The document outlines the regulatory framework governing clinical trials in India, primarily under Schedule Y and the Drugs and Cosmetics Act. It details requirements for conducting clinical trials, including informed consent, ethical committee responsibilities, and adverse event reporting. Additionally, it describes compensation rules for trial-related injuries and emphasizes adherence to Good Clinical Practice standards.

1. BY DR KUMAR GOURAV
PG resident, pharmacology
1

2.  Definition
 Introduction
 Regulatory framework of India
 Rules in schedule Y
 Good clinical practice rules
 Informed consent
 Amendments
 Organisation
 Institutional ethical committee
 Compensation rules
 SAE reporting
2

3.  Schedule Y refers to the requirements and
guidelines for permission:
1. To import
2. Manufacture of new drugs for sale or
3. To undertake clinical trials in India.
3

4.  At present the following acts and rules regulate the
manufacture, export and clinical research of drugs
and cosmetics in India :
1. Drugs and Cosmetics Act, 1940
2. Drugs and Cosmetics rules, 1945
3. Pharmacy Act, 1948
4. Drugs and Magic Remedies (Objectionable
Advertisements) Act, 1954
4

5. 5. Narcotic Drugs and Psychotropic Substances
Act,1985
6. Medicinal and Toilet preparation (Excise Duties)
Act, 1955
7. Drugs (Price Control ) Order, 1955 under Essential
Commodities Act, 1955
5

6.  The Main regulatory laws operating in India are
the Drug and Cosmetics Act (1940) and the Drugs
and Cosmetics Rules (1945).
 The Act and Rules are binding on allopathic and
other systems of medicine and regulate imports,
manufacture, distribution, and sale of drugs in
India
6

7.  The enforcement came into existence in 1988 .
 Revised version of Schedule Y in line with ICH-
GCP (International Council of Harmonization and
Good Clinical Practice) standard was put forth in
1995.
7

8.  Rules 122 A, 122 B, 122 D, 122 DA, 122 DAA,
122 DAB, 122 E, 122 DD of the Drugs and
Cosmetics Rules (1945) deals with schedule Y
8

9. RULES PERMISSION FOR
122 A To import New drugs
122 B To manufacture New drugs
122 D To Import or Manufacture fixed dose combinations
122 DA To conduct clinical trials for New Drug/Investigational
New drug
122 DAA Definition of Clinical Trial
122 DAB Reports of Serious Adverse Events (SAEs) including
deaths.
122 E New Drug
122 DD Registration of Ethics Committee (EC).
9

10.  A systematic study of new drug(s) in human
subject(s) to generate data for discovering and/or
verifying the clinical, pharmacological (including
pharmaco –dynamic and pharmaco -kinetic) and/or
adverse effects with the objective of determining
safety and/ or efficacy of the new drug.
10

11.  A drug which has not been used in the country ,
new claim for a drug already approved, FDC
(combined for the first time or change in ratio) and
all vaccines.
11

12.  Some highlights of Schedule Y in terms of its appendices;
which provide the guidelines to conduct clinical trials are:
 Appendix V – Informed consent
Appendix VII – Undertaking by the
Investigator
Appendix VIII – Ethics Committee
Appendix X – Contents of Protocol
Appendix XI – Data elements for reporting
SAE
12

13.  It shall made in Form 44 accompanied with the
following data in accordance with appendices,
namely
1. Clinical and pharmaceutical information
2. Animal pharmacology data
3. Animal Toxicology data
4. Human Clinical pharmacology data
5. Regulatory status in other countries
6. Prescribing information
13

14. 1. Approval for Clinical trials
 Clinical trials on a New drug shall be initiated only after
permission by licensing authority and approval from EC .
 All trial Investigator(s) should possess appropriate
qualifications,
 Protocol amendments if become necessary before initiation
or during the course of a clinical trial, all such amendments
should be notified to the Licensing Authority in writing
14

15. 2. Responsibilities of Sponsor
 Implementing and maintaining quality assurance
 Submit status report to the licensing authority periodically
 Serious adverse event (SAE) should be reported to the
licensing authority within 14 calendar days.
 In case of studies prematurely discontinued for any reason
including lack of commercial interest in pursuing the new
drug application, a summary report should be submitted
within 3 months.
15

16. 3. Responsibilities of Investigator
 The Investigator(s) shall be responsible for the conduct
of the trial according to the protocol
 Ensure adequate medical care is provided to the
subject
 SAE and unexpected AE should be reported to the
sponsor within 24 hrs and to the EC within 7 working
days
16

17. 4.Informed consent
 Freely given informed written consent
 Provide information about the study verbally and
in written
 Non-Technically and understandable
language.
 Legally acceptable representative
17

18. 5.Responsibilities of ethics committee
 Approval trial protocol to safe guard right, safety
and well being of all trial subject
 Particular care to protect right, safety and well
being of all vulnerable subjects
18

19. 1. Geriatrics
They should be included in Phase III clinical trials (and
in Phase II trials, at the Sponsor's option) in meaningful
numbers, if
1. The disease is characteristically a disease of aging
2. Substantial numbers of geriatric patients
25

