Detailed guidance on the Target Development Profile Toolkit

When the Innovative Licensing and Access Pathway (ILAP) was launched at the start of 2021, it was announced that the Target Development Profile (TDP) will be available to applicants to support their application through this pathway.

The Medicines and Healthcare products Regulatory Agency (MHRA) has now released detailed guidance on the tools and processes available in the TDP and how they can be used during an ILAP application.

Adaptive inspections tool

This tool is designed to support the non-clinical, clinical and manufacturing design and development pathway to ensure patient safety and reliable results. It works by providing supervisory and licensing inspections, specific to the Good Practice guidelines and tailored to the specific needs of the product. A risk-based approach will be applied which may involve:

  • Live-phase inspections for pre-clinical or clinical aspects
  • Defined pre-authorisation inspections of clinical trials and pre-authorisation assessments of the applicant’s ability to comply with post-authorisation pharmacovigilance obligations
  • Post-authorisation inspections to determine compliance with specific licence condition or routine activities such risk minimisation measures

Certifications

This tool allows manufacturers to obtain an official regulatory review of packages of Common Technical Document (CTD) data. This will allow key issues to be identified for the applicant to address.

To obtain this, applicants must confirm in the TDP which components of the CTD they which to have certified. Early engagement on the quality of their submission will enable ample opportunity for the developer to adjust the CTD ahead of a formal marketing authorisation application.

Continuous Benefit Risk Assessment integrating Real World Evidence

This tool for data collection and post authorisation vigilance is key in supporting the development of innovative medicines. It may involve developing plans for post-approval evidence requirements (including RWE) and provisional agreement of study protocols.

Clinical Practice Research datalink (CPRD) Assisted Patient Recruitment

CPRD is a service that enables one to efficiently find patients across the UK who may be eligible for a clinical trial. Developers wishing to use this service must highlight their intention to do so in the TDP. CPRD representatives will then get in touch and discuss further the process for and feasibility of using this tool.

Enhanced patient engagement

This tool fits in with the MHRA’s recent efforts to ensure a more patient-oriented approach to developing medicines. This tool has been developed in consultation with patients and will essentially involve asking the developer what activities they have already undertaken to engage with patients during product development. It will also ask them to consider how they propose to engage other stakeholders such as carers and a patient’s family, with information on how the MHRA can support this engagement

Innovative and Flexible Licensing Routes

There are numerous routes available to expedite product approval, including:

  • Accelerated assessment
  • Rolling review
  • Approval with conditions
  • Conditional Marketing Authorisations
  • Approval under exceptional circumstances
  • Project Orbis
  • Access Consortium

When using the TDP, it will recommend the most suitable routes to market based on the product and the patient population.

Novel methodology and innovative clinical trial design

This tool has been developed with the intention of encouraging and supporting novel methodologies in clinical trial designs, manufacturing and end-point development. Key activities that will enable this include:

  • Securing multi-stakeholder agreement for innovative approaches to evidence generation
  • Qualification of new methodologies via joint scientific advice procedures
  • Use of novel trial designs to ensure a flexible regulatory approach that can adapt to emerging data
  • Regulatory assurance on the requirements and acceptability of virtual, AI and decentralised elements in trial conducts as well as any e-systems technologies used to support novel trial designs
  • Generation of guideline documents on topics of interest

Rapid Clinical Trial Dossier Pre-Assessment

This service allows sponsors to receive feedback on their clinical trial authorisation application dossier before it is formally submitted. This both reduces the chance of a ‘Grounds for Non-acceptance’ being issued and speeds up the process of setting up a trial. Draft clinical, quality and/or non-clinical documentation can be submitted for pre-assessment. MHRA clinical trial unit assessors will provide rapid feedback and flag up any potential issues which can then be discussed in an informal scientific advice meeting.

Forthcoming tools

In addition to the aforementioned tools, the MHRA will look to bolster the TDP toolkit over the course of 2021. The tools stated to be in the pipeline include:

  • Advanced Therapy Medicinal Product (ATMP) Centre Accreditation – for sites with experience in ATMP development to be approved as safe for trials and/or manufacture by the MHRA
  • Coordinated approval of research involving investigation of both a medicine and a medical device – this will allow combined assessment of clinical trials that involve both an investigational medicine and an investigational medical device
  • CPRD Control Groups – using CPRD primary care real world data to develop virtual control groups which may be useful in establishing the validity of data (e.g. distinguishing treatment effects from other factors in single arm trials).
  • Development of quality standards – these will be drawn from existing MHRA standards, the British Pharmacopoeia and NIBSC

The full guidance can be found here.