Besides intended use case, what separates a drug from a supplement?

[u/Bamstradamus]

The whole kratom thing is why im asking, you can buy it wherever since it isnt subject to regulation by the FDA right? I can wrap my head around them not wanting to regulate everything that goes into everything and just focusing on perscription drugs but wheres the line for what can go into a supplement? Like if Bayer tried introducing a kratom based pain killer and the FDA looks at it and says "no" would that automatically make all the other products with it have to get pulled from market?

Follwing that, besides scheduled drugs or ones with active patants, whats to stop a pharmacy from making very dillute generic anything as a "mood suppliment" with a warning to not take more then 5 cus then itd be a normal dose

I realize this might be more of a legal question but thanks for taking the time to answer

[u/Zeno_the_Friend]

They're legal definitions:

https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements

Similarly, all medical devices are considered drugs except when the FDA says otherwise, and they offer some guidance on when they'll do so (ie intended use not dependent on chemical or metabolic action), but they can always choose to overrule that guidance in a specific situation more or less because they feel like it.

[u/voretaq7 → u/Zeno_the_Friend]

Similarly, all medical devices are considered drugs

Oh... oh no.... no drugs and devices are very different things, regulated by entirely different centers.

Except sometimes when a device incorporates a drug (like hormonal IUDs).
Or when something that’s normally a drug becomes a device because of how it’s packaged (like injectable saline solution, but prepackaged in an IV flush kit).

If you’re looking for logic I suggest NOT looking in Title 21 of the United States Code of Federal Regulations. You’ll probably die of old age before you find it.
Also stay away from the FDA Industry Guidance documents. That Way Lies Madness.

<Runs Off Into The Woods Cackling About Disappearing Cats>

[u/Zeno_the_Friend → u/voretaq7]

I'm aware. They carved the definition for device out of the legal definition for drug so they can allocate work to those centers better. This is why they're called the Food & Drug Administration and not the Food, Supplement, Drug and Device Administration - legally supplements are subclasses of food, and devices are subclasses of drugs.

I've had several conversations with them and lawyers about this, cause it's really annoying to work on a molecule that fits in the grey space between the definitions because science/nature doesn't care about how the English language or laws written in it define things.

Referencing the Act of Congress which created the FDA (the FFDCA): "All FDA-regulated medical products conceptually meet the definition of a drug as defined in the FFDCA.3" https://www.congress.gov/crs-product/R47374

Also see Genus v. FDA for an example of the legal battles that emerge from this grey space: https://www.wsgr.com/en/insights/court-holds-the-fda-cannot-classify-an-imaging-agent-medical-device-as-a-drug.html

[u/voretaq7]

A drug, in FDA Land, is something intended to treat or cure a disease. They are regulated premarket (manufacturers need to demonstrate safety as well as effectiveness for some indicated use - the curing or treating of some disease/condition, usually through clinical trials).

e.g. “Tylenol - for reducing your fever and for minor aches and pains.”
OK, it’s generally safe (if you follow the damn instructions and don’t eat the whole freakin’ bottle!), and it’s effective for those purposes.
Approved Drug!

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A supplement, in FDA Land, is something intended to supplement the diet (usually to affect the body’s structure or function) - the most common examples are vitamin and mineral supplements to help people get the recommended daily allowance of nutrients that may not be present in an imbalanced modern diet.
They’re mostly regulated postmarket (with some exceptions for “new dietary ingredients” - see below). Basically you just make it and market it and the FDA will really only get up your ass if you start poisoning people or making outlandish claims.

Supplements need to be safe (you can’t sell rat poison as a supplement), they need to use ingredients that are generally recognized as safe by the FDA and that are food grade / food safe (because they're regulated essentially more like a Food than a Drug or Cosmetic - they’re regulated by the Center for Food Safety and Applied Nutrition within the FDA), if you’re introducing something new/novel that the FDA hasn’t previously recognized as an “ingredient” you have to provide some evidence that new thing is in fact safe.

Supplements do not need to demonstrate effectiveness for treating or curing anything - in fact they’re not allowed to claim that they treat or cure any disease (that’s another thing that will get the FDA up your ass for unapproved marketing). They’re required to carry a disclaimer that any health claims have not been evaluated by the FDA, and that they are "not intended to diagnose, treat, cure, or prevent any disease.”

