EMA technical and procedural guidance on the replacement/removal of titanium dioxide (TiO2) in medicines

Last updated: 28 November 2023

See updates at the end of the post.

The European Medicines Agency (EMA) has published technical and procedural guidance on the replacement/removal of titanium dioxide (TiO2) in medicines.

The guidance is provided under the following headings:

  1. What does the Commission Regulation (EU) 2022/63 on TiO2 mean for pharmaceutical companies developing and/or maintaining an authorisation of medicines for human use?
  2. What should I do if I am an applicant of an MAA that contains TiO2?
  3. What should I do if I am an MAH of a MA containing TiO2?
  4. What are the scientific data requirements to remove/replace TiO2?
  5. What are the regulatory pathways to support a change in excipients to remove/replace TiO2 in medicinal products?

On 6 May 2021, the European Food Safety Authority published a scientific opinion on the safety assessment of titanium dioxide (TiO2) as a food additive, which concluded that based on all evidence available, a concern for genotoxicity could not be ruled out. In this post, you can read more about the timeline of deliberations concerning TiO2.

Commission Regulation (EU) 2022/63 of 14 January 2022 amending Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council as regards the food additive titanium dioxide (the Regulation) entered into force following its publication in the Official Journal of the European Union on 18 January 2022.

  • The Regulation foresees that TiO2 remains for the time being on the list of authorised additives to allow its use in medicinal products as a colourant.
  • One of the reasons for that decision is to avoid shortages of medicinal products containing TiO2 as this could impact public health and animal health and welfare.
  • The replacement of TiO2 requires investigation and testing of suitable alternatives to ensure that quality, safety and efficacy of medicines are not negatively affected.
  • The function of TiO2  is typically described as a ‘colourant’ although TiO2 exhibits multiple functionalities from a pharmaceutics perspective (e.g. opacity, enhancing contrast, inertness, protection from UV light and the finish/smoothness of the resulting product) .
  • The Regulation is applicable to all medicinal products containing TiO2 independent of its pharmaceutical form.
Further information
  1. Read blog post entitled EMA feedback to EC on the impact of the removal of TiO2 from the list of authorised food additives in medicinal products here.
  2. Pharma groups fight proposed ban on titanium dioxide in Europe –  27 November 2023,  Joanne S. Eglovitch, RAPS
Sources:

European Medicines Agency

RAPS

Update(s)
DateUpdate(s)
28 Nov 2023New section Further Information added.