Pharmaceutical Registration In India

DIA – Training CourseSurya Chitra, Savio Group Inc

Sunder Venkatraman, Asian Clinical Trials

Pharmaceutical Registration In India

DIA – Training CourseSurya Chitra, Savio Group Inc

Sunder Venkatraman, Asian Clinical Trials

Regulations in India

Central GovernmentsStatutory Functions

State GovernmentsStatutory Functions

Central GovernmentsStatutory Functions

State GovernmentsStatutory Functions

Major Regulatory Bodies

DCGI: Drugs Controller General of India

DGFT: Directorate-General of Foreign Trade

DBT:Department of Biotechnology

GEAC: Genetic Engineering Approval Committee

RDAC: Recombinant DNA Advisory Committee

IBSC: Institutional Biological Safety Committees

RCGM: Review Committee on Genetic Manipulation

DCGI: Drugs Controller General of India

DGFT: Directorate-General of Foreign Trade

DBT:Department of Biotechnology

GEAC: Genetic Engineering Approval Committee

RDAC: Recombinant DNA Advisory Committee

IBSC: Institutional Biological Safety Committees

RCGM: Review Committee on Genetic Manipulation

State Government Statutory Functions

Licensing of Drug testing labs

Approval of drug formulations for manufacture

Monitoring for quality of drugs and cosmetics, manufactured by respective states units and those marketed in India

Recall of substandard drugs

Investigation and prosecution in respect to contravention of legal provisions

Pre and Post licensing inspection

Administrative actions

Licensing of Drug testing labs

Approval of drug formulations for manufacture

Monitoring for quality of drugs and cosmetics, manufactured by respective states units and those marketed in India

Recall of substandard drugs

Investigation and prosecution in respect to contravention of legal provisions

Pre and Post licensing inspection

Administrative actions

Central Government Statutory Functions

Approve licenses to manufacture certain categories of drug as Central License Approving

Regulate CR in IndiaEstablish regulatory measures, amendments to acts and rulesScreening drug Formulations available in Indian MarketRegulate MA of new drugRegulate the standards of imported drugsConduct training programs for regulatory officials and catalyst In IndiaPublication of Indian Pharmacopoeia

Approve licenses to manufacture certain categories of drug as Central License Approving

Regulate CR in IndiaEstablish regulatory measures, amendments to acts and rulesScreening drug Formulations available in Indian MarketRegulate MA of new drugRegulate the standards of imported drugsConduct training programs for regulatory officials and catalyst In IndiaPublication of Indian Pharmacopoeia

National Government

Ministry of EnvironmentMinistry of Chemicals &

Petrochemicals

The Regulatory Affairs Organization Chart

Ministry of health andwelfare

Central Drug Standard&Control Organization

Drug ControllerGeneral of India

HQ Zonal Offices

GEAC NPPA DCP

Beyond Guidelines

Trial can be initiated only afterpermission from Licensing Authorityand approval from ethics committee.

Trial can be initiated only afterpermission from Licensing Authorityand approval from ethics committee.

Drugs are registered with DCGI( Drug Controller General of India) which is the main regulatory body.

Drug Registration and Biologics/Pharmaceuticalsin India

Drugs are registered with DCGI( Drug Controller General of India) which is the main regulatory body.

Clinical Research Guidelines/Regulations in India

Drugs & Cosmetics Act & Rules (Schedule Y1988)

GCP Guidelines, 2001

National Pharmacovigilance Programme, 2004

Schedule Y, 2005

ICMR Guidelines, 2000 (being revised)

Drugs & Cosmetics Act & Rules (Schedule Y1988)

GCP Guidelines, 2001

National Pharmacovigilance Programme, 2004

Schedule Y, 2005

ICMR Guidelines, 2000 (being revised)

New Regulations Governing Clinical Research in India

In keeping with

Global regulatory standards

India specific cultural, social, political and administrative condition

In keeping with

Global regulatory standards

India specific cultural, social, political and administrative condition

Sponsor’s Responsibilities

ProtocolReporting timelinesAdequate TrainingSponsor’s Study team, Investigators teamResources /InfrastructureInsurance/Expenses for medical management of AEsMonitoring

ProtocolReporting timelinesAdequate TrainingSponsor’s Study team, Investigators teamResources /InfrastructureInsurance/Expenses for medical management of AEsMonitoring

Compilation /Evaluation of safety reports

Dissemination

•Information (AEs /Safety Updates/ PSURs)

•All concerned parties (Regulators/ Investigators/ Ecs)

Generate “Investigator Notifications” when required

Generate periodic safety update reviews and submit to DCGI

Sponsor’s Responsibilities

Compilation /Evaluation of safety reports

Dissemination

•Information (AEs /Safety Updates/ PSURs)

•All concerned parties (Regulators/ Investigators/ Ecs)

