Regulations & Guidelines Specific to

Ethics

Schedule Y & CDSCO-GCP

Dr. K. Bangarurajan M Pharm, PhD
Deputy Drugs Controller (India)
CDSCO – West Zone
Outline

• Licensing Authority – India

- Clinical Trial:
• CDSCO Head Quarters, New Delhi
- Marketing and Manufacture:
• State Drug Control Organisation
• Recent Amendments in D & C Rules
• Other measures taken to strengthen CT regulation
• Conclusion
India-Well defined Drug Regulatory
System
Government of India
Ministry of Health & Ministry of Ministry of Ministry of Science Ministry of
Family welfare Chemicals & Commerce & Environment
(Secretary, Health) fertilizers (Compulsory Technology
Licensing of
Life saving Environmental
DGHS category
Department of DBT (RCGM) clearance to the
Pharmaceuticals drug) manufacturing
CDSCO sites and
recombinant drug
Patent Office CSIR Labs products
DCGI DTAB NPPA
(GEAC)
• Enforcement &
GMP Audit Div.
(Pricing of Drugs) Controller
• Quality Control General of
Division-DTL/CDL patents
• Registration Div.
• New Drugs Div.
• Pharmacovigilance
• Trainings
Legal Enactments to Regulate
Import, Manufacture & Sale of Drugs

Drugs & Magic

Drugs & Remedies
Cosmetics Act, (Objectionable
1940 Advertisements
Act, 1954)

Drugs & Drug Price

Cosmetics Rules, Control Order
1945 made (DPCO) 2013
under the Act
What is Regulated under DCA

Manufacture

Distribution DCA Import

Sale
What is Regulated under Rules

Clinical New
Trials Drugs

Exports
Functions of CDSCO

• Approval of New Drugs and Clinical Trials

• Import Registration and Licensing
• Licensing of Blood Banks, LVPs, Vaccines, r-DNA
products & Some Medical Devices
• Amendment to Drugs & Cosmetics Act and Rules
• Banning of Drugs and Cosmetics
• Grant of Test License, Personal License, NOCs for
Export
• Testing of Drugs
CDSCO – Geographical location
Zonal/ Sub-Zonal Offices (10)

CDSCO, HQ

New Delhi

•Mumbai

Port Offices/ Airports: 11, Laboratories: 08

Proposed Sub Zonal Offices(2): Guwahati & Indore Chennai
Proposed Port Office at Vishakhapatnam
Functions of State Licensing Authorities

• Licensing of Manufacturing Site for Drugs including

API and Finished Formulation
• Licensing of Establishment for sale or distribution of
Drugs
• Approval of Drug Testing Laboratories
• Monitoring of Quality of Drugs and Cosmetics
marketed in the Country
• Investigation and prosecution in respect of
contravention of legal provision
• Recall of sub-standard drugs
Approval of Clinical Trials, Import &
Manufacture of New Drugs
Requirements and Guidelines - Schedule Y
Rule 122 A • Permission to import new drug
• Definition of New Drugs:
o New Substance having therapeutic indication
o Modified or new claims, new route of administration for
already approved drug
o Fixed Dose Combination
Rule 122 B Permission to manufacture new drug
Rule 122 DA Application for permission to conduct clinical trials for New Drug/
Investigational New Drug.
Rule 122 DAA Definition of Clinical Trial:
o For the purpose of this Part, “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 pharmacodynamics and
pharmacokinetic) and /or adverse effects with the objective
of determining safety and / or efficacy of the new drug.]
Approval of Clinical Trials, Import &
Manufacture of New Drugs Continued

Requirements and Guidelines - Schedule Y

Rule 122 DAB • Compensation in case of injury or death during clinical trial
(G.S.R. 53(E) dated 30th January 2013).
• G.S.R. 889(E) dt.12-12-2014; Clarifications on the criteria for
eligibility of compensation (Will be implemented 6 months from
the date of publication).
Rule 122 DAC Permission to conduct Clinical trial.(G.S.R. 63 (E) dated 1st
February 2013).
Rule 122DB Suspension or cancellation of Permission/ Approval.
Rule 122 DD Registration of Ethic Committee, (G.S.R. 72 (E) dated 8th February
2013).
Rule 122 E Definition of New Drugs
What is Schedule Y

• Under Part X-A of Drugs & Cosmetics Rule 1945

• Describes information/ data required for Approval in
Clinical Trial and/or to Import or Manufacture of New
Drug for Marketing in India
• Outlines extensive study criteria in line with the
globally accepted formats such as ICH Guidelines
and US-FDA Regulations
Salient Features of Schedule Y
• Concurrent phase global clinical trials permitted
• Phase I (first-in-human) study of New Drug substance
discovered outside the country, not permitted (Repeat
Phase I is permitted)
• Stipulates responsibilities of EC, Investigators and
Sponsor
• Structure, contents and formats for CT protocols,
reports, EC approvals, ICF, SAE reporting are
incorporated
• There are 12 Appendices
• Provides statutory support to CDSCO-GCP Guidelines &
ICMR-Ethics Guidelines for Biomedical Research
What is GCP?

• International ethical and scientific quality standard

for:
• Designing
• Conducting
• Recording
• Reporting

Trials that involves participation of human subjects

Why GCP ?

