The drug development process is typically divided into the

following major steps:

I. Chemistry, Manufacturing, and Controls
a. Drug discovery
b. Drug characterization
c. Formulation development
d. Packaging development

II. Pre-clinical development

III. Clinical trial.
IV. FDA review for Drug Approval
V. Large scale manufacturing
VI. Post Marketing Surveillance

In drug development, pre-clinical development, also

named preclinical studies and non-clinical studies, is a
stage of research that begins before clinical trials (testing in
humans).

Drug safety data are collected, typically in laboratory

animals

The transition from discovery to preclinical development is

a continuum, and results of preliminary pharmacology and
toxicology testing often contribute to lead drug candidate
 selection. The boundary between preclinical development
and clinical trial is sharply defined by the filing of an
Investigational New Drug (IND; Table 1 lists preclinical
development acronyms) application, which is required prior
to initiation of the clinical trial.
.

The main goals of preclinical studies are to determine a starting,

safe dose for first-in-human study and assess potential toxicity of
the product, which typically include new medical
devices, prescription drugs, and diagnostics.

Detailed Stages of Drug Development

Discovery
Product Characterization
Formulation, Delivery, Packaging Development
Pharmacokinetics And Drug Disposition
Preclinical Toxicology Testing And IND Application
Bioanalytical Testing
Clinical Trials

Pharmacokinetics And Drug Disposition

Pharmacokinetic (PK) and ADME
(Absorption/Distribution/Metabolism/Excretion) studies provide
useful feedback for formulation scientists. PK studies yield
parameters such as AUC (area under the curve), Cmax
(maximum concentration of the drug in blood), and Tmax (time at
which Cmax is reached). Later on, this data from animal PK
studies is compared to data from early stage clinical trials to
check the predictive power of animal models.
Preclinical Toxicology Testing and IND Application
Preclinical testing analyzes the bioactivity, safety, and efficacy of
the formulated drug product. This testing is critical to a drug’s
eventual success and, as such, is scrutinized by many regulatory
entities. During the preclinical stage of the development process,
plans for clinical trials and an Investigative New Drug (IND)
application are prepared. Studies taking place during the
preclinical stage should be designed to support the clinical
studies that will follow.
The main stages of preclinical toxicology testing are:
Acute Studies
Acute tox studies look at the effects of one or more doses
administered over a period of up to 24 hours. The goal is to
determine toxic dose levels and observe clinical indications of
toxicity. Usually, at least two mammalian species are tested. Data
from acute tox studies helps determine doses for repeated dose
studies in animals and Phase I studies in humans.
Repeated Dose Studies
Depending on the duration of the studies, repeated dose studies
may be referred to as subacute, subchronic, or chronic. The
specific duration should anticipate the length of the clinical trial
that will be conducted on the new drug. Again, two species are
typically required.
Genetic Toxicity Studies
These studies assess the likelihood that the drug compound is
mutagenic or carcinogenic. Procedures such as the Ames test
(conducted in bacteria) detect genetic changes. DNA damage is
assessed in tests using mammalian cells such as the Mouse
Micronucleus Test. The Chromosomal Aberration Test and
similar procedures detect damage at the chromosomal level.
Reproductive Toxicity Studies
Segment I reproductive tox studies look at the effects of the drug
on fertility. Segment II and III studies detect effects on embryonic
and post-natal development. In general, reproductive tox studies
must be completed before a drug can be administered to women
of child-bearing age.
Carcinogenicity Studies
Carcinogenicity studies are usually needed only for drugs
intended for chronic or recurring conditions. They are time
consuming and expensive, and must be planned for early in the
preclinical testing process.
Toxicokinetic Studies
These are typically similar in design to PK/ADME studies except
that they use much higher dose levels. They examine the effects
of toxic doses of the drug and help estimate the clinical margin of
safety. There are numerous FDA and ICH guidelines that give a
wealth of detail on the different types of preclinical toxicology
studies and the appropriate timing for them relative to IND and
NDA or BLA filings.  (See Regulatory/Animal Welfare and at FDA
Guidances.)
Bioanalytical Testing
Bioanalytical laboratory work and bioanalytical method
development supports most of the other activities in the drug
development process. The bioanalytical work is key to proper
characterization of the molecule, assay development, developing
optimal methods for cell culture or fermentation, determining
process yields, and providing quality assurance and quality
control for the entire development process. It is also critical for
supporting preclinical toxicology/pharmacology testing and
clinical trials.
Clinical Trials
The Bioanalytical Team at PBL can support clinical trials. 
Clinical studies are grouped according to their objective into
three types or phases:
Phase I Clinical Development (Human Pharmacology)
Thirty days after a biopharmaceutical company has filed its IND,
it may begin a small-scale Phase I clinical trial unless the FDA
places a hold on the study. Phase I studies are used to evaluate
pharmacokinetic parameters and tolerance, generally in healthy
volunteers.  These studies include initial single-dose studies,
dose escalation and short-term repeated-dose studies.
Phase II Clinical Development (Therapeutic Exploratory)
Phase II clinical studies are small-scale trials to evaluate a drug’s
preliminary efficacy and side-effect profile in 100 to 250
patients.  Additional safety and clinical pharmacology studies are
also included in this category.
Phase III Clinical Development (Therapeutic Confirmatory)
Phase III studies are large-scale clinical trials for safety and
efficacy in large patient populations. While phase III studies are
in progress, preparations are made for submitting the Biologics
License Application (BLA) or the New Drug Application (NDA). 
BLAs are currently reviewed by the FDA’s Center for Biologics
Evaluation and Research (CBER).  NDAs are reviewed by the
Center for Drug Evaluation and Research (CDER).

