The Drug Discovery Process and the role of CROs and CDMOs

Those who follow the chemical and pharma sector often hear the terms CRO, CDMO and CRAMS. It is the direction that most chemical and pharma companies are moving in. During the race to develop a vaccine for the COVID pandemic, we often heard terms like so and so vaccine is Phase 2 or 3 of clinical trials but didn’t really understand what that meant. We are about to break down all the complex terminology around this subject and explain what these terms mean and what actually is the CRAMS industry in very simple language.

The drug development process is a very long and complex process which usually takes 10-15 years and costs hundreds of millions and a lot of times billions of dollars. This is the US FDA’s process that most new and innovative drugs have to go through before they can be sold to the public. A drug usually goes through three big phases on its way to commercialization – the discovery of the drug, the testing of the drug and manufacturing of the drug. Once we have understood this process, it will be very easy for us to understand where CROs and CDMOs come in, what is their importance and what benefits they bring to the overall value chain.

Drug Discovery

The process of drug discovery starts with the research teams who work to analyze diseases and what causes them. They analyze what part of the body a disease affects and what reaction the body has to these diseases. Once all the causes for the disease have been identified, they investigate on how to act on these causes. What would stop this disease from getting worse or even reverse their course. For this, they examine thousands of compounds like natural compounds, synthetic compounds and even bio-engineered compounds.

The research teams test tens of thousands of compounds on cell cultures (in-vitro testing) and in animals (in-vivo testing). This process is called the Pre-Clinical Testing phase. This helps them analyze what effect they could have on the human body. And through a process of elimination, they narrow down thousands of compounds to just a few compounds to make the drug or the medicine out of.

This is a very long and difficult process because researchers have to collect vast amounts of data on the possible side effects these drugs can have on the human body. This process usually takes about 5-6 years. Once they have narrowed down the compounds and collected all the necessary data, the researchers will file an IND – Investigational New Drug Application. Once the IND has been approved, they can now test the drug on human volunteers.

Clinical Trials

The clinical trials start after the IND is approved and is undertaken in 3 phases. Phase 1 is called pharmacology phase. The aim of the phase 1 study is to understand how the body reacts to the drug and what if there are any side effects. About 70% of the drugs in phase 1 move on to the next phase Phase 2 is called the exploratory phase. The aim of the phase 2 study is to study the safety and effectiveness of the drug. About 33% of the drugs in phase 2 move on to phase 3. Phase 3 is known as the confirmatory phase as it confirms the safety and efficacy of the drug on a wide range of people. Only 25-30% of the drugs make it past Phase 3. Phase 4 clinical trials are called post marketing study or surveillance as it happens after the drug has been released to the public. 70-90% of the drugs in this phase succeed in staying in the market.

Phase 0 Trials 

Before the Phase 1 trials, researchers have to conduct a small study called human microdosing study or the Phase 0 trials. The researchers give a single sub-therapeutic dose to a very small group of people – usually 10-15. A sub-therapeutic dose is a very small dose that will not have any therapeutic effect on the body. It is done to make sure that the compound, which has never been exposed to humans, is not toxic and is safe for ingestion. If the drug acts very differently than what the researchers theorized, they might have to do some additional preclinical studies.

Phase 1

In the Phase 1 trials, researchers try to figure out what is the highest dose a human can take without any serious side effects. Researchers will also try to figure out what is the best way to deliver the drug to the human body. For example, orally- which is in the form of a tablet or capsule, through an injection, a nasal spray, etc. The study is usually conducted on a small group of healthy volunteers, usually 20-100. These volunteers have to be disease free – they cannot be suffering from any kind of condition as the researchers do not yet know how the drug will react in the body of a person suffering from certain conditions. The study usually lasts for about 6 months.

There are 3 main types of studies conducted in Phase 1 trials: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and Food Effect.

  • Single Ascending Dose (SAD): In a single ascending dose, volunteers are given a single dose of the drug and are observed for a period of time. If the drug performs as intended, the next group of volunteers are given a higher dose of the same drug. The dosage keeps increasing until the side effects of the drug become apparent. This is called the maximum tolerated dose. This study is performed to understand what dosage is ideal and what dosage will cause serious side effects.
  • Multiple Ascending Dose (MAD): In multiple ascending dose, different groups of volunteers are given multiple increasing doses of the drug. This study is performed to understand how taking multiple doses of the drug over a period of time affects the body. The difference between SAD and MAD is that in SAD, each group receives only one dose of the drug whereas in MAD, each group receives multiple doses that increase with time.
  • Food Effect: The researchers also conduct tests to study how food intake affects the absorption of the drug in the body. To study this, participants are given two identical doses – one while fasting and one after a meal. This is done to understand when the drug should be administered.

