New Drug Discovery and Development (Overview) - Part 1 | Dr. Shikha Parmar

Summary

This video offers an insightful overview of the complex process of new drug discovery and development. It highlights the multi-phase journey from screening thousands of compounds to identifying a lead drug candidate. The process includes target identification, lead generation, preclinical studies in animals, and clinical trials in humans, which can take up to 15 years and cost around $1.5 billion. Post-market surveillance ensures long-term drug safety even after FDA approval. The video emphasizes the importance of monitoring adverse drug reactions, particularly in larger populations after a drug is released.

Takeaways

• 💊 Drug discovery and development is a complex, lengthy process that takes 10-15 years and costs around $1.5 billion.
• 🧪 The drug discovery phase involves screening 5,000 to 10,000 compounds to identify potential leads or drug candidates.
• 🔍 Drug discovery has two main steps: identifying a target in the disease and validating it, followed by screening active compounds to find hits and leads.
• 📊 Hits are the initial 100-200 compounds with potential, and from these, dozens of leads are optimized for effectiveness and selectivity.
• 🧬 Lead optimization involves modifying chemical structures to improve selectivity, efficacy, and the ADME (absorption, distribution, metabolism, and excretion) profile.
• 🐁 In drug development, 250 optimized compounds are tested in animals during preclinical trials, with only around five moving forward for human testing.
• 👩‍🔬 Clinical trials are conducted in three phases (Phase 1, 2, 3), and they typically last six to seven years.
• ✅ If a drug passes clinical trials, a New Drug Application (NDA) is submitted to the FDA for approval, which takes one to two years.
• 🛡️ After approval, the drug undergoes post-marketing surveillance (Phase 4) to monitor its safety in the general population.
• ⚠️ Drugs may be withdrawn from the market during Phase 4 if serious adverse effects are discovered, as was the case with the drug Sibutramine.

Q & A

What are the two main stages in the process of new drug discovery and development?

The two main stages are the new drug discovery stage and the new drug development stage.

How many compounds are typically screened during the drug discovery process?

During the drug discovery process, around 5,000 to 10,000 potentially active compounds are screened.

What are 'leads' in the drug discovery process?

'Leads' are potential drug candidates identified during the drug discovery process after screening thousands of compounds.

What is the role of high-throughput screening (HTS) in drug discovery?

High-throughput screening (HTS) is used to screen thousands of compounds to identify around 100 to 200 hits that interact with a specific target in drug discovery.

What is lead optimization, and why is it important?

Lead optimization involves modifying lead compounds chemically to produce candidates with higher affinity, selectivity, and a good ADME (absorption, distribution, metabolism, and excretion) profile, which is crucial for developing effective drugs.

What happens during the pre-clinical studies in the drug development process?

During pre-clinical studies, around 250 lead compounds are tested in animals for safety, efficacy, and toxicity. By the end of this phase, typically only 5 compounds remain for further testing.

What are the three phases of clinical trials, and how long do they take?

The three phases of clinical trials are Phase 1, Phase 2, and Phase 3, and they take around 6 to 7 years to complete.

What is the role of the FDA in the drug development process?

The FDA reviews the Investigational New Drug (IND) and New Drug Application (NDA) submissions, monitors safety and efficacy data, and grants approval for a drug to be marketed if it meets safety and efficacy requirements.

What is post-marketing surveillance, and why is it important?

Post-marketing surveillance, also known as Phase 4 trials, involves monitoring the drug's safety once it is available to the public. It helps detect rare or long-term adverse effects that may not have been observed during clinical trials.

Why was the drug 'Sibutramine' withdrawn from the market?

Sibutramine was withdrawn from the market because it was found to increase the risk of heart disease and stroke during post-marketing surveillance.

Outlines

00:00

💊 Introduction to New Drug Discovery and Development

The video introduces the process of new drug discovery and development. It highlights the significance of drugs in saving lives and improving quality of life. The process of introducing a new drug to the market is complex, involving over 1.5 billion USD in costs and taking 10 to 15 years of research. The drug discovery stage involves screening thousands of compounds to identify potential candidates (called leads), while the drug development stage focuses on testing and refining these leads for safety and efficacy.

05:02

🧪 Stages of Drug Discovery: Target Identification and Lead Optimization

This section explains the drug discovery phase, starting with the identification and validation of a target involved in a disease. High-throughput screening (HTS) methods are used to screen 5,000 to 10,000 compounds, reducing the pool to about 100 to 200 'hit' compounds. These hits are further optimized into 'leads,' which are potential drug candidates. Lead compounds are refined through chemical modifications to improve their selectivity and ADME (Absorption, Distribution, Metabolism, Excretion) profiles. About 250 compounds enter the drug development phase.

