Impact of EU Commission Regulation 2022/63

Titanium dioxide in Medicinal Products – Impact of EU Commission Regulation 2022/63

Recent EU legislation bans the use of titanium dioxide in food products after 7 August 2022; but what about its use in medicinal products?

Titanium dioxide as a food additive

Until recently, Titanium dioxide (TiO2, also known as E171) was authorised as a food additive in the European Union (EU) according to Annex II of Regulation (EC) No 1333/2008. The safety of the food additive Titanium dioxide was re-evaluated by the European Food Safety Authority (EFSA) ANS Panel in 2016 as part of the re-evaluation programme for food additives authorised in the EU before 20 January 2009. In its 2016 opinion, the ANS Panel recommended new studies be carried out to fill the gaps on possible effects on the reproductive system, which could enable them to set an Acceptable Daily Intake (ADI). Uncertainty around the characterisation of Titanium dioxide was also highlighted, in particular with respect to particle size and particle size distribution.

Following a request by the EU Commission in March 2020, EFSA updated its safety assessment of the food additive titanium dioxide (E 171), which revises the outcome of EFSA’s 2016 assessment where the need for more research to fill data gaps was highlighted. The assessment was conducted following a rigorous methodology and taking into consideration many thousands of studies that had become available since EFSA’s previous assessment in 2016, including new scientific evidence and data on nanoparticles. It concluded that Titanium dioxide could no longer be considered safe as a food additive, as genotoxicity concerns after consumption of TiO2 particles could not be excluded.

Consequently, the EU Commission has adopted early this year Regulation 2022/63 withdrawing the authorisation to use Titanium dioxide in food products. This measure was endorsed unanimously by the Member States, last Autumn, in the context of a Standing Committee on Plants, Animals, Food and Feed (European Commission’s FAQ on titanium dioxide). There is a six-month phasing out period as of February 7, 2022, until August 7, 2022, after which a full ban applies.

Impact on Titanium dioxide use in Medicinal Products

TiO2 is widely used as a colorant, opacifier, blinding agent and light-protective agent in many oral dosage forms of medicinal products due to its multiple functionalities.

In contrast to the rule on food products, titanium dioxide is still permitted as an excipient in medicinal products in the EU. This is based on the analysis by the European Medicines Agency (EMA) on the use of Titanium dioxide in medicinal products to the EU Commission request to evaluate the impact of the removal of Titanium dioxide from the list of authorised food additives on medicinal products, published in September 2021.

However, Regulation 2022/63 states that the EU Commission will “review the necessity to maintain titanium dioxide (E 171) or to delete it from the Union list of food additives for the exclusive use as colour in medicinal products in Part B of Annex II to Regulation (EC) No 1333/2008 within three years after the date of entering into force of this Regulation.”

This gives a clear signal to the pharmaceutical industry that it should make any possible efforts to accelerate the research and development of alternatives to replace titanium dioxide in both new and already authorised products, and to submit the necessary changes to the terms of the marketing authorisations concerned.

Next steps for the industry will depend on the EMA’s assessment of TiO2 which is expected in the first half of 2024.

More information: Annex I – Use of titanium dioxide as excipient in human medicines – Industry feedback to QWP Experts / EMA questions.

EMA Questions and answers concerning titanium dioxide and its replacement or removal in medicines