Drug Development A. A.

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The process of bringing a drug out of development and onto the market is very rigorous, time-consuming,
and expensive. By some estimates, the process can take upwards of 15 years, and a typical drug company
may spend close to $800 million to create a marketable new drug. The biggest hurdle a new drug must
overcome is the testing required by the FDA. As previously discussed, prescription drugs are regulated
under the Federal Food, Drug, and Cosmetic Act of 1938 (FD&C Act). Only about 1 in 5000 potential
drugs successfully pass through the testing process to be approved by the FDA for patient use.
Drug development is the process of discovering, designing, and testing new drugs for biological use. Drug
development process include;
• Target identification: identifying a biological target such as protein or receptor that is involved in
a particular disease or condition
• Lead discovery: finding a lead compound which is a molecule that shows potential for treating the
targeted disease or condition. These substances with complex structures may be obtained from
various sources, e.g.
▪ plants (cardiac glycosides),
▪ animal tissues (heparin),
▪ microbial cultures (penicillin G) or
▪ cultures of human cells (urokinase), or
▪ Gene technology (human insulin).
• Lead optimization: modifying the lead compound to improve its properties, such as potency,
selectivity, and pharmacokinetics
• Preclinical development: conducting in vitro and in vivo studies to assess the drug’s safety and
efficacy
• Investigational new drug (IND) application: submitting an application to regulatory agencies for
approval to market the drug
• Clinical trials: conducting phase 1, 2 and 3 trials to evaluate the drug’s safety, efficacy, and dosing
in humans
• Regulatory approval: receiving approval from regulatory agencies to market the drug for human
use
• Post-marketing surveillance: monitoring the drug’s safety and efficacy in general population after
approval

Preclinical testing
Preclinical testing or study refers to the research and experimentation conducted on a drug before it is tested
on humans. This stage of testing is crucial in the drug development process, as it helps to ensure the safety
and efficacy of drug and yields information on the biological effects of new substances.

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Preclinical testing typically involves;
• In vitro studies (e.g., cell culture, tissue culture)
• In vivo studies (e.g., animal models, animal testing)
• Ex vivo studies (e.g., isolated tissues, organs)
Initial screening may employ biochemical-pharmacological investigations (e. g., receptor binding assays)
or experiments on cell cultures, isolated cells, and isolated organs.
Since these models invariably fall short of replicating complex biological processes in the intact organism,
any potential drug must be tested in the whole animal. Only animal experiments can reveal whether the
desired effects will actually occur at dosages that produce little or no toxicity.
Toxicological investigations serve to evaluate the potential for:

A. toxicity associated with acute or chronic administration;

In animals, compounds under investigation also have to be studied with respect to their absorption,
distribution, metabolism, and elimination (pharmacokinetics). Even at the level of preclinical testing, only
a very small fraction of new compounds will prove potentially fit for use in humans.

Clinical trials
Clinical trials are research studies performed in people that are aimed at evaluating a medical, surgical, or
behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new
drug or diet or medical device (for example, a pacemaker) is safe and effective in people. Often a clinical
trial is used to learn if a new treatment is more effective and/or has less harmful side effects than the standard
treatment.
Phases of clinical trials or testing?

Clinical trials advance through four phases to test a treatment, find the appropriate dosage, and look for side
effects. If, after the first three phases, researchers find a drug or other intervention to be safe and effective,
the FDA approves it for clinical use and continues to monitor its effects. Clinical trials of drugs are usually
described based on their phase. The FDA typically requires Phase I, II, and III trials to be conducted to
determine if the drug can be approved for use.

Phase I: Clinical testing starts with Phase I studies on healthy subjects and seeks to determine whether
effects observed in animal experiments also occur in humans. It involves the tests of an experimental
treatment on a small group of often healthy people (20 to 80) to judge its safety and side effects and to find
the correct drug dosage. In phase I clinical trials, Dose–response relationships are determined.

Phase II: Potential drugs are first tested on selected patients for therapeutic efficacy in those disease states
for which they are intended. If a beneficial action is evident, and the incidence of adverse effects is
acceptably small, then the drug potential is a go. Phase II uses more people (100 to 300), and phase II
emphasis is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in
people who have a certain disease or condition. These trials also continue to study safety, including short-
term side effects. This phase can last several years.

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Phase III: involve a larger group of patients in whom the new drug will be compared with conventional
treatments in terms of therapeutic outcome. Phase III trial is saddle to gathers more information about
safety and effectiveness, studying different populations and different dosages, using the drug in
combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000
people. If the FDA agrees that the trial results are positive, it will approve the experimental drug.

During clinical testing, many drugs are revealed to be un-usable. Ultimately, only one new drug typically
remains from some 10 000 newly synthesized substances. The decision to approve a new drug is made by
a national regulatory body (Food and Drug Administration in the United States; the Health Protection
Branch Drugs Directorate in Canada; the EU Commission in conjunction with the European Agency for
the Evaluation of Medicinal Products, London, United Kingdom; National Agency for Food and Drug
Administration and Control in Nigeria) to which manufacturers are required to submit their applications.
Applicants must document by means of appropriate test data (from preclinical and clinical trials) that the
criteria of efficacy and safety have been met and that product forms (tablet, capsule, etc.) satisfy general
standards of quality control.

Following approval, the new drug may be marketed under a trade name and thus become available for
prescription by physicians and dispensing by pharmacists. As the drug gains more widespread use,
regulatory surveillance continues in the form of post-licensing studies (Phase IV of clinical trials). Only
on the basis of long term experience will the risk–benefit ratio be properly assessed and, thus, the
therapeutic value of the new drug be determined. If the new drug offers hardly any advantage over existing
ones, the cost–benefit relationship needs to be kept in mind.