PHARM LIZETTE EZENEKWE

Stages in the Development of a New Drug

The development of a new drug is a complex, multi-stage process that involves
scientific research, regulatory approval, clinical trials, and ultimately, bringing the
drug to market. The entire process can take years, often spanning 10–15 years or
more, and can be costly, often reaching billions of dollars. Each stage is critical to
ensuring the safety, efficacy, and quality of the drug. Below is a detailed
breakdown of the key stages in drug development.

Only one or two compounds in 10,000 tested make it through to being licensed
treatments. A potential new medicine may be rejected at any point in the
development process on safety, effectiveness, or quality grounds. Overall, it may
take 10-15 years for a new compound to get from the test tube to the medicine
cabinet.

1. Drug Discovery

This is the first stage, where scientists identify a potential drug target and start
exploring compounds that might be effective in treating a disease. The drug
discovery process involves the following key steps:

 Target Identification: Researchers identify a biological target (often a

protein or gene) that is involved in a disease. The target is often a
biomolecule or receptor that plays a key role in disease progression.
 Lead Compound Discovery: Once a target is identified, researchers look
for molecules (usually small molecules, biologics, or peptides) that can
interact with the target. High-throughput screening, where thousands of
compounds are tested for activity, can be used to identify promising
candidates (called lead compounds).
 Hit-to-Lead Optimization: Once a compound (hit) has been identified, its
structure is optimized to improve its potency, selectivity, and
pharmacokinetic properties (how the body absorbs, distributes, metabolizes,
and eliminates the drug).
 Preclinical Evaluation: The selected compounds are then tested in
laboratory settings and in animals (usually rodents) to assess toxicity,
pharmacodynamics (how the drug affects the body), and pharmacokinetics.
A fundamental first step to discovering new drugs is knowledge of the biology of a
disease. This involves understanding how cell and biological processes work in
health as well as what goes wrong in disease. This will reveal potential targets that
a drug could act on. Increasingly, research scientists have been able to understand
the shape of biological molecules at the atomic level, and to use that knowledge to
design potential new drugs.

Studies in cells and animals are crucial first steps and should not be undervalued.
However, many drugs that show promising results in cells in laboratories do not
work in animals, and many drugs that show promising results in animals do not
work in humans. The attention-grabbing headlines that promise a 'cure' or
'breakthrough' are often reporting animal studies. While these studies will be
adding valuable data to the body of knowledge about a condition, it is likely to be
many years before this can be translated into a treatment.

Many thousands of new chemical compounds are created and tested to identify
those that have potential. There is a very high dropout rate at this stage; fewer than
1 in 1,000 of all the compounds that are made ever progress to testing in humans.
A new drug that shows potential will be put through a battery of laboratory and
animal tests before being given a clinical trials authorization that allows it to be
tested in humans.

2. Preclinical Development

Before moving to human clinical trials, a drug must undergo preclinical testing to
ensure it is safe and biologically active. This stage involves the following key
components:

 Toxicity Studies: Drugs are tested in animals (typically rats, mice, and
sometimes larger animals) to determine if they cause harmful side effects.
Both acute and chronic toxicity studies are performed.
 Pharmacokinetics and Pharmacodynamics: These studies examine how
the drug is absorbed, distributed, metabolized, and excreted by the body
(ADME), as well as how it interacts with its target (mechanism of action).
 Formulation Development: Researchers develop the final formulation of
the drug (e.g., tablet, injection, or liquid). The formulation must be stable,
effective, and able to deliver the active ingredient efficiently.
  Good Laboratory Practices (GLP): Preclinical studies must be conducted
under GLP guidelines to ensure the reliability and accuracy of the data.

At the end of this stage, the pharmaceutical company has enough data to submit an
Investigational New Drug (IND) Application to regulatory authorities (such as
the FDA in the U.S.).

3. Clinical Development (Clinical Trials)

Once an IND application is approved, the drug moves into clinical development,
where it is tested in humans. Clinical trials are typically conducted in three phases,
each with a specific goal.

Phase 1: Safety and Dosage

 Objective: To assess the safety, dosage range, and side effects of the drug.
 Participants: A small group of healthy volunteers (20–100 people).
 Methods: In this phase, researchers start with a low dose and gradually
increase it to observe the effects and determine the maximum tolerated dose.
 Duration: This phase usually lasts several months.

