications for new Research tissue banks should be flagged to ensure the correct REC is involved Complete the APPLICANTS CHECK LIST to ensure that all paperwork required to support the application is sent to the REC -Include a copy of the Human Tissue Act Licence for applications for a new Research Tissue Bank • Decide where to apply and BOOK AN AGENDA SLOT at the next meeting of an appropriate REC. Bookings can be made either: direct with a local REC in the NHS domain in which the research is to be conducted. Applications for new research tissue banks are allocated centrally, however these may be reviewed locally. • or via the Central Allocation System (CAS) depending on the nature of your project SUBMISSION • • Booking confirmation sent by email, with a unique REC reference number and the closing date for the application. • Add REC reference number to the online application form, with the name of the NHS REC and submission date. Submit Parts A and B of the application electronically to the allocated REC within 4 working days of the booking, also sending paper copies of: • Application form with ink signatures , Applicant's Check List , All relevant supporting documents, VALIDATION Validation letter issued within 5 working days, acknowledging submission and confirming validity SITE-SPECIFIC INFORMATION FORM For multi-site research, PIs at each site must apply for SSI by completing Part C of the completed application and submit it to the Local REC (LREC) with area responsibility for that particular site, along with a copy of his/her CV. This does not apply for Research Tissue Banks. Site specific assessor notifies the main REC undertaking the ethical review of any objection to the research on site-specific grounds within 25 days. ETHICAL REVIEW MEETING BY REC/NOTIFICATION OF DECISION Notification of decision within 60 days of receiving valid application. Notification of the decision within 10 working days of the review meeting Final decision DENIED Provisional decision – One request for further written information 60 day clock stops during data collection APROVAL No opinion – referee needs to be consulted RESEARCH COMMENCE WITHIN 12 MONTHS OF APPROVAL Figure 9 - The Integrated Research Application System (IRAS) process Last printed 08/02/2016 20:04 Page 32 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – March 2015 7.1.2. OPTION 2 – COLLECT NEW TISSUE Where a new tissue collection is required researchers must gain Research Ethics Committee (REC) approval to collect the tissue. A Research Ethics Committee (REC) is defined as a multidisciplinary, independent body charged with reviewing research involving human participants to ensure that their dignity, rights and welfare are protected. The independence of a REC is founded on its membership, on strict rules regarding conflict of interests, and on regular monitoring of and accountability for its decisions. The REC that must be approached to collect tissue is dependent on whether the tissue is to be collected from NHS patients, or other cohorts (e.g. healthy volunteers). This is set-out below and in Figure 9. 7.1.2.1. Collecting new tissue from NHS Patients To collect new tissue from NHS patients, researchers have three main options a) Apply to set up a new study b) Apply to for ethical approval to establish a new Research Tissue Bank c) Apply to use an existing REC approved Research Tissue Banks ethics to collect new tissue These options are described below and summarised in Figure 9. Option A: Apply to set up a new study Researchers may apply via the Integrated Research Application System (IRAS) to set up a new study to collect new tissue. Full details of the proposed study must be provided, including copies of consent forms, patient information leaflets, protocol and funding arrangements. Requests are reviewed by a recognised Research Ethics Committee for ethical suitability Requests are then approved by the NHS for suitability of use of NHS patients. This is called “NHS Permissions” – previously named R&D approval. Option B: Apply for ethical approval to establish a new Research Tissue Bank Every time a researcher wishes to collect new material or use the material stored in biobank in a research project, they must obtain individual project-based Research Ethics Committee (REC) approval to do so. Last printed 08/02/2016 20:04 Page 33 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 To overcome this, organisations responsible for the management of research tissue banks anywhere in the UK may apply for ethical review of their arrangements for collection, storage, use and distribution of tissue, and become a REC approved Research Tissue Bank. Applications for ethical approval for research tissue banks is not a legal requirement, however it comes with a number of advantages, primarily the ethical approval facilitates programmes of research without the need for individual project-based ethical approval. Setting up a new bank does however come with a number of terms and conditions, including: The requirement to appoint a Research Tissue Bank Manager The requirement to submit an annual report detailing the banks activity Record keeping – maintaining records of all biobank activity Communication – informing the ethics committee of any substantial amendments to the bank, adverse events etc. Note that institutions wishing to establish a new research tissue bank (option 2), must implement documented access policies and procedures, including procedures for processing applications, the conditions of access and any governance requirements. This process must be made known to potential applicants. The QA & Development Manager and/or Designated Individual must be consulted by any group wishing to establish a new research tissue bank under the Newcastle University research sector HTA licence and the DI must sign off the REC application on IRAS. To enhance governance, efforts should be made wherever possible to avoid the unnecessary creation of additional research tissue banks, where the tissue collection may be feasible under a pre-existing research tissue bank. A number of help document have been created to support researchers who wish to establish a new REC approved Research Tissue Bank, or access samples from these banks. These documents are stored in the Human Tissue Act Virtual Research Environment (see section 1.3.1) and on the Newcastle Joint Research Office website (www.newcastlejro.org.uk). Option C: Apply to use an existing REC approved Research Tissue Banks ethics to collect new tissue Alternatively, researchers may apply to the manager of an established REC approved Research Tissue Bank to collect new tissue under the tissue banks pre-existing ethical approval. Researchers should contact the Research Tissue Bank Manager to discuss this. 7.1.2.2. Collecting new tissue from non-NHS patients Where a new tissue collection is required from non-NHS patients (e.g. healthy volunteers) University ethics committee approval must be obtained. The University Research Ethics Committee formal body responsible for developing and implementing an overall ethical framework for Newcastle University is the University Ethics Last printed 08/02/2016 20:04 Page 34 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Committee (UEC) which is a sub-committee of both Senate and Council. The framework for consideration of ethical issues in research is as follows: Formal consideration of ethical issues in research at the faculty level Monitoring at the level of the Faculty Executive Board Institutional oversight by the University Ethics Committee It is the responsibility of each Faculty Executive Board to ensure that appropriate consideration is given to ethical issues arising in and from research activity for staff and students in all disciplines within the Faculty (link to “Ethics in the Faculties”). Each Faculty uses the same broad procedures to consider ethical issues and will refer to the UEC any matters which cannot be satisfactorily resolved by the procedures established by them. The University’s Ethics Committee meets annually, the meeting is held in early January each year. For further information, including constitution and membership please refer to: http://www.ncl.ac.uk/res/research/ethics_governance/ethics/procedures/university/ethics_universi ty.htm NOTE: That material collected under ethical approval granted by a University ethics committee must be stored under a Human Tissue Act licence. Only material which has been collected under NHS REC approval from a recognised REC is exempt from requiring HTA storage. 7.1.3. OPTION 3 – PURCHASING MATERIAL FROM A COMMERCIAL SUPPLIER Although it is illegal to sell relevant material for transplantation, it is not illegal to sell this material for research purposes and many commercial suppliers have relevant material available for purchase. However, researchers wishing to purchase relevant material must be confident that they have purchased material from a reputable source, and that appropriate consent is in place for the samples. Where researchers wish to import human bodies, body parts or tissue into England, Wales and Northern Ireland, they should be able to demonstrate that the purposes for which they wish to import such material cannot be adequately met by comparable material available from sources within those countries, or is for a particular purpose which justifies import. This process will help importers to assure themselves of the integrity of the material and that, as a minimum, it has been sourced with appropriate consent. They should be able to satisfy themselves and document the need for importing in terms of accessibility, quality, timeliness of supply, risk of infection, quality of service, cost effectiveness, or scientific or research need. Last printed 08/02/2016 20:04 Page 35 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Such documentation should be available for inspection by the HTA. Furthermore, it is good practice for approval to be obtained from a research ethics authority or the local equivalent in the source country beforehand. For more information on importing material, please refer to Code of Practice 8, “Import and export of human bodies, body parts and tissue” (see Section 0). Last printed 08/02/2016 20:04 Page 36 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 7.2. CONSENT Consent is the principle that a person must give their permission for their tissues to be retained or used. The principle of consent is an important part of medical ethics and the international human rights law, and is a fundamental underlying principal of the human tissue act. Obtaining consent for participant participation in research is incredibly important. There are legal requirements, such as the Declaration of Helsinki, national, international and common laws, and institutional requirements, such as from employers or professional bodies. The key principles of consent under the HTA, including cases where consent is not required, are summarised in sections 7.2.1 to 7.2.5, below. The HTA’s full requirements for consent are set out in Code of Practice 1; “Consent” (see section 0) and in the consent standards, as set out in Appendix A, part 1. Please also refer to HTA-POL-1 for the Consent Policy. 7.2.1. Which activities require consent? Before deciding whether to proceed with the removal, storage or use of tissue for scheduled purposes, researchers should consider if the activity requires consent. Under the terms of the Human Tissue Act (2004), consent must be obtained for the removal, storage and use of human tissue or organs for certain “scheduled purposes”. Scheduled purposes (i.e. activities requiring consent) are set out in Table 3 on page 18. However, in broad terms, the Act and the HTA's codes of practice require that consent is required to: 1. store and use dead bodies 2. remove, store and use relevant material from a dead body 3. store and use relevant material from the living However, a number of exemptions exist in which consent is not required. Exemptions? Tissue from the living may be stored for use and/or used without consent, provided that: the research is ethically approved the tissue is anonymised such that the researcher is not in possession, and is unlikely to come into possession, of information identifying the person from whose body the material has come. This does not mean that samples must be permanently and irrevocably unlinked –linking can be made through a third party where necessary – nor that the persons holding the samples cannot themselves carry out the research. If members of the clinical team take part in the research, links may be retained to the relevant clinical or patient records, but they must not contain information giving direct patient identification. Last printed 08/02/2016 20:04 Page 37 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 In general, obtaining consent is preferable to developing complex systems for keeping samples unlinked. It represents best practice and has the added benefit of facilitating the process of obtaining ethical approval. Further exemptions where samples may be stored or used without consent include: “Existing Holdings”: As law cannot be applied retrospectively, it is not a requirement to have consent in place for samples collected before the implementation of the Human Tissue Act on 1st September 2006. These samples are classed as Existing holdings. However, a HTA licence is required to store these materials. Tissue for DNA analysis which is anonymised Tissue from the deceased which has been imported Tissue taken from the living which is anonymised and has received ethical approval for research without consent Consent requirements under the Human Tissue Act (2004) are summarised in Figure 10. For full information see Code of Practice 3. Was the tissue retained for research before 1st September 2006? yes no Consent not required however to ensure best practice consent should always be sought Tissue is classed as an “Existing Holding” yes Is the tissue to be used for DNA analysis? yes Is the tissue anonymised? no yes Is the tissue from the deceased? no Qualifying consent is required (that from living person DNA has been derived from) yes Is the tissue imported? no Appropriate consent is required no Will the tissue be identifiable to the researcher? no Seek ethical approval for use without consent Is the tissue from an adult lacking mental capacity to consent? yes no Has ethical approval for research without consent been granted? no yes Appropriate consent is required See clinical trials regulations 2004 & Mental Capacity Act 2005 yes Consent not required Figure 10 - Requirements for consent under the Human Tissue Act While informed consent is not a legal requirement in some cases, it is best practice to ensure that consent is in place where practical. In addition, the HTA has the power to deem consent to be in place for relevant material from someone who is untraceable, or who has Last printed 08/02/2016 20:04 Page 38 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 not responded to requests for consent to use of his/her material, if that material could be used to provide information relevant to another person. 