Simplified explanation of New Drugs & Clinical trial rule in India 2019. Need for this new rule?

1. New Drugs and Clinical Trials
Rule In India
19th March 2019
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2. Context
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Promote CR
Change in
the
Regulatory
landscape
Applicable
to New
drugs, EC,
ID

3. Systematic
study of a
drug
• Clinical effects
• Pharmacological
effects
• Adverse Effects
Establishing
Safety &
Efficacy
• Preceded by
Animal trials
• Estimated dose in
Animal trial
Before Trial
Consider
about the
new Therapy
• Specific the aims,
problems and risks
or benefits
• Scientifically sound.
• Ethically justified
Clinical
Trial

4. Dr ARYA V DEVI BDS, Student Id 6080
Phase 1
Phase 2
Phase 3
Phase 4
• Clinical pharmacology
trials or “first in man”
study
• Exploratory trials
• Confirmatory trials
• Post-marketing phase
Clinical Trial Phases in India

5. Dr ARYA V DEVI BDS, Student Id 6080
Permission from the Drugs
Controller General, India
(DCGI)
Approval from respective
Ethics Committee where
the study is planned
Mandatory registration on
the ICMR maintained
website
Prerequisites
for
conducting a
clinical trial in
India
Regulatory Mechanism

6. Dr ARYA V DEVI BDS, Student Id 6080
Drugs and
Cosmetics
Act, 1940
Central
Council for
Indian
Medicine
Act, 1970
Clinical trials
in India are
governed by
Medical
Council of
India Act,
1956

7. Features of New rules

8. Promote
Clinical
Research
Predictable
Transparent
Effective
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Faster Accessibility of New Drugs
Regulations
Features of New rules

9. Features of New rules
Reduced the Time for Approving
Applications
30 days
Indian
Drugs
90 days
Foreign
Drugs
Speedy
Processing
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10. Application will be deemed to
have Approved
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No communication from DCGI
Features of New rules

11. DCGI will decide Compensation
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Death
Permanent
Disability
Other
Injury
Trial Subject
Features of New rules

12. Dr ARYA V DEVI BDS, Student Id 6080
Monitor the Trials
Decide
Compensation For
Adverse Events
Ethics
Committee
Features of New rules

13. • If Injury to
Subject in
clinical trial
Injury
• Provide medical
management as
long as required
Management
• As per the
opinion of the
investigator
Investigator
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Features of New rules

14. NDCT Rules 2019
Chapters 13
Rules 107
Schedules 8
Forms 27

15. Chapter 1_ Preliminary
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16. Dr ARYA V DEVI BDS, Student Id 6080
Clinical trials
Ethic
Comm
ittee
New Drugs
BE &
BA
Study
Applicability

17. Academic Clinical Trial
• A clinical trial of a drug
already approved for a
certain claim and
initiated by any
Investigator, academic
or research institution
for a new indication or
new route of
administration or new
dose or new dose form,
where the results of
such a trial are intended
to be used only for
academic or research
purposes and not for
seeking approval of the
CLA or regulatory
authority of any country
for marketing or
commercial purposes
Bioavailability Study
• A study to assess the
rate and to which the
drug is absorbed from a
pharmaceutical
formulation and
becomes available in
the systemic circulation
or availability of the
drug at the site of
action
Bioequivalence Study
• A study to establish the
absence of a statistically
significant difference in
the rate and extent of
absorption of an active
ingredient from a
pharmaceutical
formulation from in
comparison to the
reference formulation
having the same active
ingredient when
administered in the
same molar dose under
similar conditions
Definitions

18. •Research including studies on basic, applied and operational
research or clinical research, designed primarily to increase
scientific knowledge about diseases and conditions, their
detection and cause and evolving strategies for health
promotion, prevention or amelioration of disease and
rehabilitation but does not include clinical trial trial
Biomedical and
health research
•The science and activities relating to the detection, assessment,
understanding and prevention of adverse effects or any other
drug- related problem
Pharmacovigilance
•Making a new drug or investigational new drug available to a
trial subject after completion of clinical trial through which the
said drug has been found beneficial to a trial subject during
clinical trial, for such period as considered necessary by the
investigator and the Ethics Committee
Post-trial access

