Crossing the Red Line

“Today, the FDA is taking action to remove petroleum-based food dyes from the U.S. food supply and from medications. For the last 50 years, American children have increasingly been living in a toxic soup of synthetic chemicals,” said FDA Commissioner Marty Makary as he kicked off an hour-long news conference this past April.

The podium was flanked by sign-holding ‘MAHA moms’ and their children, as the crowd cheered on the U.S. Department of Health and Human Services and FDA goal to revoke authorization for the eight synthetic dyes currently allowed as food color additives.

But the ‘toxic soup’ science is shaky, and many experts aren’t convinced.

“There’s so much concern about these colors being generated because of the discussions that influencers and RFK and Makary have been having — and most of it is simply not true,” says David Schoneker, president/owner of Black Diamond Regulatory Consulting.

Schoneker has spent more than 48 years addressing regulatory and quality issues in the pharmaceutical, dietary supplement and food industries. Back in the late eighties, while working as an analytical chemist for Colorcon, he examined the rat food containing the dye used in the study that ultimately drove the FDA’s January 2025 decision to revoke authorization of the cherry red additive, FD&C Red No. 3 (erythrosine), for use in food, dietary supplements and ingested drugs.

“There were no effects at any of the dose levels except at the highest dose level, where 4% of the food was pure dye — an amount that no human would ever get exposed to in food,” says Schoneker. “I saw pictures of the rats in the study and their skin had turned bright red because they’d been fed so much dye.”

In fact, the FDA concluded that the rats’ thyroid tumors were caused by a hormonal mechanism that is rat-specific and there is no direct human health risk of Red No. 3 at current exposure levels. “Studies in other animals and in humans did not show these effects; claims that the use of FD&C Red No. 3 in food and in ingested drugs puts people at risk are not supported by the available scientific information,” said the FDA press statement.

The FDA decision to revoke authorization of FD&C Red No. 3 was driven by a 1958 clause in the U.S. Food, Drug and Cosmetic Act known as the Delaney Clause (see sidebar), prohibiting additives linked to cancer in animal studies regardless of human significance. The decision mandates the reformulation of food and dietary supplements by January 2027 and ingested drugs by January 2028.

“The Delaney Clause is an over-precautionary principle that may have been appropriate in the 1950s before we had modern toxicology risk-assessment tools available, but this clause is no longer in sync with today’s scientific understanding and should be deleted from the law,” says Schoneker.

And while the MAHA movement crosshairs are currently hyper-focused on the food industry, the Red No. 3 ban signaled that the pharmaceutical industry isn’t in the clear. When a reporter during the April press conference asked Health Secretary Robert F. Kennedy Jr. about extending the request for removal of the synthetic dyes to pharma applications, he indicated that drugs were next on the evaluation table.

“I think a lot of people are hoping that this won’t come to the drug side or that somebody is going to realize the severe implications it would have in pharma when, in fact, there are no actual safety concerns with these colors,” says Schoneker. For pharma manufacturers, moving away from synthetic colorings would not be a trivial change. Natural alternatives (called “exempt colors” by FDA) can fall short in stability, color vibrancy and scalability, particularly for products requiring multiyear shelf life. reformulation may also affect product identity, patient compliance and global market compatibility. Securing a reliable supply chain at-scale for alternatives will be both extremely challenging and costly — and in many cases, not even possible.

Capsule and coating suppliers are stepping up to help pharma manufacturers navigate evolving regulations and consumer preferences, as the industry braces itself for what could be a crossroads for oral solid dose forms. With the clock ticking on the Red No. 3 ban and more potential requests for removal of synthetic colors to follow, now is the time for pharma manufacturers to advocate strongly for good science to drive decision-making, assess formulation strategies, strengthen supply chain partnerships, and invest in long-term innovation.
 

Consumer Preferences vs. Science

While the Make America Healthy Again Commission only recently became official through a presidential executive order signed this past February, within the food industry, a ‘clean label’ movement has been underway for the past 20 years. At the core of the movement, now driven by health activists and online influencers, is simplicity and transparency — a consumer preference for food that has less ingredients and is free from artificial preservatives, flavors and additives.

The current MAHA focus is to eliminate all ‘petroleum-based’ synthetic dyes from the U.S. food supply by the end of 2026. While Schoneker contends that the “chances of that even possibly happening in anyone’s wildest dream is impossible,” the lack of scientific understanding behind the movement is of greater concern than the timeline.

