PRODUCT DEVELOPMENT FOR

NEW CHEMICAL ENTITY

Submitted to:
Dr.AbuBakar Munir
CONTENTS

1. INTODUCTION
2. NEED OF DOSAGE FORM
3. PHASES OF PRODUCT FORMULATION
4. PRE CLINICAL TESTING
5. CLINICAL TRIALS
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Drug development process involves rigorous

testing and optimization of selected
compounds to identify the drug that is most
effective.

Including various step i.e. Discovery, Pre-clinical

studies, IND, Clinical Trials, NDA, Post Market
Surveillance(Clinical Phase4)
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Need of Dosage Form

Safety
Reliability
Efficacy
Safety
Physical
Chemical
Microbiological
Pharmaceutical Elegance
Appearance
Organoleptic Properties
Convenience
Ease of Use
Dosing Frequency
Patient Compliance
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Disease
understandi
ng

PRE-
Identification
DISCOVERY of target

Validation of
target
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Disease Identification of Validation of

understanding target target

biological target

demonstrate that
At molecular level Biological target
a molecular target
Gene changes for a potential
is directly involved
Affect of these new medicine is
in a disease
changes chosen
process
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Identification of lead compound

Compound that may act on the target

to alter the disease course

for example by inhibiting or stimulating

the functions of the target bio-
molecule
Optimization of lead
Lead compounds that survive the
initial testing can be optimized
further or altered to make them
safer and more effective

Optimize pharmacokinetics
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials

Laboratory and Animal Testing is Done

Animal models- mimic human disease

Is compound
Is compound safe(non-toxic)
safe(non-toxic) in
in living
living organisms
organisms ??
E.g. Nerve
E.g. Nerve Damage-
Damage- Neurotoxin
Neurotoxin

Is compound biologically active?

If YES, file an IND Application

Drug
Discovery

Pre-Clinical Trials
CLINICAL TRIALS FDA
REVIEW
10,000
Compounds 250 1 FDA
Compounds 5 Compound Approved
Drug

1.5
6.5 Years 7 Years years
New chemical entity Pre-clinical studies IND
Source: natural, high Including chemistry, (Investigational
throughput screening, physical properties, new drug)
biotechnology, lead biological , pharmacology, application
optimization. ADME, toxicology. Submission
FDA review

Pre-clinical
studies
(continued)
Post New drug Long term animal
marketing: application toxicology, product
Phase IV Submission formulation
clinical trials FDA review
Toxicology Preapproval
Product defect plant
reporting Clinical trials
inspection
Phase I
Phase II
Phase III
Introduction Pre-Discovery Discovery Pre-clinical Trials Clinical Trials
Investigation New Drug Application (IND)
IND
Review by CDER
Pharmacology/
Medical Chemistry Toxicological
Statistical

Safety Review Sponsor Submit New Data

Safety No
Clinical
acceptable for
hold
study to Notify Sponsor
Decision
proceed
Yes No
Complete Review
No Sponsor notified about
Review deficiencies
Acceptable
Yes
No Deficiencies Study on Going*
Phase 0

Phase 1
als
Phase 2
Tri
cal

Phase 3
ni
Cli

Phase 4
Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

 In Phase 0 Pharmacodynamics and

pharmacokinetics are studied.

 This Phase of clinical Trial involve about 10-15 study

patients.

 Duration of a patient’s participation is usually less

than 1 week.
Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

 Phase I studies are used to evaluate pharmacokinetic

parameters and tolerance, generally in healthy
volunteers.

 These are small Scale studies comprises of 20-100

Participants and last about several Months.

 These studies include initial single dose studies, dose

escalation and short term repeated dose studies.
Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

Phase II clinical studies are small scale trials to evaluate

a drug’s preliminary efficacy and side-effect profile in
100 to 300 patients.

Additional safety and clinical pharmacology studies are

also included in this category.
Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

 Phase III studies are large-scale clinical trials for safety

and efficacy in large patient populations (300-3,000) .

 While phase III studies are in progress, preparations

are made for submitting New Drug Application (NDA).

 This Application is reviewed by FDA.

Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

Phase IV also known as post market surveillance,

once drug is approved by FDA and allowed to be
marketed. It is reviewed that if any side effects or
toxic effects are reported.
Clinical Trials Description

Phase 0  10-15 Participants

 Less than 1 week

 Studies the Pharmacodynamics, Pharmacokinetics & tolerance

Phase 1  20-100 Participants

 Up to several months

 Studies the Safety of medication

Phase 2  100-300

 up to 2 years

 Studies the efficacy

Phase 3  300-3000 Participants

 up to 4 years

 Studies safety, efficacy and dosing

Phase 4  General Population

 Continuous Evaluation
Any
question?