Vaccine Development in Paediatric Populations – How to Proceed for SARS-CoV-2 Vaccines?
by Jerry Fuady
In response to the ongoing COVID-19 pandemic caused by SARS-CoV-2, accelerated vaccine development programmes have been implemented which significantly reduce the development time. However, while adult clinical trials of SARS-CoV-2 vaccines have rapidly moved into Phase 3 clinical trials, no clinical trials have been initiated for the paediatric population.
The impact of COVID-19 upon children is greater than observed for a number of pathogens for which we now have effective paediatric vaccines. Studies have shown that children were less likely to have severe symptoms, with 6 to 13 years old having the lowest risk of showing COVID-19 symptoms and an increasing risk among the youngest children with babies under 1 year old being more likely to suffer from severe illness. In any case, children are just as likely to be infected by SARS-CoV-2 as adults and to further transmit the disease.
As such, the role of children in SARS-CoV-2 transmission has clearly been underappreciated in the fight against the pandemic. Without a safe and effective SARS-CoV-2 vaccine, paediatric population is likely to be a reservoir, which would undermine efforts to end the pandemic. It is thus essential for vaccine developers to also plan for clinical trials in paediatric population.
Paediatric Product Development Plans for SARS-CoV-2 Vaccines
In the EU, vaccine developers are legally required to submit a paediatric investigation plan (PIP), a development plan aimed at ensuring that the necessary data are obtained through studies in paediatric population to support conditional marketing authorisation (CMA) and marketing authorisation (MA) applications. The process of preparing a PIP can be lengthy and challenging with numerous potential drawbacks along the way. An evaluation of the PIP by the European Medicines Agency (EMA) Paediatric Committee (PDCO) requires over 120 days (Figure 1). Briefly, after submission, the PIP undergoes two rounds of discussion at Day 30 and Day 60, at which point a summary report, list of outstanding issues/request for modifications or an opinion is issued. Once the modified application is submitted, the PIP undergoes a similar review procedure with the final PDCO opinion provided at Day 120. An EMA decision is provided 10 days following the final PDCO opinion.
Due to the currently ongoing pandemic, EMA has developed fast-track regulatory procedures, which include rapid agreements of PIPs and rapid compliance check. In comparison to the standard PIP procedure, no pre-specified submission deadlines are set. Furthermore, evaluation of the PIP by PDCO is reduced from 120 days to a minimum of 20 days, depending on the complexity of the programme and the flexibility of the developers in responding to questions by PDCO. In addition, the decision is provided 2 days after the final PDCO opinion instead of the standard 10 days (Figure 1). The fast-track PIP also provides flexibility, allowing vaccine developers to provide a focused scientific documentation on a case-by-case basis. Lastly, the compliance check can also be expedited to 4 days from up to 60 days if necessary.
In the US, an initial pediatric study plan (iPSP) is required from vaccine developers by the US Food and Drug Administration (FDA). Although there are many similarities between EMA´s PIP and FDA´s iPSP, a single template would not serve the regulatory needs of both agencies. Both EMA and FDA have issued a Common Commentary to streamline the administrative processes and facilitate efficient preparation and submission of both documents to the respective agencies. Given the need to develop safe and effective SARS-CoV-2 vaccines that can also be administered to paediatric population, both EMA and FDA encourage vaccine developers to submit PIPs and iPSPs early to minimise the risk of delay in CMA or MA applications.
Biopharma Excellence has been involved in assisting clients throughout all stages of vaccine development. We provide professional service to our clients by combining sound scientific knowledge on coronavirus and our experience from multiple interactions with agencies focused on the development of SARS-CoV-2 vaccines. We would be pleased to assist you in establishing and optimising your paediatric development programme in accordance with the expectations of WHO, regulatory agencies, and other stakeholders. In addition, we can support you with the preparation of your agency meetings and submission of regulatory dossiers. If you need support from a consultancy that is willing to walk extra mile with you, do not hesitate to contact us for more information.