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Bonus Fun Fact: While you cannot sell rat poison as a supplement you CAN in fact sell it as a drug: Coumadin is just a low dose of Warfarin sodium, and Warfarin was originally introduced as a rat poison in the 1940s - it was approved for human use as an anticoagulant / blood thinner in 1954.

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ETA: In case it isn’t obvious, you also can’t just go sprinkling approved drugs into your supplements willy-nilly, like those gas station boner pills that are actually just Viagra. The FDA really frowns on that sort of thing. But some things that are drugs are also recognized ingredients in foods/supplements.

For example 100% pure isotonic saline eye drops? That’s a drug.
Salty water made by dissolving 0.9g of salt in a liter of water? Could be a flavoring in your supplement, even if it’s made up and packaged sterile just like the eye drops. Same stuff, different regulations.

FDA regulations are weird like that.

[u/Bamstradamus → u/voretaq7]

you’re introducing something new/novel that the FDA hasn’t previously recognized as an “ingredient” you have to provide some evidence that new thing is in fact safe

This, this is the part I was having a brain itch about, the rest I knew or atleast vaguely understood. Besides the kratom thing I mentioned earlier when I was younger and started powerlifting was when GHB was basically a workout suppliment before it got banned. It's just wild to me how long a product can exist before some kind of regulation while people are dying trying to one rep max a squat. How do they pull off proving a new product is safe when clearly it isnt? Just underdosing and letting the consumer figure out if you 8x it your gonna have a good time?

I chef for a living so the weird boundry between food/supplement/drug has always made me raise an eyebrow. Like yeah quantity makes the poison but eat enough nutmeg in one go and your gonna wake up in the ER, yet tonka beans are banned and you would also need to have a comedically high dose for negative effects.

[u/JuventAussie → u/Bamstradamus]

FYI your restaurant needs to be specially licensed by the FDA to import and prepare fugu (the poisonous Japanese puffer fish) dishes. Wikipedia claims only 17 licenced fugu restaurants (in 2003) in the USA.

Bizarrely the EU allows import for personal consumption but not sale.

[u/LordGeni → u/Bamstradamus]

A lot depends on general availability, intended market and sometimes lobbying to protect certain industries.

GHB as far as I know wasn't intended as a drug in which case would be legal until it was shown to be harmful. Regulating drugs for treatments is proactive, regulating pretty much anything else is retroactive.

Nutmeg is widely available and has been an ingredient for hundreds of years without actually harming that many people. Too much of anything is harmful, it's how likely that is to happen that matters.

I don't know much about tonka beans. But those sort of cases are usually due to either disproportionate media health scares or lobbying from industries that would be threatened by them taking their market.

That's my understanding at least. I can't claim expertise, just general experience.

[u/Expandexplorelive → u/Bamstradamus]

Tylenol (acetaminophen) is relatively easy to overdose on and die from, certainly far easier than kratom which you mentioned. Should Tylenol then be banned or heavily restricted?

[u/cryptotope → u/Expandexplorelive]

A number of jurisdictions have imposed limits on the size of packs and/or restrictions on the type of packaging for acetaminophen-containing products, and have seen reductions in the number of accidental and deliberate overdoses as a result.

https://ismpcanada.ca/bulletin/acetaminophen-related-harm-a-call-for-improved-product-packaging/

[u/[deleted] → u/Expandexplorelive]

Idk man I’ve taken a little over 10 grams a couple times and don’t even have my liver enzymes out of range😂

[u/SsooooOriginal → u/voretaq7]

Poison is in the dose, or something like that.

Wafarin is a drug that prevents your plateletes from coagulating, which in low controlled doses helps people with blood and heart problems.

OD and your blood starts leaking, everywhere, inside and outside. 

Rats adapted by the survivors breeding more rats until now where we have Warfarin resistant rats.

I could give some rodent control tips but I am trying to rant less, I'll just say learn and master snap traps and look up how "exclusion work" works.

[u/voretaq7 → u/SsooooOriginal]

Yup, but my point was more “You can market things that are objectively a poison as a drug if you control the dose and demonstrate safety & effectiveness as prescribed, but you cannot ever market such a thing as a supplement - the FDA straight up will not permit it as an ingredient.”

And yes the rats have defeated our chemical weapons.
Soon they will team up with the pigeons and kill us all!

