The Impact of Europe’s Decision on the Use of Titanium Dioxide

According to the European Commission (EC), titanium dioxide (TiO2) is used in 91,000 human drug products to add whiteness, accentuate color, ensure uniformed color, maintain color during shelf life, and preserve the API. In 2021, the European Food Safety Authority determined TiO2 was not safe to use as an additive in food because genotoxicity could not be ruled out. The EC, therefore, requested the European Medicines Agency (EMA) review the safety of using TiO2 in drug products in the European Union (1).

The findings of EMA’s updated analysis were released in April 2024 and concluded that while some alternatives to TiO2 performed well when evaluated under certain key performance indicators (KPIs), all were inferior when assessed against all KPIs (2).

The EC announced its findings on the use of titanium dioxide (TiO2) in medicinal products in August 2025 (1); it was decided that the use of TiO2 in drug products would continue.

Pharmaceutical Technology® spoke with Bram Baert, global head of Regulatory Affairs at Lonza CHI, to get industry’s perspective on the EC’s decision.

Patient impact

PharmTech: TiO2 is used in many aspects of drug formulation. How does the EC’s decision to continue to allow it to be used in Europe impact industry? How does it impact patients?

Baert (Lonza): In its recent staff working document evaluating the possibility of replacing TiO₂ in medicines, the EC identified several important factors shaping its decision. The EC concluded that fully replacing TiO₂ in all pharmaceutical products is currently not technically feasible. Where substitution is possible, the process would be lengthy and complex, mainly due to regulatory requirements for re-approval of any new formulations. Since TiO₂ is still allowed in medicines outside the EU, reformulation efforts would likely be limited to products marketed within Europe, potentially disrupting global supply chains and complicating manufacturing and distribution.

Such changes could create significant financial challenges for pharmaceutical companies and, more importantly, threaten the steady supply of vital medications for patients. Additionally, the need to focus resources on finding replacements for TiO₂ may slow investment in new and innovative treatments, especially for conditions with unmet medical needs.

The EC’s decision offers much-needed clarity and stability for both the pharmaceutical industry and patients, since there is currently no definitive evidence highlighting safety risks from oral exposure to TiO₂ in medicines. Drug manufacturers now have regulatory certainty about the continued use of TiO₂ in approved products, enabling them to shift their efforts toward more impactful activities. Patients can also feel confident that they will continue to receive their medicines with consistent appearance and formulation.

Looking ahead, the EC is encouraging ongoing collaboration between drug manufacturers and excipient suppliers, especially in developing new drug products. This keeps the door open for continued research into alternative excipients and supports further investment in creating TiO₂-free options for the market.

Potential alternatives to TiO2

PharmTech: Is there a potential alternative to TiO2 on the horizon?

Baert (Lonza):Regulatory bodies continually assess the suitability of ingredients and additives in food and pharmaceutical products. With this in mind, drug manufacturers must stay proactive and focus on developing TiO₂-free alternatives that comply with evolving regulations and align with patient preferences while maintaining the highest ingredient quality.

When exploring alternatives to TiO₂, manufacturers encounter a number of challenges. TiO₂ is a unique ingredient as it is capable of delivering a bright white appearance and high opacity even at low concentrations. Excluding TiO2 from the current list of approved colorants still allows [for the] creat[ion of] a huge variety of color options, but those that can replicate both the whiteness and opacity of TiO₂ remain limited. For applications where whiteness is important, calcium carbonate may serve as a viable option while opacity can be achieved through materials such as iron oxides. These alternatives can meet specific performance needs depending on the expectations. Looking beyond currently approved colorants, there are substances that can provide comparable technical performance. Lonza, for example, developed Lumishield capsules, which contain phosphate salts and provide superior whiteness and opacity without jeopardizing the filling performance of the capsule. However, the adoption of such alternatives may involve regulatory complexities.

While it is clear that alternatives exist for certain applications, achieving a balance between technical performance and regulatory compliance often requires thoughtful compromise. To develop truly equivalent solutions, both from a performance and regulatory standpoint, further collaboration among excipient manufacturers, drug product manufacturers and regulatory authorities is essential. By working together, stakeholders can foster an environment that supports innovation and drives progress toward viable, future-ready alternatives.

PharmTech: Should pharma manufacturers continue to try and develop alternatives?

Baert (Lonza):Today’s pharmaceutical marketplace is shaped by a growing diversity of patient and consumer preferences, including religious dietary requirements [such as] Halal and Kosher, lifestyle choices such as veganism, and a desire for organic, non-genetically modified organism, or gluten-free options. There is also an increasing demand for transparency about product ingredients as well as heightened attention to environmental sustainability and safety.

While these considerations have traditionally mattered more in the food and supplement industries, they are now becoming increasingly important in pharmaceuticals, especially for over-the-counter products. As a result, drug manufacturers must factor in these evolving expectations when designing and formulating their products. These changes affect choices about which polymers, excipients, pigments and dyes to use, as consumers become more attentive to ingredient safety, sourcing, and sustainability.

Meanwhile, regulatory authorities are also re-evaluating the acceptability of certain ingredients and additives in both food and medicines. In this dynamic landscape, drug manufacturers must remain proactive and continue to focus on developing TiO₂ alternatives that meet future regulatory requirements and reflect shifting consumer values, all while maintaining product quality, stability, and efficacy.

A supportive regulatory environment is critical for the industry to succeed in creating innovative excipient solutions. The current lack of well-defined approval pathways for new excipients poses a major challenge to innovation. If regulators create clearer frameworks and pathways for novel ingredients, it would encourage the development and adoption of safer, more sustainable, and consumer-focused alternatives in pharmaceutical products.

References

1. EC. Commission Staff Working Document on the Use of Titanium Dioxide in Medicinal Products. Health.ec.europa.eu. Aug. 4, 2025. https://health.ec.europa.eu/document/download/34542b69-8507-4fc2-b106-bd15b481e40d_en?filename=mp_working-doc-titanium-dioxide_en.pdf
2. EMA. Feedback from European Medicine Agency (EMA) to the EU Commission Request to Evaluate the Feasibility of Alternatives to Replace Titanium Dioxide (TiO2) in Medicinal Products and its Possible Impact on Medicines’ Availability. Ema.europa.eu. April 1, 2024. https://www.ema.europa.eu/en/documents/report/feedback-european-medicine-agency-ema-eu-commission-request-evaluate-feasibility-alternatives-replace-titanium-dioxide-tio2-medicinal-products-its-possible-impact-medicines-availability_en.pdf