So called petroleum-based dyes don’t contain any petroleum; they are simply derived from synthetic chemicals through a multistep process that begins with crude oil. Typically, the initial petroleum-derived compounds are used to create a pigment that is then filtered, dried and transformed into the colorant. Every batch of FD&C synthetic dyes are rigorously tested and certified by the FDA to ensure that they contain no traces of any significant impurities and that they meet the stringent specifications outlined in the Code of Federal regulations.

“If this is how RFK is defining petroleum-based, then most drugs and dietary supplements on the market are also petroleum-based,” says Schoneker. “The safety of the chemical is based on the toxicology of the chemical — it doesn’t matter where it came from or how it was made. The only reason you use that terminology is to try to fire up the emotional side of consumers and get everybody thinking it’s something it’s not.”

It is important to highlight that, unlike the synthetic FD&C colors, once natural colors are approved for use, batches are not tested by the FDA — their quality is determined by the manufacturer without any routine FDA oversite. There has been a historical problem with adulteration of some natural colors due to the fact that they are exempt from certification and sometimes supplied by small, less reputable companies from around the globe.

“Consistent industry-wide safety standards are needed to address the manufacturing, processing, application and international trade of colors from natural sources to ensure quality and safety throughout the supply chain,” says Schoneker But yet, consumer demand for natural products has already made its way into the nutraceutical market, with a growing movement towards clean label supplements. And this consumer perception of health and wellness — whether backed by sound science or not — carries weight in the market.

Recognizing the power of consumer buying trends, capsule and coating suppliers have been proactively developing natural color solutions, particularly in the dietary supplement arena.

“Natural colorants are gaining popularity, especially in the nutraceutical space,” says Shincy Jacob, senior manager, global product management, ACG. “Our goal is to provide capsules that not only meet regulatory requirements but also align with shifting market and consumer demands — supporting a smooth transition away from restricted synthetic colors while giving our partners confidence in stability, supply and performance.”
 

“These safety concerns voiced by the MAHA movement about synthetic colors are an awful lot about nothing when it comes down to it since there is no credible scientific data to support them.”

David Schoneker, president/owner of Black Diamond Regulatory Consulting
 

ACG introduced its ACGcaps NTone™ portfolio of naturally colored capsules to the nutraceutical market in 2021. The five different color options are derived from natural sources. The company has seen a steady growth in interest from nutraceutical formulators looking for ‘cleaner’ coloring solutions.

While Red No. 3 is currently the only synthetic color that has had its FDA authorization revoked for use in dietary supplements and drugs, suppliers stress that manufacturers should not wait for additional regulatory mandates in the scenarios where alternatives are possible.

“We’re already ahead here. CapsCanada has the widest range of natural capsule colors on the market, and we move fast when it comes to reformulation. Even though regulations aren’t harmonized globally, we are offering both clean-label natural options and compliant synthetics, so our customers stay covered in every market,” says Manny Ocampo, director of sales – North America, CapsCanada.

And while suppliers are rightly focused on accommodating customer needs driven by consumer trends, scientists in the space can’t help but get hung up on the science. “These safety concerns voiced by the MAHA movement about synthetic colors are an awful lot about nothing when it comes down to it since there is no credible scientific data to support them. But technically, you can’t say consumer beliefs are nothing because those beliefs can affect what they buy, especially in the dietary supplements arena. And certainly, companies have to respond to that — even if scientifically, a lot of these concerns don’t hold water,” says Schoneker.
 

Technical Challenges

One could argue that in the food industry, the occasional off-colored cookie or crumbled piece of candy might go virtually unnoticed. But in pharmaceuticals, quality — the reliability of a product to meet specified standards and perform its intended function safely and effectively — is paramount.

While the shift to natural colors in the food industry would be a significant feat, there are even greater obstacles when it comes to using natural colors in pharmaceuticals. Tablet coatings and capsules must be stable to various environmental factors such as light, pH, humidity and heat in order to ensure efficacy over the multiyear shelf life needed in the drug space.

“If you think about stability, in the food arena, if you can get a couple months out of it, chances are that’s enough for most foods. But for drugs, if you don’t have two or three years of stability, you don’t even have a product,” says Schoneker.

The natural alternatives for Red No. 3 are, at present, extremely limited for pharmaceutical uses. The best option is cochineal extract and its aluminum lake version, carmine, which are derived from female cochineal insects. In pharmaceuticals, the Red No. 3 alternative can be used in coated tablets, syrups and gelatin capsules. While it is a fairly heat and light-stable colorant, it is not vegetarian, vegan or kosher. There is also a risk of allergic reaction in certain portions of the population, which needs to be indicated on the labeling.

