








key: cord-279637-n8acd6hj
authors: van der Plas, J.L.; Roestenberg, M.; Cohen, A.F.; Kamerling, I.M.C.
title: How to expedite early phase SARS‐CoV‐2 vaccine trials in pandemic setting – a practical perspective
date: 2020-06-19
journal: Br J Clin Pharmacol
DOI: 10.1111/bcp.14435
sha: 
doc_id: 279637
cord_uid: n8acd6hj

nan

Several bottlenecks can be identified in the vaccine development process [2] . After preclinical studies and manufacturing processes, a rate-limiting step in vaccine development is the conduct of clinical trials. In addition, the majority of vaccine candidates fail in clinical development and never reach market authorization [1] . Only 77% of the vaccine candidates will successfully transition from phase I to phase II and only 58% will successfully transition from phase II to phase III [3] . These early phase clinical trials (classical phases I and II) are essential to assess safety, tolerability and immunogenicity of the vaccine candidate, as well as preliminary information on its efficacy, before progressing further to large scale phase III trials. In the current COVID-19 pandemic it is more important than ever to identify and select the most promising vaccine candidates as early as possible and stop clinical development for failing candidates to avoid wasting valuable time and resources.

Here, we discuss several practical suggestions that could accelerate early phase vaccine trials in the COVID-19 pandemic. approval of the competent authority and MEC [6] . Legislation pertaining to the use and deliberate release of GMO's is not fully harmonized between countries. Therefore, regulation by national authorities can differ substantially between countries. In addition, regulatory bodies often work independently from each other. Obtaining the environmental permit for a clinical trial with a GMO-based vaccine can take up to several months, depending on the country-specific regulatory framework for the use of GMOs [7] . These timelines impose a significant hurdle for rapid clinical development of a vaccine against SARS-CoV-2. However, temporary legal exceptions can be made to the application process when there is a clear and urgent need for human health develop a GMO for the purpose of a vaccine. In the Netherlands, an accelerated licensing procedure has been implemented for GMO-based vaccine candidates. Following discussions between researchers and regulators, an emergency regulation has been implemented in the Netherlands by use of a ministerial decree. In short, the emergency regulation means that permits can be issued immediately, even before the clinical trial approval. This emergency regulation allows to process permit application through the regular licensing procedure, but drastically shortens the decision period of the application from 120 days to maximum of 28 days [8] .

The GMO application process can be further expedited if the applicant consults the competent authorities and advisory bodies in an early stage and the review board has previous experience with the vaccine platform. In the Netherlands, the authorities can be consulted to provide a pre-advice (before the formal clinical trial application) to help streamline the application process. Pro-active and transparent communication between applicant, sponsors and regulators are essential to complete the mandatory GMO applications in an expedited manner.

iii. Allow investigators to start preparing for trials before the formal clinical trial approval Another possibility to expedite the start-up phase is to allow investigators to start recruitment and screening of potential participants before formal approval of the clinical trial.

Recruitment and screening of participants are time consuming activities in early phase clinical trials. Significant time can be saved if potential participants can be identified, counseled and general health status assessed before the formal clinical trial approval. This can be achieved by a conditional approval of the clinical trial submission or by submitting a separate research protocol that solely aims to identify eligible participants for COVID-19 vaccine trials. This will allow the investigator to maintain an ongoing pool of (pre)screened healthy participants that are ready to be enrolled in vaccine trials. It is imperative that participants are again counseled and consented for the final, approved, study protocol prior to enrollment in the clinical trial.

However, the majority of recruitment and screening activities will than already be completed and will allow for a rapid start of the clinical trial.

iv. Centralization of facilities to perform immunogenicity assays for CODID-19

vaccines Another rate-limiting step in clinical trial start-up is the validation of immunogenicity assays.

The relevant immune assays in vaccine trials will typically depend on the mechanism of action of the vaccine candidate and possible known correlates of protection. Unfortunately, for SARS-CoV-2 such correlate of protection have not yet been identified. However, most current COVID-19 vaccine trials use some form of virus neutralizing assay to assess immunogenicity. pathways, by allowing investigators and authorities to work in parallel rather than a sequential order and by identifying, validating and centralizing immunogenicity assays as soon as possible. Early discussions with authorities and regulators about study design may also facilitate guided and rapid drug development. Vaccine development in a pandemic setting requires flexibility of both investigators, developers and authorities. In these trying times we need to find practical solutions and make joint efforts to expedite vaccine development for COVID-19.

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Accelerated procedure (fast track) review of coronavirus research files

World Health Organization. Draft landscape of COVID 19 candidate vaccines

on the Deliberate Release into the Environment of Genetically Modified Organisms and Repealing Council Directive 90/220

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Research related to treatment and vaccine COVID-19 accelerated through emergency regulation

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Developing Covid-19 Vaccines at Pandemic Speed

The authors would like to thank the Central Committee on Research Involving Human Subjects (CCMO), the Netherlands, and the Gene Therapy Office, the Netherlands, for their openness and willingness to discuss clinical trial application procedures for COVID-19.

