The European Commission, citing the EMA’s April 2024 analysis, will continue to allow titanium dioxide (TiO₂) in EU medicines under Regulation 2022/63 because no suitable replacements currently exist. TiO₂ is widely used for its whitening, opacifying, and protective qualities, including ensuring uniform tablet color and shielding active ingredients from light. The EMA projects that reformulating the entire portfolio would take between seven and 12 years.
While maintaining TiO₂, the commission has encouraged pharmaceutical companies to continue researching viable alternatives. We speak with Dr. Subhashis Chakraborty, General Manager and Head of Global Product Management at ACG Capsules, to find out more about what the ruling means for pharmaceutical manufacturers.
How do you see the EU decision affecting drug formulation strategies in the short and long term?
We need to recall the situation of a few years ago, when a potential ban on titanium dioxide in pharmaceutical products was first indicated. The concern was global. Developing standalone strategies for Europe in a global market is not straightforward. TiO₂ was used in nearly 91,000 human and 1,600 veterinary medicines in the EU, not merely as a colorant, but as a critical opacifier ensuring stability, protection, and patient compliance.
Faced with this, many scientists initiated TiO₂-free development projects as a contingency measure to avoid being caught unprepared if the ban came into force. However, the EC’s decision to continue allowing TiO₂ in medicines safeguards supply security and frees up critical resources that can now be better directed toward true innovation and patient needs rather than reactive reformulation.
However, this episode has been a wake-up call for the entire ecosystem. Manufacturers have learned the importance of building resilience into product development and preparing for sudden regulatory shifts. Regulators, on the other hand, have recognized the profound impact that such decisions can have on supply chains, access, and patient safety.
In the short term, drug formulation strategies will likely continue with TiO₂ as the preferred choice given its proven functionality. However, in the long term, the industry will continue to explore robust alternatives – not only as a risk-mitigation measure, but to align with trends toward natural excipients, patient-centric design, and global regulatory harmonization. The incident has instilled both caution and creativity, pushing the industry to think ahead and be better prepared for the future.
What are the biggest scientific and technical challenges in developing capsules without TiO₂?
The biggest challenges in developing TiO₂-free capsules stem from the fact that TiO₂ does far more than provide whiteness. It ensures opacity, masks formulation variability, creates a uniform appearance, and protects photosensitive APIs. Replicating all these functions without TiO₂ demands rethinking material science, and designing alternative colorant systems, alongside ensuring consistency at scale.
One complex challenge has been comparisons with tablets. While opacifiers can work effectively on a flat, white tablet surface, their behavior in transparent capsule shells is vastly different. Another hurdle was identifying an equivalent excipient with multifunctional performance similar to TiO₂.
We did not want to appear overconfident in our own path, so we consulted with independent experts, fellow excipient suppliers, and even experienced customers to validate that our development and product strategy were on the right track. This collaborative approach gave us the confidence to move forward without second-guessing, while ensuring that our solutions were rooted in both science and industry acceptance.
Can you elaborate on the role of your collaboration with the IQ Consortium in influencing the regulatory decision, and what insights were gained?
We contributed both technical data and practical experience from our internal studies, and we supplied customized empty hard capsules that enabled detailed experimental studies.
Maintaining continuous technical dialogue with the IQ Consortium with regular feedback loops ensured that the database reflected not only scientific findings, but real-world manufacturing challenges. The outcome was a body of evidence that was fact-based, balanced, and logical, helping regulators understand both the indispensability of TiO₂ and the limitations of current alternatives.
This collaboration highlighted two important insights: that TiO₂ remains technically indispensable in most medicines today, and that any move to alternatives must be gradual, evidence-based, and globally harmonized to avoid jeopardizing medicine supply.
How are you preparing to adapt to potential future shifts in global excipient regulations?
Further regulatory scrutiny on excipients is inevitable. As science advances and patient safety takes center stage, regulators will no longer treat excipients as “inactive.” Their role in quality, stability, bioavailability, and even patient acceptance is too critical to be overlooked.
The TiO₂ debate was just the beginning. Other widely used excipients, particularly synthetic colorants, are already under discussion as authorities and consumers alike show a clear preference for natural and cleaner-label options.
There’s no scientific or business sense in waiting for regulations to change. It makes more sense to actively and pro-actively anticipate them by engaging with pharmacopeias, regulatory agencies, and global standard-setting bodies to stay ahead of emerging expectations. More importantly, these insights should be used to guide innovation pipelines, ensuring that capsule solutions are not only compliant today, but “future-ready.” This includes developing alternatives with natural colors, while addressing challenges such as stability, consistency, and scalability.
By collaborating with industry peers, scientific experts, and regulators, ourselves, as well as other stakeholders in this field, are helping drive a more evidence-based, science-led approach to excipient evaluation.
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