Sample Management in Clinical Trials

Policy Details
Document Type Standard Operating Procedure

KHP-CTO/CT/SOP20.0
Document name
Sample Management in Clinical Trials
Version FINAL v2.0 05/01/2021

Effective from 7th January 2021

Review date 10th January 2023

Owner King’s Health Partners Clinical Trials Office

Prepared by Adam Taylor and Oluwadamilola Otiko

Reviewed by Amy Holton, KHP-CTO Quality Manager

Approved by Jackie Pullen, Director KHP-CTO

Superseded documents FINAL v1.0 13/12/18

Relevant Statutory Instrument 2004-1031

regulations/legislation/guidelines
EMA Reflection paper for laboratories that perform
the analysis or evaluation of clinical trial samples
(2012) (EMA/INS/GCP/532137/2010)

Change History
Date Version Change details Approved by
Number

5th January 2.0 Scheduled review, updated procedure for Jackie Pullen
2021 poorly labelled samples (4.2)

05Jan2021 FINAL version 2.0 Page 1 of 8

Table of Contents

1.0 GLOSSARY ................................................................................... 3

2.0 BACKGROUND AND PURPOSE .................................................. 5
3.0 SCOPE .......................................................................................... 5
4.0 PROCEDURE ................................................................................ 5
4.1 General Requirement for Sample Management ......................... 5
4.2 Samples Labelling ........................................................................ 6
4.3 Sample Storage ............................................................................ 6
4.4 Sample Tracking ........................................................................... 6
4.5 Sample Transport and Receipt .................................................... 7
4.6 Sample Processing ...................................................................... 7
4.6.1 Repeat Analysis ........................................................................................... 7
4.6.2 Unblinding and Blinding ............................................................................... 7
4.7 Sample Disposal or Long Term Storage ..................................... 7
5.0 RELATED TEMPLATES ................................................................ 8
5.1 Temperature Log .......................................................................... 8
5.2 Nitrogen Vessel Storage Log ....................................................... 8
5.3 Sample Tracking Log ................................................................... 8
5.4 Sample Transfer Log .................................................................... 8
5.5 Sample Disposal Form ................................................................. 8
6.0 RELATED DOCUMENTS .............................................................. 8
6.1 EMA Reflection paper for laboratories that perform the analysis
or evaluation of clinical trial samples (2012)
(EMA/INS/GCP/532137/2010).............................................................. 8
6.2 MHRA Good Clinical Practice Guide, Chapter 13 (2012) ........ 8
7.0 APPROVAL and SIGNATURE ...................................................... 8

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1.0 GLOSSARY

Chief Investigator (CI) - A Registered Physician, Dentist, Pharmacist or Registered

Nurse/Midwife who has overall responsibility for the conduct of the trial.
Clinical Research Associates (CRAs) – Part of the KHP-CTO Quality Team. Ensure
compliance with the Regulations, GCP and SOPs, by monitoring clinical trials.
Clinical Trial - Any investigation in human participants, other than a non-interventional trial
intended to discover or verify the clinical, pharmacological or other pharmacodynamic effects
of one or more medicinal product and/or to identify any adverse reactions to one or more such
products and/or to study absorption, distribution metabolism and excretion in one of more such
products with the object of ascertaining the safety and/or efficacy of those products.
Clinical Trial Samples - Any biological sample collected from a human participant of a clinical
trial, as required by the protocol. Samples may include but are not limited to: blood, plasma,
serum, urine, faeces, tissues and cells.
• This includes samples that are defined by the Human Tissue Act as Relevant or Non-
relevant material.
• This includes newly acquired samples as well as those in archived and existing
collections.
Co-Sponsors – Where two or more organisations take responsibility for the initiation,
management and financing (or arranging the financing in relation to) a clinical trial. Co-
Sponsors should decide which organisation will assume responsibility for carrying out the
Sponsor functions of that trial and document this accordingly.
Computer Systems – For the purpose of this SOP, computerised systems are defined as
systems (software) that collect data in electronic form and create, modify, maintain, archive,
retrieve, or transmit that clinical data.
Curriculum Vitae (CV) - A summary of a person’s education, professional history and job
qualifications.
Good Clinical Practice (GCP) - as defined in the Regulations.
Investigational Medicinal Products (IMP) - means a pharmaceutical form of an active
substance or placebo being tested, or used as a reference in a clinical trial. This includes a
medicinal product which has a marketing authorisation but is, for the purposes of the trial -
(a) used or assembled (formulated or packaged) in a way different from the form of the
product authorised under the authorisation,
(b) used for an indication not included in the summary of product characteristics (or
equivalent document) under the authorisation for that product, or
(c) used to gain further information about the form of that product as authorised under the
authorisation

