INTRODUCTION TO DRUG REGULATORY

SYSTEM.
Drug Regulation means the control of Drug by
regulatory authority to ensure safety efficacy
quality of drug.
This is achieved by following and practicing the
good practices in pharmaceutical
1
Science. Integration and convergence of the
following good practices are necessary to
achieve quality safety and efficacy of the
molecule for the desired therapeutic purpose.
The concerned good practices are
 Good clinical practice GCP
 Good Manufacturing Practice GMP

2
 Good Laboratory practice GLP
 Good Storing practice GSP
 Good Transport Practice GTP
 Good Pharmacy Practice GPP

3
 STEPS TO UNDERGO FOR A
CHEMICAL MOIETY TO QUALITY AS
DRUG MOLECULE

Plant source in crude from synthetic drugs

already Known to have Therapeutic Structure determination

Efficacy and are in use as Ayurvedic
system of Medicine Siddha and Herbal Synthetic analogs leading
drug to number of drug
molecules
Identification , Solvent
extraction & Purification Structure Activity
Relation study (SAR)
Structure determination QSAR Study

Synthetic of side chain SAR /QSAR

Study

4
 Synthesis of side chain and No. of compounds
SAR/QSAR study *** SAR/QSAR study ***

*** [Pharmacological and Therapeutic activity

determination
ED 50 / LD 50 study / therapeutic index Study
Toxicity study /Genotxicity / Repoductive study
General pharmacological screening with special study
on the biological organ having specific pharmacological
activity. ] *#

*# MOLECULES SELECTED TO UNDERGO CLINICAL STUDY

ON HUMAN SUBJECTS
5
On the basis of the aforesaid guideline Molecules
are selected for clinical study on human subjects
for conducting clinical trial (under good clinical
practice) GCP on the basis of written permission
with all conditions as the case may be from
authorized competent person ( i.e Drug
Controller General of India – DCG India.

6
UNDER 122 DA D & C RULE – Application for
permission to conduct clinical trial/
Investigational new drug.
Under 122 E of D &C rule– Definition of new drug
A new drug shall mean and include
a) A drug as defined in the act including bulk drug
substance which has not been used in the country
to any significant extent under the
7
Conditions prescribed, recommended or
suggested in the labeling there of and has not
been recognized as effective and safe by the
licensing authority mentioned under rule 21 for
the proposed claims.
Provided that the limited use, if any has been
with the permission of the licensing authority.

8
b) A drug already approved by the licensing
authority mentioned in rule 21 for certain
claims, which is now proposed to be marketed
with modified or new claims namely, indications
dosage, dosage form (including sustained
release dosage form and route of administration
c) A fixed dose combination of two or more
drugs, individually approved earlier for certain
claims 9
drugs, individually approved earlier for certain
claims, which are now proposed to be combined
for the first time in a fixed ratio, or if the ratio of
the ingredients in an already marketed
combination is proposed to be changed, with
certain claims viz. indications, dosage, dosage
form (including sustained release dosage form)
and route of administration.
10
For purpose of this rule
i) All vaccines and recombinant DNA(RDNA)
derived drugs shall be new drugs unless.
certified otherwise by the licensing authority
ii) A new drug shall continue to be
considered as new drug for period of four
years from the date of

11
its first approval or its inclusion in the India
pharmacopoeia whichever is earlier.
RULE 122 DAA – DEFINITION OF CLINICAL
TRIAL
Clinical trial means a systemic study of new
drugs in human subject(s) to generate data for
discovering and/or verifying the clinical,
pharmacological (inducing pharmacodynamics
12
and pharmacokinetic ) and /or adverse effects
with the objective of determining safety and or
adverse effects with the objective of
determining safety and/or efficacy of a new
drug.