7.2.2. Who can give consent? The term “Appropriate Consent” is used by the Human Tissue Act to define who may give consent. Consent is ideally obtained from the individual themselves, either while they are living, or after their death, as an expression of their wishes. For children, assent may be given directly by the child, if it is considered that the child is competent to do so. However, if the wishes of the deceased are unknown, or if a child is considered not to be competent to make a decision, a nominated representative will be asked to make decisions relating to donation, where applicable. If a nominated representative has not been appointed, then the appropriate consent can be given by someone in a qualifying relationship. A summary of qualifying relationships, and the order in which they are ranked, is provide in Figure 11. Friend of long standing Ranked 8th Sibling Ranked 3rd Grandparent/ Grand child Ranked 4th Niece/Nephew Ranked 5th Spouse/Partner (including civil/same sex partner) Ranked 1st Step parent Ranked 6th Half brother/sister Ranked 7th Parent or child Ranked 2nd Individual consent Taken from the living, or, After death as expression of wishes Figure 11 - Qualifying relationships to provide appropriate consent It should be noted however, that a nominated person cannot consent to the use of material for public display or for anatomical examination. Direct consent is required in these cases. Last printed 08/02/2016 20:04 Page 39 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 7.2.3. How is consent taken? The person taking consent does not necessarily have to be the clinician responsible for the patients care (nurse, doctor), but it does have to be someone suitably trained and aware and able to communicate any risks or benefits of the associated donation. Training must include Good Clinical Practice (GCP) training, and may include further training e.g. Informed Consent and Ethics. Records must be made available to demonstrate up-to-date staff training in taking consent, and competency assessed and maintained. In cases where a third party (e.g. another organisation) takes consent and collects samples on your behalf, a Service Level Agreement (SLA) or other formal agreement should be in place to ensure that consent is obtained in accordance with the Code of Practice on Consent (Code 1) and the HT Act Part 1. Consent does not have to be given in writing (i.e. by signing a consent form). Although it is easier to demonstrate that consent is in place if it is written, nonwritten consent (taken verbally, or non-verbally e.g. hand gesture) may be taken provided that an explanation is put into the notes, and is witnessed to explain the reason why consent is not written. To be valid, consent must be: Voluntary: Informed: The person who is giving Appropriate: Consent must be given voluntarily, by an appropriately informed person who has the capacity to agree to the activity in question the consent must have a clear appreciation and understanding of the facts, implications, and future consequences of an action. To ensure this, all necessary information must be provided by the person taking consent. This is classed as “informed consent” The information provided must be appropriate, and take into consideration the age and mental capacity of the individual giving consent, and any potential language difficulties. Interpreters, Braille, or large font may be provided where appropriate. All groups should ensure that their consent process (whether taken personally or by a third party) is documented, for example a Standard Operating Procedure (SOP), including the procedure for providing information on consent. A number of different methods exist for taking consent, as described overleaf in Table 4: Last printed 08/02/2016 20:04 Page 40 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 Table 4 – Methods for taking consent Informed/ Express/ Explicit Consent Informed consent, also known as valid, express or explicit consent, entails giving sufficient information about the research and ensuring that there is no explicit or implicit coercion so that prospective participants can make an informed and free decision about their involvement. Typically, the information should be provided in written form. Time should be allowed for the participants to consider their choices and the forms should be signed off by the research participants to indicate consent. Where participants are not legally responsible, their legal representatives or guardians should be consulted, as well as the participant. Where participants are not literate, verbal consent may be obtained but this should, wherever possible, be witnessed and recorded. In other circumstances, for example telephone interviews, this may not be possible. Where consent is not or cannot be secured, the researcher must submit a full statement justifying the practice to the appropriate Research Ethics Committee. The primary objective is to conduct research openly and without deception. Deception (i.e. research without consent) should only be used as a last resort when no other approach is possible. This principle also requires that research staff need to be made fully aware of the proposed research and its potential risks to them. In longitudinal research it may be necessary to explain the need for (and limitations of) enduring consent; it may also be necessary to renegotiate consent during the lifetime of the research. Implicit/Implied Consent Implied/implicit consent differs from express/explicit/informed consent in that it is not gained through formal methods, such as written or verbal approval. An example of this would be where a person completes a questionnaire. By completing the form, they imply their consent to participate. Post-hoc Consent Post-hoc consent is consent that has, as the name implies, been sought and granted after the research has taken place. This is likely to be the case in circumstances where consent needs to be obtained prior to publication. Proxy consent Proxy consent for research participants may be necessary when the participant is a vulnerable person. The best interests of the participant must be the highest importance. In sensitive research involving vulnerable populations, particularly children, the competence of the researcher to undertake the research should be considered. Proxy consent should only be used when participants are unable to consent themselves or where it is legally necessary. Care should be taken that consent cannot be sought from the participants and it should not be assumed that children are unable to consent because of their age. When proxy consent is used, agreed criteria should be used to identify signs that the participant is unwilling to take part or wishes to terminate the research interaction, and fully understands to what they are consenting. Last printed 08/02/2016 20:04 Page 41 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 7.2.4. Are there different types of consent? Donors may be asked to give consent for their tissues to be stored/ used for either project specific purposes, with exemptions (tiered) or for generic research, as described in Table 5. Table 5 - Types of consent Type of consent Application Project specific Where the patient only consents to the use of their tissues in a specific research project Where a number of “opt-outs” are available that a donor can select, for example, where the donor does not wish their samples to be Tiered Generic Used commercially (e.g. Provided to pharmaceutical companies) Used for DNA analysis Used in animals Exported Where the patient provides broad consent (in terms of duration and scope) for the tissue to be used in unspecified research It is recommended to request generic consent, where ever possible to avoid the need to return to the donor to ask for further consent to use the sample in additional research, and prevent the unnecessary disposal of samples when a research project ends It is essential that researchers understand what type of consent has been granted, and do not use tissues out with the terms of the patients consent. Information on the type of consent granted by donors, including any specific wishes, and the location of signed consent forms, should be kept alongside sample information in sample tracking systems, and made clearly visible to those accessing samples. All patient identifiable data should be kept confidentially in secure systems, and only accessed by individuals with the authority to do so. The availability of signed consent forms and security of patient data can be audited at any time by internal or external auditors (the Human Tissue Authority) to ensure that samples are being stored and used in accordance with donor wishes and confidentiality maintained. 7.2.5. Can consent be withdrawn? When a person gives consent for relevant material to be used for a Scheduled Purpose, that consent remains valid unless the person withdraws it. Consent can be withdrawn at any time, however if samples have already been used for a Scheduled Purpose (e.g. research), withdrawal of consent does not mean all relevant results Last printed 08/02/2016 20:04 Page 42 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 should be withdrawn from the research project. This should be clearly stated on the consent form, and communicated to the donor. In some instances it may not be possible to withdraw consent after sample donation, for example, where the sample has been used immediately and cannot be returned. In these instances, this must be clearly stated on the consent form. All groups should have systems in place to ensure that where consent has been withdrawn, there are methods to remove samples from use (where appropriate). Last printed 08/02/2016 20:04 Page 43 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 8. STORAGE A Human Tissue Act licence is required for establishments storing human organs, tissues and cells for research purposes “other than for a specific ethically approved research project” i.e. Biobanking for future, yet un-specified use. Therefore, if you have current Research Ethics Committee approval from a recognised NHS REC, then you do not need to store material under the Human Tissue Act. The Human Tissue Act and Research Ethics - Storage versus use An HTA licence is not needed for storage of tissue for certain ethically approved research or a specific research project for which ethical approval is pending from a recognised Research Ethics Committee (REC), which is either: A REC established under and operating to the standards set out in the governance arrangements issued by the UK Health Departments, or an ethics committee recognised by the United Kingdom Ethics Committee Authority (UKECA), to review clinical trials of investigational medicinal products under the Medicines for Human Use (Clinical Trials) Regulations 2004. The HTA and National Research Ethics Service (NRES) have agreed a position whereby NHS RECs can give generic ethical approval for a research tissue bank's arrangements for collection, storage and release of tissue, providing the tissue in the bank is stored on HTAlicensed premises. This approval can extend to specific projects receiving non-identifiable tissue from the bank. The tissue does not then need to be stored on HTA-licensed premises; nor does it need project specific ethical approval. However, a licence is required for material stored (e.g. in large biobanks) for which there is no ethical approval. Importantly - this exclusion does not apply to the University ethics committee, which is not classified as a recognised REC. Researchers storing samples collected under University ethics (e.g. from healthy volunteers) must store material under the Human Tissue Act licence and disclose it to the Designated Individual. Sample storage requirements under the HTA are described below. 