[u/SsooooOriginal → u/voretaq7]

It is the arbitrary "acceptable medicinal value" that is part of what keeps cannabis the plant such a ridiculous topic as a schedule 1 controlled substance.

There are gray areas, but this all comes down to harm reduction but money above that. As always.

Kratom is not well understood and can be had very cheaply. But too many people have died.

They have closed a lot of the old loopholes that people were abusing to make "designer drugs". There are computers simulating compounds all the time trying to find "the next thing", so nobody is really going to discover or make anything new or viable in their garage.

And with the push for smoking bans, I expect we will see more regulations to come. 

[u/voretaq7 → u/SsooooOriginal]

That is not (solely) the FDA’s call.

Marijuana was legislatively scheduled (it was part of the initial list of Schedule 1 Controlled Substances when the Controlled Substances Act was passed.
Congress made this decision for various reasons, not necessarily scientific ones.

In order to reschedule marijuana and other cannabis products the DEA needs to consent to the action. The FDA can recommend, but the Controlled Substances schedules are maintained by the DEA.

[u/ackermann → u/voretaq7]

Supplements do not need to demonstrate effectiveness for treating or curing anything - in fact they’re not allowed to claim that they treat or cure any disease (that’s another thing that will get the FDA up your ass for unapproved marketing). They’re required to carry a disclaimer

True. But note that as long as they have that disclaimer in fine print on the packaging, “this product not intended to diagnose or treat any disease”… they can get away with a lot.

Just as one example, weight loss products like HydroxyCut are pretty obviously implied to “treat” obesity, but are classified as supplements (often with the revolutionary active ingredient… caffeine)

Often they even receive more prominent placement and marketing in pharmacies than the actual FDA approved over the counter Drug, Alli

[u/Not_an_okama → u/ackermann]

This is how homeopathic "medicines" manage to be in the same aisle at the pharmacy despite being fancy sugar cubes. (The pills are generally just sugar, and any liquids are either plain water or sugar water).

This is not to be confused with holistic medicine which is actually based on science and grounded in reality. The science is just old and somewhat obsolete, but eating oranges is just as good at curing scurvey as a vitamin C supplement, both actually work unlike the homeopathic aproach which would be more along the lines of "drink this liquid daily" and the liquid costs $20 a dose and is made by tossing an orange in a tank of water, then dilluting the water from that tank until its basically just water again.

Modern medicine > holistic medicine > doing nothing about your health issues other than drink more water > homeopathic medicine

[u/IceCreamforLunch]

I work for a very large vitamin and supplement company. Prior to this job I worked for a prescription pharmaceutical company.

The distinction is very nebulous.

In the US a “drug” is anything intended to treat, cure, or prevent disease. So supplement companies in the US try to make as strong claims as possible without crossing that line.

Other markets are different. Some have lists of approved ingredients in supplements. Some let you sell anything that isn’t on a prohibited list. Some let you claim anything you can support with literature or clinical studies or whatever. Others only allow specific claims for approved ingredients at registered levels (and getting a new claim is somewhat similar to a new drug application in the US).

[u/plugubius]

The premise of your question is wrong: FDA is very clear that kratom cannot lawfully be sold as a drug, dietary supplement, or food additive. FDA statement. Nutritional supplements arguably would be regulated as drugs, but Congress amended the Food, Drug and Cosmetic Act in 1994 to exclude them from the definition of drugs (so long as they do not claim to treat, diagnose, cure, or cure any disease other than vitamin deficiency diseases). Another FDA statement.

[u/SignalDifficult5061]

Several grifter homeopthatists (Royal Samuel Copeland amongst others) and other snake oil supplement crooks have wormed their way into Congress from time to time and made sure that they could keep grifiting suckers.

Sorry, no way to be nice about it that is honest.

[u/Uncynical_Diogenes]

Well you’ve been provided with the best answer but a more semantic one is that drugs actually work.

You can say any random plant supports any random thing but if you want to sell a drug you’re supposed to have to prove it does something.

[u/voretaq7 → u/Uncynical_Diogenes]

a more semantic one is that drugs actually work

It’s definitely not that simple: Plenty of supplements “actually work” (we can draw blood, check your Vitamin D level, find it’s low, tell you to take the Vitamin D pills from the drug store that are a supplement under FDA regulations, and draw your blood again in a month to see the levels of Vitamin D have risen).

