Let’s say an armchair biochemist who has done exhaustive research on a serious health condition has finally found what looks like a major breakthrough – but instead of submitting his drug to years and years of exhaustive clinical trials and peer vetting, he wants to speed it to a handful of medically needy individuals who are rapidly declining – without any government authorization. Are there private compounding labs or production facilities worldwide that might take his molecule and Bitcoin payment and turn it into a bootleg pill? Briefly, how complex is the compounding process that sees a molecule stored on a flash drive turned into a pill in a bottle?
IANA Chemist but my understanding is that the development of a particular chemical structure is sort of like the problem where you have different sized jugs and you need to measure out a specific amount of water. If you want to make exactly 6 gallons and you have a 4 gallon bucket and a 2 gallon bucket then Bob’s your uncle; if you want to make exactly 6 gallons and you have a 3/7ths gallon bucket and a 19/11ths gallon bucket, then you might have a long journey ahead of you.
Making a particular molecule might be easy or hard, depending on the availability of materials, how reactive those are, how they like to bond to each other, and what you would need to do to break apart and glue molecules of specific types.
These days, I would expect that you can basically put a target molecule into a program and it will tell you what common input ingredients to purchase and what steps to put them through to get the output - so figuring out a relatively optimal pathway isn’t so complex - but the quickest and easiest path still might be very easy or very laborious.
There are illegal ones that seem to get drugs out to the public. There are a number of people or groups making crystal meth and similar products. They seem to be able to produce fairly high quality product, though illegal.
Back in the BALCO days of performance enhancing drugs (PEDs), someone was producing the PEDs at a quality and quantity to be available to many athletes.
What your original post suggests is something that is possibly illegal if it is not going to go through regulatory channels.
Surely manufacturing a next-gen drug for treating/curing a retrovirus (e.g. HIV) or a disabling neurological condition is far more demanding than producing PEDs or illegal drugs like crystal meth.
I can’t imagine a producer of illegal drugs pausing production to produce a medication similar to that referenced above. I have to wonder if there are freelance chemists out there who do this type of work for ultra-wealthy and ultra-sick patients somewhere.
Clearly this RX drug would be illegal without government approval, even if it had therapeutic value.
I don’t see why not, honestly. Setting up a laboratory, I have worked in an ISO 7 cleanroom before, and I have toured an ISO class 2 cleanroom before, and to be honest, I could put together a class 2 or 3 cleanroom with enough money and a good contracting crew. Knowing what equipment I would need would mean contacting my chemist and his crew, and then there is just the list of supplies. I do know that some chemicals are the dickens to purchase in the US because they are drug precursors, so the lab would have to be out of the country or the chemicals would need to be sourced then smuggled into the country to the lab.
I can think of at least 3 chemists who could set up a lab like that. Whether or not they would is different, and whether or not someone might have the drug details for manufacture is also different.
I understand that some of the new COVID meds while high SF Future sounding, they are actually moderately easy to make once you have the ‘recipe’ and the lab set up. So, it might be easier than one thinks.
I personally would kill for the money to have a compounding pharmacy take all my assorted prescriptions and make the medications for me in as few pills/capsules as possible [like my 0500, 1300, 1700 and 2100 medication times so probably 3 pills for the 0500 and 1 pill for the other 3 times] and all my meds are known and legal to do this with =)
When I was in college in the early 70s I had a job as a lab assistant for the Chemistry Department, and as such had relatively free access to the lab. An acquaintance (I didn’t really consider him a friend) once approached me and asked if he were to provide me with instructions I would be willing to try to make LSD for him. Obviously I declined (I had also refused to let him stash a “package” in my dorm room). I have no idea whether this would have actually been possible, but I wasn’t about to risk my future getting involved in something that questionable.
Back in college I asked a biochem major in my residence as a joke “how would you make Lysergic Acid Diethylamide?” He thought about it for a second, started describing the first reaction or two, the stopped and said “Hey, wait a minute!” Fortunately, I was joking and didn’t really want to know. But it seems it was a matter of reactions and refining until it was pure.
There was the famous case of the people in California who were taking a bad batch of some drug and ended up with the symptoms of severe Parkinson’s. News reports said that the problem was, many illicit concoctions are doing by reaction and refining and if the refining is not done often enough and repeatedly (and correctly) you end up with similar but less friendly molecules in the mix.
