European Medicines Agency warns about the risks of significant medicine shortages if titanium dioxide is forced to be replaced

The European Medicines Agency (EMA) concluded in an opinion on 8 September 2021 that the replacement of titanium dioxide (TiO2)  in medicines cannot be achieved without a negative impact on the quality and quantity of medicines in the EU. The EMA opinion stresses that a requirement to replace TiO2 in medicines will almost certainly cause “significant medicines shortages” in the EU market, with “major implications for patients”.

The Titanium Dioxide Manufacturers Association (TDMA) welcomes the EMA opinion which highlights the essential role of TiO2 in pharmaceuticals that are critical for patient health and well-being.

The unique properties of TiO2 make it hard to replace in medicines

On 17 May 2021, the European Commission (EC) asked the EMA to provide an analysis to define the technical purpose of TiO2 in medicinal products and assess the feasibility of its replacement. The EMA opinion published on 8 September concluded that:

  • TiO2 is extensively used in many essential medicines for humans and there is no single material that provides the same combination of properties that are unique to TiO2.
  • TiO2 is used to ensure the protection of active substances from degradation due to UV exposure, allowing for longer shelf lives and easier handling and storage. As a colorant, TiO2 also improves patient acceptability and enables to distinguish different strengths of medicinal products.
  • It is not feasible to replace TiO2 in medical products without a negative impact on the quality and availability of medicines in the EU.
  • There is a “real risk” that the time and costs for the replacement of TiO2 would result in “significant medicine shortages” or withdrawals from the market, with particular concerns for pediatric and orphan medicinal products.

The EC proposes to maintain authorization for TiO2 in medicinal products pending review

On 28 September, the EC proposed to maintain the authorisation for TiO2 in medicinal products. The EC will review the continued use of TiO2 in medical products within three years after the date that the amendment to Regulation (EC) No 1333/2008 concerning the food additive E171 comes into force. The EC’s review will be based on an updated assessment by the EMA to be performed before 1 April 2024.

No concerns identified for TiO2 in medicines

The European Food Safety Authority (EFSA) concluded on 6 May 2021 that TiO2 can no longer be considered safe for use as the food additive E171 because the Authority could not rule out a concern about genotoxicity. The EFSA did not identify any immediate health concerns linked to E171 or raise any concerns about the use of TiO2 in medicines. The EC’s proposal amending Regulation (EC) No 1333/2008 concerning the food additive E171 is expected to come into force in January 2022.

The TDMA is addressing the EFSA’s opinion by updating its science program to generate further data to confirm the safety of E171. The TDMA is committed to engaging with all relevant stakeholders to provide information about TiO2 in medicines.

The TDMA continues to stand behind the safety of TiO2 in all intended applications. The TDMA fulfilled all the data requirements requested by the EFSA, all of which showed no adverse effects. Read more about the EFSA opinion on TDMA’s website.