OBJECTIVES: In recent years, the pharmaceutical industry has received approval in the US and Europe for several products that are unique, meet previously unmet needs, and yield important reductions in mortality and morbidity. Frequently, these products are orphan and even ultra-orphan drugs targeted at very small patient populations. It is common for these products to be priced up to $500,000 per annum. This research reviewed the pricing of these unique products (including trends) and explored alternative funding strategies that have been negotiated (e.g. outcome contracts) and/or are being proposed (e.g. reimbursement methods) by payers to manage their budgets. METHODS: We conducted research on the publicly available data on unique biopharma products and their pricing through literature and internet searches of relevant websites (such as different health technology assessment agencies in Europe). Researchers conducted discussions with payers and biopharma experts to identify the perceived differences in pricing negotiations between countries. RESULTS: There are distinctive differences in the approaches to pricing negotiations between payers in the US and Europe. These lead to determinable patterns in the methods that biopharma companies leverage to price their products and in the methods that payers use, by either working with the biopharma companies or creating reimbursement mechanisms to guide the appropriate utilization of these products. European payers have more central negotiating leverage and more formalized health technology assessments, which enable them to negotiate and even mandate prices and/or develop outcome-based contracts. CONCLUSIONS: Unlike European payers, most US payers do not have the support of similar government-backed organizations for negotiating price, and most cannot optimally leverage health technology assessments. This forces US payers to seek more creative ways of managing the utilization of products through medical policies, prior authorizations and creative reimbursement methods.