19. Similar
biologic
• A biological product which is similar in terms of quality, safety and efficacy to
reference biological product licensed or approved in India, or any innovator
product approved in International Council of Harmonisation (ICH)member
countries
Orphan drug
• A drug intended to treat a condition which affects not more than five lakh persons
in India
Serious
adverse event
• an untoward medical occurrence during clinical trial resulting in death or
permanent disability, or hospitalisation of the trial subject where the trial subject
is an outdoor patient or a healthy person, prolongation of hospitalisation where
the trial subject is an indoor-patient, persistent or significant disability or
incapacity, congenital anomaly, birth defect or life threatening event

20. New
Drug
Novel Drug
Delivery
System
Living
modified
Organism
Monoclonal
Antibody
Stem Cells
Gene
therapeutic
products
Xenografts
Modified to incorporate

21. Chapter_2
Authorities & Officers
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22. Central Licensing
Authority
Delegation of
powers of Central
Licensing
Authority
Drug Controlling
Officer
Drugs Controller
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23. CHAPTER III_
Ethics Committee For
CR, BA & BE Study
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24. Dr ARYA V DEVI BDS, Student Id 6080
Ethics
Committee
lay person
woman
member
legal expert
independent
member
Medical field
scientific
area
non-
scientific
areas

25. Registration EC
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The Central Licensing
Authority
Validity_ 5 years
Renewal_ 90 days prior
to expiry

26. Functions of Ethics Committee
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review and accord
approval documents
Making review intervals
Reasons for rejection,
modification & changes
in the study
SAE reporting
EC can suspend or
terminate trial incase it
may compromise the
safety, well being of
subject
Comply with the
requirements or
conditions as specified
by CLA
allow inspection by
CDSCO or officer of the
State Drug Control
Authority.

27. Proceedings of Ethics Committee for
clinical trial
At least
these 5
member
s
medical
scientist
clinician
legal
expert
social
scientist
lay
person
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28. constitution and
composition of the EC
SOPs & Guidelines
followed by EC
copies of the protocol,
data collection formats,
CRFs, IB, etc
CV of all members of
the EC
Agenda and minutes of
EC meetings
order issued for
premature termination
of study
final report of the
study
records relating to the
serious adverse event,
medical management
of trial subjects and
compensation paid
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Maintain for five years after completion of
clinical trial
Maintenance of records by Ethics
Committee for clinical trial

29. CHAPTER V
CT, BE & BA Study of
New Drugs And IND
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Part A _Clinical Trial
Part B_ BE & BA Study

30. Clinical trial of new drug or investigational new drug
• in accordance with the permission granted by the CLA
Oversight of clinical trial site
• By EC periodically
Validity period of permission to initiate a CT
• two years from the date of its issue, unless extended by the Central
Licensing Authority.
Post-trial access of investigational new drug or new drug
• Sponsor provide to Trial subject free of cost
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31. Dr ARYA V DEVI BDS, Student Id 6080
Waived
off
Requirement
Of
Local
Clinical
Trial
Foreign (Specified by DCGI)
Approved & Marketed Drug
Indian Market

32. New Drug
Global Trial
Approved for Use In Select
Developed market
Allowed in India
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If
India
provided
Subjects
Even
if
the
Trial
is
Underway
in
India

33. New
Drug
Well
regulated
overseas
drug
markets.
Duration
Approved
and
marketed
for more
than two
years
New
Rule
Removed
regulations
on tests
conducted
on animals
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34. CHAPTER VI
Compensation
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35. • Compensation in case of injury
– 60 % of total compensation soon after the
approval of EC by Sponsor
• Medical Management
– By Investigator
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36. CHAPTER VII
BA & BE Study Centre
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37. Should be registered by CLA
Periodic Inspections by CLA officers
5 years validity
Renewal within 90 days of
expiration
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38. CHAPTER VIII
Manufacture of New Drugs or ID for CT,
BA/BE Study or For Examination, Test &
Analysis
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CHAPTER IX
Import of New Drugs or ID for CT,
BA/BE Study or For Examination,
Test & Analysis

