Research using Human Samples Knowing your Responsibilities Professor John Davey, Designated Individual (HTA Licence) Gemma Wild (Administration Officer)

Challenges Who is using human samples in their research ? What samples are they using ? What research are they doing ? Where are the samples from ? Was there consent to collect the samples ? Is there ethical approval to use the samples ? Are the samples stored appropriately and securely ? How is the use of the samples tracked ? What is the quality of the samples ? Do we need to consider all human samples ? Are the HT Act and the HTA Licence the same ? Do we have enough storage space as we increase research ?

Aims of the presentation The presentation aims to: Outline the Human Tissue Act, 2004 Describe UoW approach to research with human tissue Seek input to further inform the process Following this session, you will: Have an overview of the Human Tissue Act 2004 Know when the Act applies Understand what constitutes best practice Be armed with advice to support compliance Know where to find help

Human Tissue Regulation Provides a framework for research with human tissue: Removal Retention Use Disposal Legislation is enacted through the Human Tissue Act Previous legislative framework includes: Human Tissue Act 1961 Anatomy Act 1984 Human Organ Transplants Act 1989.

Human Tissue Authority The HTA enacts the Human Tissue Act. It licences organisations that store and use human tissue. There are 5 licensed sectors: Human application Post-mortem services Research Anatomy Public display Arms Length Body Review Functions will continue, but transferred to other organisations Risk

Warwick’s HTA Licence Our licence covers storage/use of human tissue for research. Hub = CSRI at UHCW Satellite = Gibbet Hill Key individuals Licence Holder’s RepresentativeJon Baldwin (Registrar) Designated IndividualProfessor John Davey Deputy DIDr Andrew Blanks Person Designated (CSRI)Dr Robert Eason Person Designated (Gibbet Hill)Dr Steve Stanley Roles & responsibilities Licence Holder proposes the DI, approved by HTA DI supervises our activities under the licence Deputy DI and PDs assist the DI in these activities Researcher, Lead Investigator and Person Responsible

Roles and responsibilities Researcher Suitably trained individual responsible for undertaking research involving human samples. Lead Investigator Appropriately qualified individual who has responsibility for the conduct of the research and the human samples being acquired, stored and used on the research project. Usually the Chief or Principal Investigator but who might delegate responsibility for the human samples to a suitably trained Person Responsible. Person Responsible Suitably trained individual responsible for the human samples acquired, stored and used for research, as delegated to do so by the Lead Investigator for the research project.

Human Tissue Act, 2004 – Offences Offences under the act include: Not having appropriate consent Not having appropriate ethical approval Using tissue collected for one purpose for another Carrying out licensable activities without a licence Trafficking in human tissue for transplantation purposes Penalties against individuals and institutions: Conditions/restrictions placed on the licence Suspension/withdrawal of the licence Fines and up to 3 yr imprisonment, or both

Things we need to understand We need to understand the following: Registration (researchers and projects) Relevant material Scheduled purpose Consent Ethical approval Importing samples Storage and tracking Disposal Exporting samples Inspection and audit …understand them in the context of UoW Ongoing, based on discussions with: HTA and NHS Research Ethics Service Researchers (UoW and elsewhere) NHS Research & Development UoW committees (Audit, BREC, UREC) Research Support Services

Our procedures – Quality Manual and SOPs The Quality Manual documents UoW’s Quality Management System for the governance of the acquisition, storage, use and disposal of human samples for research. Standard Operating Procedures: 1.Writing a SOP 2.Consent 3.Acquisition and Transfer 4.Storage 5.Adverse events 6.Disposal 7.Training 8.Audit HTA report “a very good and proportionate set of procedures”

Register of researchers using human material SOP7 – Training We have a ‘register’ of researchers using human material. Researchers need to demonstrate competency. Be familiar with relevant documentation Undergo training relevant to the work Maintain a training portfolio Registration is a 3-stage process: Training session with DI (Knowing your responsibilities) MRC e-learning module ( Complete a ‘declaration’ of registration Registration will need to be renewed every 3 years.

Relevant material – HT licence HT licence - material which consists of or includes human cells. Fundamental principle is that a sample containing even just a single cell from a human body is classified as relevant material. Examples of relevant material under HT licence: Specifically identified relevant material (arms, legs, heads) Bodily waste products (urine, sweat, pus, washings) Cell deposits and tissue sections on slides The following are excluded from the HT licence: Gametes and embryos outside the human body (HFEA) Hair and nail from a living person Cell lines which have divided outside the human body Samples that are more than 100 years old Samples stored incidental to export or processing to acellular (<1 wk) Samples being used for an NHS REC-approved project

Human samples at the University of Warwick ALL human samples are ‘relevant’ under the HT Act: ALL human samples at UoW will be treated as RELEVANT There will be a SINGLE set of policies and procedures These will cover ALL human samples This will provide clarity, consistency and confidence This will permit a more practical approach to tracking We will know what is under our HTA Licence, when required.

