Advanced Therapies NHS Readiness Toolkit

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

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.

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

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.

A governance checklist for both newly licenced and unlicensed ATMP trials

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

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.

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.

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).

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.

Main pages from the EMA website focussed on ATMPs

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)

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

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 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

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 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.

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

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 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.

A Pan UK Pharmacy Working Group for ATMPs resource to clarify the regulatory perspective regarding Out of Specification (OOS) ATMPs, and to provide 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.

The purpose of this guidance produced by the Pan UK Pharmacy Working Group of ATMPs is to outline the responsibilities of pharmacists where preparation of advanced therapy medicinal products (ATMPs) holding marketing authorisations is required prior to administration in hospitals. Full compliance with the summary of product characteristics (SmPC) requirements is always recommended.  This guidance clarifies where activities require the oversight of a pharmacist and distinguishes circumstances in which preparation under the supervision of a pharmacist would be a legal requirement. It provides definitions and distinction between the use of these terms.

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

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.

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.

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

The Pan UK Pharmacy Working Group (PWG) for ATMPs was established in 2018 to act as an expert and informed body to support the activities of UK Pharmacies to facilitate ATMP usage. This is a link to their homepage on the specialist pharmacy service webiste

Hospital pharmacists are likely to be faced with CAR-T as licensed medicines in the near future but should also be prepared to support commercial and academic clinical trials of novel CAR-T and this briefing document aims to address all scenarios.

This document produced by the Pan UK Pharmacy Working Group of ATMPs describes the role of Pharmacy in overseeing the governance arrangements and ensuring that Advanced Therapy Medicinal Products (ATMPs) used are of the appropriate quality for their intended use.