Single-use systems (SUS) are changing the way end users think about validation. The complex supply chains of SUS are not always as robust as necessary. This presents both manufacturers and end users of SUS with validation challenges not present with a stainless steel equivalent. Given increased regulatory scrutiny on supply chain security and risk mitigation strategies throughout the development and manufacture of a therapeutic drug product, how can end users ensure the expected level of compliance in this new world of SUS? The secret: shared responsibility for validation with your supply chain.