An earlier discussion about the cost of modern insulin mentioned it was made with altered bacteria; so it’s a bit more advanced than a simple chemical lab. I assume the same applies to things like vaccines - you need a way to construct (or steal) a modified biological or instructions on how to make it. I don’t imagine for example, that creating a usable amount of anthrax is a text-book exercise, even if you had the correct handling facilities.
Although famously, the people being guinea pigs for the first AIDS treatments were famously able to play serious games with the pharmaceuticals. Some fairly smart people facing possible death by lottery (who was the control group?) were willing to conspire to determine what worked and make or obtain that for their friends.
I’m not a chemist of any flavour, but I regularly read Derek Lowe’s blog postings In the Pipeline. Derek is perhaps best known for his postings on “Stuff I won’t work with.” But his regular postings are all about the trials and tribulations of a chemist working in the drug industry.
The general gist of things is that there is no simple way of working out how to make most modern drugs. Many drugs come about the other way around. You screen a zillion chemicals that you can make for any useful activity. If there is something useful you “just” need to work out how to make them at scale. But you did at least start with something that you can synthesise.
But a lot of modern drug discovery is about trying to find small molecules that fit known sites on large molecules operating inside a person’s operating biochemistry. And making a drug that does so without otherwise causing too many other problems, and can be successfully delivered to where it is needed.
Many modern drugs involve levels of technology that are near science fiction compared to synthesising meth.
That said, Derek recently did an interesting piece bemoaning that given the money involved, there was no shortage of gifted chemists who had turned their hand to improving the operations of illicit drug manufacture.
If the OP’s notional biochemist actually has a synthesisable drug, one that is a big step. Production at scale might be possible. If however he is truly just an armchair biochemist, one who has come up with his new drug simply by reading, one - it probably won’t work, and two, there is no useful guarantee it is synthesisable.
But cross all those bridges, and sure, there are likely many companies that given enough money would be happy to make the drug. Heck, just don’t tell anyone it is going into humans. It isn’t their problem. There are many more chemicals being synthesised for purposes other than drugs for humans. Tell them it is an experimental insecticide.
I assumed the OP is talking about something that would be moderately trivial to make but that big pharma has locked up with patents, meaning a $5 dose is $800.
I guess the distinction would be chemically synthesized vs. biologically synthesized or extracted. After all, there’s a difference between, say, complex processes on an industrial scale vs. making a small batch for a few people.
For example, (Wikipedia)
In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere.
A sustained-release form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however, the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin Depot required significantly more resources to produce than the rest of the Nutropin line[79]).
As I mentioned with the illicit drug problem in California that produced Parkinson’s, another problem is if you were trying to reproduce a therapeutic drug, how would you be sure you got it right?
Is it reasonable to assume that any new drug designed to cure a serious neurological condition would be both hard to design and hard to manufacture, simply because anything “easy” is already in circulation? Put differently, isn’t everything that reaches these labs a hugely complex problem?
In my original scenario, I acknowledge there would be no clinical safeguards to screen for side effects – and really no way to even guarantee efficacy. It would be a huge roll of the dice for very desperate patients. We see stories like this regarding late-stage cancer patients, who want access to promising, yet still-unapproved meds, and who do not care about long-term side effects.
If it were a simple matter of design the same as building a new airplane or tunnel borer, then yes - but the problem is that discovering what fits a complicated complex chemical receptor and then whether the drug as designed actually does anything. You can kill a lot of rats and monkeys being sure what you’ve come up with is even not lethal to consume. An array of test animals, plus a full synthesis lab? At what point would animal welfare get involved because you have test animals, and then wonder what you are doing? Can you hire people to look after lab animals who aren’t going to ask questions?
It just keeps getting bigger and more complex if you are not making a known substance. There’s always letting humans be your guinea pigs, but that comes with its own risks.
The early AIDS patients, and specifically the ones in the AZT trials, were able to determine who was on placebo and who was on active ingredient, because not only did their symptoms change on the active ingredient (and not always for the better ; AZT has dreadful side effects) but the capsules also smelled and tasted different. Therefore, people were doing a lot of switcherooing and compromised the test results, although in the end, enough people made dramatic improvements that the study was cut short and the drug was approved. This has happened with many other drugs over the years.
When I was in pharmacy school in the early 1990s, our professor told us what we needed to set up our own meth lab, but he added, “If you buy those things in bulk, and they find out you are a pharmacy student, you will be taken off in handcuffs.” This was before meth really took off in our area, but we did know about it.
