B.
Pharmacy 7th Semester
Subject-Industrial Pharmacy II
Topic- Regulatory Requirements for Drug Approval
Presented by-Manpreet Attri
B. Pharm (7th Sem)
71910351
School of Pharmaceutical Sciences
CONTENTS
• Introduction
• Drug Development Teams
• Non Clinical Development
• Pharmacology
• Toxicology
• Investigational New Drug Application (IND)
INTRODUCTION
New Drug Application (NDA) is an application submitted
preclinical and clinical test data for analyzing the drug
information and description of manufacturing procedures.
After agency received the NDA possibilities :
Approval
Approvable
Not Approvable
Drug Development
Teams
Drug development is the process of bringing a
new pharmaceutical drug to the market once a
lead compound has been identified through
the process of drug discovery. The process of
drug discovery and development is very long
and needs around 10-12 years which includes
the close interaction of large number of
scientific disciplines.
. Drug Development Team
Responsibilities
• 1. Planning research studies to further
characterization of drug candidate.
• 2. Integration of new research results with
previously generated data.
• 3. Preparation of detailed drug development
plan
• 4.Designing the Development milestones,
generating timelines for completion and
defining critical path
• 5. Reviewing research results from experiments
conducted by various scientific disciplines.
• 6. Monitoring the status of ongoing research
studies and modifying the plan as per new data.
• 7. Comparing research results and development
status of drug molecules of competitors. Drug
Development Team Responsibilities
The new drug approval is of two phase process:
First phase for clinical trials and second phase for
marketing authorization of drug.
Firstly, non-clinical studies of a drug are completed to
ensure efficacy and safety, and then application for
conduct of clinical trials is submitted to the competent
authority of the concerned country. Thereafter, the
clinical trials can be conducted (phase I to phase IV).
These studies are performed to ensure the efficacy, safety
and optimizing the dose of drug in human beings.
• After the completion of clinical studies of the drug, then an
application to the competent authority of the concerned country for
the approval of drug for marketing is submitted. The competent
authority review the application and approve the drug for marketing
only if the drug is found to be safe and effective in human being or
the drug have more desirable effect as compare to the adverse
effect.
• Even after the approval of new drug, government should monitor
its safety due to appearance of some side effects, when it is used in
larger population. The interactions with other drugs, which were not
assessed in a pre-marketing research trial and its adverse effects.
NON-CLINICAL DRUG
DEVELOPMENT
• Pre-clinical trial:
• A laboratory test for a novel drug or a new medical device is
usually done on animal subjects, to see if the hoped for
treatment really works and if it is safe to test on humans. It
include various studies,
• in silico : via computer simulation
• in vivo : within the living
• in vitro: within the glass (outside the living organism)
• This process of non-clinical development of medicine is very
complex, time consuming and regulatory driven.
Aim of Non Clinical
Development
• The primary aims of the non-clinical development phase is to
analyze and determine which candidate has the greatest
probability of success, assess its safety, and raise firm
scientific foundations before transition to the clinical
development phase.
• Pharmacology: Study of effects of chemical substances on
living systems
• It holds all the aspects of drug discovery, ranging from details
of interaction between drug molecule and its target to
consequences of placing the drug in the market.
Selectivity Testing
: It consists of two main stages i.e. screening for selectivity and
Binding assay. To determine the potency of drug, the
selectivity of a compound for a chosen molecular target needs
to be assessed.
Pharmacological Profiling:
This includes the determination of pharmacodynamics effect
of new compound, either on in-vitro models or in-vivo
models.
Safety Pharmacology
• This includes the scientific evaluation and study of
potentially life threatening pharmacological effects of
a potential drug which is unrelated to the desired
therapeutic effect and therefore may present a hazard.
These tests are conducted at doses not too much in
excess of the intended clinical dose.
• Safety pharmacology seeks to identify unanticipated
effects of new drugs on major organ function
• It is aimed at detecting possible undesirable or
dangerous effects of exposure of the drug in
therapeutic doses
TOXICOLOGICAL
APPROACHES TO DRUG
DISCOVERY
• Acute Toxicity:
• Acute toxicity studies: at least two species, usually mice and rats
using the same route as intended for humans.
• In addition, at least two more routes should be used to ensure
systemic absorption of the drug; this route may depend on the
nature of the drug.
• Mortality should be looked for up to 72 hours after parenteral
administration and up to 7 days after oral administration.
• The symptoms, signs and mode of death should be reported, with
appropriate macroscopic and microscopic findings where necessary.
• Long-Term Toxicity:
• These studies should be carried out in at least two mammalian
species and out of these two mammalian species one should be
a non-rodent.
• The duration of study will depend on the factor that whether
the application is for marketing permission or for clinical trial,
and in the later case, on the phases of trials.
• If a species is known to metabolize the drug in the same way
as humans, it should be preferred in long-term toxicity studies.
The drug should be administered 7 days a week by the route
intended for clinical use in humans.
Investigational New Drug
Application (IND)
• Investigational New Drug Application (INDA) Its application filed to FDA in
order to start clinical trials in humans if the drug was found to be safe form the
report of Preclinical trials. A pre-IND meeting can be arranged with the FDA to
discuss a number of issues: The design of Animal research. Protocol for
conducting the Clinical trials. Review the chemistry, manufacturing, and
control of the investigational drug.
• IND application is filled to provide the data showing that it is reasonable to
begin tests of a new drug on humans. During a new drug's early preclinical
development, the sponsor's primary goal is to determine if the product is
reasonably safe for initial use in humans and if the compound exhibits
pharmacological activity that justifies commercial development. When a
product is identified viable candidate for further development, the sponsor then
focuses on collecting the data and information necessary to establish that the
product will not expose humans to unreasonable risks when used in limited,
early-stage clinical studies.
