The various rules that come under Schedule Y of the Indian Constitution dealing with the manufacture, import and clinical trials of drugs in india

1. FARDAN QADEER
Junior Resident, Dept. of Pharmacology
SCHEDULE Y

2. • Directorate General of Health Services
Ministry of Health and Family
Welfare
• Drugs Controller General of India.
CDSCO-Central Drugs Standard
Control Organization
Retail and
Distribution
Manufacturing
Practice
Clinical Trials and
new drug
development
DRUG REGULATION IN INDIA

3. • 1. Schedule X – Narcotics
2. Schedule H – Prescription drugs
3. Schedule C and C1- Biological Products (Serums and
Vaccines)
Retail and Distribution
• 1. Schedule N
List of the equipment for the efficient running of manufacturing
wing, Qualified personnel
2. Schedule M-GMP
Manufacturing Practice
• Schedule Y
Clinical Trials and new drug development

4. The drugs and cosmetics act and
rules:
• GOVERNMENT OF INDIA MINISTRY OF
HEALTH AND FAMILY WELFARE Introduced
THE DRUGS AND COSMETICS ACT (1940)
AND RULES (1945)
An Act to regulate the import, manufacture, distribution
and sale of drugs and cosmetics in India.

5. SCHEDULE Y
Rules 122 A, 122 B, 122 D, 122 DA, 122 DAA, 122 DAB, 122 E, 122 DD.

6. • 122-A Application for permission to import
new drug.
• 122-B Application for approval to manufacture
new drug.
• 122-D Permission to import or manufacture
FDC.

7. 1. APPLICATION FOR PERMISSION:
Application for permission to import or manufacture new
drugs along with following data:
 Introduction
 Chemical and pharmaceutical information
 Animal Pharmacology
 Animal toxicology
 Human / Clinical pharmacology (Phase I)
 Therapeutic exploratory trials (Phase II)
 Therapeutic confirmatory trials (Phase III)
 Special studies
 Regulatory status in other countries
 Prescribing information

8. Chemical and pharmaceutical information
• Information on active ingredients
• Drug information (Generic Name, Chemical Name)
• Physical and chemical properties of drug
• Analytical Data
• Complete monograph specification including
• Validations
• Stability Studies
• Data on Formulation
• Dosage form
• Composition
• Excipient compatibility study

9. Animal Pharmacology
• Summary
• Specific pharmacological actions
• General pharmacological actions
• Follow-up and Supplemental Safety Pharmacology
Studies
• Pharmacokinetics: absorption, distribution;
metabolism; excretion

10. SPECIFIC PHARMACOLOGICAL ACTONS
• Actions which demonstrate the therapeutic
potential for humans.
• Scientifically validated methods should be used.
GENERAL PHARMACOLOGICAL
ACTIONS
• Safety pharmacology studies
• Effects on different organs

11. Animal toxicology
• Systemic Toxicity studies
• Single dose toxicity studies
• Repeated dose toxicity studies
• Male fertility studies
• Female Reproduction and Developmental Toxicity
Studies
• Local toxicity
• Allergy/Hypersensitivity
• Genotoxicity
• Carcinogenicity

12. Single dose toxicity
• Four graded doses should be given.
• Each group should contain at least 5 animals of either
sex.
• At least Animals should be exposed to the test
substance in a single bolus or by continuous infusion
or several doses within 24 hours.
• Animals should be observed for 14 days
• Minimal lethal dose(LDmin)
• Maximum tolerated dose

13. Dose-ranging Study
• MTD is established from the single dose toxicity
study
• Study is performed in one rodent and one non
rodent species.
• 5 animals in each group and at least 4 graded doses
should be given
• It is given consequently for 10 days
• Organ specific toxicity is established.