The need for an even more significant reformulation is also a looming possibility. Natural dyes tend to be weaker in color than synthetics, necessitating the use of more coloring to achieve the desired brightness. “On average, you usually have to use anywhere from 3-5 times as much of the natural color in your formulation than you do with synthetic color,” says Schoneker.

In the drug industry, this can be particularly problematic because the amount of natural color used could trigger potential interactions with active pharmaceutical ingredients and/or the color additive changes could exceed the maximum allowable percentage levels by regulators. Additionally, there is only a very limited list of natural colors approved for pharmaceutical uses in the U.S., which can limit the types of colors that can be achieved.

Color also matters when it comes to brand identity. Patient and health care professionals rely on colors for drug and dosage identification. Natural colorings tend to not render as bright and pure as synthetic colors and there is more color variation from natural source differences due to weather, growing locations and variable manufacturing processes from different suppliers.

“The challenge of replacing synthetic with natural is that natural colors can vary by batches, so getting the same tone sometimes can be difficult,” says CapsCanada’s Ocampo.

Changing to natural colorants will likely require the need to communicate the change to patients and health care professionals, label changes, and in some cases, the use of alternative, more opaque packaging if the natural colors are light sensitive.

“What it comes down to is if drugs have to shift to natural colors, you will generally have second-class drugs in terms of quality. You will have shorter shelf lives, color changes from the current drug colors, color variability from batch to batch and potential formulation interactions with APIs that do not exist with the synthetic colors,” says Schoneker.

Regulatory Red Tape

Globally, there is little regulatory harmonization in terms of approved colorants in pharmaceuticals. Importantly, natural doesn’t always equal permissible.

“Customers must also consider the regulations for each territory as even some natural colorants, such as carmine, are not allowed freely,” says Ocampo.

And despite the commonly repeated MAHA narrative, most synthetic dyes, including Red No. 3, are not banned for use in pharmaceuticals anywhere in the world. In the U.S., compliance with the Red No. 3 ban will be a regulatory inconvenience, but a further push towards natural colors could be a logistical nightmare.

In May 2025, the FDA issued new draft guidance intended to provide recommendations for replacing color additives in approved or marketed drug products.

“The FDA’s draft guidance outlines specific data requirements when changing colorants. Formulators must demonstrate that stability is maintained and that properties such as opacity and light protection remain unaffected. While in some cases reformulations may qualify as a CBE-30 filing, in most instances, a prior approval supplement will be required due to the reformulation impact,” explains ACG’s Shincy.

If manufacturers intend to use a color additive that is already listed in FDA’s color additive regulations for use in drugs, and the change meets the agency’s definition of “moderate,” then manufacturers will need to submit information via the CBE-30, or “changes being effected within 30-days,” form. For major changes, a prior approval supplement will be necessary. In order to assess the level of change, manufacturers will have to provide additional data including at least three months of stability data at accelerated and long-term stability conditions.

If a manufacturer or an applicant intends to use a color additive that is not already listed in FDA’s color additive regulations for the particular use, a petition must be sent to the FDA’s Human Foods Program. And according to Schoneker, the timeline for color additive petitions is lengthy — an extension petition to add drug uses for an existing color already approved for food use can usually get done in one to two years, but a new color additive can take up to five years or more to be approved.

“There are a number of colors that are being developed using new technology, such as precision fermentation, that long term I think are going to be great tools for us. They’re being made from things with a more sustainable supply, like algae, bacteria, yeast and other microorganisms,” says Schoneker. “But none of those materials have been approved as color additives by the FDA yet so they are not viable colors for commercial use at this time.”

Precision fermentation involves genetically engineering microorganisms to produce specific color compounds in a controlled environment.

“The technology enables the production of vibrant, stable pigments without relying on traditional plant or insect sources. This approach addresses many challenges such as stability, sustainability, dietary inclusivity, and consistency of supply, while also offering the potential for large-scale production,” says Shincy.

However, Shincy points out that precision fermentation may also raise additional considerations, such as GMO labeling requirements in the U.S. and EU, as well as consumer opposition to GMO products.

Here manufacturers can also lean on suppliers for their insights and experience.