20. 3.Common in the elderly are likely to be encountered
4.When the new drug is likely to alter the geriatric
patient's response
26

21.  Begin with older children before extending the
trial to younger children and then infants.
 If the new drug is for diseases predominantly or
exclusively affecting paediatric patients, clinical
trial data should be generated in the paediatric
population except for initial safety and tolerability
data
27

22.  Diseases occurring in both adults and pediatric
patients, for which there are currently no or limited
therapeutic options, pediatric population should be
included in the clinical trials early, following
assessment of initial safety data and reasonable
evidence of potential benefit.
 Written informed consent should be obtained from
the parent/legal guardian.
28

23.  They should be included in clinical trials only
when the drug is intended for use by
pregnant/nursing women or fetus / nursing infants
 Where the data generated from women who are
not pregnant or nursing, is not suitable.
29

24.  follow-up data on the pregnancy, fetus and child
will be required.
 Where applicable, excretion of the drug or its
metabolites into human milk should be examined
30

25.  closely monitored new drugs clinical safety
 Periodic Safety Update Reports (PSUR)-
to report all relevant new information
 PSUR shall be submitted every 6months for the
first 2 years
 New studies specifically planned or conducted to
examine a safety issue should be described in the
PSURs.
31

26.  conducted according to the guidance for BA and
BE studies
 Evaluation of the effect of food on absorption
following oral administration
 All bioavailability and bioequivalence studies
should be conducted according to the Guidelines
for Bioavailability and Bioequivalence studies as
prescribed.
32

27.  Good Clinical Practices (GCP) is an international
ethical & scientific quality standard for designing,
conducting, recording & reporting trials that
involve the participation of human subjects.
 It ensures the : RIGHTS
SAFETY
WELL BEING
33

28.  The International Conference on Harmonization of
Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) is a joint
initiative of the experts in pharmaceutical industry
of Europe, Japan and the United States to discuss
scientific and technical aspects of pharmaceutical
product registration.
34

29.  Released in Dec 2001(Developed by CDCSO and
endorsed by DCGI)
 In general, in line with ICH GCP
 Has Revised Schedule Y (Jan 2005)
35

30.  2.1 Clinical trials should be conducted in
accordance with the ethical principles that have
their origin in the Declaration of Helsinki, and that
are consistent with GCP and the applicable
regulatory requirement(s).
36

31.  2.2 Before a trial is initiated, risks and
inconveniences should be weighed against the
anticipated benefit for the individual , trial subject
and society. A trial should be initiated and
continued only if the anticipated benefits justify
the risks.
37

32.  2.3 The rights, safety, and well-being of the trial
subjects are the most important considerations and
should prevail over interests of science and society.
 2.4 The available nonclinical and clinical
information on an investigational product should
be adequate to support the proposed clinical trial.
38

33.  2.5 Clinical trials should be scientifically sound,
and described in a clear, detailed protocol.
 2.6 A trial should be conducted in compliance with
the protocol that has received prior institutional
review board (IRB)/independent ethics committee
(IEC) approval/favorable opinion.
39

34.  2.7 The medical care given to, and medical
decisions made on behalf of, subjects should
always be the responsibility of a qualified
physician or, when appropriate, of a qualified
dentist.
 2.8 Each individual involved in conducting a trial
should be qualified by education, training, and
experience to perform his or her respective task(s).
40

35.  2.9 Freely given informed consent should be
obtained from every subject prior to clinical trial
participation.
 2.10 All clinical trial information should be
recorded, handled, and stored in a way that allows
its accurate reporting, interpretation and
verification.
41

36.  2.11 The confidentiality of records that could identify
subjects should be protected, respecting the privacy.
 2.12 Investigational products should be manufactured,
handled, and stored in accordance with applicable good
manufacturing practice (GMP).
 2.13 Systems with procedures that assure the quality of
every aspect of the trial should be implemented.
42

37. 1. Participation
2. Title
3. Research team
4. Research funding
5. Study location
6. A brief introduction about the study
7. Need for the study
43

38. 8. No of participants
9. Reason for inclusion of that participant.
10. Duration of participation
11. Methodology in detail
12. Responsibility of the participant.
13. Benefit of the study
14. Risk of the study
44

39. 15. Protection from harm
16. Privacy
17. Protection of privacy
18. Confidentiality
19. Compensation
20. Use of data
21. Voluntariness, no force
45

40. 22. Right to refuse, right to withdraw, patient
care right not affected
23. Time to decide
24. Clarify doubts: contact information
25. Retain a copy
46

41.  Same thing should be written by the
participant with : Name
Date
Address
Phone no
47

42. 48

43.  Rule 122DAB –Compensation in case of injury or
death during clinical trial(CT).
 Rule 122DAC- Permission to conduct Clinical
Trial subject to certain Conditions, Authority for
CT inspections, Actions in case of non-compliance
 Rule 122DD -Registration of Ethics Committee -
Requirements and guidelines for registration of
Ethics Committee
49