• Legal Requirement
• Protects the rights, integrity & confidentiality of
research subjects
• Provides assurance that the data & results are
credible & accurate
• Global Acceptance
Ethics Committee Registration:

• As per Gazette Notification No. GSR 72 E dated 8th

Feb 2013, and under Rule 122DD
“No Ethics Committee shall review and accord its
approval to a clinical trial protocol without prior
registration with the Licensing Authority as defined
in clause (b) of Rule 21”, (i.e. DCG(I))
• Ethics Committee shall review and accord its
approval to clinical trial and also carry on-going
review of a trial as specified in Schedule Y and GCP
guidance document.
Ethics Committee Registration

• EC shall review and accord its approval to clinical

trial and also carry on-going review of a trial as
specified in Schedule Y and GCP guidance document.
• In case of any Serious Adverse Event (SAE)
occurring to the clinical trial subject during the trial,
the EC shall analyze and forward its opinion as per
procedure specified in APPENDIX –XII of schedule Y.
• In said rules, in Schedule Y, in APPENDIX-VIII
relating to Ethics Committee.
E.C. Registration:
Common Deficiency in the Application
• Under which authority EC is formed ?
• Undertaking in CDSCO Format
• Completion of 19 point check-list given by CDSCO
• All Standard Operative Procedures (SOPs)
• Mainly SOPs for Vulnerable Population
• Proper dossier with page numbers
• Request for Ethics Committee registration under rule
• 122 DD of Drugs & Cosmetics Rules
• Brief about Hospital / Trial Site.
SAE Reporting (Rule 122 DAB)
• All serious and unexpected adverse events should be
reported by P.I. to CDSCO, Sponsor and EC within 24 hrs
(earlier 24hrs reporting was limited to sponsor by PI)
• The detailed report of SAE after due analysis, should be
forwarded by PI & Sponsor to chairman of EC, CDSCO
and Head of Institution within 10 calendar days of
occurrence of SAEs (the SAEs of death also needs to be
forwarded to the Chairman of Expert Committee
appointed by CDSCO.)
• SAE reports submitted to the CDSCO should be in
COLOR coded binding:-
RED: SAEs or Deaths,
Blue: SAEs due to Injury,
Remaining cases of SAEs in White cover.
 Investigator
(within 24hrs of occurrence)

Sponsor / Investigator
(within 10 calendar days after analysis of SAE)

In case of Death In case of Death

Head of Chairman Chairman Ethics

Institution Expert Committee Committee (within 21
(Recommendation in calendar days after
30 days) due analysis)

DCG(I)*
(order within 3 months of occurrence)

Sponsor / Applicant Payment of Compensation within 30 days of

Order

*If required DCG(I) can constitute Expert Committee in cases of SAE other than death
Formula on Quantum of Compensation
Compensation = BxFxR/ 99.37
B= Base Amount (8 lakhs)
F= Factor depending on age (Workmen Compensation Act)
R= Risk Factor (severity & seriousness, co-morbidities etc. 0.5-
4.0)
State-Wise List of Ethics Committee
Registered By CDSCO (Total 745)
Andhra Pradesh 80 Madhya Pradesh 09
Assam 03 Maharashtra 178
Bihar 04 Mizoram 01
Chhattisgarh 01 Orissa 10
Delhi 48 Puducherry 04
Goa 04 Punjab 14
Gujarat 86 Rajasthan 24
Haryana 09 Sikkim 02
Himachal Pradesh 02 Tamilnadu 70
Jammu & Kashmir 01 Uttarakhand 02
Karnataka 75 Uttar Pradesh 32
Kerala 48 West Bengal 38
Clinical Trials Registration (CTRI)
To enhance:
- Transparency
- Accountability &
- Accessibility of clinical trials,
• Made mandatory by the DCGI’s office from June 15, 2009.
• 20 data set points of the WHO, as well as details of India
Investigators, ethics and DCGI approval (including submission
or approval documents)
• For Global clinical trials, specific information regarding the
number of patients being recruited and the date of first
enrollment in India
• www.ctri.nic.in
Other Regulations and Office Orders

• Ancillary care for any other illness afflicting patients in a

clinical trial
• Clinical trials must be conducted in accredited site after
review by accredited (and registered) IRB/REC, and only
involving certified (accredited) investigators
• Clinical investigators may participate in no more than
three clinical trials at any one time
• 50% of clinical trials must be performed in public
hospitals with over 50 beds Every informed consent must
be video-recorded by a videographer and preserved
Certification and Accreditation

• Quality Council of India chosen as central agency in

charge of standards and accreditation, including defining
process and inspections
• QCI published draft standards, posted on National
Accreditation Board for Hospitals & Healthcare Providers
(NABH):
http://nabh.co/Notice_draft_accreditation_standards.as
px#sthash.ZFPCfUxD.dpuf
India: Still Pending

• Requirement for placement of trials in 50-bed hospital

• Compensation revisions for situations not modified (e.g.
Phase 4 trials, post-marketing surveillance, non-compliance)
• Compensation formula for injury
• Definition of “ancillary care” expectation for inter-current
illness during clinical trial
• Structure, education and training of regulatory authorities
• Elevation of CDSCO/DCGI to higher authority and status in
government
• Increased investment in regulatory offices and competence of
officials Transparency of regulatory processes and decisions
Conclusion

• Clear understating of Mandate, Rules & Regulations of:

- Training to all EC members
- Accreditation/Registration by QCI
- Integrity of approvals
- Audit/ Inspection of CT sites
- Action against violators
Thank You