8.1. Sample storage requirements The HTA does not stipulate exact requirements for the storage of relevant material; however, the premises must be ‘fit for purpose’. This means that areas used for storage of human tissue for use in research must provide an environment that is safe for those working under the licence and preserves the integrity of the tissue. Furthermore these conditions must be maintained regardless if a tissue is to be held only for a short period of time, or if there are only a few items held under the authority of the licence. Last printed 08/02/2016 20:04 Page 44 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 In addition, patient data should be appropriately stored, and confidentiality maintained The HTA’s general requirements for sample storage and the options available for researchers wishing to store relevant materials under Newcastle University’s research licence are provided below. For details of the HTA standards relating to premises, facilities and equipment (PFE) refer to Appendix A part 3. Human tissue should be stored in line with good practice on: Security Risks such as theft or damage must be considered. Lockable storage facilities, alarm systems and indelible identification marking of human tissue should be used, if appropriate Maintenance Establishments and equipment must be well maintained and critical equipment subject to a program of planned preventative maintenance, validation and repair Equipment/surfaces must be clean, with a clear decontamination/cleaning policy, Monitoring Critical storage conditions should be monitored and recorded Establishment must have 24 hour contingency arrangements in place should there be an emergency situation that renders the premises unsuitable for storage, including instructions for contacting key personnel out-of hours and assessing the impact of emergencies should they occur. Traceability Records should detail the location of the materials including information about risk. Health and safety Staff should have sufficient space to work, and access to appropriate protective clothing, materials and equipment to ensure safe working Regular temperature monitoring or control, or ventilation must be considered, where appropriate. See the safety office website: https://safety.ncl.ac.uk/home.aspx Environmental controls should be in place to avoid potential contamination Transportation and handling Systems should be in place to protect the quality and integrity of human samples during transport and deliver to a destination Methods should consider the safety of all staff and others who may come into contact with the tissue during transfer. Last printed 08/02/2016 20:04 Page 45 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 8.2. Data storage and protection The Human Tissue Act storage requirements also apply to the storage of data. Data relating to donated samples may be either: • Identifiable data – Data which clearly link to a particularly individual e.g. name, address, date of birth or NHS number. • Coded/link-anonymised data – Data which cannot directly identify an individual, but can be reconnected back to the donor, if required, by the use of a controlled code. • Anonymised data – data which cannot be linked back to the original donor, as all links have been removed. Generally researchers use anonymised patient data wherever possible. However, sometimes it is necessary to access information that can directly or indirectly identify a specific individual. In the UK, the use of patient data is tightly controlled within a complex regulatory and governance framework. All personal information must be stored, handled and disposed of in accordance with the Data Protection Act (1998). The Data Protection Act (gives individuals the right to know what information is held about them, and provides a framework to ensure that personal information is handled properly. Researchers must therefore always ensure that where patient identifiable data is stored, confidentiality is maintained in compliance with the terms of The Act, including the use of secure, password protected computer systems with restricted access. Researchers wishing to store or use patient identifiable information from NHS patients must apply for permission to do so. The Caldicott application asks for information on the WHO, WHY AND WHERE of patient identifiable data. If you wish to store patient names, initials, date of birth, address, or any other patient identifiable information, you will be asked WHO will have access to the data WHAT data will be stored WHY it is needed, and WHERE the data will be stored. Last printed 08/02/2016 20:04 Page 46 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 The Caldicott Guardian may contact you to suggest alternatives. For researchers using tissues and data from the Newcastle upon Tyne Hospitals Trust patients, the Caldicott Guardian can be contacted at caldicott@nuth.nhs.uk. Or, for other NHS Trusts, consult the Newcastle Joint Research Office: http://www.newcastlejro.org.uk/contact/ Governance of data storage: Following the 1997 report of the Review of Patient Identifiable Information, chaired by Dame Fiona Caldicott) large NHS organisations (and non-NHS organisations using the data) must now nominate an appropriate Caldicott Guardian to act as the 'conscience' of the organisation, and review requests to store or use patient data. Researchers wishing to store patient identifiable data must therefore apply to the appropriate Caldicott Guardian, detailing the purpose of using confidential information and how confidentiality will be maintained. Access should be on a strict need-to-know basis, and data security protected in password protected computer systems, with restricted access. Where patient data is stored by groups working at Newcastle University, evidence must be made available to prove that approval has been granted to store this information. 8.3. What are the storage options at Newcastle University? Relevant material which requires storage under the Human Tissue Act at Newcastle University must be stored at a designated storage location. These storage locations must be maintained to high quality standards and are regularly audited to ensure compliance with the regulations. A list of approved storage locations, and the associated Persons Designate, is provided in the HTA Master File and HTA Virtual Research Environment. To request to store material at one of these locations, researchers should contact the appropriate Person Designate or the Designated Individual (for contact details refer to the HTA Master File). Storage may incur a fee. Any researcher wishing to store material elsewhere (for example, in their own laboratory) should contact the Designated Individual or Quality Assurance and Development Manager for approval. Last printed 08/02/2016 20:04 Page 47 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 However, researchers should be aware that to ensure best governance, Newcastle University aims to reduce the number of tissue collection held across the establishment, and consolidate collections where possible. Researchers who wish to set up a tissue collection themselves must therefore provide a sufficient justification to the Designated Individual to do so. Any new tissue collections which are established must meet the requirements of the Human Tissue Act and are susceptible to audit at any time by the Quality Assurance Manager or the Human Tissue Authority. Relevant material which has research ethics committee approval in place from a formally recognised REC (this does not the University ethics committee) for its use does not need to be stored under the Act for the duration of the ethical approval. Therefore, there are no HTA stipulations as to where this material is stored. However, on expiry of the ethical approval, a Human Tissue Act licence is required to govern the storage of any residual material. The researcher then has the following options: Apply to extend the REC approval and continue the project Transfer the material to HTA licensed premises Dispose of the tissue (see section 11). These options are summarised in Figure 12 I wish to store relevant material at Newcastle University Do you have current REC approval in place to use the tissue? no Material must be stored under the Human Tissue Act. Where do you wish to store the relevant material. yes End no The material can be stored at any appropriate location at Newcastle University for the duration of the REC approval (outwith the scope of the Human Tissue Act) Option 1: As part of the preapproved tissue collections shown in Figure 8 Option 2 In your own laboratory, not part of one of the preapproved tissue collections shown in figure 8 REC approval expires Contact the appropriate Person Designate for the collection Contact the Quality Assurance Manager or Designated Individual for advice Do you have any remaining residual material? Approval granted yes Do you wish to extend the REC approval for the project? yes Apply to extend REC approval for the project Approval denied no Do you wish to keep the remaining residual material? yes no Dispose of the material and inform the R&D team that the project is complete & there are no remaining samples Figure 12 - Storage options for relevant materials at Newcastle University Last printed 08/02/2016 20:04 Page 48 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 –March 2015 8.4. Subcontracting storage In some cases it may be preferable to subcontract the storage of relevant material to another organisation. In this case the suitability of the 3rd party should be assessed before undertaking a contract (e.g. audit of facility, review of compliance). A formal agreement should be signed to formally confirm these storage agreements. 8.5. Appropriate storage period In order to demonstrate respect for human tissue, and ensure the best use of any donated material, it is best practice to ensure that any tissue which is available for use in medical research is made available to the research community and access opportunities promoted. In addition, the Human Tissue Authority recommends that institutions implement systems which state the frequency of review of collections and the criteria for disposal/further storage. These policies should take into account the duty to the donor to make good use of their samples. Last printed 08/02/2016 20:04 Page 49 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 9. SAMPLE TRACKING As traceability is a fundamental principle of the Human Tissue Act, it is essential that records are maintained which provide an audit trail throughout the lifespan of the sample (i.e. from collection, transfer, storage, and use, through to disposal). Sample tracking can be undertaken by many means, but records of how many samples are in storage at any one time is key for HTA reporting. Each institute working under The Act must therefore have a secure, clear and documented sample tracking system in place which includes a clear process for tracking the import and export of samples from/to countries outside England, Wales and Northern Ireland. At Newcastle University the “Achiever Medical System” sample tracking software, delivered by the company Interactive Software Limited (ISL) is currently being rolled out across the Faculty. In 2014 this system went live in the Northern Institute for Cancer Research (NICR). This software must now be used by all staff in the institute to track samples. This software will be rolled out to other institutes across the Faculty in 2015-2016. The fundamental principles of sample tracking are set out in Code of Practice 9 (Research) and in HTA standards on Governance and Quality (see Appendix A, part 2). A summary of the key principles is provided in section 9.1. 