How far are we with the accelerated development of SARS-CoV-2 vaccines – a review and outlook
by Noemi Lupo and Michael Pfleiderer
Traditional vaccine development is a long and expensive process, which takes from 10 to 15 years (Figure 1). To respond to the ongoing pandemic caused by SARS-CoV-2, the traditional development timelines have been accelerated at an extraordinary speed in all areas of development adhering, however, to all scientific and regulatory standards established for vaccines.
We are seeing an unprecedented global commitment and cooperation among health authorities and stakeholders for the establishment of accelerated regulatory procedures and harmonized approval requirements. Moreover, a race among vaccine developers brought more than 20 vaccines into clinical trials in only a few months with some already in phase III . Such rapid development of vaccine candidates was facilitated by scientific knowledge acquired from SARS-CoV and MERS coronaviruses combined with advancements made in the development of easily adaptable vaccine platforms. In addition, this is the result of a combined effort between developers and regulatory authorities. Even though agencies are intensively working to support companies in accelerating their development process, the latest guidelines [2, 3] and statements  strongly underline how safety, efficacy and quality remain pivotal approval requirements in the EU and US. Therefore, the challenge of obtaining convincing clinical data and the manufacture of high-quality products at commercial scale in a relatively short time could become a bottleneck for the development of SARS-CoV-2 vaccines.
Which tools do companies have to accelerate the development process and meet the regulatory requirements?
Clinical research represents one of the longest and most challenging phases of vaccine development. The adoption of adaptive designs in clinical trials could accelerate the acquisition of the required safety and efficacy data. Clinical trials performed following an adaptive design are subjected to in-progress pre-specified modifications, which allow the adaptation of the protocol based on the newly identified needs (Figure 2).
Adaptive designs can be applied to all phases of clinical research and often used for combined studies (e.g. Phase II/III) to further expedite the collection of required data. The acquisition of efficacy data remains the biggest challenge companies face during the clinical development of vaccines against pandemic viruses. This is due to the difficulty of predicting in which regions outbreaks will occur, which is also applicable for the SARS-CoV-2 pandemic with outbreaks moving from one region to another. Moreover, competition in recruiting suitable study sites in regions with high pandemic activity emerges as a major issue considering the huge number of vaccines currently approaching Phase II and III. Therefore, developers should consider conducting clinical trials in multiples countries focusing on those that are most likely to present the highest number of cases in the coming months. In this regard, WHO organizes international clinical trials, in which a large number of healthy volunteers from different populations are rapidly enrolled and multiple vaccine candidates are tested in parallel against one common placebo group . However, the regulatory compliance of this approach is not yet confirmed.
Along with the clinical development, manufacturing development, commercial scale-up and large-scale manufacturing represent critical steps that can significantly delay the commercialization of candidate vaccines. The manufacturing challenge is further amplified by the high competition for manufacturing sites and raw material suppliers. Therefore, when feasible, companies should invest resources in the early identification of geographically spread manufacturing facilities and suppliers of raw materials. An opportunity for manufacturers could be represented by COVAX, a project initiated by WHO, Gavy and CEPI in the aim to ensure global access to SARS-CoV-2 vaccines via the establishment of a manufacturing facility for SARS-CoV-2 vaccine candidates . However, again the regulatory compliance of manufacturing facility and process still needs to be verified.
Acceleration of the development process cannot take place without acceleration of regulatory procedures. For this purpose, EMA has developed fast-track regulatory procedures such as rapid scientific advice, rapid agreements of PIPs, rolling review and accelerated review which is aimed to expedite the development of the most promising SARS-CoV-2 vaccine candidates . Key features of EMA fast-track procedures are illustrated in Figure 3. The access to these procedures is granted only after pre-evaluation of the candidate’s development plan. Ineligible companies can still consider submitting a request for traditional scientific advice.
CBER did not issue ad-hoc fast-track regulatory procedures but rather worked to accelerate the review of requests for the access to pre-IND meetings, fast-track designation, rolling review and accelerated review. Fast-track designation can be requested at any stage of development and is granted to the most promising candidates. Fast-track designation gives access to frequent interactions with the FDA (i.e pre-IND meetings, written communications), rolling review and eligibility for accelerated approval and priority review .
Despite the efforts made by developers and agencies, it is difficult or rather impossible to anticipate when and if a SARS-CoV-2 vaccine will be available. Nevertheless, working on the optimization of the development plan via close collaboration with agencies is of fundamental importance to increase the chances to meet the goal.
Biopharma Excellence has hands-on experience of vaccine development from the exploratory stage to licensure. Our team expertise is complemented by sound scientific knowledge on coronaviruses and by our involvement in multiple interactions with agencies focused on the development of SARS-CoV-2 vaccines. Therefore, we will be happy to help with establishing and optimizing YOUR development program according to the expectations of WHO, regulatory agencies, and other stakeholders. In addition, we can support you with the preparation of agency meetings and submission of regulatory dossiers. If interested, please do not hesitate to contact us.