Advanced Therapies NHS Readiness Toolkit

A UK Wide Survey of Current Referral Routes and Practices to Identify Gaps in the Referrals Process and Maximise Patient Access to Cell Therapy Clinical Trials

Model Clinical Trials Agreement – This model agreement captures all the specific contractual requirements of ATMP commercial clinical trials for implementation in the NHS.

This Roadmap Tool sets out the key steps and activities in the end-to-end pathway for Advanced Therapy Medicinal Products (ATMPs) in England from non-clinical research through to treatment provision & monitoring

The NIHR Clinical Trial Routemap is an interactive colour-coded tool to help navigate through the legal and good practice arrangements surrounding setting up and managing a Clinical Trial of an Investigational Medicinal Product (CTIMP). The routemap distinguishes between legal and good practice requirements, and indicates which aspects of these are relevant to wider clinical research in general. It includes an overview of trial practices, along with more detailed information available at ‘stations’ along the route.

A proforma outlining considerations for an NHS Trust prior to commencing a cell therapy / immune effector cell trial.

A template produced by The Christie NHS Trust to hold and update frequently asked questions and responses to cell therapy trial feasibility questionnaires.

A proforma for submission to the Manchester Clinical Research Facility (Christie site), which outlines NHS Trust clinical and resource requirements, prior to study set up.

An SOP outlining the procedures for the coordination and delivery of adoptive cellular therapy within The Christie NHS Foundation Trust.

A template of an apheresis weekly cleaning log.

The objectives of this SOP are to ensure products are correctly and consistently labelled to ensure the positive identification of each harvest and facilitate cell chain to track from donation to reinfusion. For products transferred to areas outside the Clinical Apheresis Unit, and those reinfused within the transplant programme.

Nursing assessment form pre-apheresis.

CAR-T checklist proforma for admissions and apheresis, with MDT communication sheet.

SOP regarding the maintenance of a safe environment in a Clinical Apheresis Unit of an NHS hospital.

This SOP aims to ensure that proposed trial protocols, requiring access to Cellular Therapy and Transplant Programme services, are reviewed by the appropriate staff prior to being authorised to open.

Training package to prove nurses with knowledge, skills and expertise to perform specific apheresis procedures for cellular therapy in a safe and professional manner.

SOP to ensure all nursing and medical staff involved in the infusion of cellular products are aware of their responsibilities, the procedure and any action to be taken in the event of adverse reactions or incident.

SOP for safe discharge and follow-up for patients, post Chimeric Antigen Receptor (CAR) T-cell therapy infusion.

Template proforma for medical assessment of patients for bone marrow harvest or therapeutic apheresis

DLBCL CAR-T follow up checklist.

CAR-T follow up checklist

SOP to outline the framework and key aspects of training for pharmacists practicing within haematopoietic cellular therapies at The Christie NHS Trust.

Policy and guidelines on the management of Cytokine Release Syndrome with cellular therapies (notably CAR-T cells) and bi-specific T cell engaging antibodies (eg blinatumomab).

Outline guide for management of inpatients receiving immune effector cells

Poster outlining the approach to developing an NIHR Clinical Research Facility which is safe for the delivery of Oncology ATMP trials.

When applying for HRA Approval you will need to check what supporting documents you will need to provide well in advance of when you expect to submit your application. This will avoid unnecessary delays to your application. This page details the required supporting documentation.

Government advice on how to apply for a clinical trial including eligibility, phases, model IMPDs, costs and how to make changes to your application.

For new for new Clinical Trials of Investigational Medicinal Products (CTIMPs) and combined IMP/device trials. A step by step guide on how use use IRAS for a combined review.

Advice on preparing and submitting applications on Integrated Research Application System (IRAS).

UK local information pack for participating NHS/Health and Social Care (HSC) organisations.

The web-based interactive Costing Tool (iCT) provides a framework for transparent cost display and calculation to support swift local site budget negotiations when planning commercial trials in the NHS.

Guidance on costing a clinical trial provided by NIHR.

The Health Research Authority’s online guidance for researchers and ethics committees on consent, and how to prepare materials to support this process.

The Health Research Authority’s (HRA) online guidance to share best practice on consent and participant information by providing examples and templates

UKCRF Network: Framework for conducting highest risk Phase 1 and Experimental Medicine Studies with NIHR CRFs and wider NHS Acute Trusts

Examples and guidance provided to University of Manchester (UoM) personnel, for clinical trial set up (UoM sponsored and hosted trials).

