In the wake of the ban on titanium dioxide (TiO2) E171 in the production of food and dietary supplements in the European Union, the pharmaceutical industry is left contemplating whether it will possibly face a similar ban — which could happen as early as 2025.
Why exactly is titanium dioxide’s safety being questioned? If its safety is really a concern, is there a possibility of phasing it out completely from the EU? How prepared is pharma to cope with this change? Won’t this decision affect other global markets? What position have other regulatory authorities already taken? What could be the potential implication of this ban across other geographies? These are just a few of the unanswered questions that remain a key concern for the pharma industry.
Although the ban is only applicable to the European jurisdiction, titanium dioxide’s restricted use or complete prohibition in the production of drug products by the European Medicine Agency could soon result in a snowball effect on other global markets. Moreover, companies supplying medicines to the EU and other regions will find themselves having to handle two parallel versions of every product — one containing TiO2 and another devoid of it. And, more importantly, imagine the drug shortage scenario that could arise if appropriate alternatives are not identified or become inadequately available.
Titanium dioxide in pharma
Titanium dioxide has been used as a coloring and opacifying agent in the pharma industry for more than half a century. From capsule shells, tablet and pellet coatings to suspensions and pastes, it is almost ubiquitously used in a wide range of dosage forms to impart product aesthetics and protect sensitive APIs from degradation.
Unfortunately, no other excipient has been able to demonstrate a similar whiteness and opacity to titanium dioxide. Therefore, although there are possibilities, replacements will have certain limitations.
While new formulation development may not be challenging, finding alternatives for more than 90,000 existing marketed products will take a heavy toll from a financial, time and resource point of view. This could also be coupled with the myriad uncertainties of drug products being withdrawn from the market, impacting the health of millions of patients.
Pharma’s diverse response
There is already diverse opinion within the scientific community regarding the ban. Many global regulators in Canada, UK, Australia/New Zealand and the U.S. have already taken an independent stance to disagree with the precautionary measures taken in the European Union.
Reformulating the existing drug products is not as simple as it appears. Replacing titanium dioxide with an alternative is a mammoth task as it requires assessment from different aspects including regulations, compatibility, safety, efficacy, processability and stability. While the International Pharmaceutical Excipients Council along with the members of the Innovation & Quality Consortium are working to explore the appropriate strategy to handle the situation, pharma companies have begun looking for titanium dioxide alternatives for their new drug developments.
The allied industry supporting the pharmaceutical sector has started offering alternative excipients such as calcium carbonate, talc and starch for white options and iron oxides for colored options. At ACG Capsules, we sensed the looming issue some time ago and, irrespective of the fate of the titanium dioxide ban in pharma, have partnered with the industry to support them by offering alternatives, including different colored variants in both gelatin and cellulose-based capsules. Additionally, we work with pharma companies on technical training — focusing on educational aspects around the different alternatives.
At this stage, there are no certain answers. With so many unforeseen obstacles along the way, it is difficult to predict whether titanium dioxide will be banned in the pharma industry. Its fate will depend upon how the scientific data and rationale being generated takes shape, and, importantly, how it will be perceived by regulatory bodies.
For now, the only option available is for excipient manufacturers and drug developers to work closely in order to ensure the pharma industry can correctly progress and is properly prepared to face the outcomes of a titanium dioxide ban.
