DRUG DEVELOPMENT PROCESS

PHARMACOLOGY
DRUG DEVELOPMENT PROCESS
1. DISCOVERY AND DEVELOPMENT
DISCOVERY
-- thousand of compounds as potential
candidates
1. Serendipitous
-- selecting promising compounds after initial
2. Systematic screening tests.
3. Rational Design
LEAD COMPOUND
• Designated by combination of letters and numbers
• Has pharmacologic/ biologic activity but has
suboptimal structure.
NEW CHEMICAL
ENTITY
 1I. PRE-CLINICAL TRIALS
-Also termed as Pre-Clinical Development
Pre-Clinical Studies
Non-Clinical Studies
-Before a new drug is administered to
humans, its pharmacologic effects are
thoroughly investigated in studies involving
animals
1. Assess safety profile
2. To ascertain whether the new drug has any
harmful or beneficial effects on vital organ
function
Target organ toxicities
Teratogenesis
Mutagenesis
Carcinogenesis
3. Determine the drug’s pharmacokinetic
properties thereby providing some
indication of how the drug would be
handled by the human body
 1I. PRE-CLINICAL TRIALS
Types of Pre-Clinical Trials Information from toxicity
studies and CMC
1. In-Vitro (isolated cells)
2. In-Vivo (biological assays)
Drug Discovery Cycle KILLED
-Determines FIH (First In Human) Dose
-Determines the CMC (Chemistry, Manufacturing and Control)
• Physico-chemical properties Information from toxicity
studies and CMC
• Proposed dosage form (manufacturing information)
• Route/s of administration
FDA

IND Application
 1II. IND APPLICATION
Requirements:
• Animal study data and toxicity data
• Manufacturing information
• Information about the investigators
• CLINICAL PROTOCOLS for studies to
be conducted developed by the
researchers
CLINICAL PROTOCOLS
-How many people will be part of the study
-How long the study will last
-Whether there will be a control group and other
ways to limit research bias
-How the drug will be given to patients and what
dosage
-What assessments will be conducted, when, and
what data will be collected
How the data will be reviewed and analyzed
IV. CLINICAL TRIALS
For the purposes of registration, a clinical trial is any research study that
prospectively assigns human participants or groups of humans to one or more
health-related interventions to evaluate the effects on health outcomes (World
Health Organization)

 People volunteer
 Compare existing interventions
 Test new ways or combine existing interventions

Trial design: Randomized Controlled Trials (RCTs)

PHASES OF
CLINICAL
TRIALS
PHASES OF CLINICAL TRIALS

PHASE OTHER NAMES PRIMARY AIMS

1 Clinical Pharmacology Establish Safety

2 Clinical Investigation Establish Efficacy and Dosage Range

3 Clinical Trials Verify Efficacy and detect ADRs

4 Post-Marketing Surveillance Watch drug’s long term effects

PHASE I: CLINICAL PHARMACOLOGY

Healthy and generally paid

Patients 20-100 volunteers *antineoplastic agents
*surgical procedures

Length of Study Several Months

Dose level at which signs of

Purpose/s Establish Safety
toxicity first appear

Dose Ranging/ Dose Escalation

Dose Administered Sub therapeutic, ascending
Studies
PHASE II: CLINICAL INVESTIGATION
100-300/ several *patients who have the disease
Patients
patients Preferably without comorbidities.

Length of Study Several Months

Evaluate biologic activity

Establish Efficacy and
Purpose/s Dose-Response Studies
Dosage Range
Monitoring ADRs and Side Effects
Phase 2A: Specifically designed to assess dosing
requirements (how much drug should be taken)
Dose Administered Therapeutic Dose
Phase 2B: Specifically designed to study efficacy (how
well the drug works at the prescribed dose)
PHASE III: CLINICAL TRIALS
300-3000/ hundreds to
Patients several thousand Patients with co-morbidities are also chosen
patients
Length of Study 1-4 years
Label expansion: to show the drug works for
additional types of patients/ disease beyond the
Verify Efficacy and original use to which the drug is investigated for.
Purpose/s
detect ADRs
Compare the safety and efficacy of the IND with that
of another substance or treatment approach

Dose Administered Therapeutic Dose Verification of dosage range and regimen.

 PHASE III: CLINICAL TRIALS
Trial Design: Randomized Controlled MULTICENTER Trials

Life Threatening and severely debilitating diseases

FDA has ways to expedite evaluation by bypassing Phase 3 of Clinical Trials
through:
Priority Review
Breakthrough Therapy
Accelerated Approval
Fast Track
 V. NEW DRUG APPLICATION
Full Story of the Drug
Comprehensive description of the methods and results of human and animal studies, manufacturing
procedures, formulation details and shelf life.

Purpose:
to demonstrate that a drug is safe and effective for its intended use in the population studied

Along with clinical results, developers must include:

 Proposed labeling
 Safety updates
 Drug abuse information
 Patent information
 Institutional Review Board compliance information
 Directions for use
 V. NEW DRUG APPLICATION
FDA REVIEW
Incomplete- FDA refuses NDA
Complete- 6 to 10 months to make a decision

Remaining issues should be resolved before the drug can be approved for marketing.

In cases where FDA determines that a drug has been shown to be safe and effective for its
intended use and has complied to all guidelines given by FDA, the IND continues to Phase IV.
VI. PHASE IV: POST-MARKETING STUDIES

Anyone seeking treatment

Patients
from their physician

PHARMACOVIGILANCE

Reporting of ADRs
Watch drug’s long-term
To determine cost-effectiveness of a drug therapy relative
Purpose/s effects and impact on a
to other traditional and new therapies.
patient’s quality of life
Finding a new market of the drug.

Drug Interactions- Reporting

Dose Administered Therapeutic Dose