Phase 2

In Phase 2 of the clinical trials, the drug is now going to be tested on people actually suffering from the disease or the condition. The researchers have determined that the drug is safe for consumption and are now looking to test its efficacy – which means that they are going to see if it is actually helpful in treating the disease. This study is conducted on about 50-300 patients. They are given the same dose that was determined to be safe in phase 1. This study lasts for upto 2 years as researchers collect data about how effective the medication is and any side effects it might cause. Participants in the study are given different doses to test what is the optimum dose required. Some participants also receive a placebo – which is a fake version of the drug that will not have any effect on the body. This is done to understand if the drug is actually helping the person suffering from the condition or not.

Phase 2 is usually conducted in 2 parts called Phase 2A and Phase 2B. In phase 2A researchers determine the ideal dose needed. And in Phase 2B they determine how effective the drug is at curing the disease at that dose. While phase 2 involves more participants than earlier phases, it’s still not large enough to demonstrate the overall safety of a medication. However, the data collected during this phase helps researchers come up with methods for conducting phase 3.

Phase 3 

Phase 3 trials are the most important and provide the researchers with long term safety data. The Phase 3 trials are randomized and double-blind. Randomized means that patients are divided into 2 groups at random. One group will receive the new drug whereas one group will receive an already existing drug. Double blind means that even the researchers do not know which participants are receiving the new medication and which are receiving the existing medication. This is done to eliminate bias on the researcher’s side. The study is  conducted on upto 3000 participants and are often multi-center trials, which means that the drug is now tested in multiple locations simultaneously. This study lasts for several years. The purpose of this study is to study the efficacy of the drug and monitor any side effects that may show up in the long term. This phase has the highest failure rate and only about 25% of the drugs pass this phase.

Filing NDA

Once all these trials have been completed, the company compiles all the data from the years of preclinical and clinical studies into a document which is filed with the US FDA. This document is called an NDA which stands for New Drug Application. This is the final authorization that is needed for the company to be able to market and sell this drug.

According to the US FDA’s website, the documentation required in an NDA is supposed to tell the drug’s whole story, including what happened during the clinical tests, what the ingredients of the drug are, the results of the animal studies, how the drug behaves in the body, and how it is manufactured, processed and packaged.

What the FDA is specifically looking for is if the drug is more effective in curing the condition than the drugs that are already on the market. They have to weigh the benefits that the drug provides against the side effects and only approve those drugs in which the benefit outweighs the cost.

Phase 4

Even though the drug has been approved for sale, the testing of the drug is not over. Phase 4 testing is called pharmacovigilance. In Phase 4, the long term effects of the drug are studied after it is released to the public. When the drug is marketed globally, it is taken by a diverse group of people from different regions who also suffer from various other diseases. The effects of the drug are monitored and if the drug has any adverse effects, it is recalled. 70-90% of the drugs that make it to phase 4 succeed in staying on the market.

Manufacturing of the drug

Now that the drug has been approved for sale, the pharma company has to scale up production to manufacture it on a commercial level. During pre-clinical trials, very small quantities of the drug were manufactured in the lab for testing. So the drug was produced at a lab scale. Then if the drug made it to clinical trials, the production had to be scaled up to manufacture the drug for a couple thousand people. This is known as pilot scale. And if the drug actually receives approval, it has to be scaled up to make millions of doses for sale to the public.

Role of CROs and CDMOs

Now that we understand the process of bringing innovative drugs to market, we can easily understand the role of CROs and CDMOs. 

Contract Research Organizations (CROs) help the pharma companies in the first 2 phases. CROs provide pharma companies with outsourced services in the research phase. They help the company in target discovery, preclinical and clinical studies. They also provide analytical services and help with the regulatory processes. In countries like India, we have skilled scientists who are able to do this job at a fraction of the cost. If you are a pharma company in the US and you have hired highly paid scientists, you would prefer for them to work on innovation rather than testing the drug. So the company can outsource the testing activities to CROs who will hire talent locally to carry out the trials and help with the regulatory process.

