regulations & guidelines specific to ethics: schedule y...
TRANSCRIPT
Regulations & Guidelines specific to Ethics: Schedule Y & Indian-GCP
A.B.RAMTEKE (Consultant){ Ex- Joint Drugs Controller (India), CDSCO, Min. of Health}
Clinical Development Service AgencyNCR Biotech Science Cluster, 3rd Mile Stone, F-G Expressway, Faridabad..
Outline
• Drug Regulatory Authorities in India• Legal provisions for regulation of Clinical
Trials, Schedule-Y & Ethics Committees• Amendments in D & C Rules in 2013-14• Other measures taken to strengthen CT
regulation• Conclusion
India-Well defined Drug Regulatory SystemGovernment of India
Ministry of Health & Family welfare(Secretary Health)
DGHS
CDSCO
DCGI DTAB
•Enforcement & GMP audit Div•Quality Control Division-CDTL / CDL•Import Registration Div•New Drugs Div.•Biologicals & Vaccine Div.•Pharmacovigilance•Trainings
Ministry of Chemicals & fertilizers
Department of Pharmaceuticals
NPPA
(Pricing of Drugs)
Ministry of Commerce( Compulsory Licensing of Life saving category drug
Patent Office
Controller General of patents
Ministry of science & Technology(DST)
DBT (RCGM)
CSIR Labs
Ministry of Environment
Environmental clearance to the manufacturing sites,And recombinant drug products(GEAC)
Legal Enactments to Regulate Import, Manufacture & Sale of DrugsDrugs & Drugs & MagicCosmetics Act, Remedies
1940 (Objectionable Advertisements Act, 1954)
Drugs & CosmeticsRules, 1945 Drug Price Control made under the Act Order (DPCO) 2013
What is regulated under the Act:
Act
Manufacture
Import
Sale
Distribution
What is regulated under Rules
New Drugs
Exports
Clinical Trials
Functions of CDSCO
Approval of New Drugs and Clinical Trials
Import Registration and Licensing
Licensing of Blood Banks, LVPs, Vaccines, r-DNAproducts & 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 and Registration of Ethics Committee
Functions of CDSCO
Functions of State Licensing Authorities
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
CDSCO – Geographical location Zonal/Sub-Zonal Offices (10)
CDSCO North Zone (Ghaziabad)
.
CDSCO West Zone (Mumbai)
CDSCO South Zone (Chennai)
CDSCO East Zone (Kolkata)
CDSCO, HQ
29 States
7 Union Territories
CDSCO Zone (Ahmadabad)
CDSCO Zone (Hyderabad)
CDSCO Sub Zone (Bangaluru)
CDSCO Sub Zone (Chandigarh)
CDSCO Sub Zone (Jammu)
CDSCO Sub Zone (Goa)
Port Offices /Airports : 11, Laboratories : 08
Proposed SubZonal offices (2): Guwahati, Indore
Proposed Port Office at Vishakhapatnam
•Mumbai
New Delhi
Chennai
Kolkata
Approval of Clinical Trials, Import & Manufacture of New Drugs
Requirements and Guidelines - Schedule Y
Rule 122 A
Rule 122 B
Rule 122 DAA
Rule 122 E
Permission to import new drug
Permission to manufacture new drug
Definition of Clinical trials
Definition of New Drugs*
• New substance having therapeutic indication
• Modified or new claims, new route of administration for already approved drug
• Fixed Dose Combination
Legal Provisions for regulation of Clinical Trials
Requirements and Guidelines - Schedule Y- 2005Rule 122 DA
Rule 122 DAA
Compensation in case of trial related injury or deathRule 122 DAB
Definition of Clinical trials
Permission to conduct clinical trial
Conditions of Clinical Trial permission & Inspection
Registration of Ethics Committee
Definition of New Drugs
Rule 122 DAC
Rule 122 DD
Rule 122 E
GCP Guidelines, 2001
What Is Schedule Y• It is “Schedule under Part X-A of Drugs &
Cosmetics Rule 1945” describe theinformation/data required for approval ofClinical Trial and/or to import or manufactureof new drug for marketing in India.
