Advanced Therapies NHS Readiness Toolkit

A summary of recommendations for Gene Therapy Patient Referrals Pathway

An infographic capturing the recommendations for Gene Therapy Patient Referrals Pathway

Nursing assessment form pre-apheresis.

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.

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.

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.

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.

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

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.

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

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

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

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

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.

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.

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.

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

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

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

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

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

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.

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

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

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.

Electric Shipper risk assessment example.

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 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 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.

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.

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

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

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

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

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

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.

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

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

Example patient discharge letter following CAR-T therapy

Example of a patient consent form for CAR-T therapy to treat Relapsed/ Refractory Acute Lymphoblastic Leukemia

Example of a patient consent form for CAR-T therapy to treat Diffuse Large B-Cell Lymphoma

A document summarising the challenges and solutions the the collection of starting materials for ATMP manufacture though apheresis

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

A standard operating procedure for the infusion of CAR T cells

This standard operating procedure for the assessment, grading and management of neurological and immunological adverse events following CAR T treatment

A tool to assess for, and grade, Immune Effector Cell Associated Neurotoxicity Syndrome neurotoxicity in a CAR-T therapy patient

Conditioning protocol for patients with Diffuse Large B-Cell Lymphoma prior to treatment with Tisagenlecleucel (CAR-T cell therapy)

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

Detailed pathway that a patient follows when undergoing adoptive T-cell therapy

There are a number of restrictions in medicines allowed (and wash-out periods recommended) for patients on CAR-T Cell therapy at each stage of the pathway (apheresis, lymphodepletion, CAR-T infusion). This guidance has been produced by the Pan UK Pharmacy Working Group for ATMPs to document useful medication restriction information for CAR-T Cell therapy.

Job Description detailing the key responsibilities, skills and behaviours applicable for an Aseptics and Cellular Therapies Pharmacist