“Our approach is highly collaborative. We work closely with manufacturers, suppliers, regulatory experts, and our in-house shade development teams to ensure every solution offers consistent quality and compliance,” says Shincy.

Ultimately, if bans spread beyond Red No. 3, pharma will have to sink more time — and money — into additional fi lings and data gathering, which means less will be available for R&D and future innovation.

Red Gold

But perhaps the most overlooked factor embedded in the rise of the natural-is-better narrative is the potential limitation of the supply chain.

“Unlike synthetics, natural colorants cannot yet match the scale of supply that global manufacturers require. replacing Red No. 3 on a large scale is restricted not only by agricultural capacity but also by sustainability challenges and higher production costs. As a result, while options are available, manufacturers face a more complex balancing act when it comes to cost, supply, and regulatory compliance,” says Shincy.

For example, the cochineal beetles that are used in carmine are primarily harvested by hand from prickly pear cactuses in Peru, Bolivia, Argentina and the Canary Islands. It takes approximately 154,000 cochineals to create one kilo of dye (70,000 cochineals per pound of dye).

There is also a cost factor. The price of carmine in the current supply situation is roughly $85 to more than $500 per kilogram. By comparison, one kilogram of Red No. 3 costs roughly $20-$120.

But if the global food, nutraceutical and pharma industries all begin competing for the same limited natural ingredients, the situation could rapidly escalate.

“You can start to see cost implications. If all of a sudden everybody starts trying to use more carmine, what do you think is going to happen to that price? Carmine is going to be red gold as the demand increases because supply is extremely limited,” says Schoneker.

What it could boil down to do is an impossible situation: “There is not enough natural color available in the world today to replace the volume of synthetic colors that we just use here in the U.S., much less what they use in Europe and everywhere else,” warns Schoneker.

May Good Science Prevail

In the food industry, the natural-is-safer narrative is already louder than the science, and consumer pressure rarely stops to listen to toxicology data. But pharmaceuticals present an entirely different set of stakes, where evidence-based decisions are expected to take precedence.

“That’s the frustrating part as a scientist, as somebody who knows the facts, to see what this MAHA misinformation is causing and the amount of eff ort that’s going to go on here in reformulation. Given the supply chain limitations and costs, and ultimately what consumers and patients are going to have to pay for this move away from synthetic colors, it’s just such a waste of resources in my opinion,” says Schoneker.

Yet the first federal ban on a synthetic color due to the outdated Delaney Clause has inked a line in the sand — and crossing it could push the industry past the threshold of science-driven formulation into an era ruled by consumer perception based on misinformation. For manufacturers, navigating this evolving landscape will require both precision and foresight — and the time to start is now. Increasing advocacy for good science to be the basis for regulatory decisions and debunking misinformation to improve consumer understanding will also be key as we move into this future environment.

“It’s certainly a hot topic and as a consultant, I guess it’s good business for me. But as a scientist, I would give all that up in a heartbeat if good science would prevail and this would not be an issue,” says Schoneker.
 

References

FDA to Revoke Authorization for the Use of Red No. 3 in Food and Ingested Drugs. (2025, Jan). US FDA. [constituent update]

Singson, B. and O’Brien, G. (2025, May). HHS and FDA Announce Plans to Phase out Synthetic Food Dyes. Mayer Brown.

Understanding How the FDA Regulates Color Additives. (2023, July). US FDA.

Simon, J., et al. (2017, Nov). Establishing Standards on Colors from Natural Sources Journal of Food Science. 82(11). 2539-255.

The Rise of Clean Labels and Transparent Food Choices. (2025, Jan). Palmer Holland.

Flanagan, M. (2009, Jan). FDA Requires Identification of Carmine and Cochineal Extract on Food Labels. Foley & Lardner.

Myth vs. Fact on Red No. 3 and Titanium Dioxide. (2023, May). IACM.

Replacing Color Additives in Approved or Marketed Drug Products. (2025, May). CDER. [draft guidance for industry]

Regulatory Status of Color Additives. US FDA. [accessed Sept 15, 2025]

Gras, C. and Müller-Maatsch, J. (2024). Chapter 21 - The “carmine problem” and potential alternatives. Handbook on Natural Pigments in Food and Beverages (Second Edition). Woodhead Publishing, 465-506.

Carman, K. How Carmine, the Red Dye Made From Bugs, Makes It Into your Food. How Stuff Works. [accessed Sept 15, 2025]

Cochineal Dye Price: What influences the cost of this Natural Red Colorant? (2025, April). Imbarex.