13
 SCHEDULE Y OF DRUGS & COSMETICS RULE &
GOOD CLINICAL PRACTICE GUIDELINES FOR
CLINICAL TRAILS IN INDIA.
It aims to ensure that the studies are (a) scientifically
and ethically sound and that the clinical properties of
the pharmaceutical substances under investigation are
properly documented
The guidelines seek to establish two cardinal principles
(i) protection of the rights of human subjects and
14
(ii) Authentically of the biomedical data generated.
These guidelines have been evolved with
consideration of WHO/ ICH /USFDA and European
GCP as well as the Ethical Guidelines for Biomedical
Research on Human subject issued by Indian council
of Medical Research.

At all stages of drug development these guidelines

should be followed.

15
CLINICAL RESEARCH ORGANIZATION (CRO)
An organization to which the sponsor may transfer
delegate some or all of the tasks duties/obligation
regarding the clinical trial.
All such contractual transfers of obligations should be
defined in writing.

A CRO is a scientific body commercial, academic or

other.

16
RESPONSIBILITY OF SPONSOR
(a) Clinical trial sponsor is responsible for

(i) quality assurance system

(ii) Data generated according to protocol
(iii) Standard operative procedure

(b) required to prepare status report in clinical trial

to licensing authority.

17
(c)In case of studies prematurely discontinued
a summary report should be submitted
within 3 months.
(d) Any unexpected serious adverse event
(SAE) should be communicated within 14days
by the sponsor to the L.A and to other
investigators.

18
RESPONSIBILITIES OF THE INVESTIGATORS
(a) To conduct trial according to protocol and GCP
guidelines
(b) The investigator should ensure that adequate
medial care is provided to the participant for any
adverse event to the sponsor within 24 hrs. and to
Ethic committee that accorded approval to the study
protocol within 7 working days.

19
INFORMED CONSENT
Both the informed consent form and the patient
information sheet should have been approved by
the ethics committee and furnish to the licensing
authority.
For unconscious patient/minor/mentally disabled
person, legally acceptable representative should
give the consent.
20
RESPONSIBILITY OF THE ETHICS COMMITTEE
Ethics committee is responsible to protect the right,
safety and well being of the subjects participating in the
study.
Ethics committee should met at appropriate intervals
and review the trials and protocol.
In case of revoking the approval, the reasons for doing so
should be recorded and informed to the LA.

21
Composition of Independent Ethics committee (IEC)
consists of 7-8 members.
1. Chairperson
2. 1-2 basic medical Scientifics ( preferably one pharmacologist)
3. 1-2 Clinicians
4. One legal expert or retired judge
5. One social scientist.
6. One philosopher/ ethicist
7. One lay person from the community
8. One member secretary.

22
Investigational New Drug (Phase -I)
Objective – safety and tolerability with initial
administration studies conducted in Phase -I
STUDIES CONDUCTED IN PHASE -I
(a)Maximum tolerability of the dose range and to
determine the nature of adverse reaction that
can be expected.
(b) Studies include both single and multiple dose
23
administration.
INVESTIGATIONAL NEW DRUG (PHASE -I)
(c) Pharmacokinetics ie. Characterization of a drugs
absorptive, distribution, metabolism and excretion
(d) To determine pharmacokinetic parameters in
different age groups to support dosage
recommendation.
(e) Potential therapeutic benefits may be conducted
in phase I study as a secondary objective.

24
THERAPEUTIC EXPLORATORY TRIALS (PHASE –II)
a) To evaluate the effectiveness of a drug for the
particular indication and to determine the short term
side effect.
b) An important goal for this phase is to determine the
dosage and regimen for Phase –III study.
c) If the application is for conduct of clinical trials as a
part of multinational climical development in India
the justification of such trial in India shall be
explained 25
THERAPEUTIC CONFIRMATORY TRAILS (PHASE -III)
a) The Primary objectives is confirmation of therapeutic
benefits.
b) To further reconfirm that the primary evidence
generated in phase II that the drug is safe and
effective for intended use.
c) To further explore the also dose response ,the drug
concentration in blood and clinical response. Further
use of the drug to a wider population.

