New drug development involves a series of pre-clinical and clinical trials. In pre-clinical trials, new chemical compounds are screened in vitro and tested in animal models to assess pharmacology, toxicity, and effectiveness. If a compound shows promise, it enters clinical trials with humans. Clinical trials have four phases - Phase I tests safety in a small group, Phase II explores efficacy in a larger group, Phase III tests efficacy in a larger patient population, and Phase IV monitors long-term safety and efficacy after market approval. The drug development process aims to establish that a new drug is safe and effective for its intended use through rigorous multi-stage testing.

2.  New drugs- developed through a series of laborious steps
 New molecular entities(NMEs) or new chemical
entities(NCEs) are novel compounds created in the
laboratory by various means from sophisticated computer
modeling to coincidence.
 The compounds are then screened for activity in vitro by
established technique.
 If activity is noted, the drug is screened for activity in animal
models for pharmacology, toxicology and effectiveness.
 If the compound appears to have desirable activity and is
relatively safe, it will be formulated for clinical trial testing.

3.  Study for the evaluation of drug’s toxic and
pharmacologic effects through in vitro & in vivo
laboratory animal testing.
 At the pre-clinical stage, the FDA will generally ask, at
a minimum that sponsors;
 Develop a pharmacological profile of the drug
 Determine the acute toxicity(in at least 2 sps of animals)
 Conduct short term toxicity studies(2 weeks – 3 months)*
 (Some animal testing continues after human test begins to learn whether
long term use of a drug may have carcinogenic or congenital effects.)

4.  Animal studies:
 Drug companies make effort to use as few animal
as possible
 2 or more sps are tested
 Types:
 Short term study(2 weeks – 3 months)
 Long term study(few weeks – several years)

5.  After completing pre-clinical testing, the company files an
IND with FDA to begin to test the drug in people.
 The IND becomes effective if FDA doesn’t disapprove it
within 30 days.
 The Investigational New Drug shows:
 Result of previous experiments
 How, where and by whom the new studies will be conducted
 The chemical structure of the compound
 How it is thought to work in the body
 Any toxic effects found in the animal studies
 How the compound is manufactured.

6.  Clinical trials are carefully & ethically designed set
of experiments in human being with the aim of
assessing the therapeutic merit of the drug under
question.
 It is carried out in humans after sustained evidence
of drug efficacy & safety in pre-clinical trials using
some appropriate animal models.

7. Phases of clinical trials;
 Phase I
 Phase II
 Phase III
 Phase IV
I – III Phases are done before drug has been marketed &
Phase IV is done after drug has been marketed.

8. Objectives;
 To assess tolerability as well as safety of gradually
increasing dose
 To obtain basic PK/early PD information
 Evaluate pharmacokinetics parameters, side effects
▪ Cmax, Tmax, AUC, T1/2, Protein binding
 To assess dosing range
Types of studies
 First exposure in humans
 Single dose tolerability
 Multiple dose tolerability
 Dose ranging

9. Study size
 20–80 healthy volunteer
Time
 Several months to one year
Limitations:
 The subjects are healthy adults, likely to have compromise
drug handling authority ,thus the potential risk of using
drugs in patients at extremes of age or in those with poor
hepatic or renal function is not tested
 Also many drugs don’t have any pharmacological effects in
healthy individuals eg: anti-inflammatory, antibiotics,
antipyretics, etc

10. Phase I clinical trial addresses:
 How rapidly the drug is absorbed?
 Where is the drug distributed in the body?
 Which organ system are involved in the
metabolism of drugs?
 How quickly is the drug eliminated from the body?
During phase I trial,sufficient information about the
drug’s pk and p’cological effects is obtained to plan a
well controlled phase II trial.