9.1. Key Principles of sample tracking 9.1.1. Assigning unique sample numbers It is an HTA requirement that there is an identification system which assigns a unique code to each donation and to each of the products associated with it, as shown overleaf. Last printed 08/02/2016 20:04 Page 50 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Sample 1a Sample 1b1 Sample 1b Sample 1c Samples 1b2-1b7 Sample 1d Parent/Original Sample e.g. 10mL Blood Sample Sample 1 Products Further Products Four 1mL derivatives (Child samples) are created from some of the parent sample & given their own unique numbers Some of Sample 1b is used to create 1 plasma sample (nonrelevant material) and 6 slides. Samples 1 a, 1b, 1c, 1d Samples 1b1, 1b2, 1b3, 1b4, 1b5, 1b6, 1b7 9.1.2. Sample Tracking Records It is also a HTA requirement that there is a records system that maintains an audit trail for all samples, including Location of the human tissue (e.g. fridge/freeze/laboratory) A description of the tissue & specific donor requests If the sample is a relevant material under the Human Tissue Act Consent details: Location of signed consent forms (or uploaded copies of consent forms), type of consent (e.g. tiered, specific, generic, and any opt-outs). Sample history – where it was obtained, if it is a derivative of another sample, transfers, any adverse events relating to the samples Sample tracking records may take a number of formats e.g. paper records, Microsoft Word, Excel or Access, or bespoke databases. However, regardless of the method used, the system should be: Backed up Secure – restricted access Have an audit trail Example Excel Sample tracking sheet: Last printed 08/02/2016 20:04 Page 51 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Once a sample has been assigned to a Research Ethics Committee (REC) approved project there is no longer an HTA requirement to track the sample under the HTA. However, researchers should have records of where the samples have been transferred to. 9.1.3. Material and data tracking during transfer In line with the HTA’s policy on traceability, the transfer of relevant material must be tracked. If human tissue is transferred between establishments, consideration must therefore be given to safety, and minimising the likelihood of theft, damage or loss during transport. In addition, data should be carefully controlled during transfer to protect donor confidentiality. Therefore, some form of formal arrangement, should define how the human tissue and any associated data is protected, any potential contamination risks associated with the material, and who is responsible for disposal if applicable (Code of Practice 9, section 112). If a member of staff at Newcastle University wishes to transfer human material in to, or out of the University from another establishment (i.e. external transfers), some form of formal transfer agreement is required to maintain traceability of the samples during transfer, document the terms and conditions of the transfer and any key responsibilities. Last printed 08/02/2016 20:04 Page 52 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 At Newcastle University, the main type of transfer agreement which is used to establish arrangements for transfers to other establishments is called a “Material Transfer Agreement”, or MTA. The Grants and Contracts team at Newcastle University are responsible for organising MTAs on behalf of researchers for both incoming and outgoing material. Please refer to HTA-SOP-07 and the Newcastle Joint Research Office (NJRO) for guidance www.newcastle.jro.org.uk,, or submit the following questionnaire to allow a transfer to be set up on your behalf: Incoming Material Questionnaire: o http://forms.ncl.ac.uk/view.php?id=1682 Outgoing Material Questionnaire: o http://forms.ncl.ac.uk/view.php?id=1698 In some instances, the terms of the transfer may be covered by another formal agreement e.g. a collaboration agreement, or protocol. In these instances researchers must be confident that the arrangement satisfies the requirements of the HTA regulations. For any queries, please contact the Grants and Contracts team via the NJRO website. For internal transfers (i.e. within Newcastle University) transfer agreements are not required. However, materials should be transferred in accordance with local Health and Safety procedures and packaged accordingly. For further information please refer to the Safety Office website: http://safety.ncl.ac.uk/transportofbiologicalhazards.aspx 9.1.4. Safety during transportation The transfer of biological samples must comply with safety requirements for sample transport in line with UN3733 standards. The processes which must be followed to arrange a material transfer, including safety requirements, are provided in HTA-SOP-07. Last printed 08/02/2016 20:04 Page 53 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 10. SAMPLE USE A Human Tissue Act licence is required for the storage of samples, and does not cover the use of the samples. To use a sample, researchers must apply for Research Ethics Committee (REC) and NHS Permissions (previously called R&D approval) to do so. This should be conducted using the Integrated Research Application System (IRAS) - see Figure 9. https://www.myresearchproject.org.uk/ Last printed 08/02/2016 20:04 Page 54 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 11. SAMPLE DISPOSAL As the collection and use of Human Tissue is considered to be a precious gift, according to the underlying principles of The Act, to make the best use of samples, sample destruction should be avoided unless it is absolutely necessary – for example. If the integrity of the samples has been irretrievably compromised If the patient has withdrawn consent for use If the ethical approval or consent for a study dictates that samples must be destroyed at the end of a particular study. However, where sample destruction is required, researchers must be aware of the ethical consideration, and associated requirements under the Human Tissue Act. Researchers should therefore consult Code of Practice 5: Disposal of Human Tissue. http://www.hta.gov.uk/legislationpoliciesandcodesofpractice/codesofpractice/code5disposal.c fm?faArea1=customwidgets.content_view_1&cit_id=713 The key requirements of disposal are summarised below. For full disposal standards as set out by the HTA, see Appendix A, part 4. For the disposal policy adopted as part of the Quality Management System for the HTA licence, please refer to HTA-POL-03. 11.1. Key considerations in sample disposal There are particular sensitivities relating to the use and disposal of tissue, therefore it is essential for researchers to recognise the nature of the material being handled, the sensitivity of the feelings of the donors and the bereaved. This may be particularly sensitive in cases following pregnancy loss. What does this mean for researchers? Where researchers are responsible for collecting human tissue, processes should be in place to inform individuals, or their relatives, how tissue will be disposed of after use. Staff should be prepared to discuss the issue of disposal, explaining the options available and who will be responsible for any associated costs. Staff should be appropriately trained, and be familiar with the establishment’s arrangements, including what is available locally, basic legal requirements and the options available to those wanting to make their own arrangements to dispose of tissue. Where appropriate, such information should be available in writing for people to take away with them. They may wish to discuss it with relatives or community members before making their choice. Staff should be sensitive to cultural/religious and language differences, whilst being aware that choices are for the individual or relative to make. Last printed 08/02/2016 20:04 Page 55 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 What does this mean for researchers...? Prior to disposal, donor consent and any decisions made by an Ethics Committee regarding disposal should be examined to determine the donor wishes. 11.2. Disposal options Depending on whether the tissue is from the deceased or the living, a number of different disposal options are available, which must be carefully selected. These are summarised in figure 14. Is the Tissue from the living? no Tissue is from the deceased yes For surplus tissue For “Existing Holdings” i.e. samples held prior to 1st September 2006 For pregnancy loss before 24 weeks gestation For surplus tissue For “Existing Holdings”? i.e. samples held prior to 1st September 2006 For stillbirths or neonatal deaths? Dispose via incineration Dispose via incineration Burial/Cremation or incineration (where appropriate) may be requested Dispose via incineration Is the material identifiable? Cremation or burial Dispose via incineration/ burial Dispose via incineration/ burial or cremation Figure 13 - Sample disposal options In 2015 the Human Tissue Authority will be issuing new guidance on the disposal of fetal remains. Researchers disposing of this material must therefore consult the HTA website for further guidance on disposing of this material. In general however, the disposal of any tissue should be handled in accordance with any reasonable wishes expressed by the donor or their relatives, as long as the method of disposal is legal. Whichever method of sample disposal is utilised, appropriate documentation of the disposal route must be maintained. Last printed 08/02/2016 20:04 Page 56 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 11.3. Maintaining proper documentation In accordance with the Human Tissue Act’s requirements for sample tracking (see Section 9) establishments must ensure that they have systems in place to maintain proper records and documentation for all tissue they acquire or pass on to others. This includes at minimum: The date/time of disposal The method of disposal (route used & place) Reason for disposal This information should be recorded in the tissue tracking database used within each department, in accordance with local policies/procedures and these records must be made available to auditors on request to demonstrate sample traceability throughout its full lifecycle. Decisions regarding the retention period for this documentation will be made at a department level in line with the establishments documented policy. 11.4. Preventing unnecessary waste of human tissue To avoid any unnecessary destruction of human tissue, which may have otherwise been kept for use in valuable research, generic consent for research should be sought where ever possible (see section 7.2). The provision of generic consent ensures that tissues can be retained for further use, hence promoting the most effective use of the tissue. However, requests for generic consent must be treated on a case-by-case basis, and handled sensitively by the requestor. Last printed 08/02/2016 20:04 Page 57 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 12. THE QUALITY MANAGEMENT SYSTEM (QMS) Failure to comply with the HT Act is a criminal offence. Where any institution is shown to have failed to comply with its responsibilities under The Act, the institution may face a number of serious consequences. To promote high quality standards at Newcastle University, and ensure compliance with The Act, a Quality Management System (QMS) has been implemented. This system is described below. 12.1. The Quality Manual This Quality Manual sets out the key features of the Human Tissue Act, and Newcastle University’s responsibilities under its remit. The aims of this manual are set out in section 2. All researchers working under Newcastle University’s Human Tissue Act licence must therefore abide by the standards set out in this manual. The manual can be accessed electronically, via the human tissue pages of the Newcastle JRO website (http://www.newcastlejro.org.uk/ ) or in the Human Tissue Act Virtual Research Environment (see section12.2). When printed, this manual expires within 7 days. 12.2. Document Management The quality standards relating to the management of documents/records under the Human Tissue Act are summarised below: Quality Standards relating to Records: All aspects of the establishments work must be supported by ratified documents, policies and procedures as part of the overall governance process. o Policies and procedures should be in place to cover all licensable activities, and be approved by authorised personnel o Documents must be legible, easily identifiable and readily available o Documents must contain a unique identifier, the review date or date of issue, version number, total number of pages and the name of the authoriser o Appropriate risk management systems must be in place o There must be a documented system of quality management and audit A document control system should be in place covering all quality documents, which is regularly audited o Change control should be in place for the implementation of new or revised operational procedures Last printed 08/02/2016 20:04 Page 58 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Quality standards continued: There must be a systematic and planned approach to the management of records o Documented procedures must be in place for the creation, amendment, retention and destruction of records o There must be back-up/recovery facility in the event of loss of records In addition, biobank management at each tissue collection should ensure that a master list is maintained of all groups documents which are currently authorised for use and their location. These standards will be assessed by the Quality Assurance Manager during internal audits. Further information on the University’s approach to document management is provided below. 12.3. Document Control For full information on the approach to document management adopted under the licence, please refer to HTA-SOP-01 “Document Management - The creation, amendment, retention and destruction of records under the Newcastle University research sector HTA licence (Ref. 12534)” For full information on the change control procedure, please refer to HTA-SOP-08. 1.3.1 Document Management System All high level quality documents adopted as part of the Quality Management System for the HTA licence are stored in two locations: - On the Newcastle Joint Research Office website (www.newcastlejro.org.uk) On the Human Tissue Act Virtual Research Environment (VRE). https://researchtools.ncl.ac.uk/portal In addition, all groups must hold a HTA Master File containing a core set of documents. These systems are described below. 