18.1.2022
EN
Official Journal of the European Union
L 11/3
(14)
Directive 2009/35/EC of the European Parliament and of the Council (6) restricts the use of colours in human and veterinary medicinal products to those authorised in accordance with Regulation (EC) No 1333/2008 on food additives, for which specifications are laid down in Commission Regulation (EU) No 231/2012 (7).
Uses of excipients other than colours in medicinal products are subject to the Union rules on medicinal products and are evaluated as part of the overall benefit risk profile of a medicinal product.
(15)
In response to a request from the Commission, the European Medicines Agency (EMA) provided on 8 September 2021 a scientific analysis on the technical purpose of the use of titanium dioxide (E 171) in medicinal products, the feasibility of replacement and possible timeframes for alternatives.
In its conclusions, EMA indicated that titanium dioxide is mainly used in medicinal products as a colour and opacifier, even if it has multiple functions.
It also stressed that titanium dioxide is used frequently in a number of essential medicinal products in oral-solid and oral semi-solid dosage forms.
EMA also stressed that, from a technical point of view, it should be possible to find alternatives to replace titanium dioxide (E 171)-containing coatings, both as colour and for other uses.
However, it also underlined that its feasibility is not confirmed at this stage, as replacing titanium dioxide (E 171) would impact in a negative manner the quality, safety and efficacy of medicinal products.
EMA highlighted the need to carefully assess alternatives, notably to ensure their compatibility with the various components of individual pharmaceutical products.
The replacement of titanium dioxide (E 171) in authorised medicinal products would require an individual review and assessment, possibly requiring bioequivalence studies.
Furthermore, EMA concluded that it is difficult at this stage to recommend a precise transition period timeframe for the replacement of titanium dioxide (E 171) used in medicinal products, as the time needed to reformulate each individual product could take several years, depending on the complexity of reformulation and studies required.
Finally, considering the scale of the use of this excipient and the volume of products impacted, and taking into account global supply chains, EMA stressed that a requirement to replace titanium dioxide (E 171) would almost certainly cause significant medicines shortages on the Union market.
(16)
On the basis of the EMA scientific analysis, and in order to avoid shortages of medicinal products that could have impacts on public health, titanium dioxide (E 171) should remain provisionally on the list of authorised additives to allow its use in medicinal products as a colour, pending the development of adequate alternatives to replace it while ensuring the quality, safety and efficacy of the medicinal products concerned.
During this time, titanium dioxide (E 171) should however be included in the list of colours that may not be sold directly to consumers.
(17)
It is of critical importance that the pharmaceutical industry makes any possible efforts to accelerate the research and development of alternatives that would be used as a replacement for titanium dioxide (E 171) in medicinal products, and to submit the necessary variation to the terms of the marketing authorisations concerned.
In the absence of such efforts, competent authorities may request the concerned stakeholders to submit objective and verifiable reason explaining the non-feasibility of the replacement.
(18)
The Commission is committed to review the necessity to maintain titanium dioxide (E 171) or otherwise delete it from the Union list of food additives for exclusive use as a colour in medicinal products within three years after the date of entering into force of this Regulation.
This review should be based on an updated assessment of the EMA to be performed before 1 April 2024.
It should take into account the progress made during this period to develop alternatives to titanium dioxide (E 171) in medicinal products both for new products and for replacing it in authorised products, and possible impacts on quality, safety and efficacy, as well as on the availability of medicinal products.
Where replacement of titanium dioxide (E 171) in medicinal products has not taken place or been initiated within this period, only objective verifiable reasons related to the lack of feasibility of its replacement should be taken into account.
(19)
Annexes II and III to Regulation (EC) No 1333/2008 should therefore be amended accordingly.
(20)
The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Plants, Animals, Food and Feed,
(6) Directive 2009/35/EC of the European Parliament and of the Council of 23 April 2009 on the colouring matters which may be added to medicinal products (OJ L 109, 30.4.2009, p. 10).
(7) Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council (OJ L 83, 22.3.2012, p. 1).