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Hello Teamliquid, I decided to start a blog and I wanted to share something new with you guys. I do not believe I have seen an extensive discussion of the pharmaceutical industry on this forum before. I would like to take this opportunity to share some of my knowledge on the pharma and biotech industry in general. Now I am a relatively new comer to the pharma industry itself but I do have a decent grasp of the industry in general. I will also try to make this accessible to the non-science audience as well. So without further ado, let us begin.
What is the modern process of drug development? Broadly speaking it can be divided into 6 stages.
1) Establishing a target and find something that can bind to the target.
2) Preclinical
3) Phase I
4) Phase II
5) Phase III
6) Post-Market or Phase IV
1) Establishing a target and find something that can bind to the target.
The first two stages is pretty much the R of R&D. during this stage, researchers from academia or the pharma company itself finds a druggable target. For the sake of simplification, this target is essentially a particular protein. Proteins are molecular machinery in cells that is responsible for everything from transportation to signaling. For this theoretical case, the researchers found that a gene is linked to the expression of a particular protein. When there is a mutation in this gene, the protein is implicated in cancer. Through some more molecular bio experiments, we find that the mutated protein has a new shape. This new shape allows it to bind and activate proteins that is responsible for cell division[1].
So once a target is found, how do we shut off this protein that is associated with the mutant gene? I have to go through the concept of rational design first. We can elucidate the structure of the protein via x-ray crystallography or NMR. Once we have the structure of the protein, medicinal chemist can design chemical compounds that interfere the binding between the mutated protein and the protein responsible for cell division[2]. So they play around with the chemistry until they find something that binds to the mutated protein strongly enough to prevent binding with the cell division protein. Then it is time to test these compounds in cancer cells that have the mutated gene in question[3]. Further chemical tinkering occurs with our small molecule as our medicinal chemist weigh the benefits/risk between increasing specificity of the compound and potential for side effects and delivery issues. The head scientist(actual title in pharma) for that group submit this compound to above and they decide if this compound is worth pursuing. Luckily for this group, this compound is deemed to have potential and moved to the preclincal phase, or the animal trials as it is more commonly known.
footnotes
[1]- To be more precise, this protein is part of the signalling pathway for cell division.
[2] - I did not mention protein based drugs, or biologic. This will definitely show up sometime in the future.
[3] - I decided to forgo mentioning synthetic compound library tested against protein targets or cancer cell line.
I was originally going to write about all 6 stages today, but then it hit me how long all this is. Looking back, I think I manage to hit the sweet spot where it is too basic for anyone with a biology or chemistry background and still a little too technical for the average person. Oh well, I would definitely like feedback on this point.
To be honest, I really want to discuss drug pricing and the economics behind the pharma industry. But I feel it is important to set the background first. Looks like it is going to be a little while before I get there.
Thank you guys for reading through this and all questions/feedbacks are welcome.
Cheers
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Hi, may i ask what role do you play in the industry?
researcher? investor? accounts? sales? marketing?
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Sure, I play a QC role on the post-production side. Tracking safety issues once the products are on the shelves. I do want to get into health economics eventually though.
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I'm not sure that you need to go through all the steps in that much detail in order to explain why drugs are so expensive. The research and development of drugs is complex and requires different experts in different fields. As you mention you need biologists, biochemists, crystolagrophers, organic chemists, medicinal chemists, and analytical chemists just to come up with a couple of potential molecules. You then need to scale up the process so you need process and chemical engineers as well as formulators to actually create the tables. All of this expertise is not cheap and they all require expensive resources and equipment.
On the other side, the government will not let you sell anything to the public that isn't both effictive and safe. Human beings are funny in that we're all different and so something that is harmless to one person can kill someone else (like peanuts). So the drug manufacturer has to spend a lot of money in order to prove to the FDA (and other government's drug agencies) that the drug does exactly what you say it does and nothing else. This costs A LOT! And on top of it all it's often that the drug will fail while going through these clinical trials so all that money you spent on developing a molecule goes down the drain which means that the price of successful drugs has to include costs to recoup the failed drugs as well. This whole process takes a long time (5-10 years from beginning to end) The way that patent law works you have a very limited amount of time on the market to actually make money since you have to patent the molecule when you first dicover it (so about 4-8 years before it will reach market and start selling) so when it actually does release the drug companies have to raise the price in order to make the money back in a short amount of time (and obviously make a profit) before the generic manufacturers can start making the same drugs and sell them for much cheaper since they have virtually no R&D invested in the drug. On top of it all drug manufacturers have to invest millions in order to protect their IP since other drug manufacturers (and generics as well) are always trying to break each others patents because the chemistry behind drug effectivness is extrememly comlicated and different configurations of the same molecule can have very different effects. And that is why a tablet that might cost less then a cent to make actually costs hundreds of dollars to buy.
P.S. all of this only applies to small molecules. Biotech companies work differently in that it's both much harder to develop and much harder to break the pattents on large molecules.
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How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose.
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On December 06 2013 02:45 Awesomedrifter wrote:
How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose.
How is it stagnated and how do you propose it change its methadology?
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On December 06 2013 00:39 FryBender wrote:
I'm not sure that you need to go through all the steps in that much detail in order to explain why drugs are so expensive. The research and development of drugs is complex and requires different experts in different fields. As you mention you need biologists, biochemists, crystolagrophers, organic chemists, medicinal chemists, and analytical chemists just to come up with a couple of potential molecules. You then need to scale up the process so you need process and chemical engineers as well as formulators to actually create the tables. All of this expertise is not cheap and they all require expensive resources and equipment.