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Investigator Site File (ISF) – A standard filing system which contains all essential documents
held by Principal Investigator(s) conducting a trial which individually and collectively permit the
evaluation of the conduct of a trial and the quality of the data produced.
King’s Health Partners (KHP) - King’s Health Partners Academic Health Science Center is a
pioneering collaboration between one of the King’s College London (University) and three of
London’s most successful NHS Foundation Trusts – Guy’s & St Thomas’, King’s College
Hospital and the South London & Maudsley.
King’s Health Partners Clinical Trials Office (KHP-CTO) - Established in 2006 by King’s
College London, Guy’s & St Thomas’ NHS Foundation Trust, South London and Maudsley NHS
Foundation Trust and King’s College Hospital Foundation Trust to provide a streamlined
approach for all aspects of trial administration.
KHP-CTO Quality Team – Comprises the Clinical Quality Manager, Clinical Research
Associate(s), Clinical Trial Administrator(s), Systems Executive, Training Executive(s) and
Training Assistant.
KHP-CTO Standard Operating Procedures (SOPs) - "Detailed, written instructions to achieve
uniformity of the performance of a specific function," SOPs are the base on which Quality
Systems and Processes are conducted and monitored against.
Monitoring Plan (MP) – A document written by the CRA detailing how all the monitoring
activities for the trial will be carried out based upon the trial risk assessment.
Principal Investigator (PI) - A Registered Physician, Dentist, Pharmacist or Registered
Nurse/midwife who has responsibility for the conduct of the trial at a site.
Quality Assurance (QA) - Systems and processes established to ensure that a trial is
performed and the data are generated in compliance with GCP.
Quality Control (QC) - The operational techniques and activities undertaken within the quality
assurance system to verify that the requirements for quality of the trial-related activities have
been fulfilled.
Research & Development Dept. (R&D) – NHS department responsible for confirmation of
capacity and capability for all clinical research.
Research Ethics Committee (REC) – The REC that undertakes the review of the research
protocol, including the content of the patient information sheet and consent form rather than
just site specific approval for each centre.
Serious Breach of GCP - a “serious breach” of the principles of GCP that is likely to affect to
a significant degree, the safety or physical or mental integrity of the participants of the trial; or
the scientific value of the trial.
Sponsor - The organisation who takes responsibility for the initiation, management and
financing (or arranging the financing) in relation to a clinical trial. The Sponsor organisation
has responsibility for carrying out the sponsor functions of that trial (as defined in the
Regulations).
Standard Operating Procedures (SOPs) – “detailed, written instructions to achieve uniformity
of the performance of a specific function,” SOPs are the base on which Quality Systems and
Processes are conducted and monitored against.
The Regulations - The Medicines for Human Use (Clinical Trials) Regulations 2004,
transposed the EU Clinical Trials Directive into UK legislation, as Statutory Instrument 2004

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1031. This became effective on the 1st May 2004. An amendment to implement Directive
2005/28/EC was made to the Regulations as Statutory Instrument 2006 no 1928. As amended
from time to time.
Trial Master File (TMF) - A standard filing system which allows the effective storage and
location of essential documents, that is the large volume of regulatory documents and
approvals needed for clinical research. The filing system can be in the form of a single project
file or a number of files/filing cabinets, depending on what is deemed most appropriate for a
particular clinical trial given its size and complexity. The regulatory documents and approvals
within the TMF will be maintained alongside case report forms and source documentation.

2.0 BACKGROUND AND PURPOSE

The purpose of this SOP is to describe the management of laboratory samples taken for
protocol endpoint analysis in clinical trials, is in accordance with the study protocol, GCP and
applicable regulations and associated guidance.

3.0 SCOPE
All clinical trials sponsored by one or more of King’s Health Partners Organisations, or clinical
trials where the sponsor responsibilities are managed by the KHP-CTO, where laboratory
samples are collected for the purpose of assessing protocol endpoints. These include:

• samples collected as routine clinical care, but also contribute to trial endpoint analysis..
• samples collected and managed for study objectives only.
• samples prepared and stored before shipping to a specialist laboratory.
• samples collected for use in an exploratory/experimental assay.

Samples managed by the local hospital or clinical laboratory as per routine standard of care,
that do not contribute to protocol endpoint analysis, are outside the scope of this SOP.
However, reference ranges and Clinical Pathology Accreditation (or equivalent) certificates will
be filed within the trial TMF.

4.0 PROCEDURE

4.1 General Requirement for Sample Management

The trial sponsor is responsible for ensuring that laboratories managing sample analysis
comply with the principles of GCP. It is the responsibility of the Laboratory Manager (or
delegate) to ensure that samples are managed by an appropriately delegated, trained and
qualified member of the trial team.

Clinical Trial Samples will be collected and processed in accordance with the approved trial
documents – i.e. protocol, Participant Information Sheet & Consent form and in accordance
with documented consent given by the participant.

Instructions and processes for key activities relating to the management of samples may be
detailed in the protocol or separate laboratory manual, work instruction, analytical protocol or

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analytical plan. If a document other than the protocol is utilised it must be written in accordance
with the protocol (and any subsequent amendments), be reviewed by the KHP-CTO CRA (or
delegate) and approved by the Laboratory Manager (or delegate). The agreed sample
management document must be in place prior to any sample management being undertaken
for a trial.