This first step in testing a new drug is to determine the safety of single doses in
a small number of healthy volunteers. This stage helps researchers understand
some aspects of how it works and establishes the likely dose required.

Phase 2: Efficacy and Side Effects

 Objective: To evaluate the effectiveness of the drug in treating the targeted

disease or condition, and further monitor its safety.
 Participants: A larger group of individuals (100–300) who have the disease
the drug is intended to treat.
 Methods: This phase involves more rigorous testing to determine whether
the drug has the desired therapeutic effect. Patients are monitored for side
effects.
 Duration: This phase typically lasts several months to two years.

If the treatment proves to be safe, studies begin to determine the effectiveness of

the drug in people with the condition to be treated. These studies may last several
months or years and involve larger numbers of people, perhaps one or two
hundred. The study may be:

 controlled - the drug is compared with the standard treatment or placebo

(dummy treatment)
 double-blind - neither the investigators nor the participants know which
treatment they are receiving
 randomised - participants will be randomly allocated to receive active
treatment or placebo.

Phase II studies typically measure the number of lesions seen in MRI scans at the
beginning and end of six months of treatment.

Phase 3: Confirmatory Trials

 Objective: To confirm the drug's effectiveness, monitor long-term safety,

and compare the drug with existing treatments or placebos.
 Participants: Thousands of patients (1,000–3,000), often in different
geographic locations.
 Methods: Randomized, controlled trials are conducted to provide robust
evidence of the drug's efficacy and safety. The data from these trials will be
used to support a New Drug Application (NDA).
 Duration: This phase can last 1–4 years.

If a drug shows effectiveness, a larger study is conducted in hundreds of people.

These clinical trials take place at different locations (multi-centre) and across
several countries and may last several years. These studies allow researchers to
assess the potential of the new drug more accurately in a wider range of people and
compare it to existing treatments.

Phase III studies generally run for two years and compare the number of relapses
in people taking the new drug with those taking the standard treatment or placebo.

4. Regulatory Review and Approval

Once the clinical trial data is collected, the pharmaceutical company can submit a
New Drug Application (NDA) or Biologics License Application (BLA) to the
regulatory authorities (e.g., FDA in the U.S., EMA in Europe, NAFDAC in
Nigeria). The review process includes:

 Evaluation of Data: The regulatory authority reviews all preclinical and

clinical trial data to determine the drug’s safety, efficacy, and quality.
 Approval: If the data supports the drug’s use, the regulatory agency
approves the drug for commercial sale. This can take anywhere from 6
months to several years, depending on the complexity of the drug and the
disease it is meant to treat.

In some cases, a Fast Track, Breakthrough Therapy, or Priority Review

designation can expedite the review process for drugs that treat serious conditions.

5. Post-Market Surveillance (Phase 4)

Once a drug is approved and available on the market, ongoing monitoring

continues through Phase 4 trials and post-market surveillance. This phase includes:

 Post-marketing Studies: Companies may conduct additional clinical trials

to gather more data on the drug’s long-term safety and effectiveness in the
general population.
 Pharmacovigilance: Ongoing monitoring of adverse effects, which may not
have been detected in earlier clinical trials due to limited sample size or
duration. Healthcare providers report side effects to regulatory authorities,
who may take regulatory action, such as issuing warnings or removing the
drug from the market if serious issues arise.
 Real-world Evidence: Real-world data from the general population, such as
patient registries, electronic health records, and insurance claims data, helps
to identify rare side effects or long-term effects.

6. Drug Manufacturing and Commercialization

After approval, the drug must be manufactured in large quantities, a process that
involves:

 Good Manufacturing Practice (GMP): Compliance with regulatory

guidelines ensuring the drug is produced consistently and meets quality
standards.
 Standard Organisation of Nigeria
  Supply Chain Management: Ensuring the drug is distributed efficiently
and meets demand across different markets.
 Market Launch: Pharmaceutical companies develop marketing strategies,
educate healthcare providers, and ensure the drug is available in pharmacies
and hospitals.

Conclusion

The development of a new drug is a lengthy, complex, and highly regulated

process. It involves a series of stages, from initial discovery through preclinical
testing, clinical trials, regulatory approval, and post-market surveillance. Each
stage is critical to ensuring that the drug is safe, effective, and beneficial to
patients. While the process can be lengthy and expensive, it is essential to bring
innovative treatments to the market that can improve the quality of life and address
unmet medical needs.