On the other side, the government will not let you sell anything to the public that isn't both effictive and safe. Human beings are funny in that we're all different and so something that is harmless to one person can kill someone else (like peanuts). So the drug manufacturer has to spend a lot of money in order to prove to the FDA (and other government's drug agencies) that the drug does exactly what you say it does and nothing else. This costs A LOT! And on top of it all it's often that the drug will fail while going through these clinical trials so all that money you spent on developing a molecule goes down the drain which means that the price of successful drugs has to include costs to recoup the failed drugs as well. This whole process takes a long time (5-10 years from beginning to end) The way that patent law works you have a very limited amount of time on the market to actually make money since you have to patent the molecule when you first dicover it (so about 4-8 years before it will reach market and start selling) so when it actually does release the drug companies have to raise the price in order to make the money back in a short amount of time (and obviously make a profit) before the generic manufacturers can start making the same drugs and sell them for much cheaper since they have virtually no R&D invested in the drug. On top of it all drug manufacturers have to invest millions in order to protect their IP since other drug manufacturers (and generics as well) are always trying to break each others patents because the chemistry behind drug effectivness is extrememly comlicated and different configurations of the same molecule can have very different effects. And that is why a tablet that might cost less then a cent to make actually costs hundreds of dollars to buy.
P.S. all of this only applies to small molecules. Biotech companies work differently in that it's both much harder to develop and much harder to break the pattents on large molecules.
The primary reason I went relatively in depth is because I believe the devil is in the details. That was a good overview of the R/D expenditure for a pharma company. It actually leads to the point Awesomedrifter is pointing to, the stagnation of the pharmaceutical industry. A good majority of the pharma companies are in the midst of a patent cliff currently. This means patents on their blockbuster drugs are expired or about to be retired and they don't have the new drugs in the pipeline that can replace the lost revenue. This has led to many cutbacks at pharma companies although some of them are still doing pretty well at the moment. There is quite the doom and gloom in this industry and the future is rather uncertain. The industry is heading toward consolidation and acquisition of small biotech firms for their IP. (Although acquiring successful IP is very much hit and miss as well). I will politely ignore the question of how to change the methodology of pharma company at this moment. It is a difficult question and we can have a ten page discussion about it. It is something that will be coming forward in future blogs.
I want to capture some of the subtler points regarding research and clinical trials in my upcoming blog posts. As I believe topics such as clinical trial designs, negotiation process between pharma companies and the FDA, the role of marketing are integral for getting a picture of why there is a innovation crisis in the pharma industry right now. The devil is in the details and there will be a payoff once I finish the world building process.
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On December 06 2013 04:00 FryBender wrote:Show nested quote +On December 06 2013 02:45 Awesomedrifter wrote:
How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose. How is it stagnated and how do you propose it change its methadology?
Profit margins on drug development have almost vanished, its a horribly inefficient process, yet they will neglect alternative therapy and insist drugs and drugs alone will solve all health problems. If you suggest something against the established model it will be hard to obtain even modest research funds. Research institutions are typically very conservative.
I have not heard promising things for those pursuing this field at this current time, its more profitable to get into industries that are beginning to grow imo.
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On December 06 2013 06:46 Awesomedrifter wrote:Show nested quote +On December 06 2013 04:00 FryBender wrote:On December 06 2013 02:45 Awesomedrifter wrote:
How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose. How is it stagnated and how do you propose it change its methadology? Profit margins on drug development have almost vanished, its a horribly inefficient process, yet they will neglect alternative therapy and insist drugs and drugs alone will solve all health problems. If you suggest something against the established model it will be hard to obtain even modest research funds. Research institutions are typically very conservative. I have not heard promising things for those pursuing this field at this current time, its more profitable to get into industries that are beginning to grow imo.
Well besides surgical intervention, modern healthcare pretty much relies on drugs and drugs alone to solve all health problems. What else is there that the drug companies are neglecting? Homeopathy? Accupuncture? Shaman rituals?
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TLADT24920 Posts
On December 06 2013 06:46 Awesomedrifter wrote:Show nested quote +On December 06 2013 04:00 FryBender wrote:On December 06 2013 02:45 Awesomedrifter wrote:
How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose. How is it stagnated and how do you propose it change its methadology? Profit margins on drug development have almost vanished, its a horribly inefficient process, yet they will neglect alternative therapy and insist drugs and drugs alone will solve all health problems. If you suggest something against the established model it will be hard to obtain even modest research funds. Research institutions are typically very conservative. I have not heard promising things for those pursuing this field at this current time, its more profitable to get into industries that are beginning to grow imo.
alternative therapies? CAM?
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On December 06 2013 06:46 Awesomedrifter wrote:Show nested quote +On December 06 2013 04:00 FryBender wrote:On December 06 2013 02:45 Awesomedrifter wrote:
How does it feel to work in a stagnated industry that refuses to change its methodology?
This look like a pretty good write up, I'll be looking forward to the future parts. Perhaps you might want to go to the topic of interest and just cite resources to find the background if they so chose. How is it stagnated and how do you propose it change its methadology? Profit margins on drug development have almost vanished, its a horribly inefficient process, yet they will neglect alternative therapy and insist drugs and drugs alone will solve all health problems. If you suggest something against the established model it will be hard to obtain even modest research funds. Research institutions are typically very conservative. I have not heard promising things for those pursuing this field at this current time, its more profitable to get into industries that are beginning to grow imo.
Alternative therapy is just therapy that hasn't been scientifically proven, or has been scientifically proven... not to work. Why would any healthcare professional recommend something not evidence based?
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Hi, please continue with this blog and provide even deeper insights into the industry! This is something relevant to my interests and the more detail the better!
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EPT