1.3.2 Newcastle Joint Research Office (NJRO) Website All high level documents relating to the Newcastle University research HTA licence are stored on the Newcastle Joint Research Office website: www.newcastlejro.org.uk Last printed 08/02/2016 20:04 Page 59 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 1.3.3 The Virtual Research Environment (VRE) The Virtual Research Environment (VRE) is an electronic cloud that is used to store all high level documents relating to the University’s licence. This system is backed up on University servers, and provides staff access with these documents from the staff home page. To view HTA documents, users must be given access to the environment. Screen shot from the Virtual Research Environment home page, found via Research Tools: For information on how to gain access to the VRE, and use the tool, please refer to HTA-SOP-09. Help documents on how to use the VRE are also found on the NJRO website. Group specific quality documents (SOPs, policies, training documents etc.) may be stored at the group’s discretion provided this complies with the Human Tissue Act quality standards, as set out in section 12.2. Documents may be in hard copy or electronic and may be digital, photographic or written, provided the approach to document management complies with these standards. 1.3.4 The HTA Master File All groups operating under the Newcastle University Research HTA licence must hold a HTA Master File. The Master File contains a core set of documents describing the organisational Last printed 08/02/2016 20:04 Page 60 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 and local structure, including copies of ethics documentation, and equipment, staff and documentation logs. These must be kept up-to-date, and presented to auditors during inspections. For information on how to set-up and maintain a HTA Master File, please refer to HTA-SOP10. 1.4 Documentation supporting the QMS A number of core HTA documents have been added to the VRE to support the Quality Management System adopted under the research HTA licence. These include Standard Operating Procedures (SOPs), policies and risk assessments, all denoted “HTA” in the document code. These quality documents must be adhered to by al groups working under the University’s Research HTA licence and aim to ensure a consistent set of standards across the University in relation to key aspects of the Act. A master list of these documents (denoted “HTASOP-" or “HTA-POL” etc.) is provided in the HTA Master File and in the HTA Virtual Research Environment. When a new/edited document has been uploaded, the Quality Assurance and Development Manager will contact all Persons Designate and Research Tissue Bank Managers by email to highlight the presence of the new document, and stress the need for staff to read these documents and record training. In addition to these core documents, it is recommended that all groups working under the HTA have records in place which document their local procedures and provide evidence that activities are being performed in compliance with the requirements of the Quality Management System. Each group should therefore have documented policies and procedures which cover all aspects of activity relating to their biobank, including but not limited to consent, collection, storage, release and transport of tissue and data, the management of the biobank and its adherence to applicable quality and regulatory standards. These topics, and information that should be included, are summarised in Table 6. Last printed 08/02/2016 20:04 Page 61 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Standard Operating Procedures: A separate SOP is not required for each topic (topics can be combined) however each group should ensure that they sufficiently document their local procedures such that they are easily understandable (e.g. by auditors, new starters, other staff). Table 6 - Recommended topics to be included in local SOPs Topic To include Sample receipt, storage and tracking Details on the banks procedure for receiving, logging and tracing samples to ensure traceability. Any local procedures for transferring samples should also be described. Access policy Tissue collections, in particular research tissue banks, must have a formal access policy in place to document the procedure to follow for requesting and reviewing access to samples. Consent The procedure for providing information on consent and the consent process. Where consent is managed by 3rd party, information should be provided on how evidence of consent is obtained, and where consent forms are stored. Training Department specific methods for identifying training requirements and recording training Temperature monitoring Methods used to ensure sample integrity is maintained. E.G. Freezer monitoring system used, UPS, emergency rota. Equipment maintenance & calibration Methods and frequency of equipment maintenance and calibration and where this information is stored. Cleaning & decontamination Methods, frequency and documentation methods. Contingency (disaster) planning Procedures to be followed in the event of equipment/system failure. Risk assessment and safety Methods for conducting and documenting risk assessments in the local environment. Disposal Disposal methods and recording disposal. Note that this list is not exhaustive, and groups may have other SOPs in place to document local practices. All SOPs must be made readily available to all staff and inspectors and training provided and documented. Last printed 08/02/2016 20:04 Page 62 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Risk assessments It is an HTA standard that appropriate risk management systems are in place to protect staff and samples. Risk assessment of the establishment’s practices and processes must be completed regularly to ensure they are fit for purpose, and recorded and monitored appropriately. Risk assessments templates can be obtained from the Newcastle University Safety Office website: https://www.safety.ncl.ac.uk/riskassessment.aspx In addition, a HTA risk assessment against risk against the HTA standards will be conducted by the Quality Assurance and Development Manager during 2015 internal HTA audits. Completed risk assessments must be stored in each group’s HTA Master File. For any further advice, please contact the QADM. 1.5 Adverse events An adverse event is any occurrence which threatens, or has the potential to threaten, the integrity of samples, and/or associated data, the safety of staff, or undermines good practice. Adverse events, or near misses, will be managed according to HTA-SOP-3. All corrective and preventative actions (CAPA) must be managed in a timely manner to maintain the integrity of samples, protect patient data and ensure staff safety. 1.6 Complaints Complaints relating to the University’s research sector HTA licence, received either internally (from University staff) or externally (from other organisations), should be managed in accordance HTA-SOP-6. Researchers should contact their local Person Designate in the first instance, or contact the QA Manager. All complaints should be managed promptly, and escalated where necessary. Last printed 08/02/2016 20:04 Page 63 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 1.7 Validation and change control For computer systems that support HTA relevant material or clinical trial material, validation may be required dependent on the complexity of the system being utilised. In addition, in the case of critical procedures, processes, equipment (such as freezers), facilities or utilities may need to be qualified to ensure they are secure and appropriate for use.In all cases a risk assessment should be completed to ensure that the level of validation is proportionate to the risk and establish which elements require validation. Validation may be conducted as part of the manufacturer installation process, in which case regular checks may be made to maintain the validation e.g. through a maintenance contract to provide calibration of the system. Changes to systems which have previously been validated, or hold a validation exemption certificate need to be controlled to maintain the validated state. These changes must be assessed to determine what level of re-validation or testing is required to test the new functionality, or to document the reason why no further testing is required.Change control should be managed following discussion with the Quality Assurance and Development Manager. 1.8 Audit Official inspections reviewing compliance with the Human Tissue Act are conducted on a regular basis. These audits may be either: Typically conducted by the Quality Assurance Manager or Designated Individual. May be self-inspection audits within groups conducted by the Human Tissue Authority Internal audits - External audits - The format of each audit type, and what researchers can expect, is set out in HTA-SOP-4. Audit frequency will be conducted based on a risk analysis. All internal HTA audit reports conducted by the Quality Assurance and Development Manager, or suitably trained delegate, will be stored electronically and can be provided to regulators on request. Last printed 08/02/2016 20:04 Page 64 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 1.9 Training It is essential that all staff working with human tissue under The Act are appropriately trained in the techniques relevant to their work and are continuously updating their skills. All staff should therefore receive appropriate training, which is appropriately documented. The documentation of training may be managed at the each group’s discretion; however on inspection this documented evidence must be readily available on request (e.g. records confirming attendance at training courses). The qualifications of staff (e.g. CV, job description) should also be readily accessible. As part of their induction, new starters must be provided access to all relevant SOPs and procedures, any other associated material (e.g. COSSH assessments), as appropriate. Staff appraisal/review should be regularly conducted to review competence, and further training conducted where necessary. Training can also be obtained from the following sources: E-Learning A Newcastle University Human Tissue Act E-Learning package is due for completion in 2015. For further information, please contact the QADM. The QA Manager and DI host regular Human Tissue Act training courses. For training dates, and information on how to register, please refer to the human tissue pages of the Newcastle Joint Research Office: http://www.newcastlejro.org.uk/r For further information, or to request additional training dates, please contact the Quality Assurance and Development Manager In addition to these training sessions, the CRN (Clinical Research Network) offer a range of training including Good Lab Practice, and Informed Consent and Ethics. This is available to research staff working in the NHS who are Class room training working on NIHR Portfolio Studies or funded by NIHR or its Clinical Research Network and employed by the NHS or have an honorary contract or a ‘Letter of Access’ However this may apply to Newcastle University staff in some instances. Staff should refer to the CRN training webpage for full information, including how to register for courses: Safety related training can be obtained through the safety office: https://safety.ncl.ac.uk/training.aspx. For other University training, please refer to the Staff Development Unit (SDU): http://www.ncl.ac.uk/staffdev/ Last printed 08/02/2016 20:04 Page 65 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Quality Documents 1.10 Staff may be trained via reading quality documents such as quality manuals, Standard Operating Procedures (SOPs), policies and user manuals. All training should be recorded (e.g. read and understood registers) and made evidence of training available on request. Communication with stakeholders To ensure that Human Tissue Act related news, issues and opportunities are communicated to all staff working with human tissue, it is the responsibility of the Persons Designate to hold regular, minuted meetings to communicate with staff in their local area. The Newcastle Joint Research Office website has also been updated to include Human Tissue Act pages which can be readily accessed by staff, which includes a summary of the regulations and resources which can be used by researchers. http://www.newcastlejro.org.uk/ In addition, the Quality Assurance and Development Manager issues regular HTA newsletters, which are distributed across the University to Persons Designate, Institute Managers and other relevant parties. Newsletters are also added to the human tissue pages of the Newcastle Joint Research Office website: To facilitate communication and knowledge share between the Persons Designate, a joint mailing account has also been established that can be used by anyone at the University: person-designate-res@newcastle.ac.uk Details of all tissue collections will be provided on the Newcastle Biomedicine Biobank website (www.ncl.ac.uk/nbb). Last printed 08/02/2016 20:04 Page 66 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 1.11 Governance 1.11.1 Management commitments To ensure compliance with The Act, the Designated Individual, Persons Designate and Quality Assurance and Development Manager have ultimate responsibility for the implementation of the Quality Management System (QMS). These individuals will have oversight of the biobank and will be responsible for its day to day operation, organisation and policies. It is their role to provide leadership and demonstrate commitment towards continually reviewing and improving the QMS. In the absence of the Designated Individual, a Person Designate will be delegated to represent the DI. Bi-annual meetings are held between the management committee, to review and discuss the University’s licence, and address any issues in line with the biobank management’s governance