10:03

🧬 Pre-Clinical Studies: Testing in Animals

In this paragraph, the pre-clinical phase of drug development is outlined. It involves testing the 250 optimized compounds on animals to assess their safety and efficacy. Pre-clinical studies take about 1 to 2 years and typically result in only five compounds advancing to the next stage. The data collected from these studies is compiled into an Investigational New Drug (IND) application, which is then submitted to the FDA for review before human trials can begin.

👩‍⚕️ Clinical Trials: Phases of Human Testing

Here, the video explains clinical trials, which follow the FDA's approval of the IND application. Clinical trials are conducted in three phases (Phase 1, 2, and 3) over a span of six to seven years. These trials evaluate the drug’s safety, efficacy, and ADME profile in human subjects. By the end of the trials, all but one drug candidate is typically eliminated. The data from these trials is compiled into a New Drug Application (NDA), submitted again to the FDA for final approval before the drug can be marketed.

✅ FDA Approval and Post-Marketing Surveillance

Once clinical trials are completed, the FDA reviews the NDA for one to two years. If satisfied with the drug's safety and efficacy, the FDA grants approval for large-scale production and marketing. However, even after approval, pharmaceutical companies are required to monitor the drug's safety through post-marketing surveillance, also known as Phase 4 studies. These studies track adverse drug reactions and long-term effects in a larger population, ensuring continued safety. In some cases, drugs are withdrawn from the market due to severe side effects.

🔬 Overview of the Entire Drug Development Process

The final section summarizes the entire process of drug discovery and development. It recaps the major steps, from target identification and screening of thousands of compounds to pre-clinical and clinical trials, FDA approval, and post-marketing surveillance. The process is long and expensive, taking up to 15 years to complete. The importance of Phase 4 studies is highlighted, especially in detecting rare adverse effects after the drug is widely available. The video concludes by emphasizing the need for ongoing monitoring to ensure drug safety.

Keywords

💡Drug Discovery

Drug discovery is the process of identifying potential compounds that could become new medications. It involves screening thousands of compounds, from 5,000 to 10,000, to find promising candidates, known as 'leads.' This phase takes about 3 to 5 years and is the first major stage of bringing a new drug to market, as outlined in the video.

💡Lead Compounds

Lead compounds are potential drug candidates identified during the drug discovery phase. They are refined through chemical modifications to improve their efficacy, selectivity, and safety profile. The video explains that lead compounds serve as templates for further development, eventually narrowing down the list to around 250 compounds for drug development.

💡Preclinical Studies

Preclinical studies involve testing drug candidates in animals to assess safety, efficacy, pharmacokinetics (ADME), and toxicity. This stage occurs before human trials and reduces the list of drug candidates to approximately five. Preclinical studies last 1-2 years, as described in the video, and are essential for determining which compounds can proceed to clinical trials.

💡Clinical Trials

Clinical trials are tests conducted in humans to evaluate the safety and efficacy of a drug. The trials are divided into three phases, each progressively larger in scope. According to the video, clinical trials are crucial for determining the final drug candidate, with only one out of five preclinical candidates typically making it through. The trials last 6-7 years.

💡FDA Approval

FDA approval is the formal process by which the Food and Drug Administration reviews data from clinical trials and decides if a drug can be marketed. The video emphasizes that FDA approval can take 1-2 years and is necessary to ensure that the new drug is safe and effective for public use. It also mentions that after approval, the drug is produced and sold to treat specific conditions.

💡High Throughput Screening (HTS)

HTS is a method used to rapidly test thousands of compounds for potential biological activity against a target. In the drug discovery process, this technique helps narrow down the list of candidates from 5,000-10,000 to 100-200 hits. The video highlights HTS as a critical early step in drug discovery.

💡ADME Profile

ADME stands for Absorption, Distribution, Metabolism, and Excretion, which are key pharmacokinetic factors that determine how a drug behaves in the body. According to the video, a good ADME profile is necessary for a drug candidate to proceed through lead optimization and further development.

💡Post-Marketing Surveillance

Post-marketing surveillance, or Phase 4 studies, refers to the monitoring of a drug’s safety after it has been released to the public. The video explains that this phase is crucial for identifying adverse drug reactions that may only become evident after the drug is used by a larger population over time.

💡Target Identification and Validation

Target identification is the process of finding a biological molecule or pathway that a new drug can interact with to produce a therapeutic effect. Validation confirms that the identified target is appropriate for drug development. In the video, this step is the foundation of the drug discovery process, as modifying the target's function is essential for the drug's effectiveness.