I also read about some people who were living in China during WWII, in an area that was not much affected by the war, but one thing they couldn’t get was commercially made insulin. They found some people who had enough knowledge of chemistry to figure out how to extract it from animal pancreases (which was how it was made until the early 1980s, and some countries still have it available) and asked local butchers to save them, which they did, probably because they or a family member needed this service. Anyway, what they got was brown with impurities and not standardized like the insulin they got from Lilly, and it caused terrible skin reactions, but it kept them alive until the war ended. Some of them fell to the ground, sobbing, when they were once again able to obtain “real” insulin.
It has been a few years so I can’t find the reference, but there was an investigative reporter, I think from the Netherlands, who investigated this very question. He found that in China if you knew who to talk to you could get many of the most expensive drugs for very little. All under the table. He specifically was asking about a new drug that was available in the US for upwards of $1 million for a course of treatment. A guy in the back room pulled out a small barrel and invited him to mix up the powder as much as he wanted and take a sample for analysis. As he was flying out of the country it occurred to him that he had a million dollars in a small envelope in his pocket. When he got home he had it analyzed and while it was so new they couldn’t be sure, the lab said they thought it was the real deal.
So yeah, as long as you don’t care too much about quality control or licenses, I believe you can get just about any drug. Using it properly, and avoiding contaminated drugs would be on your head, but if you have to have the drug this may be your only option.
I did drug licensing for a career and can answer a lot of this - but I’m limited because I’m on vacation. Here are a few thoughts though.
If the new drug is aimed at a large patient population, all the financial incentives point toward legitimate licensing. So there the scenario doesn’t really exist.
For tiny patient populations, this circumstance has been envisioned by governments/regulatory agencies and (some) provisions put in place by them, working together with the pharmaceutical industry. For example, such patients may be on a registry and thus eligible for immediate access to trials or compassionate use programs. Plus much more that I’m not able to go into right now.
Do labs exist that can do sophisticated illegal manufacturing? Hell yes. See for example the notorious case of Belgian Mix.
If it’s just a small molecule without any complicated formulation needs (like required for the COVID RNA vaccines), synthesis will typically be accessible. A biologic? Less so.
But the devil is in the details. Chemical selectivity isn’t perfect. Nor is purification. And you can get some nasty side products without proper controls.
Hard to design but not necessarily to manufacture.
And often the design isn’t the hard part. E.g., after CGRP was implicated in migraines, three drugs targeting either the protein or its receptor were all approved within a year of each other.
Further to my earlier post, regarding Medicines Agency provision for rapid access to new drugs, the European Medicines Agency has published several documents that are relevant.
The European Union (EU) pharmaceutical legislation includes several provisions to foster patients’ early access to new medicines that address public health needs
These include
Compassionate use is a treatment option that allows the use of an unauthorised medicine. Under strict conditions, products in development can be made available to groups of patients who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials
Most “developed” (sorry) countries operate systems to allow access to unlicensed drugs, but these systems are strictly monitored by the relevant medicines regulatory authority.
To address what I presume is the spirit of the OP (again from a European perspective; I can follow up for the US if you really want, but I’m unfamiliar with the detail there) in the EU, broadly speaking, something that purports to be a medicine falls under the legislation which covers medicines and therefore is subject to licensing procedures. If you try to circumvent this, yes, you probably can find a lab to manufacture (depending on the complexity of the drug in question, etc) but distribution to your intended patients requires you to stick your head above the parapet and contact them, at which point trouble ensues. I don’t remember the penalties off the top of my head.
It depends a lot on the compound. But probably yes. There’s a very big gulf between theorizing that something is a major breakthrough and finding that it actually works in live people. So the odds of this hypothetical drug working as intended are low. All that being said, there’s also a legal way to get it to your desperate loved one, if you are wealthy enough. You fund a study, and enroll your relative. The very earliest studies, before they do a randomized clinical study, can involve giving the drug to a tiny number of people. (Well, they usually start with animals, but then they give it to people.) You want to test for safety before giving it to a bunch of people, so people who are likely to die soon anyway are good prospects.
I imagine bootleg pharmacopeia more about stealing someone’s ideas. When a possible discovery makes a splash, it will still be a decade or two before it becomes a commercial product. Perhaps some people have more money than time and are willing to give such drugs a try. Like this article:
One of several articles recently about pausing or reversing aging. In this instance, it’s using biological genetic techniques rather than drugs, but the concept is there. The same could be true of alleged Alzheimer’s cures touted occasionally in the news. Some people don’t want to wait and see.