policy. Governance Policy The objectives of this management review are: a) To review HTA activity across the facility, including the hub and all satellite sites. b) To establish that the QMS is achieving the expected results and meeting regulatory requirements, c) To establish that the QMS is continuing to satisfy researchers needs and expectations, and functioning in accordance with the established Standard Operating Procedures. d) To expose irregularities or defects in the System, identify weaknesses and evaluate possible improvements. e) To review the effectiveness of previous corrective actions, and to review the adequacy and suitability of the QMS for current and future operations of the Biobank f) To review any complaints received, identify the cause and recommend corrective action if required. g) To review the finding of internal/ external audits and identify any areas of recurring problems or potential improvements. h) To review the reports of nonconforming items and trend information to identify possible improvements. i) To review any updates in policy from the HTA and their effect on internal systems. Last printed 08/02/2016 20:04 Page 67 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 During management meetings, the biobank management committee will review the progress reports submitted by research tissue banks. If a collection or sub-collection appears to be under used this will be further investigated, including a review of the biobanks access policy. The consent, collection and release of tissue from collections held under the Newcastle University HTA licence tissue collections will be managed by the appropriate tissue custodian in line with local access policies and arrangements for ensuring ethical approval for research. For research tissue banks, it is the individual curators’ responsibility to maintain the ethical approval status of the Research Tissue Banks and provide annual progress reports to the appropriate research ethics committee. A list of all current approved research tissue banks will be held in the HTA Master File and HTA Virtual Research Environment. These parameters will be assessed during internal HTA audits 1.11.2 Access and governance committee In addition, an access and governance committee has been established to review applications for access to tissue from University biobanks. The remit and terms of reference of this committee are provided below. I. Ensure measures are in place to achieve compliance with the HTA a. Grant permission to store tissues and withdraw permission if necessary b. Undertake review of internal audit reports c. Oversee the submission of periodic reports to the HTA (when introduced) II. Provide independent oversight of the operation of generic biobanks a. Approve the constitution of access review committees prior to approval by the DI of applications to LREC for the establishment of generic biobanks. b. Facilitate access review if requested c. Review annual reports to LREC III. Oversee interactions with commercial partners a. Approval of commercial arrangements b. Oversight of commercial strategy group The Governance Board includes I. II. III. IV. The PVC of Faculty of Medical Sciences (the HTA licence holder) (Chair) The Designated Individual for the University HTA research licence The Dean of Research The Dean of Medicine Last printed 08/02/2016 20:04 Page 68 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 V. VI. VII. VIII. The Research Operations Manager, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (Secretary) The HTA Quality Assurance and Development Manager An external representative At least one lay member Meetings are held approximately every 6 months with additional ad hoc meetings as required. 1.11.3 Laypersons Lay persons play a vital role in the activities conducted under the HTA licence by providing feedback from the lay perspective of a non-expert, representing the public, and ensuring that Biobank processes are designed with full consideration of patients and the public. They also help to make participant information more appropriate and accessible to increase awareness and participation in research activities, particularly in less easily accessed communities. To ensure best practice at least one layperson should be a member of any steering/management/operations or access committees. A laypersons role description and information pack can be obtained from the QADM or DI, and suitable training will be provided. Responsibilities include: Attend the bi-annual Access and Governance meeting and other meetings, as required Engage with other lay persons and donors to gain an appreciation of the public perception of biobanking to allow biobank processes and communications to be enhanced Engage with the public, particularly across minority groups, to provide feedback on different viewpoints in medical research. Review documents and other resources (e.g. websites) intended for donors to ensure that suitable language is used, format is appropriate and easily accessible Provide feedback on applications to use human tissue stored as part of the Biobank to ensure that the research is ethical. Lay summaries will be provided. Last printed 08/02/2016 20:04 Page 69 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2. APPENDICES 2.3 APPENDIX A - Minimum and best practice standards for the use of human samples in research The following table provides researchers with the “minimum” and “best” practice standards for the use of human samples for research at Newcastle University. However researchers should always strive to achieve best practice, wherever possible. Furthermore, it is recommended that these standards should be applied to all human samples, including DNA, regardless if they are included in the scope of the Human Tissue Act (i.e. relevant & non-relevant material, and samples held with or without research ethics approval) to promote best practice at all times. This section is divided into 5 parts Part 1: Consent Part 2: Quality systems Part 3: Governance Part 4: Premises, facilities and equipment Part 5: Disposal Last printed 08/02/2016 20:04 Page 70 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 PART 1 – CONSENT STANDARDS 1. Consent Standards C1 Consent is obtained in accordance with the requirements of the Human Tissue Act (2004) and as set out in the code of practice Minimum practice: Consent forms comply with the HTA’s Code of Practice Consent forms are in records and are made accessible to those using or releasing relevant material for a scheduled purpose Where applicable, there are agreements with third parties to ensure consent is obtained in accordance with the requirements of the HT Act 2004 and the HTA Codes of Practice C2 Best practice: Researchers should aim to obtain generic consent wherever possible to avoid the need to obtain further consent in the future, and to make the best use of available samples. Where DNA is to be used in genetic testing/ research, this should be included in the patient information leaflet and associated consent form. Other options in tiered consent should also be included where appropriate e.g. commercial use, export, use in animals Copies of blank consent forms should be obtained as part of the material transfer agreement to ensure that they comply with the HT Act 2004 and the HTA’s Codes of Practice & capture sufficient information As tissue samples and consent forms may be received at different times for some tissue banks, consent forms should be routinely audited to provide further assurance that valid consent is in place for all samples. Agreements with third parties, including the location of consent forms and methods for confirming that consent is in place, should be documented in a consent SOP. Information about the consent process is provided and in a variety of formats Minimum practice: Best practice: Standard Operating Procedures (SOPs) detail the procedure for providing information on consent Independent interpreters are available when appropriate Information is available in suitable formats Last printed 08/02/2016 20:04 Where appropriate, information should be made available in a number of different formats, such as large font, audio tapes, videos, computer programmes, Braille Page 71 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 1. Consent Standards C3 Staff involved in seeking consent receive training and support in the implications and essential requirements of taking consent Minimum practice: Best practice: Standard Operating Procedures (SOPs) detail the consent process Evidence of suitable training of staff involved in seeking consent Records demonstrate up-to-date staff training Competency is assessed and maintained Last printed 08/02/2016 20:04 Training record files should be available for all staff documenting all training completed, reading records & competencies Training should be repeated every 3 years at minimum Page 72 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 PART 2 – GOVERNANCE AND QUALITY SYSTEMS STANDARDS 2. GQ1 Governance and Quality Systems Standards All aspects of the establishments work are supported by ratified documented policies and procedures as part of the overall governance process Minimum practice: Policies and procedures are in place covering all licensable activities Appropriate risk management systems are in place Regular governance meetings are held; for example health and safety and risk management committees, with agendas and minutes Complaints system GQ2 Best practice: A Quality Manual is in place for licensable activities, referencing the University’s policies on consent, records management and disposal of human tissue and the relevant codes of practice. The Newcastle University HTA licence maintains core quality documents covering all activities related to the storage of relevant material for research. Documents uploaded into document management system,version controlled and regularly reviewed A documented back-up/recovery facility exists in the event of loss of records Risk assessments regularly reviewed to ensure they reflect current practice. Risk management approaches are expanded to cover, for example, the security and confidentiality of paper records; Agendas and minutes made available electronically to ensure that they can be accessed by all appropriate personnel. Staff meetings should be held not less than every 3 months Complaints system clearly visible on website or other suitable visible location Complaints system to include internal complaints (e.g. staff, students) and external complaints (public) There is a documented system of quality management and audit Minimum practice: Best practice: A document control system covering all documented policies and standard operating procedures (SOPs) All documents should be identified in a document control database which records review dates Paper versions of quality documents marked as only valid for 7 days after printing. PDs read quality documents and ensure these are made available/ highlighted to all relevant research staff Last printed 08/02/2016 20:04 Page 73 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2. GQ3 Governance and Quality Systems Standards Systems in place to ensure the regular review of quality documents (e.g. regular self-inspection) An audit trail should show any changes to electronic records, who made the changes and the date Self-inspection audits with results fed back to the Quality Assurance and Development Manager Schedule of audits Internal audits conducted every 2 years at a minimum The change control system should incorporate the requirements to undertake an assessment of the risks Change control mechanisms for the associated with the change, to validate implementation of new operational fully any new technique and procedures procedures before they are introduced and to monitor the potential cumulative effects of multiple minor changes. Staff are appropriately trained in techniques relevant to their work and are continuously updating their skills Minimum practice: Best practice: Qualifications of staff and training are recorded, including records showing attendance at training CVs and job descriptions available on request for all staff Individuals have their own training record files with up to date information and attendance certificates where applicable. Reading of quality documents is recorded Orientation and induction programmes Documented training programme (e.g. health and safety, fire, risk management, infection control) including development training GQ4 All staff should complete HTA training every 3 years at minimum Continuing Personal Development (CPD) in place Basic GCP/GLP training to highlight the interests of patients at all times. Training and reference manuals Provision of a quality manual Staff appraisal/review records and personal development plans are in place Competency regularly assessed There is a systematic and planned approach to the management of records Minimum practice: Documented procedures for the creation, amendment, retention and destruction of records Last printed 08/02/2016 20:04 Best practice: All biobank documents should be identified with the document title, author, owner, approver, date issued, version Page 74 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2. Governance and Quality Systems Standards number and for paper-based systems, a copy number. Superseded versions of documents should be archived and copies removed from circulation. A description of