A CDMO is not involved with the preclinical phase. They come in after the drug receives clearance to be tested on humans. They help in scaling up the drug from lab scale to pilot scale, and if approved, they help scale the drug to production scale. They assist the pharma company in developing the API for the drug and the formulation. They also manufacture and package the drug for sale in the market. So they are more like partners for the pharma companies because they help bring the drug to market right from the trials stage.

Contract manufacturing firms are not concerned with the development of the drug. Rather, they come in when the drug is approved and needs to be mass manufactured.

There are also fully integrated players in the market who provide all of the above services. From target discovery to manufacturing of the final drug This is called CRAMS – Contract Research And Manufacturing Services. So CRAMS is basically a CRO and a CDMO. They are treated as partners by the pharma companies who often co invest in manufacturing facilities.

CRAMS is a mutually beneficial relationship for the pharma company and the CDMO. Think about this. If you are a pharma company and you are developing a new drug, you will have to invest in capacities before a drug has been approved to reduce time to market. If the drug fails in Phase 3 trials, then that investment has gone to waste. So by hiring a CDMO, a pharma company can be asset light. Besides, CDMOs also have expertise in manufacturing the drug at a large scale which the pharma company may not have. The Pharma company may also choose to manufacture the drug themselves and have the CDMO as a backup in case they face issues in the future with their own manufacturing facilities. And with the manufacturing side of things taken care of, the pharma company can focus on innovation and not worry about the complexity that goes into manufacturing the drug. 

The manufacturer on the other hand receives stable and predictable cash flows. CDMOs are paid to take the drug through clinical trials. If the drug fails, they still get paid. But if the drug is approved, they get to manufacture the drug at a commercial scale. Indian companies do not come up with innovative drugs which is a very high margin business. Indian manufacturers are more focused on generic drugs. This is a way for Indian players to get a piece of the high margin business of patented drugs. The innovators also provide the CDMO with the technology to manufacture these drugs which they may not have had access to in any other scenario.

2,415 thoughts on “The Drug Discovery Process and the role of CROs and CDMOs”

  1. The majority of mesothelioma cases are settled without ever having to enter the courtroom.
    Compensation may come from many sources including asbestos law (Robbie) trust funds and insurance companies as well as the Department
    of Veterans Affairs.

  2. The Reasons You Should Experience New York City Accident Lawyer
    At The Very Least Once In Your Lifetime injury attorney new
    orleans (Joel)

  3. Bandar Togel Terpercaya Tools To Improve Your Everyday Lifethe Only Bandar Togel Terpercaya Trick That Should Be Used By
    Everyone Be Able To bandar togel terpercaya (Hassie)

  4. Best Childrens Bunk Beds Techniques To Simplify Your Everyday Lifethe Only Best Childrens Bunk Beds
    Technique Every Person Needs To Know childrens bunk beds [Trina]

  5. Best Childrens Bunk Beds Techniques To Simplify Your Everyday Lifethe Only Best Childrens Bunk Beds
    Technique Every Person Needs To Know childrens bunk beds [Trina]

  6. Its like you read my thoughts! You appear to understand so much about this, like you wrote the guide in it or something. I believe that you just can do with a few p.c. to drive the message house a bit, but instead of that, this is excellent blog. A fantastic read. I will definitely be back.

  7. Hmm is anyone else experiencing problems with the images on this blog loading? I’m trying to determine if its a problem on my end or if it’s the blog. Any responses would be greatly appreciated.

  8. Hello I am so grateful I found your weblog, I really found you by error, while I was browsing on Askjeeve for something else, Anyhow I am here now and would just like to say thanks a lot for a incredible post and a all round thrilling blog (I also love the theme/design), I don’t have time to browse it all at the moment but I have book-marked it and also added in your RSS feeds, so when I have time I will be back to read much more, Please do keep up the great job.

  9. When I originally commented I clicked the “Notify me when new comments are added” checkbox and now each time a comment is added I get several e-mails with the same comment. Is there any way you can remove me from that service? Thank you!

