Impact of possible removal of the Titanium dioxide from human medicines formulations was discussed during the CMDh meeting held on 14-17 September

by Ruggero Rusmini
Regulatory Affairs – PQE Group

Introduction

On 6 May 2021 the European Food Safety Authority (EFSA), the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain, updated its safety assessment of the food additive titanium dioxide (E 171), following a request by the European Commission in March 2020.

Titanium dioxide can no longer be considered safe as a food additive.

The updated evaluation overturned the outcome of EFSA’s previous assessment published in 2016, since the Panel concluded that titanium dioxide can no longer be considered safe as a food additive and the experts could not exclude genotoxicity concerns after consumption of titanium dioxide particles. Genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer.

Quality Working report on impact of removal and related documents is expected to be discussed.

Besides its use in the food industry, Titanium dioxide covers a crucial role in many pharmaceutical formulations, acting as pigment, coating agent, etc. A recent survey conducted by the representing association of Europe’s pharma industry – Medicines for Europe, the European Federation of Pharmaceutical Industries and Associations (EFPIA) – found that more than 90% of oral dosage forms contain titanium dioxide.

Following the EFSA Opinion, relevant concern arisen over TiO2 safety in pharmaceutical products due to the legislative link that exists between the use of a substance as a coloring matter in medicinal products and food additives: Directive 2009/35/EC restricts the use of pigments in human and veterinary medicinal products to those authorized in Regulation (EC) No 1333/2008 on food additives.

A High-impact workload on CMC update dossiers

Recently, in the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) meeting on 14-16 September 2021, an item on the agenda concerns itself the role of Titanium dioxide as excipient: a Quality Working report on impact of removal and related documents is expected to be discussed.

If Pharmaceutical Companies will be asked to remove titanium dioxide, this will necessarily imply reformulation, which could take years for each product, depending on the need for studies to determine stability, bioequivalence, and other formulation requirements.
In the same way, the workload regarding the CMC update dossiers will be very impactful, having to re-write most of the sections and then proceed to the submission of the appropriate variation to the Competent Authorities.

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