Generate “Investigator Notifications” when required

Generate periodic safety update reviews and submit to DCGI

Investigator’s responsibilities

Understand Protocol requirements

Training of his team members

Provision of necessary resources & infrastructure

Monitor, capture & documents ALL AEs

Medical care including follow up AE

Report to sponsor and IEC

Archives

Understand Protocol requirements

Training of his team members

Provision of necessary resources & infrastructure

Monitor, capture & documents ALL AEs

Medical care including follow up AE

Report to sponsor and IEC

Archives

Responsibilities of Ethics Committees and DSMBs

ECs

Review: safeguard rights, safety and well-being of participant

Monitor: SAE reports, annual reports, project reports

DSMBs

Ongoing Review

ECs

Review: safeguard rights, safety and well-being of participant

Monitor: SAE reports, annual reports, project reports

DSMBs

Ongoing Review

Schedule Y(2005 Amendment) -Statute

Guidelines:

Declaration of Helsinki

ICH-E6 GCP Guidelines

ICMR Guidelines

Guidelines:

Declaration of Helsinki

ICH-E6 GCP Guidelines

ICMR Guidelines

Schedule Y

Ethics Committee

–Composition, quorum prescribed

–SOPs mandatory

–Amendment approvals

– Review of agreements

– Approval format prescribed(http:// www.cdsco.nic.in)

Ethics Committee

–Composition, quorum prescribed

–SOPs mandatory

–Amendment approvals

– Review of agreements

– Approval format prescribed(http:// www.cdsco.nic.in)

Freely given, informed, written consent in prescribed form Appendix V

Constitution, quorum and approval format as per Appendix VIII

Ethical Issues

Freely given, informed, written consent in prescribed form Appendix V

Constitution, quorum and approval format as per Appendix VIII

Investigators may accept Approval granted by EC of another siteor approval granted by an independent ethics committee

Provisions for Using Independent EC

Investigators may accept Approval granted by EC of another siteor approval granted by an independent ethics committee

Roles and Responsibilities

PSUR mandatory

Protocol Format (Appendix X)

Report format (Appendix II)

Reporting Timelines specified: Unexpected SAEs within14 days to DCGI and other investigators

Stability testing

Sponsors

Roles and Responsibilities

PSUR mandatory

Protocol Format (Appendix X)

Report format (Appendix II)

Reporting Timelines specified: Unexpected SAEs within14 days to DCGI and other investigators

Stability testing

Training/Qualifications

Investigators to document SOPs for all tasks performed by them

Responsible for conduct of trial according to protocol and GCP

Compliance as per undertaking

Medical care for AEs

SAE reporting to EC (7days) and Sponsor (24hrs)

Informed consent

Investigators

Training/Qualifications

Investigators to document SOPs for all tasks performed by them

Responsible for conduct of trial according to protocol and GCP

Compliance as per undertaking

Medical care for AEs

SAE reporting to EC (7days) and Sponsor (24hrs)

Informed consent

6 monthly for 2 years; annually for 2 years

Within 30 calendar days

Different dosage forms/formulations/ indications in one report

New studies planned for safety to be described

PSURs

6 monthly for 2 years; annually for 2 years

Within 30 calendar days

Different dosage forms/formulations/ indications in one report

New studies planned for safety to be described

Pharmacovigilance in India

1998:

•India established national centre at AIIMS

•Joined Uppsala programme

•WHO Special Centre at KEM Hospital

2004:

•National PharmacovigilanceProgramme launched on 23rd November 2004

1998:

•India established national centre at AIIMS

•Joined Uppsala programme

•WHO Special Centre at KEM Hospital

2004:

•National PharmacovigilanceProgramme launched on 23rd November 2004

National Pharmacovigilance Advisory Committee

Advisory Committee to Government

16 members

Supervise activities of National PvigProgram

Advisory Committee to Government

16 members

Supervise activities of National PvigProgram

Protocol Amendments

Amendments which do not require notification or permission of the Licensing Authority

Administrative and logistic changes,Minor protocol amendment and additional safety assessments

Amendments which require notification to Licensing Authority, but sponsor need not wait for permission.

Additional investigator sites,Change in investigator, with the consent to withdraw from the earlier investigator.,Amended IB or ICF

• Amendments which require prior permission of the Licensing Authority

Additional Patients to be recruitedMajor changes in protocol with respect to study design, dose and treatment .Any change in inclusion/exclusion criteria

Amendments which do not require notification or permission of the Licensing Authority

Administrative and logistic changes,Minor protocol amendment and additional safety assessments

Amendments which require notification to Licensing Authority, but sponsor need not wait for permission.

Additional investigator sites,Change in investigator, with the consent to withdraw from the earlier investigator.,Amended IB or ICF

• Amendments which require prior permission of the Licensing Authority

Additional Patients to be recruitedMajor changes in protocol with respect to study design, dose and treatment .Any change in inclusion/exclusion criteria

Global Clinical Trials are classified into 2 categories:

Category A:

It includes clinical trials whose

protocols have been approved by

USA, UK, Switzerland,

Australia, Canada,Germany,

South Africa, Japan or the EMEA.

The regulatory (DCGI) will reach to a

decision whether to approve the

trial within 2-4 weeks.

It includes clinical trials whose protocols

have been approved in other countries

which are not listed in category A.

The regulatory (DCGI) turnaround time

for these applications

will be 8-12 weeks.

