Titanium Dioxide And Alternatives Industry Submission To EMA Feb 2024

INDUSTRY FEEDBACK TO QWPEXPERTS/EMA QUESTIONSFINALREPORTFEB 2024 Table of Contents Introduction...........................................................................................................................................2Overview................................................................................................................................................3Titanium Dioxide as a ubiquitous excipient in medicines globally.......................................................3Timeline of Developments..................................................................................................................31.EFSA 2021............................................................................................................................32.Industry Assessment and EMA report (EMA/504010 2021).................................................33.Legislative requirements.......................................................................................................4Summary of outreach and engagement between industry, EU institutions and the EU regulatorynetwork...............................................................................................................................................5Investigation of Alternatives to Titanium Dioxide in Capsules and Coatings................................8Excipients industry efforts to identify alternatives to Titanium Dioxide...............................................8Process to assess alternatives to Titanium Dioxide............................................................................8Titanium Dioxide Alternatives Consortium..........................................................................................9Summary and timeline of industry activities to identify and assess alternative coatings and capsules..........................................................................................................................................................10EMA Questions to Industry-2023....................................................................................................11A. TiO2possible alternatives................................................................................................................11Question 1.............................................................................................................................................11Assessment of TiO2alternative materials in film coat systems and hard capsule shells..................11Selection of Alternative TiO2Film Coat and Hard Capsule Shell Systems.......................................11General Compliance Assessment.....................................................................................................121.Tablet Film Coats–Compliance Assessment....................................................................122.Capsule–Compliance Assessment...................................................................................133.Manufacturingand Quality Summary of TiO2 Alternatives Consortium Assessment ofAlternatives....................................................................................................................................154.Safety Assessment of Alternatives......................................................................................18Question 2...........................................................................................................................................23Film Coating Systems.......................................................................................................................231.Appearance: Opacity (Industry experience)........................................................................232.Mechanical Strength (industry experience of coat adhesion).............................................253.In-vitro Performance: (Consortium experience of impact on dissolution)............................264.Chemical Stability: (Consortium experience)......................................................................265.Photostability (Chemical) (Industry Experience).................................................................28Hard Capsule Shells.........................................................................................................................291.Mechanical Strength of Capsules (Consortium Experience)...............................................29 2.Appearance: Capsule (Industry Experience)......................................................................303.Photostability: Capsule Shell Appearance (Consortium Experience).................................314.Photostability (Chemical) of Capsules (Industry Experience).............................................31Question 3...........................................................................................................................................33Timeline estimates........................................................