Pharmaceutical innovation is a continuous process and does not stop after a medicinal product has been approved for marketing. Post-innovation innovation fuels research into new applications, better profiling of the target population of a product and other methods to ensure a sustained benefit-risk balance over time. Over the last couple of years several new legislative frameworks with relevant innovation spin-offs (i.e. applications for new indications, risk management plans, biosimilars, active control comparisons) have been introduced into the European regulatory system with challenging opportunities for continuous learning and post-innovation innovation. Regulators have the task to reflect on these frameworks in terms of how these contribute to patient safety, public health and innovation.