OBJECTIVES: To gain a better understanding of the pricing and reimbursement processes and evidence requirements at national, regional, and local levels with regards to a biologic obtaining a license in a second indication in the UK, France, Italy, and Spain.  METHODS: In countries with a largely national system (UK, France), five telephone interviews were conducted; as Spain and Italy also have local and regional systems, 17 and 18 interviews, respectively, were conducted. Stakeholders included payer-advising clinicians, hospital administrators and pharmacists, regional payers, and local payers.   RESULTS:  In the UK and France, pricing and reimbursement is agreed at a national level, with few restrictions at regional and local levels. In the UK, NHS England is likely to be responsible for funding of new biologics and relies on guidance from NICE before adopting a product in a new indication; therefore, demonstrating cost-effectiveness is key. In France, the ASMR issued by the transparency commission is important; funding usually is through the groupe homogéne de séjour. In addition to demonstrating clinical benefits, pharmacoeconomic studies may be required for high-cost drugs. In contrast, in Italy, although AIFA needs to approve a new product on a national level, subsequent requirements vary by region and sometimes specific location. Similarly, in Spain, once approved nationally, regions develop their own recommendations, and local decisions are made by hospital formularies. Evidence requirements in Italy and Spain vary at national, regional, and local levels. CONCLUSIONS: A biologic obtaining a license in a new indication must undergo the same procedure as a new product. The process and restrictions for biologics may be stricter than for other medications due to the perceived high cost. The level of national, regional, and local requirements and restrictions varies; it is important that appropriate evidence is submitted to decision makers at each level.