Training and supporting materials provided by the European Medicines Agency (EMA) on how to use the Clinical Trials Information System (CTIS).

Information provided by the European Medicines Agency (EMA) on the European Union (EU) pharmaceutical legislation known as the Clinical Trials Regulation, entered into application on 31 January 2022.

Summary of workshop findings re: barriers to effective ATIMP trial set up, changes required to overcome them and key ATIMP trial metrics.

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an overview of the requirements for labelling human tissues and cells for use as starting materials for advanced therapy medicinal products using the ISBT 128 system.

This guidance produced by the Pan UK Pharmacy Working Group for ATMPs describes the legal basis for associated activity and provides guidance for Pharmacy clinical trial sites who may need to outsource these services.  The information provided will guide Pharmacy trial sites in establishing appropriate partnerships and understand the regulatory position with regard to the activities contracted.

PowerPoint presentation for an educational seminar on ATMP pharmacy.

A presentation on ATMP Pharmacy Gene Therapy treatments.

Slides from a pharmacy teaching session on ATMPs from Manchester University NHS Foundation Trust

Template for the feasibility and risk assessment of all clinical trials (not just ATIMP)

Risk assessment form that is the basis for assessment of capacity and capability within Manchester University NHS Foundation Trust.

Guidance produced by the Pan UK Pharmacy Working Group for ATMPs regarding the operational implications of the UK exit from the EU for NHS Pharmacy clinical trial sites, including ATiMPs

An example SOP from University Hospitals Bristol and Weston NHS Foundation Trust detailing effective shared care between the treatment centre and referring centre.

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an overview of the procedural requirements for the procurement of human tissues and cells but does not discuss in depth the consent and ethics requirements

Advice produced by the Pan UK Pharmacy Working Group for ATMPs for Pharmacy sites on costings for clinical trials of ATMPs, using the NIHR interactive costing tool.

An overview of points to consider and SOPs required when establishing a new pathway for the collection of tissues to isolate tumour infiltrating lymphocytes (TIL). Relevant for both research and clinical tissue collection.

An overview of patient pathways relating to the collection of tissues to isolate tumour infiltrating lymphocytes (TIL).

The process for consenting patient’s tissue to be stored in a biobank for use in medical research, relating to tumour infiltrating lymphocytes (TIL)

This SOP will describe the patient recruitment process for prospective breast tumour sample collection (for medical research relating to adoptive T-Cell Therapy)

SOP re: consenting Hepato-Pancreatico-Biliary (HBP) patients for biobank

This SOP provides the basis for the standardised collection of solid tumour and fluid samples from cancer patients undergoing surgical treatment, where there is excessive tumour tissue available which can be collected without effecting the normal standard of care.

The purpose of this document is to provide clear guidance on the procedures to be followed during the processing of ovarian tumour tissue to establish a) a tumour infiltrating lymphocyte culture; (b) an autologous tumour cell culture; (c) a cryopreserved aliquot of tumour culture digest; (d) subsequent cryopreservation of TIL and autologous tumour cultures for future assays.

An overview of surgical sites and services in Greater Manchester, relating to the collection of tissues to isolate tumour infiltrating lymphocytes (TIL).

A training needs package and competency guide for healthcare and academic professionals involved in the delivery and direct care of patients receiving advanced therapy treatment; it provides information and signposting to external resources for independent training, learning and further reading on a number of key areas relevant to these medicines.

Cryopreservation is now integrated into the manufacturing workflow of approved ATMPs. However, a comprehensive end-to-end solution for large scale ATMP production is still under development. This document provides an overview of the current state of cryopreservation in ATMP workflows by: addressing where cryopreservation fits into the workflow, the rules and regulations, the major challenges of cryopreservation logistics; reviewing the effects of cryopreservation of starting materials on the final product safety and efficacy and how developing technologies are set to help optimize cryopreservation processes for scalable manufacturing.

A guidance document providing an oversight of the purposes and contents of a Quality Technical Agreement (QTA) for use between advanced therapy clinical trial Sponsor and Participating Organisation. The document set outs a proposed standardised format for advanced therapy clinical trial QTA with example roles and responsibilities.

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user a refresher of standard clinical trial studies and explains the additional features which impact on the design of trials for investigational advanced therapy medicinal products (ATIMPs) and how they can be addressed. Roles and responsibilities, governance and sources of support for ATIMP clinical trials are also outlined.

SOP re: tissue consent for Neurological patients relating to TIL therapy research/ treatment.

