GCP Audits in Southeast Asia and Turkey

Current Updates from recent GCP Audits in Southeast Asia and Turkey

Shehnaz VakhariaPrincipal ConsultantTheraverity

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, Drug Information Association Inc., DIA and DIA logo are registered trademarks. All other trademarks are the property of their respective owners.

2

2010 Statistics

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

Asia – 10%

East Asia

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

South Asia

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

Southeast Asia

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

Middle East

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

Clinical Trials - 2010

# of Studies

0

10

20

30

40

50

60

70

80

Countries

India

Korea

Isreal

China

Taiwan

Singapore

Turkey

Thailand

Phillipines

79 77

51

46

2216

1310

Reference: ClinicalTrials.gov; Phase I, II, III Interventional StudiesPeriod: 1-Jan-2010 to 1-May-2011

US FDA Inspection History

22

6

9

13

4

1

6 7 7

0

5

10

15

20

25

Countries

India

Korea

Isreal

China

Taiwan

Singapore

Turkey

Thailand

Phillipines

5 yrs

2 yrs

18 yrs

10yrs

8 yrs

2 yrs

09yrs

12yrs

# of Inspections

Deficiencies

0%

20%

40%

60%

80%

100%

Deficiency Code 18

Deficiency Code 16

Deficiency Code 15

Deficiency Code 14

Deficiency Code 6

Deficiency Code 5

Deficiency Code 4

Deficiency Code 3

03 = Inadequate Informed Consent Form

04 = Inadequate Drug Accountability

05 = Failure to follow investigational plan

06 = Inadequate and Inaccurate records

14 = Failure to obtain or document IRB Approval

15 = Failure to notify IRB of changes, failure to submit progress reports

16 = Failure to report adverse drug reactions

18 = Other

Deficiencies

Audits 2010Recent Audits (2010)

India85%

China6%

S Korea6%

Turkey3%

India

China

S Korea

Turkey

India

patients / day / OPD

South Korea

patients / day/ OPD

China

patients / day / OPD

Turkey

patients / day / OPD

50-100 70-140 80-150 200-400

Comparison

High patient load

India

South Korea

China

Turkey

Principal Investigator Medically Qualified

Medically Qualified

Medically Qualified

Medically Qualified

Sub-Investigators Medically Qualified

Medically Qualified

Medically Qualified

Medically Qualified

Study Co-ordinators Science Degree

Medically Qualified

Medically Qualified

Nursing / Science Degree

Qualified Site Personnel

Comparison

India South Korea China Turkey

Paper Yes Yes

However Prescription Records - Electronic, linked to Hospital Pharmacy

Yes Yes

Comparison

Paper Source records

India South Korea China Turkey

English Local

Prescription Records - English

Local Local

Comparison

Source Records Language

India South Korea China Turkey

90% * 100%Prescriptions - Hospital Electronic System

100% 100%

Comparison

OPD records retained by the patients rather than physicians

Issues Availability of past medical records to verify the inclusion / exclusion criteria is a challenge

Comparison

OPD Registration System

OPD Files / Document Storage with the Hospital MRD Improvements

Issue

Lack of Awareness

India South Korea

China Turkey

Hospital Medical Records Division (MRD)

Yes Yes Yes Yes *

Comparison Hospitalization records retained by Hospital Medical Records Division (MRD)

Hospital MRD records for over 70% subjects were not available for review during the audit in Turkey and had never been monitored with the data recorded in the eCRF

Issue

India South Korea China Turkey

Yes * Yes Yes Yes

Comparison

Use of Protocol Specific Source Templates

Issue In about 20% of the audits in India and 100% audits in China and Turkey the monitoring had been performed only with the Protocol Specific Source Templates !!!

India South Korea China Turkey

50% 90% No No

Comparison

Identification of clinical trial participation on source files

Improvement

Issue Subject Safety Jeopardized

India South Korea

China Turkey

ICH GCP Awareness Yes Yes Yes Yes

Understanding of ICH GCP

Yes Yes Yes Questionable

Comparison

Good Clinical Practice (GCP)

Example

Impartial witness not present during informed consent discussion, but had signed the ICF later.

Reason: Hospital Employee, not involved in the study. Had a busy schedule, so it was not possible for the witness to be present through the informed consent process

Signed informed consent document was destroyed by the site Reason: Subject had withdrawn consent

Subject Diary Cards had not been dispensed to the subjects enrolled in the study, per protocol requirement.

Reason: According to the sub-investigator, the subject’s relatives were not comfortable in completion of the diaries.

Treating investigators were present in the room where un-blinded

pharmacists prepared study medicationReason: To help pharmacists

Examples Turkey

India South Korea

China Turkey

Training on ICH GCP Yes Yes Yes Yes

Training on Local Regulations

NO NO NO NO

Comparison Training

Comparison

Protocol Deviations

India South Korea China Turkey

Yes Yes Yes Yes

Major Protocol Deviations

India South Korea China Turkey

20 % No No Yes

India South Korea

China Turkey

Secure with limited access

Yes Yes Yes Were not allowed

Fire Protection 50 %

Fire Extinguishers

Water Sprinklers

Central System (Powder)

Central System (Powder)

Temperature and Humidity Monitoring

NO * NA NA NA

Comparison Document Storage Facilities

Difference however is in Medical Records Room storage facilities vs that maintained by the investigator sites (Clinical Research Facility)

Medical Records Room, Hospital Facility Clinical Research Document Storage

Temperature and Humidity Monitoring ??

India South Korea

China Turkey

Secure with limited access

Yes Yes Yes Yes

Fire Protection 50 %

Fire Extinguishers

Water Sprinklers

Yes Yes

Comparison Study IP Storage Facilities

Improvements observed in newer investigator site facilities in India for IP Storage

Examples

10% of investigator sites audited in India had installed Biometric Access for the IP storage facility

100% investigator sites had air-conditioning units installed in the IP storage facility 20% investigator sites had B.O.D (Biochemical Oxygen Demand) Incubators with

temperature control and secure access for storage of IP between 15 to 30 °C 50% investigator sites had UPS back-up for the IP storage facility 50 % investigator sites had generator back-ups lasting 8 hours

Most Common Issues

Documentation

Changes

File Notes

Inadvertently!!!!!!

InsertionsCancellations

Back-dating

Whether Source Notes, EC Approvals, IP Dispensing

Missing

Recent Updates- CDSCO, INDIA

Recent News- INDIA

Recent News- INDIA

Questions?

Shehnaz Kairas Vakharia, MSPrincipal Consultant, Theraverity

Indiashehnaz@theraverity.com

+(91) 9821543016

THANK YOU