7. THE TYPES OF STUDIES INCLUDED IN PRECLINICAL TRIALS

1.Screening Test 2. Tests on isolated organs, bacterial cultures 3.
Tests on animal models of human disease 4. General
observational test 5. Confirmatory tests and analogous activities
6. Mechanism of action 7. Systemic pharmacology 8. Quantitative
test 9. Pharmacokinetics 10. Toxicity test
8. 1. Screening test: These are simple and rapidly performed tests
to indicate presence OR absence of a particular
pharmacodynamic activity. For example, analgesic OR
hypoglycemic activity. 2. Tests on isolated organs, bacterial
cultures: These also are preliminary tests to detect specific
activity, such as anti-histaminic, anti-secretory, vasodilator,
antibacterial, etc
9. 3. Tests on animal models of human disease: Animal models
used such as kindled seizures in rats, genetically hypersensitive
rats, experimental tuberculosis in mouse, etc.
4. General observational test: Drug is injected in tripling doses to
small groups of mice which are observed for overt (hidden)
effects. Preliminary clues are drawn from the profile of effect
observed.
10. 5.Confirmatory tests and analogous activities: Compounds
found active are taken up for detailed study by more elaborate
(Complex) tests which confirm and characterize the activity.
Other related activities also measured, like antipyretic and anti-
inflammatory activity in an analgesic.
6. Mechanism of action: Attempts are made to find out the
mechanism of action. E.g. whether an anti-hypertensive is an α
blocker/β blocker/ ACE inhibitor/ calcium channel blocker, etc.
11. 7. Systemic pharmacology: • Irrespective of the primary
action of the drug, its effect on major organ systems such as
nervous, cardio-vascular, respiratory, renal are worked out.
8. Quantitative test: The dose-response relationship, maximal
effects and comparative efficacy with existing drug is carried out.
12. • 9. Pharmacokinetics: • The dose-response relationship,
maximal effects and comparative efficacy with existing drug is
carried out. •
10. Toxicity test: Acute toxicity: • Single high doses are given to
small groups of animals that are observed for overt (hidden)
effects and mortality for 1-3 days. • The dose which kills 50%
animals is called as LD50. • Organ toxicity is examined by
histopathology on all animals.

Phase 0
Phase 0 trials are the first clinical trials done among people. They aim to learn how a drug is processed in the
body and how it affects the body. In these trials, a very small dose of a drug is given to about 10 to 15 people.

Phase I
Phase I trials aim to find the best dose of a new drug with the fewest side effects. The drug will be tested in a
small group of 15 to 30 patients.

Phase II
Phase II trials further assess safety as well as if a drug works. The drug is often tested among patients with a
specific type of cancer. Phase II trials are done in larger groups of patients compared to Phase I trials. Often,
new combinations of drugs are tested. Patients are closely watched to see if the drug works. However, the new
drug is rarely compared to the current (standard-of-care) drug that is used. If a drug is found to work, it can be
tested in a phase III clinical trial.
Phase II of a clinical trial involves several hundred participants who are
living with the condition that the new medication is meant to treat. They’re
usually given the same dose that was found to be safe in the previous
phase.

Investigators monitor participants for several months or years to see how

effective the medication is and to gather more information about any side
effects it might cause.

While phase II involves more participants than earlier phases, it’s still not
large enough to demonstrate the overall safety of a medication. However,
the data collected during this phase helps investigators come up with
methods for conducting phase III.

Phase III of a clinical trial usually involves up to 3,000 participants who

have the condition that the new medication is meant to treat. Trials in this
phase can last for several years.

The purpose of phase III is to evaluate how the new medication works in
comparison to existing medications for the same condition. To move
forward with the trial, investigators need to demonstrate that the medication
is at least as safe and effective as existing treatment options.

Phase IV clinical trials happen after the FDA has approved medication.
This phase involves thousands of participants and can last for many years.

Investigators use this phase to get more information about the medication’s
long-term safety, effectiveness, and any other benefits.