Department of Molecular and Clinical Cancer Medicine

Liverpool GCLP Facility: Good Clinical Laboratory Practice

Good Clinical Laboratory Practice (GCLP) is a quality standard for the analysis of clinical trial samples which incorporates the legal requirements of Good Clinical Practice (GCP). Liverpool GCLP Facility aims to produce transparent, reliable, reproducible results whilst also giving traceability, auditability and accountability. Liverpool GCLP Facility is developing and building on current systems to ensure GCLP compliance and excellent standards.

GCP is a legal requirement governing translational research with samples from participants on clinical trials. To police this, GCP laboratory facilities are subject to spot inspections by the MHRA. The MHRA have published a description of the legal requirements for such facilities (July 2009) that is subject to inspection. The legal requirements include proof of fitness for all equipment (e.g. service and maintenance contracts) and audit evidence that management have provided a quality assurance programme.

Experimental Cancer Medicine Centres (ECMCs) were established by Cancer Research UK and the Department of Health (NIHR) with the aim of offering laboratory support to early phase clinical trials directed towards the cure or relief of any form of Cancer. ECMC status was awarded to Liverpool in April 2007. The ECMC worked with the Liverpool Cancer Trials Unit which co-ordinates national and international trials. On this basis, a biobanking and biomarker facility was established in the Liverpool ECMC, compliant with the standards of GCP. A major focus of the Liverpool ECMC within its first year was the establishment and equipping of dedicated laboratories for sample collection and analyses from clinical trials to the standard of GCLP. The facilities were further expanded in 2009, now comprising the main GCLP Laboratory, Instrument Room, Molecular Biology Laboratory, Microbiology Laboratory and Biobank Freezer Room. There are three core research technicians and a postdoctoral research fellow appointed. There is also a Quality Assurance Manager to ensure GCLP compliance. In addition, University of Liverpool staff, working on diverse clinical trials, have been inducted and use the facility.

In the GCLP facility all work is carried out using Standard Operating Procedures (SOPs) produced before work can begin, they are version controlled and dated and signed by the authors and by a Quality Assurance (QA) Manager (funded by the Cancer Research UK Centre). All staff allowed to work in the GCLP facility will have to provide evidence of regular training in GCP as it applies to the laboratory Equipment used in the GCLP facility is all quality controlled on installation (IQ) and in use for the purpose specified, the latter requiring an independent Operational Quality (OQ) certification and Performance Quality (PQ) control. Records of the quality control and maintenance of equipment are stored and can be cross-referenced with laboratory books. All this means that any experiment can be inspected with the confidence that a commitment to use a given protocol was made before the experimental data was obtained and the all data was stored including data on failed experiments.

GCP requirements include constant monitoring of all storage conditions and meticulous longitudinal recording of all environmental changes that might affect each and every sample.

Thus the GCLP facility, Liverpool, not only endeavours to ensure that sample collection, storage, analyses and reporting comply with the law, but is in itself a centre of excellence for quality assured research.

The Liverpool ECMC now operates under the name Liverpool Early Drug Development Unit (LEDDU). LEDDU was set up in 2012 leading on from the establishment of GCLP laboratories and Core Facilities for Biological Tissue Storage (also working to GCLP). There are dedicated LEDDU Clinical Beds that undertake phase I and phase I/II trials.

Clinical trials, particularly Randomised Control Trials (RCTs) offer the gold standard for determining if a remedy or investigation really offers a benefit. They fundamentally require that the research is unbiased. The International Conference on Harmonization [ICH] for Good Clinical Practice [GCP] established the need to make trials auditable with rigorous vetting of protocols and clear requirements to follow these protocols. The guidelines also established a chain of responsibilities leading from the researcher all the way up to the sponsor. EU Directives were formulated in 2001 (2001/20/EC) and 2005 (2005/28/EC) to allow for enforcement of GCP guidelines. These were passed into UK law as statutory instruments (SI) 1031, 1928, 2984 and 2031. Enforcement of the new statutes in the UK was delegated to the Medicines and Healthcare Products Regulatory Agency (MHRA). Guidance for the maintenance of regulatory compliance in laboratories that perform the analysis and evaluation of samples from clinical trials were published by the MHRA in July of 2009. The EU directives and UK statutory instruments will be replaced by new EU clinical trial regulations in 2016.

The purpose of the Liverpool GCLP facilities is to collect, store and analyse samples from trials. The assumption is that all samples that could impact on evaluation of trial outcomes would be covered by the new clinical trial legislation and should be amenable to MHRA inspection.

The GCLP facility will support any study subject to adoption by the Liverpool Cancer Trials Unit, the Pancreas Biomedical Research Unit or the Cancer Research UK Early Drug Development Unit. It currently services 22 clinical trials.

The Operational Director of the GCLP facility (Dr Bill Greenhalf) sits on the ECMC Quality Assurance and Translational Science (QATS) Steering Committee and is involved in setting up guidelines for biobanking through the Confederation of Cancer Biobanks.

GCLP Facilities

1) Main Laboratory

– Sample reception, processing

– Cell/Tissue Culture laboratory

– DNA robots

– Preparation area

– Analysis (Luminex, Microbeta, ELISA).

2) Instrument Room

– Mass spectroscopy

– FACS Analyser.

3) Molecular Biology Laboratory

4) Microbiology Laboratory

5) Freezer Room (Biobank)

• Storage of patient samples from diverse cancer clinical trials.

• Downstream processing of patient samples.

• Translational analysis

– DNA

– RNA

– Proteomics.