This SOP provides clear guidance on the procedures to be followed during the acquisition of tissue for therapeutic purposes undertaken within the institute/trust.

Example SOP for the procurement of Advanced Therapeutic Medicincal Products (ATMP) – CAR-T Cells.

Form to be completed on the disposal of IMP or ATMP

This document sets out an example generic checklist for receipt and storage of fresh, autologous, cellular Advanced Therapy Medicinal Products.

This document can be used to help prompt consideration and recording of the competencies that are needed to work safely while thawing.

This document can be used to help prompt consideration and recording of the competencies that are needed to work safely with dry shippers and/or dry ice.

This example SOP considers general principles for the handling and administration of an example in vivo GMO gene therapy in a clinical area which can be adapted to accommodate local procedures or product-specific requirements.

Some ATMPs contain living cells. These cell-based therapies may be cryopreserved to extend their shelf life, requiring carefully controlled thawing prior to administration. Failure to thaw the product correctly may impair the integrity of the cells (viability and/or function) and the product may be rendered unfit for purpose. This document describes and example procedure for thawing cryopreserved ATMPs using a water bath.

A checklist to follow to confirm all steps are appropriately carried out for cell therapy starting materials to be sent to manufacturer

A checklist to confirm ATMP is received appropriately from the manufacturer prior to administration to a patient

Checklist to follow on thawing and administering ATMP to patients

Form to complete when receiving, processing and releasing fresh cells for manufacturing

A look at some of the recent impacts of ATMP treatments on children at the Royal Manchester Children’s Hospital

Terms of Refence for the Research and Innovation ATIMP Board (a sub-committee of the ATMP board) at The Christie Hospital Manchester. Included are aspects such as the boards powers and membership.

This guidance document presents a consensus view on standardised approaches to mononuclear cell procurement to reduce unnecessary complexity and variation

Self-assessment questionnaire to assess regulatory compliance in The Christie Pathology Partnership Laboratories to perform the storage and release of ATMPs

Checklist to be completed on the issue of IMP or ATMP

HSE (Health and Safety Executive) guidance to help organisations to choose the most appropriate regulatory procedure, particularly those wishing to undertake studies involving the administration to humans of substances based upon genetically modified microorganisms (GMMs)

Focussing on four upcoming ATMPs in 2021, how they work, how patients might benefit, how they are given and other practical issues staff need to aware of.

This publication reports on a study to assess institutional readiness (IR) of NHS sites that form part of the Northern Alliance Advanced Therapy Treatment Centre to deliver advanced therapy medicinal products, and discusses the development of an assessment tool to support self-assessment of IR in healthcare institutions

Full job description for a lead clinical trials nurse focussing on advanced therapies

An audit template for the oversight of pharmacy with the stem cell laboratory for the storage and handling of ATMPs

This paper highlights the major themes found in designing and applying flow cytometric analysis for cellular therapies and discusses practical solutions to common problems

This SOP considers general principles for the management of a Class 1 or 2 GMO gene therapy spillage or accidental exposure in a clinical area.

This document produced by the Pan UK Pharmacy Working Group for ATMPs provides guidance on the management of acute CAR-T cell toxicities to help inform the development of local guidelines and to standardise the management of acute CAR-T cell toxicities across the UK. This is a consensus guideline developed with input from the pharmacists and consultants from the first and second wave CAR-T centres.

This document sets out an example generic checklist for transfer of shippers containing Advanced Therapy Medicinal Products (ATMPs) to clinical areas, and their return to the sending laboratory.

This document sets out an example generic checklist for autologous, cryopreserved, cellular Advanced Therapy Medicinal Products (ATMPs)

This document sets out an example generic checklist for receipt and storage of fresh, allogeneic, cellular Advanced Therapy Medicinal Products

This document sets out an example generic checklist for allogeneic, cryopreserved, cellular Advanced Therapy Medicinal Products (ATMPs).

A webinar giving an overview of governance, operational and clinical challenges which need to be overcome in order to implement these novel medicines

A Pan UK Pharmacy Working Group for ATMPs resource.

