During a keynote presentation at the Botanical Safety Consortium on Sept. 29, Thomas Brendler, PhD, a scientist and consultant with over 30 years of experience in the field of natural products, described Article 8 as “a narrow instrument with a high evidentiary bar.”
Brendler’s central argument revolved around the idea that while concerns about certain botanical ingredients are valid, the evidence used to trigger Article 8 procedures rarely provides the full picture.
For example, regulators often use high-dose toxicity data to initiate regulatory action without evaluating actual consumer intake. Safety thresholds are also often calculated for isolated, pure compounds, but bans are then applied to whole-plant preparations.
“Regulatory concerns about botanicals and food supplements are not per se illegitimate, but the instrument being used to act on them, I feel, is miscalibrated in several identifiable ways,” Brendler said.
What is Article 8 and how has it been used historically?
Article 8 of Regulation (EC) 1925/2006 is the legislative tool used to establish a list of plants and other ingredients (excluding vitamins and minerals) which are prohibited in food supplements.
Article 8 procedures may be initiated by either the European Commission (EC) on its own initiative or at the request of an EU Member State. They typically respond to preliminary scientific research indicating a potential risk to human health or highlighting significant uncertainty regarding the safety of a substance.
EFSA then reviews all available toxicological, clinical and epidemiological data, and the Commission votes on a final legal act. The ingredient is then placed into one of three categories within Annex III of Regulation 1925/2006: Part A, B or C.
Part A results in an outright ban of an ingredient, Part B restricts the ingredient’s use, and Part C allows food business to submit new safety data within a four-year window.
Brendler said that there are several issues with this process. The first is how safety is initially determined through screening questions, which seek to determine whether there is a “potential risk” resulting from consumption of the substance due to “hazards”. Brendler argues that risks and hazards are not the same thing, yet dossiers can proceed on hazards alone, even when consumer exposure data is missing.
“Hazards without exposure is half a risk assessment presented as a whole one,” he said.
In addition, preliminary safety screenings are often used as the basis for bans or restrictions. Brendler highlighted that the 2024 Heads of Agencies (HoA) report used only existing platform data, performed no new literature searches and deliberately excluded European Medicines Agency (EMA) monographs. Based on this research, 13 priority substances were deemed eligible for an Article 8 procedure.
What is the significance of the HoA report on food supplements?
In January 2024, the European Parliament asked the EC for an EU negative list of botanicals. Five months later, the Heads of Agencies (HoA) published a report which reviewed 117 substances.
The working group singled out 13 ingredients—including melatonin, piperine, curcumin in Curcuma preparations, and ashwagandha—as presenting potential risks to human health when consumed in food supplements. The report recommended that these substances undergo the Article 8 procedure.
The report raised widespread concerns among industry stakeholders, including the European Federation of Associations of Health Product Manufacturers (EHPM). The trade association raised concerns about the nature of the report, including potential overstepping by food safety agencies into risk management decisions and a perceived shift toward banning ingredients based on potential hazards rather than demonstrated risk.
“[HoA] describes its own output as suitable for priority setting and a good starting point for a final risk assessment of the selected substance by EFSA,” Brendler said. “If the exercise had stopped there, there would be no criticism to make.
“The problem is the escalation, because the same 13 summaries in annex C were, in the report’s words, prepared following previous mandates from the EC to EFSA and could therefore serve as template for new mandates. The parliament asked for a negative list built on exactly this class of material. So, what we’re looking at is a screening exercise being asked to carry evidentiary weight it was never designed for.”
The other primary issue with the current system lies in Part C of the annex, according to Brendler. Four years may seem like an ample amount of time for food business operators to submit safety data, but he argued that it is a costly and time-consuming practice. Some businesses simply do not have the means to fulfil this request, which can result in some substances being banned when their safety has not been determined.
Finally, Brendler noted that isolated compounds are often conflated with whole plant preparations. He emphasized that a marker compound is not a preparation, and preparations are not final products, yet regulators routinely use these to apply safety thresholds. For example, a bioavailability-enhanced curcumin formulation was used to create an Acceptable Daily Intake (ADI) level, but this recommendation was then applied to a whole class of curcumin preparations.
For Brendler, Article 8 is therefore not itself a threat; rather the issue is how it is applied.
“Article 8 needs to be applied when a safety risk arises and not for an arbitrary classification purpose otherwise it could set a concerning legal precedent, and that is an objection to the purpose of the exercise, not merely its method,” he said.
Making Article 8 procedures ‘defensible’
Despite these issues, Brendler said that regulatory concern about certain botanicals and other supplement ingredients are legitimate. Supplements deliver a concentrated active ingredient, and these ingredients are often purposefully made more bioavailable, warranting extra safety considerations for certain preparations.
He also highlighted that since there is no pre-market authorization required for supplement ingredients, safety reviews are necessary to decide whether certain products should have market authorization. Finally, when food supplements and fortified foods are flagged widely on the EU Rapid Alert System (RASFF), there is need for further investigation.
To make Article 8 procedures ‘defensible’—or proportionate, practical and scientifically sound—Brendler suggested four core adjustments. This includes evaluating actual consumer intake from supplements and using this exposure data to create a recommendation.
Secondly, the plant part, extraction solvent and overall preparation should be considered, as a genus is not an ‘assessable object’. In addition, when monographs exist, warnings about high doses should be used to inform restrictions, placing them in Part B, rather than Part A (an outright ban).
Finally, he suggested that enforcing quality standards through compendial monographs and validated chemical assays is a far more targeted regulatory solution than outright prohibition. This is because prohibition removes compliant ingredients as well as fraudulent ones.
In the meantime, Brendler recommends that food business operators characterize their own preparations and generate exposure data in order to inform monographs before ingredients come under scrutiny. Collaboration should also be encouraged.
“Trade bodies should encourage collaboration around toxicology,” he said. “No single small operator can fund a battery of tox studies, which is most likely why the scrutiny window is close to empty. Yohimbe went to prohibition that way in 2019 and monacolins and senna are going the same way now.”
