Erika Fisher Lietzan

Biosimilar monoclonal antibodies: the scientific basis for extrapolation

Introduction: Biosimilars are biologic products that receive authorization based on an abbreviated regulatory application containing comparative quality and nonclinical and clinical data that demonstrate similarity to a licensed biologic product. Extrapolation of safety and efficacy has emerged as an important way to simplify biosimilar development. Regulatory authorities have generally reached the consensus that extrapolation of similarity from one indication to other approved indications of the reference product can be permitted if it is scientifically justified. Areas covered: Recently, the first biosimilar, biosimilar infliximab (Remsima/Inflectra) to the innovator monoclonal antibody infliximab (Remicade), was approved in the European Union, Canada and South Korea; the USA subsequently approved its first biosimilar, a less complex molecule (filgrastim-sndz). Based on two clinical trials of biosimilar infliximab in patients with rheumatoid arthritis and ankylosing spondylitis, the European Medicines Agency allowed extrapolation to all eight approved indications for innovator infliximab, whereas Health Canada did not permit extrapolation to the indications for ulcerative colitis and Crohn’s disease. These differing decisions on extrapolation of indications for biosimilar infliximab highlight important unanswered regulatory and scientific questions. Here, we propose substantive scientific considerations for indication extrapolation. Expert opinion: The preclinical and clinical criteria that are currently required to merit indication extrapolation have not been rigorously evaluated.

Current Regulatory and Legal Considerations for Follow-On Biologics

As patents for the first generation of biotechnology‐derived medicines expire, regulators must develop standards for follow‐ons. Requirements for traditional generic drugs will often be insufficient because follow‐on biotechnology medicines will not be identical to reference products. Policymakers must also consider what products to include, how to set data requirements, whether to permit interchange of follow‐ons and reference products, what postmarket requirements to impose, and how to balance cost savings from follow‐ons against incentives for innovation.

Outpatient Civil Commitment in North Carolina: Constitutional and Policy Concerns

This article examines preventive outpatient commitment, which targets those not ill or dangerous enough to be committed to inpatient facilities under state commitment laws. After discussing the history and design of the NC scheme, it explores constitutional and practical difficulties. Ultimately, it argues that individualized case management through local mental health clinics is the more effective and humane way of serving the interests of both the individual and the state.