Advanced Therapies NHS Readiness Toolkit

An infographic capturing the recommendations for Gene Therapy Patient Referrals Pathway

A summary of recommendations for Gene Therapy Patient Referrals Pathway

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.

A guidance document providing an oversight of the purposes and contents of a Starting Material, Quality Technical Agreement (QTA) for use between customer and supplier. The document set outs a proposed standardised format for Starting Material QTA with example roles and responsibilities.

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

Case Study poster illustrating the process pharmacy division followed for a successful implementation of governance and operational procedures inline with current regulations.

A governance checklist for both newly licenced and unlicensed ATMP trials

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.

The Job description for a Band 8c Consultant Pharmacist in clinical trials and advanced therapies

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 to provide a safe and effective framework by which lymphodepletion can be performed in the outpatient setting, prior to admission for CAR-T Cell infusion.

An example SOP from University Hospitals Bristol and Weston NHS Foundation Trust detailing the inclusion and exclusion criteria when referring patients to the Ambulatory Care (AC) BMT service.

An example SOP from University Hospitals Bristol and Weston NHS Foundation Trust to provide a framework by which high-dose melphalan and autologous stem cell rescue (autologous stem cell transplant, ASCT) can be performed in the outpatient setting

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

Initially set up to facilitate the onboarding of Wave 3 CAR-T centres in England, this template Technical Agreement produced by the Pan UK  Pharmacy Working Group for ATMPs is suitable for adaptation by NHS Pharmacies, when there is a requirement to outsource any aspect of cell or tissue based ATMP handling for ATMPs which hold a marketing authorisation.

A guidance checklist for NHS staff in preparation for ATMP starting material procurement site qualification. This document would be best utilised when beginning to set up a service for procurement of a new cell or tissue type but could be used as a checklist for existing cell or tissue type procurement

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.

Prior to receiving CAR-T cell therapy, patients will receive lymphodepletion chemotherapy.  CAR-T cell therapy and lymphodepletion regimes can increase the likelihood of certain side effects and infections so supportive medicines are recommended.

These consensus recommendations, prepared by the Clinical Pharmacy subgroup of the Pan UK Pharmacy Working Group for Advanced Therapy Medicinal Products (ATMPs), relate to supportive medicines recommended for adults receiving licensed CAR-T cell therapy.

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

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.

Advanced Therapy Medicinal Product (ATMP) Cost Model which supports NHS institutions to assess finance and resource implications arising from the adoption of an ATMP into clinical practice.

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.

An example training matrix for staff working in research and development departments in a hospital setting, including suggestions for ATMP specific mandatory training.

This poster presentation is the product of a short live working group of ATMP industry partners and captures the non-label (not appearing on the product label) data produced during an exemplar apheresis process. The poster aims to demonstrate the ability for standardisation of data transfer from NHS to manufacturers.

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.

Micro costing analysis toolkit for Advanced Therapy Medicinal Products.

Cost Comparison of Tumour Collection Strategies for TIL Therapy.

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.

In vivo gene therapies are a type of Advanced Therapy Medicinal Product. Many in vivo gene therapies use an adeno-associated vector (AAV) to deliver the genetically modified material into the cell. These shared care guidelines describe a typical pathway for an in vivo gene therapy utilising an AAV.

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

Electric Shipper risk assessment example.

A flow diagram showing the pathway a patient follows when receiving a CAR T.

A quick reference guide to preparing and infusing frozen stem cells.

Example business case for gene therapy cabinet in aseptic unit.

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 exemplar guideline suggests roles and responsibilities between CAR T cell referring centres and treatment centres. It also outlines common late adverse effects that may occur when patients have returned to their referring centre.

This document sets out what training in advanced therapies is already available and what is required to ensure staff are equipped to understand these medicines

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.

As Gene Therapy Medicinal Products (GTMPs) and Gene Therapy Investigational Medicinal Products (GTIMPs) are Advanced Therapy Medicinal Products (ATMPs), it is important that organisations have a defined governance process in place for their approval and implementation. This document gives an example of a Trust Policy for approval of GTMPs/GTIMPs by a Trust Genetic Modification Safety Committee (GMSC).

An example assessment form to be used for storage of medicinal products in non-pharmacy departments.

