When Does a Plant Stop Being a Supplement and Start Being a Drug?
In 20 years, only 4 botanical drugs have been approved in the U.S. Botanical drugs receive less funding because unrefined plant mixtures are difficult to patent, harder to standardise, and face complex regulatory hurdles that scare off investors. In the U.S. a bill may be about to pass that could encourage more botanical drug development. This is interesting to us here in Australia as it can have a knock-on effect and could well create a distinction between supplements (a relatively unregulated yet massive market) and plant medicine. As well as considering how our own plant actives – Terpinen-4-ol and Cineole – can be used, with Cineole most notably already being tested in clinical trials as an ingestible medicine for pain relief and acute rhinitis.
Twenty years of regulatory stagnation may be reversing
For two decades, the botanical drug pathway has sat almost unused. That's changing fast, with new legislation, an open FDA comment period, and a joint workshop with European regulators all landing within weeks of each other. Here we discuss what is going on, and why the distinction at the centre of it, a complex mixture versus isolated compound, matters more than it first appears.
What is a botanical drug?
The FDA's definition is specific: a botanical drug is a medicine derived from plant material, algae, or macroscopic fungi, intended to diagnose, treat, or prevent disease. It can take almost any form: tea, powder, tablet, tincture, topical, even an injection.
What makes the category unusual is what it allows a medicine to be. A botanical drug is permitted to remain a complex mixture, often with dozens or hundreds of interacting constituents and no single confirmed "active ingredient." That is normally disqualifying in drug development, where regulators want one molecule, one mechanism, one dose-response curve. Botanical drugs are the exception, provided they still go through the same rigorous approval pathway as any prescription medicine, backed by full clinical trials.
What about penicillin and morphine?
It's a fair question: penicillin comes from a mould, morphine and codeine come from the opium poppy, so why aren't they botanical drugs too?
The answer is isolation. Both were purified out of their natural source down to a single, defined chemical entity, then manufactured and dosed as that one molecule. The botanical drug category is reserved for products that stay as the whole mixture; the plant chemistry left largely intact, not stripped down to its most active-seeming piece. The moment a single compound is isolated and purified from a plant or fungus, it becomes a conventional drug, regardless of its origin.
That line, complex mixture versus isolated compound, is precisely where the industry's current confusion sits. Roy Upton, founder of the American Herbal Pharmacopoeia, has put it plainly: the US doesn't appear to have a clear threshold for when a supplement crosses into drug territory. Is a botanical ingredient a food-supplement providing modest, synergistic benefit, or an isolated compound at pharmaceutical potency, meant to intervene therapeutically? Increasingly, that's a question regulators can't answer with a clean rule.
Two decades, four approvals
Since the botanical drug pathway was formalised, only four products have made it all the way through:
- Veregen — a green tea extract, approved for genital warts
- Mytesi (Fulyzaq) — from the dragon's blood tree, for HIV-related diarrhea
- NexoBrid — a pineapple stem–derived enzyme, for burn wounds
- Filzuvez — a birch bark extract, for a rare skin condition (epidermolysis bullosa)
A handful of other botanicals, like psyllium and witch hazel, reached the market through separate OTC safety monographs rather than the full botanical drug pathway.
Four approvals in twenty years is a strikingly low number, and the reasons given are consistent on both sides of the Atlantic. Dr. Joerg Gruenwald, founder of the research firm Analyze & Realize, describes the barrier as "tough requirements, high investment costs, and a long process," a combination that discourages development regardless of jurisdiction. Plant material adds its own layer of difficulty on top of that: batch-to-batch variability that a single-molecule drug simply doesn't have to contend with. The EU's own herbal drug pathway shows the same pattern, sitting underused while the supplement category around it grows substantially faster.
What's changing now?
Three things have converged in the space of a few weeks:
In August, Congresswoman Lauren Boebert introduced the Advancing Botanical Drug Development Act, proposing 12 years of market exclusivity for botanical drug developers. Notably, the bill goes out of its way to state that "botanical drugs are FDA-approved medicines, not dietary supplements," an attempt to draw a firmer line, not blur one.
At the same time, the FDA has opened a public comment period, running through November 3, to reassess the botanical drug landscape, following a Reagan-Udall Foundation roundtable earlier this year.
And later this month, the FDA and the European Medicines Agency are holding a joint workshop specifically to compare regulatory approaches to botanical medicines on both sides of the Atlantic.
The real sticking point
It's tempting to read this as simply a funding and incentive problem – add exclusivity, attract investment, get more approvals. But the people closest to the category argue the bigger obstacle is definitional, not financial. Without a clearer, shared understanding of where "supplement" ends and "drug" begins, stronger IP protection may not be enough to move the needle.
It's also worth seeing this in its broader context. Botanical drugs are just one part of a wider pattern — alongside peptides and IV-delivered therapies — of supplement-adjacent categories drifting toward pharmaceutical-style development and regulation. Call it the "pharmafication" of the natural products world. However this particular legislative and regulatory push plays out, it's a signal worth watching: the boundary between a plant-based supplement and a plant-based medicine is being actively redrawn, and the outcome will shape how the whole category is regulated for years to come.
Sources
All of a Sudden, It’s All about Botanical Drugs SupplySide SJ — "All of a sudden, it's all about botanical drugs"
Botanicals as “new” drugs: US development. Science Direct. https://www.sciencedirect.com/science/article/abs/pii/S1525505015004126
What is a Botanical Drug? https://www.fda.gov/about-fda/cder-offices-and-divisions/what-botanical-drug
A New Pathway: Botanical Drugs and the FDA https://jintegrativederm.org/doi/10.64550/joid.ysj2js31