• It is also describe the pre-clinical, animalstudies requirement, including toxicity studies.
• There are Templets for Clinical Trial Protocol,Inform Consent, Trial Report Submission etc.
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, notpermitted( Repeat Phase I is permitted)
• Provides statutory support to Indian GCPGuidelines & ICMR- BIO-Ethics Guidelines.
• Stipulates responsibilities of EC, Investigators andSponsor.
• Structure, contents and formats for CT protocols,reports, EC approvals, ICF, SAE reporting areincorporated .
• There are 12 Appendices.
What are GCPs
International ethical and scientific quality standard for :
• designing• conducting• recording• reporting
Trials that involves participationof human subjects
•Legal Requirement
• Protects the rights, integrity & confidentiality of research subjects
• Provides assurance that the data & results are credible & accurate
• Global Acceptance
Why GCP
INDIAN GCP BOOKLET : 2001 CONTAINS• Definitions, Pre-requisite of the Study,• Protocol, Relevant components of Protocol,• Ethical & Safety consideration,• Inform Consent Process, Compensation for subjects,• Responsibility-Sponsor, Monitor & Investigator,• Record keeping & Data Handling,• Quality Assurance, Statistics• Special Concerns- C/T Vaccines, Contraceptives,
Devices, Herbal Remedies & Medicinal plants;• Five Appendices- Sch-Y, Decl. of Helsinki,r-DNA
product requirement, IB and Essential Documents.
Drugs And Cosmetics Act And Rules
• Rule 122DA. Application for permission to conductclinical trials for New Drug/Investigational New Drug.
• Rule 122DAA. Definition of Clinical trial.--For thepurpose of this Part, “Clinical trial” means asystematic study of new drug(s) in human subject(s)to generate data for discovering and/or verifying theclinical, pharmacological (includingpharmacodynamics and pharmacokinetic) and /oradverse effects with the objective of determiningsafety and / or efficacy of the new drug.]
• Rule 122DB. Suspension or cancellation ofPermission/Approval.
Drugs And Cosmetics Rules
• Rule 122 DAB. – Compensation in case of injury ordeath during clinical trial. (G.S.R. 53 ( E ) dated30th January 2013).
• Rule 122 DAC. Permission to conduct Clinicaltrial.( G.S.R. 63 ( E ) dated 1st February 2013).
• Rule 122 DD - Registration of Ethic Committee, (G.S.R. 72 ( E ) dated 8th February 2013).
• Amendment to Rule122DAB –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)
• As per Gazette Notification No. GSR 72 E dated 8th Feb2013, and under Rule 122DD
“ No Ethics Committee shall review and accord itsapproval to a clinical trial protocol without priorregistration with the Licensing Authority as defined inclause (b) of Rule 21”, (i.e. DCG(I))
Ethics Committee Registration:
Regulatory Authority and Ethics Committee
• The government establishes the legal framework forthe national regulatory authority and the ethicscommittee(s).
• Independent and complementary functions.• Approval of both is needed for a trial to commence.• Continued oversight by both is needed during the life
of a trial
Regulatory Authority
• Reviews CT application• Quality, Safety, Efficacy• Authorized trial• Continued oversight of ongoing trial• Reviews amendments• Oversight of Safety• Up to end of trial• Maintenance of safety and CT
• Inspection• Sanctions• Transparency• GMP
ETHICS COMMITTEE• Reviews CT application
• Relevance of protocol and design
• Anticipated benefit outweighs risk
• Investigator staff and facilities
• Information -subjects/recruitment
• Compensation/indemnity/insurance
• Continued oversight of ongoing trial
• Reviews amendments, safety
updates, new information to subjects
Up to end of trial
• Indian GCP
Comparison (Functions)
• Ethics Committee shall review and accord its approvalto clinical trial and also carry on-going review of atrial as specified in Schedule Y and GCP guidancedocument.
• In case of any Serious Adverse Event (SAE)occurring to the clinical trial subject during the trial,the EC shall analyse and forward its opinion as perprocedure specified in APPENDIX –XII of scheduleY.
