Good clinical practices tutorial- v7.015--shehnaz_june-10_v 3.0

GCP Issues Related to Conducting Clinical Trials in India

Shehnaz Vakharia, MScPrincipal ConsultantTheraverity

46th Annual MeetingWashington, DC - 2010

Disclaimer

• The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated.

• These PowerPoint slides are the intellectual property of the

individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners.

2


Agenda

3

• Regulatory Framework in India• Applicable Local Regulations• India Advantage• Challenges & Issues• Positive Developments


Regulatory Framework in INDIA

4

Drugs Controller General of India (DCGI)

Ministry of Health

Central Drug Standards Control Organization

Permission to Conduct Clinical Trials In India


Applicable Local Regulations

• Schedule Y, amended, 2005• GCP for Clinical Research in India, issued by

CDSCO in 2005

http://cdsco.nic.in/


India Advantage• Regulatory Approvals

within reasonable timeframe

http://cdsco.nic.in/


India Advantage• High incidence of lifestyle & other diseases common in

the west – Search of Clinical Trials Registry-India (as of 2-Jun-10) indicated

majority of clinical trials in India are conducted in the following indications

• Diabetes (89 Trials registered)• Cancer (85 Trials registered)• Asthma (27 Trials registered)• COPD (17 Trials registered)

• Shortened Lead Times– Faster Recruitment

• Large Treatment-Naïve population• Primary mode of communication and business is English

– All Medical Records and Regulatory Submissions are in English


India Advantage

• Technical Capability – Over 600000 doctors– 17000 medical graduates per year– Over 40000 private hospitals– 162 Medical Colleges– Well established IT Industry

• Over 1800 FDA 1572 filed from India• India participates in 7 % of global Phase III studies and 3.2 % of

Phase II Studies (Studies started in 2008)

http://www.ey.com/Publication/vwLUAssets/Clinical_research_in_India_-_26_August/$FILE/Clinical%20research%20in%20India_FINAL%2826%20Aug%29.pdf http://www.ficci.com/PressRelease/508/GLOBAL-PHARMA.pdf

Ref Ernest and Young / FICCI Report, (26 Aug 2009)


Challenges & Issues

Challenge• Shortage of GCP Trained Investigators• Documentation Practices

– Brief records – Scanty or no past medical records– Back Dating– Making non-substantiated changes


• Date of report changed from 23-Jul-09 to 06-Jul-09. The changes had been signed and dated by the PI and the Radiologist as 06-Jul-09

• The source document and the CRF showed the test was performed on 06-Jul-09

• The film of the scan however, showed that the scan had been performed on 08-Jul-09

The subject had been source verified!!!!!!

Significant Issues


• Pre-printed measurement was cancelled and a new measurement handwritten.

• Both the cancellation and hand-written addition were signed and dated by the PI and the Radiologist on 15-Apr-09 (the day of the CT Scan Report).

• The subject had been monitored and the original CRF Page had been retrieved.

• The copy of the CRF page at site showed the measurement of lesion as 2.3 !!!!!!

Significant Issues


Challenge:

Past Medical Records and Eligibility

Challenges & Issues


Challenges & Issues

Challenge:• Busy Schedule of trained investigators

• High Patient Load • Affiliations with various institutions• Private Clinics: Evenings and Week-ends

Issues:• Lack of Principal Investigator Oversight• Protocol Non-Compliances• Non-compliance to local regulations


• Ethics Committees• Registration of Ethics Committees not mandatory• Ethics Committees are not audited by Sponsors /

Sponsors representatives

Challenges & Issues


• Culture• Desire to please “Never say No”• Conflict Avoidance – Better to avoid than confront• Respect for Hierarchy

Other Challenges


Other Challenges

• Variable Infrastructure• Equipment Availability• Equipment Calibration and Maintenance • Record Retention Facilities


Example-Infrastructure

Cancer Protocol: Requirement – Preparation of Investigational Product (IP) in a Laminar Flow and infusion within a few hours

• Situation:• Laminar Flow Hood situated in corridor leading to the patient

ward, next to an overflowing bin• Laminar Flow not in working condition, but IP was prepared in

the hood, per protocol• Not reported as an issue by the CRA

• Justification• According to the PI, the IP was prepared in this hood and infused

to the subjects within a span of 5 minutes. So where was the question of contamination?


Positive Developments

• 14 Inspections in India by US FDA – 2005 (2)– 2006 (1)– 2007 (5)– 2009 (6, 3 in Dec 2009)

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/ucm073059.htm


http://www.accessdata.fda.gov/scripts/cder/CLIIL/index.cfm?fuseaction=Search.ShowAdvancedSearchResults&SortField=InspectionType&SortRequest=1&NewSearch=0


• 08 of 14 Investigator Sites had ‘NAI’• None of them resulted in Official Action Indicated• Deficiencies revolved around codes 04, 05 & 06

– Deficiency code 04:Inadequate drug accountability – Deficiency code 05:Failure to follow investigational plan – Deficiency code 06:Inadequate and inaccurate records

US FDA Inspection Results


CDSCO-US FDA Collaboration


Advantage

Issues


QUESTIONS?

Shehnaz Kairas Vakharia, MS

Principal Consultant, Theraverity

India

[email protected]

+(91) 9821543016

Health & Medicine

Good clinical practices tutorial- v7.015--shehnaz_june-10_v 3.0