title: Elaborating European Pharmacopoeia monographs for biotherapeutic proteins using substances from a single source.
abstract: For more than twenty years, the European Pharmacopoeia (Ph. Eur.) monographs for biotherapeutic proteins have been elaborated using the multisource approach (Procedure 1), which has led to robust quality standards for many of the first-generation biotherapeutics. In 2008, the Ph. Eur. opened up the way towards an alternative mechanism for the elaboration of monographs (Procedure 4-BIO pilot phase), which is applied to substances still under patent protection, based on a close collaboration with the Innovator company, to ensure a harmonised global standard and strengthen the quality of the upcoming products. This article describes the lessons learned during the P4-BIO pilot phase and addresses the current thinking on monograph elaboration in the field of biotherapeutics. Case studies are described to illustrate the standardisation challenges associated with the complexity of biotherapeutics and of analytical procedures, as well as the approaches that help ensure expectations are met when setting monograph specifications and allow for compatibility with the development of biosimilars. Emphasis is put on monograph flexibility, notably by including tests that measure process-dependent microheterogeneity (e.g. glycosylation) in the Production section of the monograph. The European Pharmacopoeia successfully concluded the pilot phase of the P4-BIO during its 156thsession on 22-23 November 2016.
authors.affiliation: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France, corresponding author's e-mail: mihaela.buda@edqm.eu.
authors.forename: M
authors.initials: M
authors.lastname: Buda
authors.affiliation: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Wicks
authors.affiliation: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France.
authors.forename: E
authors.initials: E
authors.lastname: Charton
mesh_terms: D001691:Biological Therapy / Q000379:methods / Q000639:trends; D059451:Biosimilar Pharmaceuticals / Q000032:analysis* / Q000627:therapeutic use; D005060:Europe; D005164:Factor IX / Q000032:analysis* / Q000627:therapeutic use; D015942:Factor VIIa / Q000032:analysis* / Q000627:therapeutic use; D006801:Humans; D010602:Pharmacopoeias as Topic / Q000592:standards*; D010865:Pilot Projects
chemical_list: D059451:Biosimilar Pharmaceuticals; D005164:Factor IX; D015942:Factor VIIa
keywords: biotherapeutics; complexity; flexibility; monograph specifications; production; public standards; reference standards