14. Male Fertility Study
• Six animals are taken in each group
• Animals should be treated with the test substance by
the intended route of clinical use for minimum 28 days
and maximum 70 days
• They are paired with female animals of proven fertility
in a ratio of 1:2 for mating for at least 10 days.
• Females getting thus pregnant should be examined for
their fertility after day 13 of gestation.
All the male animals should be sacrificed at the end of
the study and organs of reproduction are examined

15. Female Reproductive Studies
• These studies need to be carried out for all drugs
proposed to be studied or used in women of child
bearing age
• These are done under 3 segments:
SEGMENT I Albino mice or rat Female Fertility Study
SEGMENT II Albino mice or rat Teratogenicity Study
SEGMENT III Albino mice or rat
+
Albino rabbits
Perinatal Study

16. Local toxicity
These studies are required when the new drug is
proposed to be used by some special route (other than
oral) in humans:
It includes:
• Dermal toxicity
• Vaginal toxicity
• Rectal toxicity
• Parenteral toxicity: injection site toxicity
• Ocular and inhalational toxicity studies

17. Genotoxicity and Carcinogenicity
It is required for a drug that is intended to be used for
a chronic illness or a drug that is used for a long period
of time(>6 months)
Genotoxicity data are not required before Phase I and II
trials. But these studies should be completed before
applying for Phase III trials.

18. • 122-DA Permission 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

19. Clinical Trial
“Clinical trial” means a systematic study of new drug(s) in
human subject(s) to generate data for discovering and/or
verifying the clinical, pharmacological (including
pharmacodynamic and pharmacokinetic) and/or adverse
effects with the objective of determining safety and / or
efficacy of the new drug.”
122 - DAA

20. New Drug
A new substance of chemical, biological or biotechnological
origin, in bulk or prepared dosage form; used for prevention,
diagnosis, or treatment of disease in man or animal; which
except during local clinical, trials, has not been used in the
country to any significant extent and which except during
local clinical trials, has not been recognised in the country
as effective and safe for the proposed claims.
122-E

22. Post Marketing Trials (Phase IV)
Subsequent to approval of the product, new drugs
should be closely monitored for their clinical safety once
they are marketed.
The report is to be submitted every six months for the
first two years after approval of the drug is granted to
the applicant. For subsequent two years need to be
submitted annually and may be extended if necessary.
It is done to detect unexpected adverse effects and drug
interactions.

23. DRUG DISCOVERED
IN INDIA
DRUG DISCOVERED
OUTSIDE INDIA
STARTED FROM
PHASE I
PHASE II TRIAL
PHASE II TRIAL
PREVIOUS PHASE I
DATA
APPROVED

24. 2. CLINICAL TRIAL
PERMISSION
Licensing AuthorityThe ethics committee.
INVESTIGATORSPONSER
• Quality assurance
• Submission of status report.
• Reporting of any serious
adverse effect
• To ensure that laboratories
used for generating data for
clinical trials should be
compliant with Good
Laboratory Practices
• Conduct of the trial
according to the protocol
and the GCP Guidelines
• Follow the SOP’s.
• Ensure that adequate
medical care is provided
to the participant for any
adverse events.

25. Serious Adverse Events
• Any undesirable experience associated with the use of
a medical product in a patient
• It should be reported within 14 days by the Sponsor to
the Licensing Authority and to the other
Investigator(s) participating in the study
Death Life-threatening
Hospitalization Disability or Permanent Damage
Congenital Anomaly/Birth Defect Required Intervention to Prevent
Permanent Impairment or Damage
(Devices)
Other Serious (Important Medical
Events)
122- DAB

26. The Drugs and Cosmetics Rule made an amendment
GSR 53(E) dated 30-01- 2013 inserting a Rule 122DAB
and a new Appendix-XII in Schedule Y
It determine the quantum of compensation, if any, to be
paid by the Sponsor or his representative, whosoever
have obtained permission from the Drugs Controller
General(India) in a time bound manner.
B = Base amount (i.e. 8 lacs)
F = Factor depending on the age of the
subject (based on Workmen
Compensation Act)
R = Risk Factor