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.

The use of immune effector cell therapies can result in significant toxicities that are directly associated with powerful immune-mediated responses. The most frequently observed of these is cytokine release syndrome (CRS). CRS represents a life-​threatening situation that requires early recognition of symptoms and signs and prompt intervention. This short training video can be used to support healthcare professionals and others to gain an introduction to CRS presentation, diagnosis and clinical management.

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

This webinar to showcases the Pan UK Pharmacy Working Group for ATMP’s pragmatic advice which clarifies the regulatory perspective regarding OOS ATMPs, and provides guidance to NHS organisations which are provider sites for ATMPs, about governance in the event of an OOS ATMP being supplied for one of their patients.

Checklist to follow on thawing and administering ATMP to patients

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an introduction into the basics of ATMPs including classifications and nomenclature

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) focussing on the use of viruses to deliver advanced therapies to patients

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an understanding of cell therapy and how this works

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an introduction into CAR T cell therapy and how this is currently implemented

E-learning on the NHS e-learning platform e-learning for healthcare (registration required) giving the user an introduction to the challenges posed when moving advanced therapies around a hospital and how effective teamwork is required

An example job description for a senior clinical practice facilitator to help develop the advanced therapies team through education

Gene therapies for the eye often lead the field of advanced therapeutics, introducing exciting new technologies and techniques to the clinic. Topics include the first FDA approved gene therapy (Luxturna), gene editing trials for inherited vision loss, and how a protein that helps algae move is being repurposed into vision saving technology.

This paper outlines observations and recommendations on developing the role of pharmacy in delivering ATMPs in NHS Scotland

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

Transplantation of insulin-producing cells purified from a donor pancreas is established within the NHS. This is restricted to people with life-threatening complications of type 1 diabetes as liberation from injected insulin cannot yet be guaranteed and life-long immunosuppression is needed. The potential for harnessing regenerative medicine and tissue engineering to deliver truly transformative outcomes is discussed.

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

A visual guide to the preparation, administration and disposal of non-cellular, genetically modified organisms (GMOs), in a clinical setting

This webinar will focusses on genetically modified immune cells as a treatment choice for solid tumours discussing the use of tumour-infiltrating lymphocyte therapy to treat H&N cancer in the context of a clinical trial

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.

The Specialist Pharmacy Service produces a range of information to support managed entry of new drugs into the NHS, to assist organisations in developing medicines management policies and to inform prescribing decisions when a product has been launched. The service provides ways to track the development of drugs from when key trials start until they launch in the UK.

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

The CAR T cell patient journey from a nursing perspective, some of the challenges faced, and a some of patient case studies.

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

The HTA is the regulator for human tissue and organs, this includes activities using  human tissues or cells used as starting materials in the manufacture of ATMPs

Main pages from the EMA website focussed on ATMPs

The AAC is bringing together industry, government, regulators, patients and the NHS to remove barriers and accelerate the introduction of ground-breaking new treatments and diagnostics which can transform care, including ATMPs

The guideline describes specific aspects of pharmacovigilance, risk management planning, safety and efficacy follow-up of authorised ATMPs, as well as some aspects of clinical follow-up of patients treated with such products.

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)

A presentation of the findings from the CPROR team’s recent publication “Patient and public perspectives on cell and gene therapies: a systematic review” and the CPROR’s ongoing work to develop a an evidence-based toolkit to facilitate the design of patient-focused educational resources.

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.

The training passport is designed for all pharmacists providing pharmaceutical care to HSCT patients including those undergoing autologous and allogeneic transplant, patients admitted to the HSCT unit with post-transplant complications and patients attending post-transplant out-patient clinics

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

This discusses the new approaches to treating spinal muscular atrophy with advanced therapies. The talk is by Rafeal Yanez, Professor of Advanced Therapy at the Royal Holloway, London

A summary of the cellular therapy and transplant programme and the documents modified existing or created in order to deliver advanced therapies and comply with JACIE’s immune effector cell
standards

Template form used to review and assess a new ATMP clinical trial

A presentation summarising the importance of JACIE regulation as applied to immune effector cell therapy

A training webinar exploring the principles of gene editing and what the applications may be in the clinical potential

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