Using mechanistic models to support development of complex generic drug products: European Medicines Agency perspective

Model- informed drug development (MIDD) approaches receive wide regulatory acceptance in the European Medicines Agency (EMA) to support new drug devel-opment. For generic drugs, the European regulators have not reached a common position on how to use these methods. This commentary expands on the exist-ing EMA regulatory framework for bioequivalence and physiological based phar-macokinetic (PBPK) modeling to propose conditions where mechanistic models could support or potentially waive clinical bioequivalence (BE)/bioavailability (BA) studies

Selective serotonin reuptake inhibitors and suicidality in children and young adults: analyses of pharmacovigilance databases

BACKGROUND: Since the warnings by the United States (US) and European regulatory authorities in 2004 and 2005 it had been discussed whether there is some link between selective serotonin reuptake inhibitors (SSRIs) and suicidality in the pediatric population. The aim of our study was to describe trends and patterns in spontaneous reporting data referring to suicidality in children, adolescents and young adults treated with SSRI after the warnings. METHODS: Descriptive analyses of reports for 0–24 year olds referring to suicide/suicidal ideations, self-harms and overdoses with SSRIs reported as suspected submitted to the US (FAERS) and the European (EudraVigilance) adverse drug reaction databases until 2019 were performed. The causal relationship was assessed in accordance with the WHO criteria for the European reports. For Germany, prescription data for SSRIs were provided and reporting rates (number of reports/number of prescriptions) were calculated for the reports with possible causal relationship (so called “confirmed reports”). RESULTS: Since 2004, the number of reports referring to suicide/suicidal ideations, self-harm and overdoses increased steadily in the US and EU. However, only a slight increase was seen for the confirmed EU reports. After 2008, the proportion of reports informing about suicidal ideations increased, while the proportion of fatal suicide attempts decreased. Reporting rates were higher for females and adolescents (12-18 years). CONCLUSIONS: Our results demonstrate the importance of further monitoring suicidality in 0–24 year olds treated with SSRI in order to recognize suicidality early avoiding fatal suicide attempts. The higher reporting rates for females and adolescents should be further investigated

Developing clinically relevant dissolution specifications (CRDSs) for oral drug products: virtual webinar series

A webinar series that was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics focus group in 2021 focused on the challenges of developing clinically relevant dissolution specifications (CRDSs) for oral drug products. Industrial scientists, together with regulatory and academic scientists, came together through a series of six webinars, to discuss progress in the field, emerging trends, and areas for continued collaboration and harmonisation. Each webinar also hosted a Q&A session where participants could discuss the shared topic and information. Although it was clear from the presentations and Q&A sessions that we continue to make progress in the field of CRDSs and the utility/success of PBBM, there is also a need to continue the momentum and dialogue between the industry and regulators. Five key areas were identified which require further discussion and harmonisation