An opportunity to work on regulatory guidelines for the manufacture of human challenge agents
Research using Controlled Human Infection Models (CHIM), or Challenge Studies, has the potential to rapidly advance understanding of disease and host immunity, and accelerate the development of vaccines for diseases of global public health importance. The purposeful exposure of healthy people to pathogens is ethically complex, and one element of risk – in addition to the pathogen itself – is the manufacture, storage and administration of the challenge agent. Challenge studies have an excellent safety profile, but one area of potential weakness identified by the research community at a workshop at the Academy of Medical Sciences in 2018 (https://acmedsci.ac.uk/policy/policy-projects/controlled-human-infection...) is the paucity of international guidelines for challenge agent manufacture.
In the US, challenge agents require FDA approval and must be manufactured in compliance with GMP standards. Most countries outside of the US carrying out challenge research do not follow the same approach; common practice is that manufacture and use of a challenge agent is subject to scrutiny by an Ethics Review Committee (REC), then overall responsibility lies with the sponsor of the study. General opinion is that applying blanket GMP regulation internationally is overly stringent and will be prohibitive to challenge studies, and furthermore it is not always possible to adhere to GMP for certain challenge agents. But there is an unaddressed need for workable manufacturing guidelines to ensure the continued safety of challenge studies in the future, particularly as the CHIM landscape expands.
Project Goals and Scope of Services
HIC-Vac and the Wellcome Trust wish to support the development of international standards that pertain to challenge agent manufacture and storage, extending the current general WHO guidelines relating to challenge studies1. The aim is to create guidelines that define ‘GMP-like’ – fulfilling GMP requirements to as much as is practically possible without being GMP certified. This will allow flexibility to manufacture challenge agents outside of GMP-certified premises, but with guidelines to ensure safety, quality and consistency are maintained.
GMP-like guidelines should take into consideration amongst other factors; characterisation of seed-material or cell lines if applicable, comparative virulence studies, well-characterised and documented growth/maintenance media, adequacy of facilities and demonstrable consistency of manufacturing process, freedom from adventitious agents (including TSEs), identity and safety testing including full traceability, environmental control and storage/transportation conditions, and batch release tests including infectivity and stability and antimicrobial sensitivity where appropriate.
A meeting conducted with the UK’s NRA, the MHRA, concluded that guidelines similar to those that govern excipients might be a useful template for challenge agent guidelines.
Our aim is to generate draft guidelines as an output of the ‘Human Challenge Trial Workshop: Focus on Quality Requirements for Challenge Agents’ (October 22, 2019, Paul-Ehrlich-Institut, Germany), supported by the Wellcome Trust. It is a valuable opportunity to observe discussion around these points, and for fuller consideration of how to define GMP-like in relation to challenge agents, and how much flexibility is required to make the guidelines practical. The draft guidelines would be made available to the WHO as input towards potential WHO-endorsed international guidance.
Anticipated Selection Schedule
Request for RFP: 30 August, 2019
Deadline to Submit Proposal: September 27, 2019
Selection and notification of unsuccessful proposals: October 4, 2019
Submission of Proposals
Please submit all proposals by email to the named contact person, with CHIM regulatory guidelines in the subject field.
The project will be initiated by attendance at the ‘Human Challenge Trial Workshop: Focus on Quality Requirements for Challenge Agents’ (October 22, 2019, Paul-Ehrlich-Institut, Germany). Attending this meeting is mandatory, so please ensure you have availability for this date.
The first draft of guidelines should be ready no later than April 2020. There will be a consultation period with experts in the field with the final feedback expected August 2020, ready to inform the final draft preparation in October 2020.
HIC-Vac and Wellcome Trust will provide support during the consultation period, providing an expert panel to review the draft guidelines.
Content of Proposal
Please ensure your proposal contains, at a minimum, the following elements:
• Description of the firm or organisation where you are employed (if freelance please state).
• A one-page narrative outlining your skills, strengths and distinguishing expertise as they relate to the task of writing regulatory guidelines. Include relevant experience. We are particularly looking for good knowledge of the preparation of challenge agents under GMP and GMP-like conditions.
• A representative portfolio of relevant projects you have contributed towards (including the scale of contribution).
There is no fixed budget for this project, we will be accepting competitive bids. Please provide a budget and a breakdown of these costs in the proposal. Please also include a justification of the costs included.
Please note that Hic-Vac and Wellcome will not be held responsible for any costs associated with the production of a response to this Request for Proposal.
Organisation Name: HIC-Vac & Wellcome Trust (joint call)
Location: London, UK
Contact Person: Dr Emma Smith
Telephone Number: +44 (0)207 594 3853
Email Address: email@example.com
1.Human challenge trials for vaccine development: regulatory considerations http://apps.who.int/medicinedocs/documents/s23329en/s23329en.pdf
2.Controlled Human Infection Model Studies Summary of a workshop held on 6 February 2018 (Academy of Medical Sciences) https://acmedsci.ac.uk/file-download/55062331
- India: Side Meeting on the Current Global Regulatory and Ethical Landscape for CHIM studies [meeting summary]
- Zambia: Development of an Ethical and Regulatory Framework for the Conduct of Controlled Human Infection Studies [Expert Consultation Report]
- Melissa Kapulu: Malaria transmission and human infection studies [Interview@University of Oxford]