Some medicines, including many ATMPs, achieve greatest stability at ultra-low temperatures. Therefore the use of -80°C and below is commonplace to achieve optimal product shelf-life. As the usage of ATMPs is increasing, Pharmacy departments are becoming required to receive shipments and to store products at ultra-low temperatures

A webinar to give an introduction into the considerations for dosing patients with ATMPs

This training webinar gives an overview of the preparations required prior to treating patients with ATMPs

This training webinar gives an overview of basics of cell therapy and some applications

This is a training webinar that covers the basics and introduction of in vivo gene therapy

A training video demonstrating the thawing of a cryopreserved cell therapy product using a waterbath

Form to complete when receiving, processing and releasing fresh cells for manufacturing

Nitya, a university student from Gloucestershire, was the first patient to undergo CAR T cell therapy at the trust in February 2019. Hear from Nitya what it was like to receive CAR T cell therapy

Ex vivo gene therapy medicinal products are ATMPs, which require pharmacy oversight, even when being handled elsewhere within a healthcare organisation. This document produced by the Pan UK Pharmacy Working Group for ATMPs outlines the key areas where chief pharmacists should focus pharmaceutical expertise prior to an organisation implementing any ex vivo (cell based) Gene Therapy Medicinal Product (GTMP)

The purpose of document produced by the Pan UK Pharmacy Working Group for ATMPs is to outline the key areas where chief pharmacists should focus pharmaceutical expertise prior to an organisation implementing any in vivo (virus based) Gene Therapy Medicinal Product (GTMP) e.g. IMP for Clinical Trials or Marketed ATMPs.

This guidance from the Pan UK Pharmacy Working Group for ATMPs has been written in collaboration with the HTA and MHRA. It clarifies the regulatory requirements for healthcare organisations who are procuring (harvesting) patient’s own cells or tissues to be used as starting materials in the manufacture of an ATMP where the subsequent ATMP manufacture occurs outside of the EU. In the event of a no deal EU exit, it will also be relevant for ATMPs manufactured in the EU

The purpose of this document produced by the Pan UK Pharmacy Working Group for ATMPs is to outline the key areas where Chief Pharmacists should focus pharmaceutical expertise prior to an organisation implementing any Somatic Cell Therapy Medicinal Product (sCTMP). This document presents a flow diagram outlining a stepwise approach to implementing processes to prepare and administer sCTMPs. It is followed by checklists which relate to the various steps presented in the diagram

The purpose of this document produced by the Pan UK Pharmacy Working Group for ATMPs is to outline the key areas where chief pharmacists should focus pharmaceutical expertise prior to an organisation implementing any Tissue Engineered Product.

A tool to assess for, and grade, cytokine release syndrome in a CAR T therapy patient

A training resource on the importance of correctly thawing and inspecting cell therapy medicinal products

To describe the procedure for managing CTPs used as ATMP which are manufactured outside The Christie NHS Foundation Trust, received, stored and issued by The Stem Cell Laboratory at The Christie Pathology Partnership which has been prescribed by an appropriate prescriber

A summary of activities across NA-ATTC hospitals geared towards patient centred, safe and efficient trial set-up, delivery and completion

An example risk assessment form to be completed prior to the use of genetically modified organisms (GMO’s) within a hospital

A Pharmacy Working Group of ATMPs resource. CAR-T treatments require governance and management by Chief Pharmacists. They present risks which Chief Pharmacists should ensure are minimised. Whilst collaboration with expert cellular product handling colleagues will be key operationally, it may present challenges for Pharmacy to embed this new working relationship

A training video explaining the logistics supply chain for ATMPs and autologous therapies in particular

Guidance produced by the Pan UK Pharmacy Working Group for ATMPs, providing definitions of oversight and supervision and clarifies where each are required when implementing Advanced Therapy Medicinal Products

A Pharmacy Working Group for ATMPs resource. Pharmacy is often the first port of call when an organisation wishes to use a gene therapy and needs to provide pragmatic guidance to facilitate the introduction of these innovative products. This document is designed to give practical advice to centres wishing to undertake gene therapy trials and need to understand the requirements and recommendations for governance and, in particular to have in place a Genetic Modification Safety Committee. The document also gives practical advice for centres to help them understand operational requirements including deciding the optimal location for preparation.

This guidance summarises the authorisation process for Genetically Modified Organisms (GMO) as Investigational Medicinal Products (IMP) for contained use (CU) within the United Kingdom (UK). These submissions are unique to GMOs, in addition to Clinical Trial Authorisation (CTA) and Ethics

Governance structure organogram for supporting the introduction of ATMPs at the Christie Hospital

Exemplar terms of reference for an ATMP Education and Training Committee at The Christie NHS Foundation Trust

An example risk assessment used to fully review the risk posed by GTMP/GTiMPs in preparation for submission to local genetic modification safety committee

This guidance documents accompanies the ATMP model clinical trials agreement and can be use as a guide to allow the proper use of the model agreements.