changes made should be included in revised documents. Regular audit of record content to check for completeness, legibility and accuracy Back-up/recover facility in the event of loss of records Review of documents every 2 years at minimum, with new versions issued. Documented back up/recovery systems made available. Systems ensure data protection, confidentiality and public disclosure (whistle-blowing) GQ5 There are documented procedures for distribution of bodies, body parts, tissues or cells. GQ6 A coding and records system facilitate traceability of bodies, body parts, tissues and cells, ensuring a robust audit trail Minimum practice: Best practice: There is an identification system which assigns a unique code to each donation and to each of the products associated with it An audit trail is maintained which includes details of when and where the bodies/body parts were put, when the bodies/body parts were transferred and to whom Last printed 08/02/2016 20:04 The audit trail contains full details of consent (i.e. specific, tiered generic consent and location of signed consent form), full details of where samples were received from and sent to. A suitable transfer agreement (e.g. MTA) is used where appropriate Risk assessment of transportation method includes verification of maintenance of cold conditions where necessary by use of data loggers, with data retained on file. Page 75 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2. GQ7 Governance and Quality Systems Standards There are systems to ensure that all adverse events are investigated promptly Minimum practice: Best practice: Investigation check-list completed, and adverse event report provided to QA Manager and DI in accordance with HTA-SOP-03 PD and associated staff register to receive e-newsletters from HTA. Systems to receive and distribute national and local information (e.g. HTA Regular internal HTA newsletter with communications) PD distribution to relevant employees Use of email distribution lists Risk assessments of the establishments practices and processes are completed regularly and are recorded and monitored appropriately Minimum practice: Best practice: Safety office template used Documented risk assessments for all (https://www.safety.ncl.ac.uk/riskassessme practices and processes nt.aspx) Risk assessments are reviewed when appropriate Staff can access risk assessments and are made aware of local hazards and training Corrective and preventative actions are taken where necessary and improvements in place are made GQ8 Last printed 08/02/2016 20:04 Page 76 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 PART 3 – PREMISES, FACILITIES AND EQUIPMENT STANDARDS 3. PFE1 Premises, Facilities and Equipment Standards The premises are fit for purpose Minimum practice: Best practice: A risk assessment has been carried out of the premises to ensure that they are appropriate for the purpose Policies are in place to reviewed and maintain the safety of staff, authorised visitors and students Where appropriate, policies are in place to ensure that the premises are of a standard (and maintained to that standard) that ensures the dignity of deceased persons The premises have sufficient space for procedures to be carried out safely and efficiently Policies are in place to ensure that the premises are secure and confidentiality is maintained PFE2 Biobanked samples and associated data should be in restricted areas (e.g. locked cabinets, card key access, password protected databases). Environmental controls are in place to avoid potential contamination Appropriate separation of relevant material Air classification system and maintenance of air quality including control and monitoring of environmental conditions Documented cleaning and decontamination procedures PFE3 Risk assessment may be in place to assess risk associated with sample use/handling Staff are provided with appropriate protective equipment and facilities that Visitors don protective garments to minimise risk of contamination the same level as staff, even if they are not in direct contact with the samples. There are appropriate facilities for the storage of bodies, body parts, tissues and cells, consumables and records Relevant material, consumables and records are stored in suitable Fridges/freezers are locked when in environments and precautions are taken areas assessable to general to minimise risk of damage or theft and laboratory personnel. ensure the security of holdings EMS (environmental monitoring Critical storage conditions are monitored systems) in place to facility conditions and recorded (e.g. temperature, humidity) Last printed 08/02/2016 20:04 Page 77 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 3. Premises, Facilities and Equipment Standards PFE4 PFE5 Alarm system is checked for correct working on a minimum once a month basis. Web based Freezer temperature is recorded by an independent device on a 24 hour basis. Records indicate exact location of the sample including for example building (storage facility) & freezer Fire safes used for backup tapes and system software for critical equipment and for critical documentation e.g. validation documentation, backup manual procedures for emergency use. System to deal with emergencies on a 24 hour basis UPS (Uninterruptible Power Supply) available to storage area Provision of formal contingency plan (e.g. as a SOP) with clear roles and responsibilities and back-up arrangements e.g. 3rd party providers Systems are in place to protect the quality and integrity of bodies, body parts, tissues and cells during transport and delivery to a destination Documented policies and procedures for the appropriate transport of relevant MTA in place material, including a risk assessment for transportation A system is in place to ensure that traceability of relevant material is maintained during transportation Records of transportation and delivery Records are kept of transfer agreements with recipients of relevant material Records are kept of any agreements with courier or transport companies Equipment is appropriate for use, maintained, quality assured, validated and where appropriate, monitored Records of calibration, validation and maintenance, including any agreements with maintenance companies Users have access to instructions for equipment and receive training in use and maintenance where appropriate Staff aware of how to report an equipment problem Contingency plan for equipment failure Last printed 08/02/2016 20:04 Page 78 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 PART 4 – DISPOSAL 4. D1 Disposal Standards There is a clear and sensitive policy for disposing of human organs and tissue Minimum practice: Best practice: Documented storage policy Efforts should always be made to prevent unnecessary sample disposal (e.g. seek extended consent for use) to prevent wastage and make best use of tissue. Clinical waste must be disposed of separately from general waste to demonstrate respect for material Policy is made available to the public Compliance with health and safety recommendations D2 Disposal is documented The reason for disposal and the methods used are carefully documented Tracking database includes all tracking to exhaustion of sample in use including any processing derivatives made, transfer to another establishment or disposal with comment. Tissue bank databases record the reason for, and date of, disposal of tissue samples. Standard Operating Procedures (SOPSs) for tracking the disposal of relevant material detail the method and reason for disposal Where applicable, disposal arrangements reflect specified wishes Last printed 08/02/2016 20:04 Page 79 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2.4 APPENDIX B – Glossary Acquisition: The collection and receipt of human samples. Consent from the donor must be in place unless exemptions to the consent provisions under the HT Act apply. Adverse event/incident: An event or incident that may, or has the potential to, result in the theft, damage or loss of human samples or may compromise the University’s compliance with the licensing obligations under the HTA, or with the codes of practice as issued by the HTA, or the good governance and output of research using human samples. Appropriate Consent: This must be in place to use and store relevant material, taken from the living or the deceased for research and to hold bodily material with the intention of analysing its DNA. The HT Act defines appropriate consent in terms of the person who may give consent. This is either the consent of the person concerned (the donor of the human samples), their nominated representative or (in the absence of either of these) the consent of a person in a qualifying relationship with the donor (e.g. spouse or partner; parent; child; etc.). Audit: The evaluation of a system, process or procedure in order to ascertain its effectiveness and the validity and reliability of the information. Biobank: a collection of human tissues, cells and blood that can be used for medical research, or for other purposes. It can contain many different types of biological samples (e.g. tissue samples, DNA and blood) and information (e.g. health records, diet and lifestyle information, and family history of disease, gender, age, and ethnicity). Designated Individual (DI): The named individual designated for the licence as the person under whose supervision the licensed activity is authorised to be carried out. This person is responsible for ensuring that other persons to whom the licence applies are suitably trained and qualified; that suitable practices are carried out in the course of carrying-on the licensed activity; and for compliance with the conditions of the licence. The HTA must be satisfied as to the suitability of the person nominate as DI. Disposal: The permanent removal or destruction of human samples previously used and/or stored for research. Existing Holdings: September 2006. Human samples (relevant material) held immediately prior to 1st Hub site: HTA term for the main site under a licence, this is the Medical School for the Newcastle University Research Licence. Human Tissue: Any and all constituent parts of the human body formed by cells. Human Tissue Act 2004 (HT Act): Legislation that regulates the removal, storage and use of human tissue, defined as material that has come from a human body and consists of, or includes, human cells. The HT Act covers England, Wales and Northern Ireland, although the use of DNA extends to Scotland. Consent is the fundamental principle of the legislation and underpins the lawful removal, storage and use of body part, organs and tissue. Different Last printed 08/02/2016 20:04 Page 80 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 consent requirements apply when dealing with tissue from the deceased and the living. The HT Act lists the purposes for which consent is required (Scheduled Purposes). Human Tissue Authority (HTA): The independent regulator established by the HT Act to protect public confidence by ensuring human tissue is used safely and ethically, and with proper consent. The HTA licenses and inspects organisations that collect, store and use human tissue for the Scheduled Purposes, for which consent from the donor is required (unless exemptions apply). HTA Codes of Practice: Provide guidance and lay down expected standards for each of the sectors regulated by the HTA (e.g. research) and under the HT Act. They are designed to support professionals by giving advice and guidance based on real-life experience. The most recent code for Research, along with revisions of previously published codes, were approved by Parliament in July 2009 and came into force on 15 September 2009. HTA Standards: Core standards in four key areas that must be met for an organisation to obtain an HTA licence, relating to the provisions in the HT Act and the regulatory requirements: Consent; Governance and Quality Systems; Premises, Facilities and Equipment; Disposal. Licence Holder: The person or corporate body responsible for applying for the Licence and who would also apply to vary the Licence e.g. to change or substitute the DI. In the case of a corporate body, a named individual will act as its representative. The HTA must be satisfied as to the suitability of this person and prefers individual licence holders to be more senior than the DI. Material transfer agreement (MTA): Agreement established between organisations that govern the transfer of one or more materials from the owner (or authorised licensee) (‘the provider’) to a third party (‘the recipient’) who may wish to use the material for research purposes. Newcastle Joint Research Office (NJRO): The NJRO is a partnership that bridges researchers in both Newcastle University and Newcastle Hospitals supporting the joint development, implementation and successful delivery of world-class research. Person Designated (PD): A person to whom the Licence applies, and who is named on the licence. In the Medical School, there is a PD for each group storing human tissue under the licence. At the satellite sites, there are lead PDs who co-ordinate and monitor compliance within their site. The PD assists the DI in supervising the licensable activities within their groups. Principal Investigator (PI): Is the appropriately qualified individual at each project site who has responsibility for the conduct of the project at that site. Procurement: The process by which tissues and cells are made