Category B:Category A:

It includes clinical trials whose

protocols have been approved by

USA, UK, Switzerland,

Australia, Canada,Germany,

South Africa, Japan or the EMEA.

The regulatory (DCGI) will reach to a

decision whether to approve the

trial within 2-4 weeks.

It includes clinical trials whose protocols

have been approved in other countries

which are not listed in category A.

The regulatory (DCGI) turnaround time

for these applications

will be 8-12 weeks.

Advances in Schedule Y

Removal of Phase Lag Statutory support of GCP & GLP Conversion of EC,

Sponsor, Investigator responsibilities to legal requirements

Uniform processes for submission and approval of EC documents and Informed Consent

Reinforcement of pharmacovigilance through Phase IV studies, SAE reporting, PSUR etc

Removal of Phase Lag Statutory support of GCP & GLP Conversion of EC,

Sponsor, Investigator responsibilities to legal requirements

Uniform processes for submission and approval of EC documents and Informed Consent

Reinforcement of pharmacovigilance through Phase IV studies, SAE reporting, PSUR etc

Implementation of Schedule Y

GCP: Shared responsibility amongstdifferent stakeholders in clinical trials

Need for imparting training to all theplayers

Future directions

Implementation of Schedule Y

GCP: Shared responsibility amongstdifferent stakeholders in clinical trials

Need for imparting training to all theplayers

Drugs and Cosmetics Act 1945

Rule Permission for

122 A

122 B

Import

Manufacture [except drugsunder schedule C and C(1)]

122 B

122 D

122 DA

122 DAA

122 E

Manufacture [except drugsunder schedule C and C(1)]

Fixed dose combination

Clinical trial

CT definition

New drug definition

122 E: New drug definition

Not used in the country

Approved drug : 1. New claims (Indications, dosage, dosage form, route)

2. FDCs (New / Modified

All Vaccines are considered New drugs unless certified by Licensing Authority under Rule 21

A New drug is considered new for the period of 4 years from the date f its first approval or the date it is included in the Indian Pharmacopoeia, whichever is earlier

Not used in the country

Approved drug : 1. New claims (Indications, dosage, dosage form, route)

2. FDCs (New / Modified

All Vaccines are considered New drugs unless certified by Licensing Authority under Rule 21

A New drug is considered new for the period of 4 years from the date f its first approval or the date it is included in the Indian Pharmacopoeia, whichever is earlier

Intent to conduct Phase I*,II or III Pharmaceutical product or Medical

Device Clinical Trial in India

Determine ifSubmission to be made

under Category A or B

Parallel submission to Ethics Committee

Category A Category BIn Case Central lab outsideIndia used

Note: fill aayat niryath form according to category A or B

In case of category A

Category AClinical trial already approved by other regulatory agencies (US-FDA,MRHA etc. as defined in the MoM-DCG(I) Oct-06) and approval letters

are available

Application compiledper checklist on

CDSCO website APPROVED

NOC received from DCG(I)

if trial approved (Internal process)

Application made to DCGIfor approval in form 44& import license in form 12; fees paid

Application evaluated for Completeness if found appropriateapproval normally granted in4-6 weeks

REJECTED

NOC received from DCG(I)

if trial approved (Internal process)

DGFT (Delhi) Approval receivedwithin 4-6 weeks

Apply to Jt.DGFTof the respective city/state

with cover letter &NOC from DGFT Delhi

Export license

received Within

2 weeks

Resubmit Application

In case of category B

Determine ifSubmission to be made

under Category A or B

Category B

If study approvals as required for Category A

are not available

NOC received from DCG(I)if trial approved

(Internal process)

DGFT (Delhi) approval received within

4-6 weeks

If study approvals as required for Category A

are not available

Application compiledper attached appendix

Application made to DCGI for approval in form 44 & Import license in form 12;

fees paid as required.

Application evaluatedIf found appropriate approval normally

granted in 8-12 weeks

DGFT (Delhi) approval received within

4-6 weeks

Apply to Jt.DGFTof the respective city/state

with cover letter &NOC from DGFT Delhi

Export license received within 2 weeks

Medical Device guidelines amended in Mar. 1, 2006

bringing discipline to medical devices sector

The newly included “drugs” are Cardiac stents, drug eluting stents, catheters, intraocular lenses, IV Cannulae, Bone cements, heart valves, scalp vein set, orthopedic implants and internal prosthetic replacements.

Medical Device guidelines

Medical Device guidelines amended in Mar. 1, 2006

bringing discipline to medical devices sector

The newly included “drugs” are Cardiac stents, drug eluting stents, catheters, intraocular lenses, IV Cannulae, Bone cements, heart valves, scalp vein set, orthopedic implants and internal prosthetic replacements.

New guidelines have been introduced on Recombitant Pharma.

There Approval bodies is DCGI but there are asisstingbodies like GEAC, RCGM, IBSC.

Recombitant Pharma guidelines

New guidelines have been introduced on Recombitant Pharma.

There Approval bodies is DCGI but there are asisstingbodies like GEAC, RCGM, IBSC.