39. CHAPTER X
Import or manufacture of New Drug for
Sale or for Distribution
CHAPTER XI
Import or manufacture of unapproved
New Drug for treatment of patients in
Govt hospitals & Govt Medical
Institutions
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40. Should grand licence / Permission from CLA
Inspections by CLA with or without prior notice
Cancellation incase of failure to comply with provisions
Product should be kept in containers with proper
labelling
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41. CHAPTER XII
AMENDEMENTS OF DRUGS AND
COSMETICS RULES, 1945
• Part XA and Schedule Y shall not be
applicable in respect of new drugs
and investigational new drugs for
human use
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42. CHAPTER XIII
MISCELLANEOUS
Pre-submission meeting
Post-submission meeting
Constitution of expert committee
or group of experts by CLA
Name of countries for purpose of
new drug approval
Mode of payment of fee
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43. FIRST SCHEDULE
• GENERAL PRINCIPLES AND
PRACTICES FOR CLINICAL TRIAL
SECOND SCHEDULE
• REQUIREMENTS AND GUIDELINES
FOR PERMISSION TO IMPORT OR
MANUFACTURE OF NEW DRUG FOR
SALE OR TO UNDERTAKE CLINICAL
TRIAL
THIRD SCHEDULE
• Conduct of CT
FOURTH SCHEDULE
• REQUIREMENTS AND GUIDELINES
FOR CONDUCT OF BIOAVAILABILITY
AND BIOEQUIVALENCE STUDY OF
NEW DRUGS OR INVESTIGATIONAL
NEW DRUGS
FIFTH SCHEDULE
• POST MARKET ASSESSMENT
SIXTH SCHEDULE
• FEE PAYABLE FOR LICENCE,
PERMISSION AND REGISTRATION
CERTIFICATE
SEVENTH SCHEDULE
• FORMULAE TO DETERMINE THE
QUANTUM OF COMPENSATION IN
THE CASES OF CLINICAL TRIAL
RELATED INJURY OR DEATH
EIGHTH SCHEDULE
• APPLICATION FOR
REGISTRATION/RENEWAL OF
ETHICS COMMITTEE RELATING TO
CLINICAL TRIAL OR BIOAVAILABILITY
AND BIOEQUIVALNENCE STUDY OR
BIOMEDICAL HEALTH RESEARCH
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44. Key Issues with Clinical Trials
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45. But presence of
ambiguous language is a
concern.
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2013 Amendments to the Drugs and
Cosmetics Act led to better protection of
vulnerable groups
Key Issues with Clinical Trials

46. Over-representation
of low-income groups
among trial subjects.
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The big problem plaguing clinical research is an
Sometimes CROs recruit them selectively
and exploit their ignorance.
Their only reward from the trial is financial.
Key Issues with Clinical Trials

47. Many times consent of the
participants in the clinical trials is not
taken.
In most cases ethics committee is not constituted and
people on such committees are not well trained.
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There is lack of independence for ethics committee working.
Key Issues with Clinical Trials

48. There is need to register with Clinical Trials
Registry of India for all clinical trials
conducted in India.
But registration is mostly done for
positive trial cases.
So there is lack of transparency.
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Key Issues with Clinical Trials

49. There are no well developed
International standards dealing with
clinical trials.
India is a signatory of the Declaration of Helsinki
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But that is voluntary in nature and lack regulatory
mechanisms.
Key Issues with Clinical Trials

50. Three tier approval mechanisms has also
led to delays in approval.
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Key Issues with Clinical Trials
Approval for DCGI
Apex
Committee
Technical
Committee
Subject
Expert
Committee

51. • Collusion between drug companies and doctors.
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• Compensation for participating in research as well
as research related injury is a major bone of
contention these days.
• Moreover, regulatory failure and unethical
clinical trials are also major issues.