💡Investigational New Drug (IND) Application

The IND application is a formal request submitted to the FDA to begin clinical trials in humans after preclinical studies. The video states that this document compiles all findings from animal studies and, if approved, allows for the testing of the drug in human trials. The IND marks the transition from preclinical to clinical research.

Highlights

The entire process of introducing a new drug to the market takes around 10 to 15 years and costs approximately 1.5 billion US dollars.

Thousands of potentially active compounds (5,000 to 10,000) are screened during drug discovery, with unsuitable compounds rejected at each step.

The process of new drug discovery involves two main stages: new drug discovery and new drug development.

During drug discovery, the goal is to identify lead compounds from 5,000 to 10,000 compounds screened.

Lead compounds are the potential drug candidates that are further optimized during the discovery process.

New drug discovery takes around 3 to 5 years, focusing on identifying potential candidates and optimizing leads.

The next stage, drug development, involves further screening of lead compounds in animals and humans to ensure safety and efficacy.

Only 5 compounds from the initial 250 generated in pre-clinical studies proceed to clinical trials.

Clinical trials are conducted in three phases (Phase I, II, III), taking 6 to 7 years to complete.

Data from clinical trials is compiled into a New Drug Application (NDA) submitted to the FDA for approval.

FDA review and approval of a new drug can take around 1 to 2 years.

After FDA approval, the drug is manufactured on a large scale and launched for the treatment of specific diseases or conditions.

Post-marketing surveillance, or Phase IV studies, monitor the safety of the drug once it's available to the public.

Post-marketing studies are essential for detecting adverse drug reactions, which may only emerge after a drug is prescribed to large populations.

An example of a drug withdrawn due to adverse effects is Sibutramine, which was removed from the market after it was found to increase the risk of heart disease and stroke.

Transcripts

[Music]

