Post-approval changes (PACs) to the registered information of authorised medicinal products, hereafter referred to as ‘variations’, are introduced routinely worldwide to: enhance the robustness and efficiency of the manufacturing process; improve quality control techniques; respond to changes in regulatory requirements; and upgrade to state-of-the-art facilities. This continued effort is critical to continuously improve existing medicines and is, in many ways, as important as bringing new medicines to the market.
Once marketed, medicinal products are used more widely than the population in clinical development and this helps to refine knowledge of the product safety profile. For the benefit of patients and Health Care Professionals (HCPs), it is critical that such information is reflected in the product label in a timely manner, through variations to the prescribing information.
As regulatory systems develop and evolve worldwide, the requirements to submit and review variations in multiple markets are becoming even more complex. International collaboration and cooperation towards regulatory convergence has been recognised as the way to address the challenges of National Regulatory Agencies (NRAs)’ to address such increases in workload (see WHO working documents on Good Regulatory Practice - QAS/16.686). Industry believes that global convergence will provide a more efficient environment for the management of post-approval changes to Marketing Authorisations (MAs) worldwide, and will contribute to ensuring patients’ continuous access to state-of-the-art medicines, and up-to-date product safety information. At the same time, industry acknowledges that more measures like advanced planning of changes at start of the life-cycle, more strategic combination of changes as well as transparent communication of supply challenges need to be taken from their side to contribute to complexity reduction. Ultimately, all of these activities will contribute to enhancing global public health.
This paper aims to describe the challenges with the current landscape for managing variations, and presents opportunities and recommendations for global convergence and improvement, in line with the World Health Organisation (WHO) guidelines. The paper addresses both quality variations (also referred to as Chemistry Manufacturing and Control, CMC) and safety label updates, and the recommendations aim to bring consistency and predictability to the global management of variations, whilst contributing to patients’ timely access to quality medicines and the latest safety information.