44.  Informed Consent
1. A-V recording of informed consent process is
required for vulnerable subjects in NCE/ NME trials.
2. For anti-HIV & anti-leprosy drug trials, only audio
recording.
3. Essential elements in ICF
–Possibility of failure of investigational
product .
–Placebo will not any therapeutic effect .
50

45.  The CT in relation to a new drug or investigational
new drug in humans has to generate data for
discovering or verifying its pharmacological
interactions including pharmacodynamics,
pharmacokinetic and adverse effects in order to
determine the safety, efficacy or tolerance of new
drugs.
51

46.  The New Drug Regulatory Process come under the
purview of the Drugs Controller General of India
(DCGI), who is the head of the Central Drugs
Standard Control Organization (CDSCO), located
in New Delhi.
52

47. 53

48.  The DCGI is supported by various bodies, such as
the Indian Council of Medical Research (ICMR)
and Department of Biotechnology (DBT) in the
evaluation of specific therapies or clinical trials.
 The ICMR, for example, provides expert advice in
evaluation of Phase I trials or clinical trials
relevant to national priorities, eg, malaria, AIDS
etc.
54

49. Consist of 8-12 members:
1. Chairperson
2. 1-2 from basic medical science area
3. 1-2 clinicians
4. 1 legal expert
5. 1 representative of NGO
6. 1 philosopher
7. 1 lay person from the society
8. Member secretary
55

50.  To provide competent review of all ethical aspects
of the project
 Undertake review free from bias and influence
 Provide advice to the researchers on all aspects of
welfare and safety of research participants
 To protect dignity, rights and well-being of the
potential research participants.
56

51.  To ensure universal ethical values and international
scientific standards in terms of local community
values and customs.
 To assist in the development and the education of
research community responsive to local health care
requirements
57

52. 58

53.  Rule of compensation applies to only those adverse
events (AEs) that are required to be reported.
 As per the rules, all serious AEs (SAEs) are to be
reported within a stipulated time frame.
 AE that do not fall into the SAE category are not
required to be expeditiously reported and, therefore, do
not fall under the clause of compensation.
59

54.  The final formula for calculating compensation is:
(8,00,000 x age factor x risk factor)
99.37
-where 800,000 rupees is the base amount;
-age factor varies from 228.54 (≤ 16 years) to 99.37
(≥ 65 years);
-the risk factor (ranging from 0.5 to 4.0) is decided
on the basis of trial participants
60

55. (i) SAE causing permanent disability to the subject.
Compensation = (D x 80 x C)
100 x 100
where, D = percentage disability the subject has
suffered,
C = quantum of compensation which would have
been due for payment to the subject’s nominee(s)
in case of death of the subject
61

56. (ii) SAE causing congenital anomaly or birth defect.
The following four situations may arise due to congenital
anomaly or birth defect:
(a) Still birth.
(b) Early death due to anomaly.
(c) No death but deformity which can be fully corrected
through appropriate intervention.
(d) Permanent disability (mental or physical)
62

57.  For all the above-mentioned situations,
compensation of a fixed amount of 400,000 rupees
is applicable.
 However, for situations (c) and (d), medical
management, as long as required, has to be
provided by the sponsor, in addition to the above-
mentioned fixed amount of 400,000 rupees.
63

58. (iii) SAE causing life-threatening disease.
Compensation = N x W
where N = number of days for which the trial subject
remained in a life-threatening situation requiring
medical care, irrespective of number of days of
hospitalization;
W = minimum wage per day of an unskilled worker.
64

59. (iv) Reversible SAE in case it is resolved.
In this situation, the compensation amount will be
double the amount applicable for situation (iii),
explained above.
65

60. 66

61.  An event is serious when the patient outcome is:
1. death
2. Is life-threatening
3. Requires inpatient hospitalization or prolongation of
existing hospitalization
4. Results in persistent or significant
Disability/incapacity
5. Is a congenital anomaly/birth defect
6. Require intervention to prevent permanent damage
67

62. A. As per the regulations (Schedule Y of Drugs &
Cosmetics Rules), all Unexpected SAEs have to
be reported to CDSCO within 14 calendar days.
B. Every report (both initial as well as follow-up
reports) should be submitted along with a
covering letter. A template of covering letter is
available in Annexure II.
68

63. C. Covering letter should be prepared using the
template as guide, and printed on the company’s/
CRO’s letter head.
D. Instructions are provided in the template as
highlighted text in “Italics”. Please delete all
instructions from your final letter.
69

64. E. All the sections of the covering letter should be
completed.
G. Capture whether it is “initial” or “follow-up”
report.
70

65. 71

66.  http://www.cdsco.nic.in/writereaddata/CDSCO-
GuidanceForIndustry.pdf
 Drugs and Cosmetics act and rules 1945 available at
http://www.cdsco.nic.in/writereaddata/Drugs&CosmeticAct. pdf
 Gupta YK, Pradhan AK, Goyal A, Mohan P. Compensation for
clinical trial-related injury and death in India: Challenges and
the way forward. Drug Saf. 2014;37:995–1002.
72

67. 73