26
Safety and efficacy of the drug in combination with
other drug.
d) Safety and efficacy of the drug in Indian patients.
Licensing authority may require pharmacokinetic
studies to be under taken to verify that data generated
in Indian population is in confirmatory will data already
generated abroad.
e) In case of multinational clinical trials, no of sites in
India as well as justification shall be provided to the LA
along with application. 27
POST MARKETING TRIALS (PHASE -IV)
a) These trials go beyond the prior demonstration the
drug’s safety, efficacy and dose definition.
These trials may not be considered necessary at the
time of new drug approval but may be necessary by L.A.
for optimizing the drug’s use.
b) Phase –IV trails include (i) additional drug drag
interactions (ii) dose response or safety studies and
trials designed to support use under approved
indications. 28
STUDIES IN SPECIAL POPULATION
GERIATRICS
Geriatric patents should be included in Phase –III
Clinical trials ( and in phase II trials at the sponsor’s
option.) in meaning full numbers.
i) If disease intended to be treated is characteristically a
disease of aging. Or
ii) Population to be treated include substantial number
of geriatric patients or.
29
iii) Specific reason to expect that conditions
common in the elderly are likely to be
encountered or.
iv) When the new drug is likely to alter the
geriatric patients response (with regard to safely
or efficiency) compared with that of non
geriatric.

30
PEDIATRICS
i) For a drug expected to be used in children,
evaluation should be mode in the appropriate
age group.
ii) It is usually appropriate to begin with older
children before extending the trial to younger
children and the infants.

31
iii) The pediatric studies should include
a) Clinical trials
b) Relative bioequivalence comparisons of the pediatric
formulation with the adult formulation performed in
adults.
c) Definitive pharmacokinetic studies for dose selection
across the age ranges of pediatric patients.
d) Pediatric subjects are legally unable to provide
written informed consent, and are dependent on
their 32
Parents/ legal guardian to assume responsibility for
their participation in clinical studies.
Written informed censer should be obtained from the
part/legal guardian.

PREGNANT OR NURSING WOMEN

a) Pregnant or nursing women should be included in
clinical trials only when the drug in intended for use by
pregnant /nursing women or foetuses, nursing infants

33
and where the data generated from women who are not
pregnant or nursing is not suitable.
b) New drug intended for use during pregnancy,
follow-up data (pertaining to the period appropriate
for that drug) on the pregnancy, foetus and the child
will be required.
e) Where applicable, excretion of the drug or its
metabolites in human milk should be examined and the
infants should be monitored for predicted
pharmacological effects of to drug. 34
POST MARKETING SURVEILLANCE
(Period safety Update Reports) PSUR
i) Subsequent to approval of the product, new drug
should be closely monitored for their clinical safety
once they are marketed.
ii) The PSUR shall be submitted every six month for
first two years after approval is granted.
For subsequent two years the PSUR need to be
submitted annually. 35
L.A may extend the total duration of study
if it is considered necessary in the public
interest.
A PSUR should be structured as follows:-
a) Title page applicants name period
covered, date of approved / date of
marketing.
b) Introduction 36
c) Current world wide market
authorization status
d) Update of actions taken for safety
reasons information.
e) Changes to reference safety information.
f) Estimated patient exposure
g) Presentation of individual case histories
37
h) Other information
i) Overall safety information
j) Conclusion
k) Appendix  providing material relating
to indications dosing pharmacology and
other related information.

38
SPECIAL STUDIES : BIOAVAILABILITY
BIOEQUIVALENCE
i) For drugs approved elsewhere in the world
and absorbed systemically bioequivalence
should be carried out. Data on the extent of
systemic absorption may be required for
formulations other the those designed for
systemic absorption.
39
iii) Dissolution and bio availability data submitted with
new drug application must provide information that
assures bioequivalence or established bioavailitiblty
and dosage co relations between the formulation soft
to be marketed and those used for clinical trials during
clinical development of the product.
iv) All bioavailability bioequivalence studies should be
conducted as per guidelines. For bioavailability and
bioequivalence studies as prescribed.
40