27. Age……………..F Factor Age……………..F Factor Age……………..F Factor
>16 . . . . . . . . 228.54
17 . . . . . . . . . 227.49
18 . . . . . . . . . 226.38
19 . . . . . . . . . 225.22
20 . . . . . . . . . 224.00
21 . . . . . . . . . 222.71
22 . . . . . . . . . 221.37
23 . . . . . . . . . 219.95
24 . . . . . . . . . 218.47
25 . . . . . . . . . 216.91
26 . . . . . . . . . 215.28
27 . . . . . . . . . 213.57
28 . . . . . . . . . 211.79
29 . . . . . . . . . 209.92
30 . . . . . . . . . 207.98
31 . . . . . . . . . 205.95
32 . . . . . . . . . 203.85
33 . . . . . . . . . 201.66
34 . . . . . . . . . 199.40
35 . . . . . . . . . 197.06
36 . . . . . . . . . 194.64
37 . . . . . . . . . 192.14
38 . . . . . . . . . 189.56
39 . . . . . . . . . 186.90
40 . . . . . . . . . 184.17
41 . . . . . . . . . 181.37
42 . . . . . . . . . 178.49
43 . . . . . . . . . 175.54
44 . . . . . . . . . 172.52
45 . . . . . . . . . 169.44
46 . . . . . . . . . 166.29
47 . . . . . . . . . 163.07
48 . . . . . . . . . 159.80
49…………….....156.47
50………………..153.09
51…………...…..149.67
52………………..146.20
53…………………142.68
54………………..139.13
55………………..135.56
56………………..131.95
57………………..128.33
58………………..124.70
59………………..121.05
60………………..117.41
61………………..113.77
62………………..110.14
63 . . . . . . . . . 106.52
64 . . . . . . . . . 102.93
65 or above … 99.37

28. RISK FACTOR INDEX(R) RISK FACTORS
0.50 terminally ill patient (expected
survival not more than (NMT)
6 months)
1.0 Patient with high risk
(expected survival between 6
to 24 months)
2.0 Patient with moderate risk
3.0 Patient with mild risk
4.0 Healthy Volunteers or subject
of no risk

31. • 122 – DD Registration of Ethics Committee (EC).

32. ETHICS COMMITTEE
It is the responsibility of the ethics committees that reviews and
accords its approval to a trial protocol to safeguard the rights, safety
and well being of all trial subjects.
• Care of the vulnerable group in the study: patients with
incurable diseases, unemployed or impoverished
persons, patients in emergency situation, others
incapable of personally giving consent
• Ethics Committee(s) should make, at appropriate
intervals, an ongoing review of the trials for which they
review the protocol
122 – DD

33. • The number of persons in an Ethics Committee
should have at least seven members
Chairperson
outside the institution
Member Secretary
(a)basic medical scientists (preferably one
pharmacologist).
(b) clinicians
(c) legal expert
(d) social scientist/ representation of non-
governmental voluntary agency /
philosopher / ethicist / theologian or similar
person
(e) lay person from the community

34. INFORMED CONSENT
In all clinical trials freely given, informed written consent
is required to be obtained from each study subject
• Verbal information of the study using a patient
information sheet
• Language that is nontechnical and understandable by
the study subject.
• Where a subject is not able to give informed consent,
the same may be obtained from a legally acceptable
representative.

35. STUDIES IN SPECIAL POPULATION
• Geriatrics:
• Geriatric patients should only if the disease intended to
be treated is characteristically a disease of aging
• The conditions to be treated should be common in the
elderly are likely to be encountered
• When the new drug is likely to alter the geriatric
patient’s response compared with that of the non-
geriatric patient.

36. • Pregnant or nursing women:
Pregnant or nursing women should be included in
clinical trials only when the drug is intended for use
by pregnant/nursing women or foetuses/nursing
infants and where the data generated from women
who are not pregnant or nursing, is not suitable.

37. Paediatrics:
• When clinical development is to include studies in
children, it is usually appropriate to begin with older
children before extending the trial to younger children
and then infants.
• Initial safety and tolerability data should be obtained
from the adult population data before starting trial in
children.
• Written informed consent should be taken from the
legal guardians.

38. PRESCRIPTION INFORMATION
The full
prescribing
information
should be
submitted as
part of the new
drug
application for
marketing