available, including the physical act of removing tissue and the donor selection and evaluation. Quality Assurance and Development Manager (QADMM): The individual responsible for providing leadership and drive in coordinating and maintaining the governance support for research using human tissues, including samples registered under the Newcastle University HTA Research Licence and across the Faculty of Medical Sciences Last printed 08/02/2016 20:04 Page 81 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Quality Management System (QMS): Centralised governance framework policies, procedures, training, provision of advice and guidance, documentation and data records relating to all aspects of acquisition, storage, use and disposal within their organisation. Relevant Material: Material other than gametes, which consists of or includes human cells. In the Human Tissue Act, references to relevant material from a human body do not include: a) embryos outside the human body b) hair and nail from the body of a living person c) cell lines d) any other human material created outside the human body e) serum, plasma, DNA and RNA. The HTA has produced a supplementary list of materials on which guidance as to their status as relevant material has been given. This list is not intended to be exhaustive or exclusive. Research: A study which addresses clearly defined questions, aims and objectives in order to discover and interpret new information or reach new understanding of the structure, function and disorders of the human body. Research attempts to derive new knowledge and includes studies that aim to generate hypotheses, as well as studies that aim to test them or develop practical applications of new knowledge. Research Ethics Committee (REC): An National Research Ethics Service committee established to advise on matters which include the ethics of research investigations on relevant material which has come from a human body. Research Tissue Bank (RTB): A tissue collection which has gained generic ethical approval for a broad range of future, yet unspecified research within a given scope. Sample label: Indelible and unique identification code securely attached to the container holding each individual human sample which must be appropriate to the storage conditions. Sample Tracking: Process by which all human samples can be identified and traced from their acquisition through to their disposal. Satellite site: Premises within the same organisation on a different site to the main (hub) site, that is under the same governance processes and quality management system, and supervised by the same Designated Individual. Scheduled Purposes: The activities relating to the removal, storage and use of human organs and other tissue that require consent, listed in Schedule 1 of the HT Act e.g. research in connection with disorders or the functioning of the human body. Service level agreement: Agreement that exists between a client and their service provider(s) detailing the level of service that will be provided. Standard Operating Procedure (SOP): Detailed, written instructions to achieve uniformity of the performance of a specific function which is an integral part of the quality management system. In the context of research using human samples, the centralised SOPs document Last printed 08/02/2016 20:04 Page 82 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 all the processes that affect the quality and safety of those samples e.g. acquisition, storage, transfer and disposal. Storage: The holding of human samples securely in appropriate facilities and under appropriate controlled conditions to ensure the integrity and traceability of the samples and protect the health and safety of the individuals handling them. Samples which are relevant material and are not subject to licensing exemptions (e.g. held for the purposes of a RECapproved research project) must be held under an HTA licence. Virtual Research Environment (VRE): An electronic cloud set up via the Newcastle University Research Tools system, to electronically store quality documents. Last printed 08/02/2016 20:04 Page 83 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2.5 APPENDIX C– List of “Relevant Materials” under the HTA For the most up to date list, please always refer to the HTA website (www.hta.gov.uk) : The following material was accessed from the above website on 28th September 2012. 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 Relevant materials for the purposes of the Human Tissue Act 2004? Antibodies No Artificially created stem cells* No Bile Yes Blood Yes Bone Marrow Yes Bones/Skeletons Yes Brain Yes Last printed 08/02/2016 20:04 Page 84 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Breast Milk*** Yes Breath Condensates and exhaled gases No Buffy coat layer (interface layer between plasma and blood cells when blood is separated) Yes Cell lines** No Cells that have divided in culture No CSF (Cerebrospinal fluid) Yes Cystic fluid Yes DNA No Eggs* No Embryonic stem cells (cells derived from an embryo)** No Embryos (outside the body)* No Extracted material from cells, e.g. nucleic acids, cytoplasmic fraction, cell lysates, organelles, proteins, carbohydrates and lipids. No Faeces Yes Fetal tissue Yes Fluid from Cystic lesions Yes Gametes* No Hair (from deceased person) Yes Hair (from living person) No Joint Aspirates Yes Lysed Cells No Mucus Yes Nail (from deceased person) Yes Nail (from living person) No Nasal and Bronchial Lavage Yes Non blood derived stem cells (i.e. derived from the body) Yes Non fetal products of conception (i.e. the amniotic fluid, umbilical Yes Last printed 08/02/2016 20:04 Page 85 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 cord, placenta and membranes) Organs Yes Pericardial fluid Yes Plasma No Please note: Depending on how plasma is prepared and processed, it may contain small numbers of platelets and other blood cells. If any of these cells are present then the plasma must be regarded as relevant material). Platelets Yes Pleural fluid Yes Primary cell cultures (whole explant/biopsy present) Yes Pus Yes RNA No Saliva Yes Serum No Skin Yes Sperm* No Sputum (or Phlegm) Yes Stomach contents Yes Teeth Yes Tumour tissue samples Yes Umbilical cord blood stem cells Yes Urine Yes * 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 Last printed 08/02/2016 20:04 Page 86 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 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. Last printed 08/02/2016 20:04 Page 87 of 95 2.6 APPENDIX D –Copy of the Newcastle University Research HTA Licence 2.6.1 Hub Licence Last printed 08/02/2016 20:04 Page 88 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2.6.2 Satellite licences Last printed 08/02/2016 20:04 Page 89 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Last printed 08/02/2016 20:04 Page 90 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Last printed 08/02/2016 20:04 Page 91 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Last printed 08/02/2016 20:04 Page 92 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 2.7 APPENDIX E – Document Revision History Section affected Description of changes Reason for change Page 1 Removal of terminology Newcastle Biomedicine Biobank Due to rebranding to remove the NBB brand – due in July 2015. Throughout Removal of the NBB code. All SOPs have been renamed “HTA”. Rebranding of the NBB. All documents will now be named HTA under the Newcastle University HTA licence. Change of title of QA Manager to Quality Assurance and Development Manager (QADM) Page 7 Scope section added as new section 4& transfer of table 2 “HTA licences held in Newcastle” moved from page 12 of previous edition, to this section. Change in job title of QA Manager Not present in previous versions. Table is required up front to summarise the different contact details for other licences. The numbering of all subsequent sections has been affected (increased by 1) 5.1. What is the HTA section – wording on the background of the HTA added to say “and many other trusts” To clarify that the Redfern report found the retention of human tissue was widespread throughout the NHS and not restricted to the BRI or Alder Hey. 5.1.2.1 Moved from 4.2.3 in previous version – title “Do I need a human tissue act licence removed” and changed to “Categories of relevant material” This section sits better under the Relevant Material definition, and provides clarity on the different categories of this material 5.2. Licensing. Sentence added to stress that this quality manual related only to the research sector Figures 3 & 5 moved to fit into the licensing section – now Figure 3 & 4 due to reordering. For clarity and flow of information. 5.2.2 Premises section moved up (previously section 4.2.5) in document & clarity that premises are licensed, not people Flow of information and clarification that people do not require to be individually licensed. 5.2.3. Table updated - taken directly from Code of Practice 1, Consent. To harmonise with HTA codes of Practice. 5.2.4 Title changed from exemptions to” licensing” exemptions, and moved up from section 4.2.7. To distinguish between other sections called exemptions. 5.3 Title changed from “what are the consequences of not complying with the licence” to “Consequences of non compliance with the Act” To make this title easier to identify and less wordy. Last printed 08/02/2016 20:04 Page 93 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Section affected Description of changes Reason for change 6.2. Institute for Ageing and Health Brain Tissue Resource renamed CAV For consistency with HTA licence nomenclature 6.3 Introduction added to the section. Research Tissue Bank Manager role added, and QADM added Clarification of RTB Manager role, and new job title for QADM. Section split into sub sections for each role. For ease of search from the main contents page. Removal of section on “what does this mean for researchers” This is covered in new section 6.3.4 (Responsibilities of all other staff working under the licence) The wording “also known as a RTB” added to biobank Consistency with ethics documentation and HRA terminology Removal of Central Biobank contact details Due to rebranding of the NBB and changing information 7.1.2 Section updated to include collection from NHS and non-NHS patients Missing in last version. To clarify that different types of REC exist – recognised NHS RECs and University RECS, which have different implications on the HTA. 7.1.2.1 Setting up a new RTB section added Missing in last version and required for further support for researchers. 7.2.3 Table on types of consent added Omitted in last version, and to harmonise with the Newcastle University website which contains this information. Page 30 Sentence added to state that research tissue banks can include relevant and non-relevant material Omitted in last version. 8 Updated introduction to storage section to clarify that material only requires HTA storage when REC approval is in place from a recognised REC, and clarify that University ethics does not count as an exemption. Details on what constitutes a recognised REC added Missing in last version and essential to the HTA. 9 Introductory sentence on the importance of sample tracking added, plus image of sample tube. Plus new reference to Achiever ISL Sample tracking software. Visual enhancement and flow of information. To add reference to new sample tracking software being rolled out across the Faculty. 9.1 Key principles of sample tracking separated into 4 new subsections, with a new diagram on sample numbering To clarify sample tracking requirements and add a graphic to explain numbering of sub-aliquots, which has been found to be 7.1.1 Last printed 08/02/2016 20:04 Page 94 of 95 Quality Manual for HTA Research Licence (No. 12534) Edition 3.0 – February 2015 Section affected Description of changes Reason for change 9.1.1 New section on assigning unique numbers poorly understood during audits. 9.1.2 New section on tracking records with image of sample tracking database example Image of sample tracking system added as an example to researchers of what databases can look like. 9.1.3 References to SLAs removed SLAs no longer in use. 9.1.4 Safety during transport section added Safety was not included in last version and is an important element. 10 New section on sample use To clarify that sample use is not covered by the HTA, but by the HRA and ethics. Not clear in last version 12.3 Section relabelled Document control, with subsections on each element of control 12.3.2 NJRO website – new section added To enhance the layout of this section 12.3.3. VRE – new section added 12.3.4 HTA Master File – new section added The NJRO website, VRE and HTA Master File are all new since the last version, and must be included. QPulse has also been removed, and all reference to QPulse must be removed. 12.4 Risk assessments now included in the documents supporting the QMS section Risk assessments fit alongside SOPs and other documents supporting the QMS as opposed to a stand-alone section 12.9 Training in Quality Documents added To be clear that training may be face-toface, online, or via reading (absent in previous version) Appendix C Appendix C from previous document (Role Descriptions) removed These documents are now held separately in the HTA Master File and removed from this section for future proofing, should any changes occur. 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