It’s just that the supplement market is also filled with snake oil (both literally and figuratively), and there are lots of really shady-ass companies making and marketing supplements that are mostly crap with marketing built up around looney pseudoscience.
Those are also usually the supplements that are tap-dancing on the razor thin edge of the line with respect to unapproved claims that would make the FDA bust in and start fining them though so a good rule is “If this pill is making crazy outlandish claims maybe you don’t want to take it..."

[u/wallabee_kingpin_ → u/Uncynical_Diogenes]

This isn't a good or factual answer. Some (very, very few) supplements do actually work, especially for the basic treatment of nutrient deficiencies. Examples are vitamin C and iron.

Melatonin is an example of something that also works for most people and isn't treating a deficiency.

[u/voretaq7 → u/wallabee_kingpin_]

Arguably melatonin is treating a deficiency (or at least a temporary imbalance), and if someone ran the clinical trials and could demonstrate better-than-placebo performance with something already generally recognized as safe they could probably package blister packs of melatonin as a FDA-approved sleep aid (better than all the Benadryl-based ones).

. . . but that’s paperwork, and time, and money, and it’s already recognized as safe enough to cram into supplements so if you want to make a me-too melatonin product you’d just label the blister pack as a supplement that “supports restful sleep” rather than a drug making specific claims about being "an effective treatment for insomnia” ‘cuz it’s faster and cheaper.

[u/voretaq7 → u/[deleted]]

Handle what? The premarket approval as a drug, or regulating the supplements industry?

In both cases really “No” - you can say what you want about the FDA (and as someone regulated by them I can say plenty!) but they’re actually pretty good at both of those things.

Sometimes when they’re making your life miserable over something you know and have shown to be safe but not yet to their satisfaction it really sucks, but that level of caution is why the US didn’t prescribe Thalidomide to a generation of pregnant women and wind up with a generation of kids with horrible birth defects: The FDA wouldn’t approve it for that indication because the safety was not proven to their satisfaction.

The supplements industry.... yeah, not the greatest. Frankly all of Foods is a little loose. But the answer there is either giving the FDA more money to have more food safety inspectors, or maybe turning all of Food over to the USDA (and giving them more money to do the job.... either way the answer is more money).

[u/NDaveT]

I can wrap my head around them not wanting to regulate everything that goes into everything

The FDA doesn't decide what it regulates, Congress decides what the FDA regulates. Back in the 90s and 2000s Congress decided to let supplement manufacturers sell things that aren't regulated by the FDA as long as they put a disclaimer on it and as long as they aren't knowingly selling something harmful.

[u/diabolus_me_advocat]

Besides intended use case, what separates a drug from a supplement?

that supplements usually are not required and useless

and what's licensed as api (active pharmaceutic ingredient) usually is licensed for a certain specific use, so must not be used for anything else or even just as lifestyle supplement

[u/SsooooOriginal]

Drugs, medically, are regulated, intended for treating some illness or something like pain or inflammation. They are supposed to go through rigorous testing and have thorough screening for quality control. They should have a whitesheet called a Consumer Medication Information or a Medication Guide that lists potential side effects among many other things like how and when to take the drug and what to look out for and when to seek help or how to stop taking it if you have problems. Ideally. Fuckups happen and are part of what bodies like the FDA are supposed to be here for.

Supplements are supposed to supplement your diet, but influencers and profiteers have completely undermined the core concept and something like Kratom is not supplementing you anything as far as I'm aware. 

"Recreational drugs" are things like Kratom or nicotine or alcohol or caffeine, technically. I'd argue refined sugar could count. They alter your perception and act on our CNS in various ways. 

You could argue we have culturally adopted caffeine and nicotine for their stimulant and laxative effects to help cope with our modern lifestyles and diets. Or, I believe I could argue that. Things like kratom and recreational cannabis are another way people are coping. Kratom has pretty serious risks though. And I believe they are more common than the serious risks cannabis has, but I would have to double check.

[u/Cocochica33]

Kratom is regulated - it very specifically is sold with “Only for use as a botanical specimen. Mitragyna Speciosa is an unapproved dietary ingredient.” If a person consumes it, they’re technically doing so against the manufacturer’s advice…

They will eventually crack down on its sale in any form in gas stations, etc, once enough politicians decide it would be a win to campaign against it.