11. Once a drug has shown to be safe, then it must be tested for
efficacy.
Objectives
 To determine efficacy of the new drug in treating the disease
against which it is being tested.
 To detect S/Es & toxicity symptoms not manifested in animal
studies.
 i.e. Dose finding & Evaluating safety profile(determining adverse
rxns)
Types of studies
 Small controlled trials in patients
 Dose ranging
 Most of these trials are randomized trials

12. Study size
 100-200 patients with relevant indication
Time
 Few months to several years(longer than phase I)
Phase II trial addresses:
 What is the minimum effective dose?
 What is the maximum tolerated effective dose?
 Is the drug effective in mild, moderate and severe cases of the
disease or condition?
 Is the drug effective for all expected indications?
If a new drug is found to be safe and effective in phase II trials,it’s
development is moved to next phase of development.
In case of lack of efficacy, the development of drug is stopped at this
phase itself.

13. Phase III studies are planned when there is evidence that;
 An adequate degree of efficacy exists
 The risk profile of adverse reactions appears to be acceptable in
terms of demonstrated efficacy.
 Selection criteria is more related to clinical setting
 Compare the results of the patients on the experimental trial to
those patients utilizing standard diagnostic studies or treatment
 Studies move into this phase only after a diagnostic agent,
modality, or treatments have shown promise in phase I and II trials.

14.  These trials are typically multi-centric trials.
 Many phase III trials are randomized and blinded.
Objectives
 To determine therapeutic effects
 Verify effectiveness
 Monitor adverse reactions from long-term use
i.e. to establish the safety and efficacy of a new drug vis-à-vis existing
standard of placebo to form the basis for regulatory submission.
Types of studies
 Carried out in targeted patients
 Randomised, controlled trial
 Placebo controlled
 Double blinded
 These are better known as trials of safety and efficacy.

15. Study size
 Several hundred subjects needed
Time
 1-4 years
Phase III trial addresses;
 Overall risk benefit relationship
 Adverse rxns in a large group of pts over a longer period of exposure
 The ideal dosage regimen
 Should the drug is allowed to be marketed?
If a new drug is found to be safe and effective in phase III trials, a NDA is filed to
the regulatory authorities for seeking marketing permission.
Limitation of phase II & III studies
 Restricted patient population
 Limited duration of patient exposure
 Limited patient numbers

16.  Following the completion of all three phases of clinical
trials,the company analyzes the data and files an NDA with
FDA if the data successfully demonstrates safety and
effectiveness.
 The NDA must contain all of the scientific information that
the company has gathered.
 By the law,FDA is allowed 6 months to review an NDA(may
take more time practically)
 Once FDA approves NDA, the new drug becomes available for
physician to prescribe
 The company must submit periodic reports to FDA

17.  Involve safety surveillance and ongoing technical support
of a drug.
 Sometimes mandated by the FDA for additional testing
including interactions with other drugs and testing on
certain populations.
 Adverse effects detected by Phase IV trials may result in
withdrawal or restriction of a drug.
-example:Thalidomide.

18. Objectives
 To determine drug efficacy in prolong use where
perhaps the natural course of disease may be modified
over a several months or year
 Adverse reactions which may only occur with long term
use or which rarely occurs
 Long term comparative data with standard drug’s
detailed examination of non-responder assessment of
overdose & misuse or abuse liability
 New dosage forms
 New indication
 Drug interaction

19. Types of studies
 The patient under real clinical disease conditions
are followed in selected medical centers under the
guidance of qualified investigators
Study size
 More than 10000 patients
Time
 Post marketing studies may continue as long as
useful information is gathered on the safety &
effectiveness of the product.

20. Phase IV trial addresses:
 More about the S/E & Safety of the drug
 What the long term risks and benefits of the
drug are?
 How well the drug works when it’s used more
widely than in clinical trials?
Regulatory authorities can withdraw the marketing
authorization of a drug anytime if there are safety
concerns on its usage.

21.  Vital role ,
 which is to safeguard participants, healthcare professionals
and theTrust by ensuring Investigational Medicinal
Products (IMP’s) are appropriate for use and are procured,
handled, stored and used safely and correctly.
 Reviewing study protocols
 Writing & approving dispensing procedures
 Staff training
 Randomization of products
 The safe & secure ordering, receipt, storage, issue
and destruction of Investigational Medicinal
Products (IMP) used in clinical trials
 Accurate record keeping
 Audit and monitoring of clinical trial activity.