  10. I believe this is among the so much important information for me. And i’m satisfied studying your article. But wanna observation on few normal things, The site taste is perfect, the articles is actually great : D. Excellent process, cheers

  11. A mesothelioma attorney with experience will help you determine the most appropriate asbestos lawsuit (Chance) claim to make.
    National firms are able to file lawsuits where asbestos exposure has occurred in multiple states.

  12. Pretty component to content. I just stumbled upon your weblog and in accession capital to assert that I acquire in fact enjoyed account your blog posts. Anyway I will be subscribing for your feeds and even I achievement you get admission to consistently rapidly.

  13. Its like you read my mind! You appear to know so much about this, like you wrote the book in it or something. I think that you can do with a few pics to drive the message home a bit, but instead of that, this is great blog. A great read. I’ll definitely be back.

  14. Hmm it looks like your website ate my first comment (it was super long) so I guess I’ll just sum it up what I submitted and say, I’m thoroughly enjoying your blog. I too am an aspiring blog writer but I’m still new to the whole thing. Do you have any tips for first-time blog writers? I’d definitely appreciate it.

  15. Hi there, just became alert to your blog through Google, and found that it is truly informative. I’m going to watch out for brussels. I’ll be grateful if you continue this in future. Lots of people will be benefited from your writing. Cheers!

  16. Double Glazed Front Doors Near Me Techniques To Simplify Your Everyday Lifethe Only Double Glazed Front Doors Near Me
    Trick That Every Person Must Know double glazed Front door (nitka.by)

  17. Can I simply say what a comfort to uncover a person that really knows what they’re talking about online. You definitely realize how to bring an issue to light and make it important. More people must read this and understand this side of your story. I was surprised you aren’t more popular given that you definitely possess the gift.

  18. ADHD Assessment Private Tips To Relax Your Everyday Lifethe Only ADHD Assessment
    Private Trick That Should Be Used By Everyone Be Able To adhd
    assessment private (Leon)

  19. Guide To Volkswagen Replacement Key Cost Uk: The Intermediate Guide Towards
    Volkswagen Replacement Key Cost Uk volkswagen replacement key cost uk (Maryjo)

  20. Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.

  21. Why French Door Fridge With Ice Maker Isn’t A Topic That People Are Interested In French Door Fridge
    With Ice Maker mitsubishi french door fridge with ice maker (Erma)

  22. Strollers Strollers Tools To Ease Your Everyday
    Lifethe Only Strollers Strollers Trick Every Individual Should Be Able To strollers strollers (Aisha)

  23. My partner and I absolutely love your blog and find most of your post’s to be just what I’m looking for. Do you offer guest writers to write content in your case? I wouldn’t mind publishing a post or elaborating on some of the subjects you write related to here. Again, awesome web site!

  24. Glazing Specialists London Tools To Improve Your Everyday Lifethe Only Glazing Specialists London Trick That Every Person Should Be Able To glazing specialists london (Trent)

  25. 4 Dirty Little Secrets About French Door Fridge Freezer With Ice Maker And The French Door Fridge
    Freezer With Ice Maker Industry french door fridge singapore (Doyle)

  26. Pretty section of content. I just stumbled upon your
    blog and in accession capital to assert that I get actually enjoyed account your blog posts.

    Anyway I will be subscribing to your feeds and even I achievement
    you access consistently quickly.

  27. You can shop and buy UK CBD oils, capsules, gummies and creams here.

    But for now, its use would be “at their own risk, because we still don’t have clinical studies that have proven that cannabidiol can be good for some conditions as chronic pain, insomnia, or anxiety,” she said.
    Lab Results/Tests: Good CBD companies will test their products for potency and purity.
    This will positively help you in getting the ideal advantages from the item.
    We’ve mentioned value before, but there’s no better value than getting 100 mg of CBD per every dose in a 30 ml bottle.

    While CBD oil has been legalized, Caulfied said it could be better regulated in Canada.
    You should check out third-party sites like Trustpilot and
    Better Business Bureau to see what others are saying there.
    The double-blind study, whose objective was to “assess the efficacy of a cannabis-based medicine in the treatment of pain due to rheumatoid arthritis”,
    was carried out over the course of five weeks on 58 RA patients.
    However, due to the unregulated nature of the market, customers need to stay vigilant.
    Canna Mag is able to provide any genuine CBD product which is pure in nature without any
    contamination.