Scheduled purpose – research Our licence allows us to carry out ‘research’. Research attempts to derive new knowledge and includes studies that address 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. Our licence covers some other (limited) purposes – Appendix 1. Includes public display, clinical audit, health education & training Research is not: Having a look to see what happens Gathering preliminary data for a grant application Checking something from a paper Seeing if the samples are any good Using up left over material

Register of projects involving human samples We will ‘register’ all projects involving human samples. All projects will require a research proposal: Externally funded projects Internally funded projects Own-funded projects Unfunded projects Research proposals will be captured from various sources: Applications for ethical approval Applications for external funding Applications for internal funding Descriptions of student projects

Consent Consent is a central tenet of the HT Act. It is best practice to obtain consent If this is not possible, seek reassurances and/or consider the issues There is an increasing trend towards ‘generic’ consent Consent is considered in applications for ethical approval The HT Act provides limited and specific exemptions: Old samples (“existing holdings”, prior to Sept 2006) Imported samples (from outside England, Wales, Northern Ireland) Anonymised samples (with NHS REC approval) – Appendix 2 UoW will hold information related to consent for all samples: Patient Information Sheets and consent proforma (ethics application) Individual consent forms can (and will) be requested during audits

Ethical approval Ethical approval is required for all studies using human samples. Ethical approval should be specific and current. Approval can be ‘specific’ for an experiment, project or programme Ethical approval must be granted by one of the following: NHS Research Ethics Committee o NHS patients/data/staff/resources Overseas Ethics Committee UoW Biomedical Research Ethics Committee o Healthy individuals o Overseas studies might need local review (expedited process) Ethical approval is part of the application to Tissue Banks.

Issues to consider about ethical approval When was ethical approval obtained ? Updating NHS REC approvals is straightforward (and fast) What is the ethical approval for ? We need the original ‘full’ application for ethical approval Overseas applications/approvals must be in English Translations need to be by an approved service Is Warwick and/or the researcher named in the application ? Changes should be by amendments not through new applications Amendments should be considered by the original committee NHS REC approvals can be amended easily Amending approvals from overseas committees is possible

Importing human samples into UoW SOP3 - Acquisition and Transfer The Lead Investigator or Person Responsible must: Complete an “Authority to Import Human Samples” form Complete a “Biological Material Risk Assessment” form One set of forms is required for each contractual obligation (MTA) Ongoing collections require forms to be updated annually Import from another organisation requires an agreement (MTA): Prepared by Research Support Services Signed/agreed by an official signatory (RSS Director, not researcher) Names of UoW researchers and their roles/responsibilities What we have agreement to do The length of time the agreement is for Fate of samples at end of agreement (retained, returned, destroyed) Use of the retained samples when the agreement ends

Storing and tracking samples SOP4 – Storage Samples need to be traceable from consent to disposal. You need to demonstrate a sample is what you think it is You need to demonstrate a sample is where you think it is You need to catalogue the location of ALL samples. Information to be recorded on Tissue Register (securely) You need to track EVERY use of EACH sample. Researchers maintain a record of usage in laboratory books (GLP) Tissue Register is updated only when sample is finished/disposed Human samples to be separated from non-human samples.

Tissue Register Tissue Register will record the following details: Sample location (freezer, shelf & rack number) Sample unique identifier code Sample container type Sample type and amount (wt/vol) Name of Lead Investigator or Person Responsible HTA licence status Supplying individual/organisation Import authorisation reference number MTA reference number Date of import Research proposal reference number and/or RSS SAP project code Ethical approval reference and end date Project start date and end date Project completion details Shipment or transportation details

Samples are ACTIVE or STORED Active samples are being used in an ongoing research project Research proposal, consent, custodianship, ethical approval Samples are catalogued on Tissue Register Researchers record the use of samples in lab books Stored samples: Not being used in an ongoing research project There is appropriate consent and/or custodianship Samples are catalogued on Tissue Register Researchers do not have access to STORED samples Access will be available when the samples become ACTIVE

Disposal of human samples SOP6 – Disposal The Lead Investigator is responsible for the disposal of samples. Lead Investigator can delegate responsibility to Person Responsible Disposal of human samples must: Observe due care & respect for the samples, the donor and/or family Be recorded on the “Human Samples Disposal” form Be carried out separately from other waste Human samples to be disposed of should be: Sealed in a separate clear autoclave bag Autoclaved at 131 o C for 30 min Stored in a thick gauge yellow plastic clinical waste bag until collection Tissue Register must be updated following disposal of samples.

Exporting human samples Lead Investigator is responsible for the export of samples. Lead Investigator can delegate responsibility to Person Responsible The Lead Investigator or Person Responsible must: Complete an “Authority to Export Human Samples” form Export to another organisation requires an agreement (MTA): The agreement is to transfer custodianship, not the samples Prepared by Research Support Services and/or Warwick Ventures Signed/agreed by an official signatory (not the researcher) Tissue Register must be updated following export of samples.

Inspection and audit HTA inspection Phase 2 site inspection on 21 & 22 July 2010 Reviewed people, premises, processes and paperwork HTA concluded we are ‘suitable’ to hold our licence They made several recommendations for advice and guidance There is a condition added to our HTA licence: The DI shall ensure that all aspects of the quality manual, SOPs and training programme are implemented. The HTA is likely to make a follow-up inspection in 2011/2012. We are reviewing all human samples, researchers & projects. SOP8 – Audit

We are here to help John Davey (Designated Individual) Tel: Gemma Wild (Administrative Officer) Tel:

Appendix 1 – Other scheduled purposes Our HT licence also covers some other (limited) purposes: Determine the cause of death Establishing after a person’s death the efficacy of any drug or other treatment administered to him/her Public display Clinical audit Education or training related to human health Performance assessment Public health monitoring Quality assurance

Appendix 2 – Anonymisation of samples Relevant material without consent can be used for research. But ALL the following MUST apply: The material came from a living person (when taken) It is anonymous to the researcher It has approval from an NHS Research Ethics Committee Anonymisation The researcher cannot identify the donor Robust coding of samples is acceptable Code must be kept securely by an appropriate guardian