Aim: Biologicals are jointly responsible for growing healthcare expenditures due to their innovation, patent protection, and the increasing number of indications they are used for. The aim of the study was to investigate how costs and prescription volumes of several biologicals developed in a collective of insured persons in statutory health insurance (SHI) and private health insurance (PHI) in Germany over a period from 2016 to 2020. Subject and methods: Primary outpatient prescription data of pharmaceuticals from an SHI and a PHI collective was used focusing on the monoclonal antibodies adalimumab, infliximab, rituximab, and trastuzumab, as well as the differences between their reference drugs and biosimilars. Results: Total prescription volumes of the anti-rheumatic drugs increased while those of the oncologicals decreased. Prescriptions for reference drugs fell in all cases, particularly after the market launch of the first biosimilars. However, while the decline in prescriptions of adalimumab and infliximab in PHI occurred later and more slowly than in SHI, the trend for rituximab and trastuzumab was almost parallel in both systems. In most cases, costs developed in line with prescriptions. Market competition and statutory control mechanisms had a positive impact on overall costs. Conclusion: Statutory control mechanisms such as prescription target quotas and reference price groups in SHI are effective for the drugs investigated. Nevertheless, biosimilar rates in SHI and PHI are not as far apart as the generics rate. For more expensive active substances, a switch to the cheaper biosimilars is more likely than for comparatively cheaper drugs.