Where samples are to be sent to an external organisation for storage or analysis, a contract
must be in place prior to any sample shipment.

In order to fully reconstruct laboratory work, records must be maintained, including records for
the preparation of buffers, standards and reagents required by the analytical method. This is to
ensure that the quality of the reagents are traceable and that they were fit for purpose. In
addition, the equipment to be used must be fit for purpose and there must be records to
demonstrate the calibration and maintenance of equipment used to measure trial parameters.

4.2 Samples Labelling

Clinical Trial Samples should be labelled clearly with information regarding trial identification,
participant ID, date and time of collection and the type of specimen. Steps should be taken to
ensure that label information remains intact during sample storage. If samples are poorly
labelled or missing the CI and Sponsor must be informed. Any poorly labelled samples should
not be analysed until it has been identified (unless delay in processing would lead to
degradation of the sample in which case analyse sample and quarantine results until identity
established). If the identity of the sample cannot be established the result should not be
reported and the sample must be destroyed.

4.3 Sample Storage

A system for recording the storage conditions within the fridge/freezer or other containment
method must be in place to ensure storage conditions are kept within defined limits and meet
protocol requirements. Temperature logs for sample storage will be reviewed by the KHP-CTO
CRA as described in the monitoring plan.

A copy of all temperature logs will be filed in the Laboratory File at the end of the study.

In the event of a temperature excursion, a system must be in place to report and record any
temperature excursions and corrective actions taken such as moving samples to a backup
location. Temperature excursions in storage / transit should be recorded and retained in the
TMF / ISF to be reviewed by the KHP-CTO CRA at intervals specified in the monitoring plan.

4.4 Sample Tracking

It is a requirement to provide a chain of custody and audit trail of samples from collection to
disposal by way of sample tracking.

Automated systems or manual sample tracking logs can be used to track samples (see 5.3
template Sample Tracking Log).

Sample tracking logs must be retained in the TMF / ISF to be reviewed by the KHP-CTO CRA
at intervals specified in the monitoring plan.

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4.5 Sample Transport and Receipt
If samples are transported for storage or analysis, documentation detailing the date of shipment,
the number of samples being shipped and the nature of the samples will be maintained and filed
within the ISF or TMF as appropriate

Details for shipment conditions and packing materials will be described in the protocol or agreed
sample processing document.

The laboratory receiving the samples will provide a signed receipt confirming that the correct
number of samples have been received in an appropriate condition.

Details of all shipments and receipts will be filed in the TMF/ISF and reviewed by the KHP-CTO
CRA as detailed in the study specific monitoring plan. The sponsor and the CI will be notified of any
issues identified during sample shipment.

4.6 Sample Processing

An approved and validated sample handling and analysis process must be in place at the
laboratory prior to the conduct of sample handling or analysis.

Data from analysis must be recorded accurately, legibly and promptly. A QC check will be
conducted and documented to confirm the accuracy of the data.

4.6.1 Repeat Analysis

There may be instances where repeat analysis of specific samples or batches is required e.g.
in the case of equipment failure. Repeat analysis must only be undertaken in accordance with
a written procedure which will include reasons for the repeat analysis, authorisation decisions
for repeat analysis and how the repeat analysis will be conducted. Appropriate documentation
for the rationale behind the decision, the original and results, along with the reason why one
result is accepted over the other must be maintained in the TMF and must be reflected in the
final study report.

4.6.2 Unblinding and Blinding

The KHP-CTO CRA or delegate must ensure that measures are taken to protect the integrity
of the blind with respect to sample analysis. This will include ensuring that laboratory data are
only communicated to appropriate members of the trial team.

4.7 Sample Disposal or Long Term Storage

Once an End of Study notification has been submitted. All remaining samples will be disposed
of or transferred for long term storage, in an appropriate HTA licensed area, in accordance with
the trial protocol, ethical approval and each participant’s consent status.

Samples must be either disposed of or transferred to long term storage within twelve (12)
months of the End of Study notification or the time specified in ethics application.

If consent has been given for storage for future research or biobanking, relevant samples must
be transferred to suitable storage within a Human Tissue Authority (HTA) licensed premises.
Consent forms must be retained for the duration of sample storage.

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Sample disposal must be documented and retained by the laboratory.

All documents pertaining to sample management must be retained by the laboratory.

5.0 RELATED TEMPLATES

5.1 Template Temperature Log

5.2 Template Nitrogen Vessel Storage Log

5.3 Template Sample Tracking Log

5.4 Template Sample Transfer Log

5.5 Template Sample Disposal Form

6.0 RELATED DOCUMENTS

6.1 EMA Reflection paper for laboratories that perform the analysis
or evaluation of clinical trial samples (2012)
(EMA/INS/GCP/532137/2010)

6.2 MHRA Good Clinical Practice Guide, Chapter 13 (2012)

7.0 APPROVAL and SIGNATURE

07 January 2021
_________________________________ _________________
Jackie Pullen Date
Director
King’s Health Partners Clinical Trials Office

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