Sciencemadness Discussion Board

Four thieves vinegar

heksogen - 14-10-2017 at 00:16

Hi there,

I couldn't find an existing relevant topic so decided to make one. I've recently come across a very interesting initiative:
https://fourthievesvinegar.org/
Basically, the idea is to provide open source solutions for drug synthesis in order to make the essential medicines available to people in third world countries. Also the neglected diseases patients might benefit, as in many countries their life is dependent on the government reimbursement programs which may unexpectedly end.
There is much more reson to discuss the topic of clandestine (for non commercial use) pharmaceutical drug synthesis than there is for explosives, psychotropic drugs or poisons, I suppose. The initiative seems to exactly fit the profile of sciencemadness; the ingenuity and vastness of knowledge of the users of this forum could bring appropriate solutions.

I think that this noble idea may as well not work at all due to several resons:
- the synthesis of pharmaceutical drugs in not simple, however the development of independently verified procedures similar to that found in Org Syn may help overcome that,
- the syntheses would be unlikely successful when not performed by well trained individuals with access to at least some sort of quality controll/analytical equipment,

Assured Fish - 14-10-2017 at 00:58

The issue is that even if we were able to synthesize these pharmaceuticals, the companies who own and market the drugs would not allow anyone to sell them without licencing.
Not to mention the laws and regulation about how you are allowed to make and sell certain consumable items such as drugs.

I have seen several of this guys videos on youtube before.
Im sorry to inform you though that it is a pipe dream.

He does not understand organic chemistry enough to comprehend the shear magnatude of a total synthesis of a pharmeceutical compound.
The prices that the pharmaceutical companies usually sell there drugs are usually about as cheap and efficient as it could get for such an operation and if an amateur were to make the same compounds they would likely have to market the compounds considerably higher in price just to break even.

If anyone on the forum wants to twist there nuts into a knot then by all means watch his presentation.
https://www.youtube.com/watch?v=Py5TkirrO-U
I must warn you though it will likely drive you to homicidal thoughts.

He had one good idea and one good idea only and that was the epipencil.
It seems this idea made him think he was smart.

Fulmen - 14-10-2017 at 01:35

Assured Fish: If we limit ourself to third world countries I'm positive the governments would tell the owners to go f*ck themselves. And while many generic drugs are sold at low cost many cost far more than production cost would suggest. But I don't think this approach will change anything for those drugs, any company with the capability to mfg such drugs should also have the resources to figure out the synthesis on their own.

Having worked in the pharmaceutical field I know a bit about what it takes to produce such drugs in quantities, and it's not something that can be done with a ghetto setup.

Assured Fish - 14-10-2017 at 02:09

I won't disagree with many drugs being over priced but it is the legal and moral right for the companies who went through the effort and spent tens of millions of dollars developing these drugs, to market them at the price that they see fit within reason.

If you put me in a lab and told me to make pharmaceuticals and sell them then there is no way in hell id do it for free. Id expect to get paid a pretty hefty sum and then there would be production costs on top of that.

Technically speaking all drugs could be synthesized in a well equipped lab without the need for large $20,000 equipment. As you say Fulman producing them in large quantities is what would require some serious investment.

Not sure what you mean by ghetto setup, i would call a beer bottle still and copper coil reflux condenser ghetto but not a setup consisting of multineck RB flasks, Dimroth and long liebig condenser, sintered funnel, pressure equalized addition funnel and sep funnels, claisen adapters, heating mantles and chromatography columns all ground glass joints as well as a good source of vacuum.
Many of the members of this forum do have all these things and i have most of them.

A synthesis could be accomplished its just nobody is willing to do the legwork for no reward and getting a reward may mean getting sued.

Given that the entire system by which new drugs are found is basically supported by the knowledge that if you succeed you get to make lots of money, I very much doubt running such an operation would go down well with anyone except the people you are trying to sell the drugs to.
I also doubt these 3rd world governments would be willing to face the wrath of the pharmaceutical companies.

I stand by the idea being a pipe dream, however if you want to make a certain pharmaceutical compound then by all means make a thread about it and im sure many of us would absolutely love to help you do so.

heksogen - 14-10-2017 at 04:23

Quote:

A synthesis could be accomplished its just nobody is willing to do the legwork for no reward and getting a reward may mean getting sued.


Assured Fish, I think you are wrong in some aspects:
- nobody is considering illicit production of pharmaceuticals for reward,
- the original idea is to provide easily implementable solutions - it is a knowledge based initiative,
- there are people who are willing to help others and work without profit - I think it shares some similarities with the work of Médecins Sans Frontières,
- there are still many countries that did not sign the Patent Cooperation Treaty; moreover the companies often do not choose to pay for patent protection in the third world countries as that is simply not profitable - then there is little conflict of interest with the companies,
- the technical feasibility of the syntheses is dependent mainly on the structure of the compound - some syntheses could be successfuly performed by an undergraduate in an improvised setup, while others may not be possible at all,
- most organic syntheses can be performed in simple apparatus, as the repertoire of organic (and metaloorganic) transformations is gigantic - it is mainly dependent on the persistence of the chemists and availability of the chemicals,
- the cost of New Chemical Entity development is nowadays ridiculously high (~1,5 bln $ per NCE) and in fact the R&D process takes a very tiny fraction of it.

