The COVID-19 pandemic has shown itself to be an unprecedented challenge for vaccines which are widely recognized as the most important tool to exit this pandemic. We have witnessed vaccine scientists, developers, manufacturers, and stakeholders deliver several vaccines in just about a year. This is an unprecedented achievement in an environment that was not ready to manage such a global public health crisis. Indeed, the pandemic has highlighted some hurdles that need to be addressed in the system in order to streamline the regulatory processes and be in a situation where life-saving pharmaceutical solutions such as vaccines can be delivered quickly and equitably to people across the globe. More precisely, trade-offs had to be made between the need for regulatory flexibility in the requirements for manufacturing and controls to enable rapid availability of large volumes of vaccines vs the increased stringency and the lack of harmonization in the regulatory environment for vaccines globally. It is also characterized by a high heterogeneity in terms of review and approval processes, limiting equitable and timely access. We review and highlight the challenges relating to several topics, including process validation, comparability, stability, post-approval-changes, release testing, packaging, genetically modified organisms and variants. We see four areas for accelerating access to vaccines which provide solutions for the regulatory concerns, (1) science- and risk-based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. These solutions are not new and have been previously highlighted. In recent months, we have seen some progress at the health authority level, but still much needs to be done. It is now time to reflect on the first lessons learnt from a devastating pandemic to ultimately ensure quick and wide access to medicines and vaccines for the citizens and patients.