• In said rules, in Schedule Y, in APPENDIX- VIIIrelating to Ethics Committee.
E.C. Registration:
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..
• All serious and unexpected adverse events should bereported 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 beforwarded by PI & Sponsor to chairman of EC, CDSCO andHead of Instt. within 10 calendar days of occurrence ofSAEs. (the SAEs of death also needs to be forwarded to theChairman of Expert Committee appointed by CDSCO.)
• SAE reports submitted to the CDSCO should be in COLORcoded binding:-RED -for SAEs or Deaths, Blue - for SAEs due to Injury,
remaining cases of SAEs in White cover.
SAE Reporting (Rule 122 DAB)
Investigator (within 24hrs of occurrence)
Sponsor / Investigator (within 10 calendar days after analysis of SAE)
Head of Institution
ChairmanExpert Committee
(Recommendation in 30 days)
Chairman Ethics Committee (within 21 calendar days
after 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
In case of Death
In case of Death
• Formula on Quantum of Compensation Compensation =BxFxR/99.37B= 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 COMMITEE REGISTERED BY CDSCO (Total 953) as on 1st June 2015• Andhra Pradesh / TG : 99 • Assam : 05• Bihar : 05• Chhattisgarh : 02• Delhi : 60• Goa : 05• Gujarat : 113• Haryana : 12• Himachal Pradesh : 02• Jammu & Kashmir : 01• Karnataka : 97• Kerala : 49• Madhya Pradesh : 11
STATE WISE LIST OF ETHICS COMMITEE REGISTERED BY CDSCO.• Maharashtra : 231• Mizoram : 01• Orissa : 12• Puducherry : 08• Punjab : 20• Rajasthan : 32• Sikkim : 01• Tamilnadu : 91• Uttarakhand : 05• Uttar Pradesh : 50• West Bengal : 41
{ Courtesy CDSCO Web-site}
Clinical Trials Registration in India(CTRI)
To enhance – transparency- accountability &- accessibility of clinical trials,- made mandatory by the DCGI’s office from June 15th 2009.
• 20 data set points of the WHO, as well as details of Indian PI’s,ethics and DCGI approval (including submission or approvaldocuments)
• For Global clinical trials, specific information regarding thenumber of patients being recruited and the date of firstenrollment in India.
• Clinical Trials Registration (www.ctri.nic.in).
30
MCI Regulation 2002:
• 7.22 Research: Clinical drug trials or other research involving patients or volunteers as per the guidelines of ICMR can be undertaken, provided ethical considerations are borne in mind.
• Violation of existing ICMR guidelines in this regard shall constitute misconduct.
• Consent taken from the patient for trial of drug or therapy which is not as per the guidelines shall also be construed as misconduct.
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.aspx#sthash.ZFPCfUxD.dpuf
• Also at CDSCO web-site www.cdsco.nic.in
National Accreditation Board for Hospitals and Healthcare Providers
(NABH)
• Accreditation Standards for Clinical Trial in India
• Ethics Committee, Investigator and Clinical Trial Site
Accreditation of Ethics Committee List of applicable Policies / Procedures
• Composition, procedures for new induction and resignation of members.• Frequency of ethics committee meetings.• Receipt, review and decision making of proposals.• Review of protocol amendments.• Procedure for deliberations and maintaining minutes.• Periodic review and oversight.• Procedure to be followed for vulnerable population.• Review of Informed Consent Document (subject information sheet and
informed consent form) and informed consent process.• Reporting, analysis of SAEs and making opinion on compensation.• Handling issues related to non-compliances, protocol violation, complaints by
the participants and other stakeholders.• Declaration of conflict of interest and confidentiality agreement.• Financial declaration of payments received and disbursed.• Training for committee members• Communication with different stakeholders.• Control and archiving of records.• SOP on SOP.
Conclusion
• Clear understating of Mandate, Rules &
Regulations for clinical trials, GCP and EC.
• Training to all EC members
• Accreditation/Registration by QCI
• Audit / Inspection of CT and EC sites
• Taking action against violators
Thank You