Research using Human SamplesKnowing 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 2004.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 ReviewFunctions 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 individualsLicence Holder’s Representative Jon Baldwin (Registrar)Designated Individual Professor John DaveyDeputy DI Dr Andrew BlanksPerson Designated (CSRI) Dr Robert EasonPerson Designated (Gibbet Hill) Dr Steve Stanley

Roles & responsibilitiesLicence Holder proposes the DI, approved by HTADI supervises our activities under the licenceDeputy DI and PDs assist the DI in these activitiesResearcher, Lead Investigator and Person Responsible

Roles and responsibilities

ResearcherSuitably trained individual responsible for undertaking research involving human samples.

Lead InvestigatorAppropriately 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 ResponsibleSuitably 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 UoWOngoing, 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 SOP2. Consent3. Acquisition and Transfer4. Storage5. Adverse events6. Disposal7. Training8. 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 (www.rsclearn.mrc.ac.uk)• 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 asingle 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 consentIf this is not possible, seek reassurances and/or consider the issuesThere is an increasing trend towards ‘generic’ consentConsent 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 individualso 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 131oC 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: 02476 524204J.Davey@Warwick.ac.uk

Gemma Wild (Administrative Officer)Tel: 02476 968583G.Wild@Warwick.ac.uk

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