Flavian-Ștefan Rădulescu
About the speaker
Flavian Rădulescu is associate professor at the Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila Bucharest, Department of Biopharmaceutics.
Currently, he is head of the Department Drug Industry and Pharmaceutical Biotechnologies, the coordinator of the residency program in Pharmaceutical Industry and Cosmetics, as well as one of the coordinators of the Center for Drug Sciences, a laboratory dedicated to the development of in vitro methodologies and their use in the screening of drugs and drug products. The Center is based on the collaboration of the Romanian Academy, Section of Medical Sciences, and the University.
Dr. Rădulescu previously worked in the research and development of liquid, oral and ophthalmic dosage forms, but also in bioequivalence studies.
He is member of the FIP Dissolution / Drug Release Focus Group. His main areas of interest are compendial and non-compendial in-vitro drug release methodologies, development of formulations for low solubility drugs, in-silico and in-vitro screening of solubility/permeability profiles.
For topical semisolids, he coordinates collaborative projects with the pharmaceutical industry, using correlated in vitro release and rheological comparative assessments for the demonstration of Q3 (microstructural) similarity.
Presentations
The presentation will focus on the latest revisions, draft versions and finalized guidance documents and compendial chapters addressing the in vitro dissolution and drug release methodologies, bioequivalence / pharmacokinetic studies published since the last edition of the International Conference From Science to Guidance and Practice.
The EMA guideline on quality and equivalence of locally applied, locally acting cutaneous products (EMA/CHMP/QWP/708282/2018 Corr.1*) marks a long pathway in adopting a regulatory framework adapted for the complexity of topical dosage forms. The concept of extended pharmaceutical equivalence was introduced back in 2014 and gradually evolved into an approach which is similar to the one published by US-Food and Drug Administration (FDA). The document marks a clear relation between formulation strategy and the strategy demonstrate the bioequivalence between a generic and the reference product. It also validates an assembly of methodologies alternatives to clinical endpoint studies which includes in vitro release, in vitro permeation, in vivo pharmacokinetic or pharmacodynamic studies. The presentation will focus on the current requirements, similarities with FDA Q1/Q2/Q3 concepts, as well as difficulties or unclarities in definition or application of the stepwise approach.
The Topical drug Classification System (TCS) was proposed by Dr.Vinod P.Shah as a simple, reliable and science-based framework adapted to the complexity of topical semisolid drug products.
It relies on the in-depth comparative evaluation of the qualitative and quantitative composition, microstructure and in vitro performance of a test formulation and a reference product.
The presentation will include the evolution of the classification concept, its relationship with the draft guidance documents issued by the regulatory authorities and the central role of the in vitro release tests.
The in vitro release test (IVRT) has been proposed initially for the evaluation of the impact of controlled changes in composition and manufacturing process (scale-up and post approval changes). Gradually, the role of IVRT has been extended by publication of product specific draft guidances (US Food and Drug Administration). It is part of the aggregate weight of evidence approach and it has an assumed ability to reflect in aggregate the influence of several physical and chemical properties. The 2108 Draft guidance on quality and equivalence of topical products published by European Medicine Agency mentions IVRT as required to support the new concept of Extended Pharmaceutical Equivalence. The significance of comparison of in vitro performance depends on adequate understanding of the compared products, characterization of the degree of similarity / differences and evaluation of their impact on the in vivo outcome. The presentation will focus on current applications and trends in IVRT.