  28. Tier 2 Links Seo Techniques To Simplify Your Everyday Lifethe Only Tier
    2 Links Seo Trick Every Person Should Be Able To tier 2 links seo – Floyd,

  29. You’ll Never Guess This French Style Fridge Freezer With Water And Ice Dispenser’s Tricks
    french style fridge freezer with water and ice dispenser (Raina)

  30. Guide To Situs Togel Dan Slot Terpercaya: The Intermediate Guide
    To Situs Togel Dan Slot Terpercaya situs togel dan slot terpercaya (Gino)

  31. Replacing Panel In Upvc Door Tools To Help You Manage Your Daily Lifethe One Replacing Panel
    In Upvc Door Trick That Every Person Must Know replacing panel in upvc door (Sherita)

  32. Hi there, I found your web site by means of Google at the same time as looking for a similar topic, your web site got here up, it seems great. I have bookmarked it in my google bookmarks.
    Hi there, just become aware of your blog thru Google, and located that it is really informative. I’m going to watch out for brussels. I will appreciate in case you continue this in future. Many folks can be benefited from your writing. Cheers!

  33. After looking over a number of the articles on your website, I really like your technique of blogging. I bookmarked it to my bookmark webpage list and will be checking back in the near future. Please check out my web site too and let me know how you feel.

  34. Have you ever thought about including a little bit more than just your articles? I mean, what you say is fundamental and all. However think about if you added some great pictures or video clips to give your posts more, “pop”! Your content is excellent but with pics and videos, this site could definitely be one of the greatest in its field. Fantastic blog!

  35. Howdy! This is kind of off topic but I need some help from an established blog.
    Is it tough to set up your own blog? I’m not
    very techincal but I can figure things out pretty fast.
    I’m thinking about creating my own but I’m not sure where to begin. Do you have any ideas or suggestions?
    Thanks

  36. Good V I should definitely pronounce, impressed with your website. I had no trouble navigating through all the tabs and related info ended up being truly simple to do to access. I recently found what I hoped for before you know it at all. Quite unusual. Is likely to appreciate it for those who add forums or something, website theme . a tones way for your client to communicate. Nice task..

  37. I have been exploring for a little for any high quality articles or weblog posts in this kind of house . Exploring in Yahoo I at last stumbled upon this site. Studying this information So i?¦m happy to exhibit that I have a very just right uncanny feeling I came upon exactly what I needed. I most for sure will make sure to don?¦t put out of your mind this web site and provides it a glance regularly.

  38. Cadastre-se no portal online dօ cassino online Pin Uⲣ Brasil е
    participe slots gratuitamente οu com dinheiro real!|Еntre no
    jogo de caça-níqueis е participe em jogos de cassino no Pin Uρ Brasil, о site oficial ρara entretenimento е prêmios.|Εntre no cassino
    Pin Up Brasil e divirta-se jogando сaça-níqueis de graça ou aposte com dinheiro real!|Ⲛo
    Pin Uⲣ Brasil, você pode participar еm cɑça-níqueis
    e jogos de cassino sem custo оu fazeг apostas reais.
    Cadastre-ѕe já!|O site oficial Pin Up Brasil oferece
    сaça-níqueis de graça е apostas сom dinheiro real.
    Crie sua conta aɡora!|Participe Ԁo cassino online Pin Up Brasil, jogue gratuitamente ou aposte рara ganhar prêmios еm
    dinheiro real.|Participe ϲaça-níqueis e explore o mundo do cassino online no Pin Up Brasil, com jogos grátis ⲟu jogos com dinheiro.|Ⲟ cassino online Pin Up Brasil tеm slots
    e jogos ⅾe cassino. Cadastre-se е participe com dinheiro real οu de graça.|Entre no Pin Up Brasil, aproveite caça-níqueis e cassino gratuitamente оu faça apostas ⲣara ganhar prêmios.|Νⲟ
    Pin Up Brasil, o site oficial do cassino online, aproveite ϲaça-níqueis e jogos ⅾe
    cassino dе graçɑ ou ϲom apostas reais.|Crie sua conta no Pin Uр Brasil е aproveite seus
    ⅽaça-níqueis favoritos ߋu aposte em jogos ⅾe cassino com
    dinheiro real.

    Ꮇy webpage :: Pin-Up Casino

Leave a Comment

Your email address will not be published. Required fields are marked *