52. Significance of New Rules

53. • Near 70 million population in India suffer
from rare disorders and many of which still not
curable and their treatment is also very high.
• Moreover, the research in India is more skewed
towards non-communicable diseases. So, clinical
trials in this field will bring much anticipated balance.
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Significance of New Rules

54. • The new rules and are expected to promote clinical
research in the country through a transparent
process yielding faster approvals.
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55. • The new rules state that any drug discovered in India,
or research and development of the drug has been
done in India, and which is proposed to be
manufactured and marketed in the country, will be
deemed approved for clinical trials within 30
working days by Central Licensing Authority (CLA).
• In the event that there is no communication from the
CLA to applicant within the stipulated time, then the
permission to conduct clinical trial shall be assumed
to have been granted.
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56. • The DCGI would now accept the data generated
outside the country thereby making the process
easier and application time shorter.
• The drug companies considering India as a
market for running local clinical trials get
additional benefits if the drugs are approved and
marketed in the European Union, the UK, Australia,
Canada, Japan and the US.
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57. • Removal of the compensation clause should be
considered as a welcome move for all the subjects
participating in clinical trials in India. Earlier there
was no clarity and there were long and cumbersome
legal hassles which created a question mark on the
safety of trials.
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get 60% of their total compensation soon after the opinion of
the ethics committee.
This was welcomed by civil society and public health watchers
and seen as a measure that put patients ahead of
pharmaceutical companies.

58. • Foreign companies based out of the US and
Europe who have been eyeing China as a
trial market are yet to gain confidence and are
closely watching the scenario, post the
new rule in 2019.
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59. • Based on research the total number of clinical trials
registered till Q1 2018 in India, the market might
grow up to 8.5-9 per cent from 2019-2021
and then may pick up faster
2022-2026 to around >12 per cent, if the
rules implemented in 2019,
yields results in 2019-20 and saves time and cost for
the multinational companies.
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60. • The new rules will end the unnecessary
repetition of trials and speed up the availability of
new drugs in the country, lower the cost of drugs and
will improve the ease of doing business for drug
makers.
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61. Dr ARYA V DEVI BDS, Student Id 6080
Criticism of New Regulations

62. • Monopolistic tendencies in the CRO market
remains unaddressed.
• Waiver should be only for drugs required urgently
for national emergency.
• To prove a injury due to the trial is problematic
and it is prone to manipulation.
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63. • As India has the vast ethnic diversity the need
of bridging trials for ethnically diverse
populations to check drug suitability
population is not addressed.
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64. Dr ARYA V DEVI BDS, Student Id 6080
Way Forward

65. • To reap the benefits of clinical trials, our
objective should be to bring about more
clinical research in the country while
maintaining high standards to ensure
patient safety and accuracy of data.
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66. • A clinical trial should be planned and
conducted by a trained investigator
following the latest rules and regulations
with meticulous record keeping and
reporting.
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67. • It is crucial to maintain highest standards,
as any compromise may jeopardize public
confidence and participation in the clinical trials
and may ultimately affect the availability of safe
and effective products.
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68. • With digital revolution touching all the
major metros and mini-metros, patients
can be monitored real time.
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69. • Compared to markets like
– Indonesia where commuting is an issue, or
– African countries where communication is a major
problem or
– Western Europe where the cost of trials are expensive
and patients have limited health issues, but language
is major barrier;
India offers infrastructure, easy policies (in
2019) and the government has propensity
to facilitate more companies considering
Indian market as a ground for clinical trial.
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70. • More and more mid and SME in the CRO
segment should be incentivised to promote healthy
competition and break down the monopoly.
This will directly bring down the cost of
conducting trials in India.
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71. Dr ARYA V DEVI BDS, Student Id 6080
Unless closely nurtured, this industry
can lose its way and get entangled in
the complexity of trials.
Thank You