Imagine a chemist in a underdeveloped country who has the access to some laboratory equipment of a local school/hospital/university and who is willing to synthesise compounds and distribute them freely - do you consider it not moral to provide solutions to such individuals?
Is it moral to set the same pricing for drugs in countries with two orders of magnitude different per capita GDP's? On the other hand, it is the strategy that prevents the illicit export of the drugs from poor countries. It is worth to note that the inequality will be the most important problem of the XXI century and there are no simple solutions for the underdeveloped countries to overcome that. Just try to compare the infant mortality in western world and Afghanistan - this could be fixed to some extent with a better availability of simple pharmaceuticals.

XeonTheMGPony - 14-10-2017 at 06:14

I personally feel it is vital for the maximum amount of people to know how to make the basic medicines, people do not grasp just how fragile the whole system is, We on the North American continent have enjoyed the pleasure of very calm protected state of life.

Any major upset will need groups able to fill the gaps., patents only come into play if you try and do it at a commercial/industrial level, but for a single guy doing it to help a friend or his family they'd use more simpler conventional laws like practicing medicine with out a license. But given the alternative small price to pay, and odds are at that level since it isn't a "evil" illicit drug odds are they'd look the other way.

AvBaeyer - 14-10-2017 at 19:24

What sorts of drugs would be made in this grand moral effort? Keep in mind that many drugs are already made freely or very cheaply available in third world countries. The biggest problem in these countries is infrastructure for health care and patient compliance, not lack of medicines.

But for the sake of the argument, let's assume that a chosen drug can be made in a third world country. Do you understand the quantity of drug compound that needs to be made? You are looking at 10's to perhaps 100's of kilos. This is not going to be made by a boy and his dog in the garage with a glassware kit. Where is the infrastructure to assure quality, formulate the drug product under sterile conditions and then produce the tablets, capsules or sterile solutions? Then there is the problem of proper packaging to assure storage stability. All of this all requires considerable capital investment as well as technical expertise which may not be available in the local environment. This is only a small part of the challenge. You have got to understand that a medicine is more than a compound in a bottle.

I spent my career in the pharma business and it just is not as simple as most amateurs think. If it was, all these academic "drug discovery" geniuses would have solved all the world's problems by now.

AvB

kavu - 14-10-2017 at 22:07

Drug synthesis is complicated by the purity requirements for all stages including the final API. There are plenty of examples where minor (beyond amateur lab detection level) impurities have caused severe side effects. Syntheses can probably be carried out no problem, the real problem here is quality control. This includes issues with crystallizations and wrong polymorphs.

[Edited on 15-10-2017 by kavu]

Assured Fish - 14-10-2017 at 23:57
Quote:

There are plenty of examples where minor (beyond amateur lab detection level) impurities have caused severe side effects.

Evidence please. this seems unlikely.
Quote:

This includes issues with crystallizations and wrong polymorphs.

Again evidence.

JJay - 15-10-2017 at 00:25

The "Apothecary MicroLab" doesn't look so bad. I'm not sure it will accomplish its intended purpose, but if I had one, I think I would use it. I imagine the price tag is a little steep, though, and what features does it actually have?

kavu - 15-10-2017 at 04:41

Quote: Originally posted by Assured Fish  

Quote:

There are plenty of examples where minor (beyond amateur lab detection level) impurities have caused severe side effects.

Evidence please. this seems unlikely.
Quote:

This includes issues with crystallizations and wrong polymorphs.

Again evidence.


The fda guidelines on these issues can be found at https://www.fda.gov/downloads/Drugs/Guidances/UCM172002.pdf

Multitude of examples of impurity characterization can be found in the scientific literature, but just as an example: 10.3762/bjoc.7.5.

The whole problem is actually already prevalent in the world: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137817/

Assured Fish - 15-10-2017 at 20:56
Quote:

An impurity may be defined as any substance in the product that is neither the chemical entity defined as the drug nor an excipient [44]. Impurity profiling is required as part of the registration process by many regulatory authorities, including the FDA and the European Union's Committee for Medicinal Products for Human Use (CHMP). Impurities fall into one of three categories – organic substances, inorganic substances and residual solvents [45] – and may include starting materials, intermediate compounds, reagents and catalysts, heavy metals, degradation products, polymorphic forms (alternative crystal forms with potentially different dissolution profiles) and enantiomeric impurities, as well as extraneous contaminants.

from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137817/

Alright kavu you got me there, from what ive read the crystaline structure of a drug can actually have affect on bio-availability, solubility as well as stability of a substance to an extent.