hello students

today's video is a very important video

in this video i will give a quick

overview or outline of the process of

new drug discovery and development

now this video is first in the series of

videos on new drug discovery and

development

now as we all know drugs are substances

that save lives and also improve quality

of life

introducing a new drug in market is a

highly complex process

it costs a pharmaceutical company around

1.5 billion us dollars and 10 to 15

years of research and development by

hundreds of research teams

now during discovery of a new drug

thousands of potentially active

compounds around 5000 to 10 000

compounds are screened unsuitable

compounds are rejected at each step

now the entire process of new drug

discovery and development has two main

stages or phases

the first stage is the new drug

discovery and the second stage is the

new drug development

now as we know five thousand to ten

thousand active compounds are screened

to get a new drug new drug discovery is

the process which aims at identifying

potential candidates from five thousand

to ten thousand compounds that are

screened

now these potential compounds that are

identified during drug discovery are

called as leads so leads or potential

drug candidates are identified during

drug discovery and the entire process of

new drug discovery takes around three to

five years

now next stage is the drug development

now drug development is the process of

further screening and evaluating lead

compounds which are generated during the

process of drug discovery now lead

compounds are further evaluated and

screened in animals and human beings so

that a new

safe and very effective drug could be

identified

its suitable formulation and dosage

forms are developed indications are

decided and if the new drug is approved

by fda it is manufactured on the large

scale and launched in the market for the

treatment of a specific disease or

condition

now the main steps during new drug

discovery are

the first step is the target

identification and validation now target

involved in a specific disease is

identified whose functioning could be

modified by a new drug to produce the

therapeutic effect

now once this target is identified it's

validated that is reconfirmation that

the target identified is correct

now next step is the screening of around

5 to ten thousand potentially active

compounds by high throughput screening

that is hds method hts screening methods

now from 5000 to 10 000 compounds around

100 to 200 compounds

specific for the target are selected and

these are called as hit these compounds

are called as hit so the next step in

the new drug discovery is the

identification of hit and these hits are

derived by the screening of 5000 to 10

000 active compounds

now from these 100 to 200 hits dozens of

lead compounds with affinity and higher

selectivity for the target are

identified now leads interact only with

the specific target excluding all the

other related targets so the next step

is the lead generation and optimization

now after the leads are generated they

are optimized

now

in the lead optimization lead compounds

are used as templates and from the lead

compounds more potential candidates are

designed by chemical modification

now these compounds which are produced

by chemical modification they possess

higher affinity higher selectivity for

the target they show good admi profile

that is absorption distribution

metabolism and excretion profile and

good structure activity relationship so

around 250 compounds

are designed from the lead compounds and

these 250 compounds that are designed

they enter the process of drug

development

now the process of new drug discovery

ends when the leads are generated and

optimized it is completed in around

three to five years and the next step is

the new drug development now around 250

compounds that were generated by the

chemical modification of leads are

further screened and are further

evaluated in animals and then in the

human beings now let's see what are the

different steps of drug development

now the first step here is the

pre-clinical studies now pre-clinical

studies refer to the testing of all

these 250 compounds in animals

now by the end of pre-clinical studies

only five compounds only around five

compounds are left to be further

screened all other compounds are

rejected and the process of pre-clinical

studies takes around one to two years

now findings of pre-clinical studies are

compiled

in a

investigational new drug application

that is ind application now this

application is submitted to fda that is

a food and drug administration for

review

now if application is approved by fda

all the five potential drug candidates

which were identified during the

pre-clinical studies are further

screened

and evaluated in human beings now these

studies in the human beings are called

as the clinical trials now clinical

trials are performed in three phases

phase one phase two and phase three

studies all three phases of clinical

trials are completed in around six to

seven years now data obtained from the

clinical trials is compiled in new drug

application and again submitted

to fda for review

now fda review takes around one to two

years

now if fda is satisfied with the safety

efficacy adme profile of the drug

official permission is granted by the

fda to launch the drug in the market

so drug is formulated indications are

decided it is manufactured on the large

scale and made available in the market

for the patients now the entire process

of

drug discovery to the launching of drug

in the market takes around 10 to 15

years

now following fda approval

fda once the drug is available in the

market fda requires pharmaceutical drug

companies to monitor the safety of drug

and the safety of drug is monitored

using the fda adverse event reporting

system

so this process is called as a post

marketing surveillance that is a very

close

monitoring of drug is dr is done to

ensure that the drug is safe

now these studies are also called as a

phase four studies which are conducted

when the drug is in market and available

to the prescribers and to the patients

now look at this figure

it gives a compiled schematic

representation of new drug discovery and

the development process now let's once

again quickly review the entire process

so uh the

drug discovery stage

the drug discovery involves

identification of target to be modified

by the drug to produce the therapeutic

effect then screening of around 5000 to

10 000 compounds active compounds and

identifying around 100 to 200 hits

further screening of hits to generate

the leads

and once the leads are generated these

leads are used as templates and around

250 molecules are designed by chemical

modification of the leads and the entire

process of drug discovery takes around

three to five years

now during uh drug development further

screening of

250 compounds derived

from the leads

are screened and evaluated first in the

animals and the studies are called as a

preclinical studies so during

pre-clinical studies pharma these are

the pharmacological studies that are

performed on the animals to determine

safety

and efficacy of all 250 compounds

then pharmacokinetic studies

evaluate uh administration distribution

metabolism and excretion that is adme

profile of all 250 compounds in the

animals while toxicity studies performed

during the pre-clinical studies

determine safe dose of the drug and the

dose range

so by the end of pre-clinical studies

almost all the drug candidates are

rejected and around five compounds are

left to be further screened so five

compounds are left at the end of

pre-clinical studies now the entire

process of pre-clinical studies takes

around one to two years now data that is

obtained from these preclinical studies

is compiled in investigational new drug

application that is ind application and

this application is submitted to fda for

review and approval

now further

if the fda finds investigational new

drug application satisfactory approval

is granted to conduct studies in the

human beings and thus clinical trials

are conducted

now clinical trials are conducted in

three phases namely phase one phase two

and phase three

and by the end of

clinical trials all the compounds are

rejected

and only one drug

candidate called as a new drug is

identified it is developed indications

are decided now data of these clinical

trials is compiled and new drug

application that is nda is submitted to

fda for again review

now all the three phases of clinical

trials are completed in around six to

seven years

now if fda

approves the new drug it's given

marketing approval grant of approval by

the fda is completed in about one to two

years

so now new drug is made available in the

market for the patients

now to further ascertain and confirm the

safety of new drug investigational

studies are continuously performed when

the drug is in the market

now the main name of these studies is to

report if any adverse drug reaction has

been observed with the use of new drug

now these studies are called as a

post-marketing surveillance or phase

four studies or the phase 4 4 trial

now when in market the drug is

prescribed to a large number of patient

population drug is studied in large

population and for a very long period of

time

and therefore it has been found that

several times some major adverse drug

reactions are detected only when the

product has been prescribed to

a large patient population

now many a times a drug is withdrawn

from the market because of serious is

adverse drug reactions for example

cybertron

and appetite suppressant now

cybertramine was withdrawn from the

market as it increase the risk of heart

disease and stroke so monitoring of

drugs safety is very essential when the

drug is in the market so phase 4 trials

are very important for the reporting of

adverse drug reactions especially uh

unpredictable adverse drug reactions for

example

idiosyncratic reactions so this is in

brief a quick overview of the entire

process of new drug discovery and

development if you find the video useful

kindly like subscribe and share this

video thanks for watching this video

[Music]

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