WHO Public Inspection Report of a Contract Research ...

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WHO Public Inspection Report of a Contract Research Organization

The report is the property of the organization responsible for performing the inspection.

Part 1: General information

Name of organization Lotus Labs Pvt. Ltd

Physical address where the Lotus House
inspection was performed No. 07, Jasma Bhavan Road
Millers Tank Bed Area
Opp. Gurunanak Bhavan, Vasanthanagar,
Bangalore-560052, India

Name of the clinical facility Lotus Labs Pvt. Ltd
(not physically inspected) Centre for Clinical and Pharmaceutical Research
# 56 (old 116) Ragas Building, Dr. Radhakrishnan Salai,
Postal address Mylapore, Chennai 600 004, India
Lotus House
No. 07, Jasma Bhavan Road
Millers Tank Bed Area
Opp. Gurunanak Bhavan, Vasanthanagar,
Bangalore-560052, India

Telephone number + 91 80 22370912/13/14/15

Fax number +91 80 22370911
Summary of activities
Performance of preclinical and clinical studies, including
bioequivalence trials (clinical and bio-analytical parts)

WHO reference number HA 403 Efavirenz 600 mg Tablets
Study Study: 1022/06
Study Title: A randomized, open label, two treatment, two
Start and stop dates for each period, two sequence, single dose, crossover, bioequivalence
phase of the clinical study study of Efavirenz 600 mg tablets of Matrix Laboratories
Investigational Products Limited, India and Sustiva® (Efavirenz) 600 mg tablets of
Bristol-Myers Squibb Co., NJ, USA, in healthy human adult
subjects, under fasting conditions.
Period I : 14/11/06 to 17/11/06
Period II : 12/12/06 to15/12/06

Efavirenz Tablets 600 mg
Manufactured by Matrix Laboratories Limited, India
Batch No.: EFZA 536001
Batch Size: 1,50,000 tablets
Manufacturing Date: November, 2006

WHOPIR Page 1 of 5
Lotus Lab, Bangalore , India
June 2008

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Reference Products Sustiva® (Efavirenz) Tablets 600 mg
Distributed by: Bristol-Myers Squibb Company, Princeton, NJ
WHO reference number 08543, USA
Study Batch N°: EUA120A
Date of expiry: October 2008
Start and stop dates for each
phase of the clinical study HA 411
905/06
A randomized, open label, two treatment, two period, two
sequence, single dose, crossover, bioequivalence study of
Lopinavir 200 mg + Ritonavir 50 mg tablets of Matrix
Laboratories Limited, Hyderabad, India and Kaletra®
(Lopinavir 200 mg + Ritonavir 50 mg) tablets of Abbott
Laboratories, USA, in healthy human adult subjects, under
fasting conditions.

Period I : 04 January 2007 to 06 January 2007
Period II :11 January 2007 to 13 January 2007

Investigational Products Lopinavir/Ritonavir 200/50 mg tablets
Manufactured by Matrix Laboratories Limited, India
Reference Products
Batch number: LORA536001
Sponsor Batch Size: 1,03,000 Tablets
Date of inspection Date of manufacture : December, 2006
Project Kaletra® (Lopinavir / Ritonavir) Tablets 200 mg/ 50 mg.
Manufactured By: Abbott Laboratories, North Chicago, IL
60064 USA.
Lot number: 311069Y40
Expiry date: 01 August, 2007
Matrix Laboratories Limited, India
20 and 21 June 2008

Prequalification Programme : Priority Essential Medicines

WHOPIR Page 2 of 5
Lotus Lab, Bangalore , India
June 2008

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Part 2: Summary

Lotus Labs Pvt Ltd started in 2001 as a CRO. It was acquired in 2005 by Actavis an Icelandic generic
manufacturing company. The CRO has 4 different settings, three in Bangalore and one in Chennai.
The 3 following sites are located in Bangalore :

- Vasanthanagar : including a 74 beds clinical facility and the central bio-analytical laboratory
with 11 LCMS/ MS and 4 HPLC.
- St John's : including a 72 beds clinical facility and a 10 beds phase1 facility.
- Jakkur : is a new site with a 120 bed clinical facility and the central bio-statistical
department.

One clinical facility with 80 beds is located in Mylapore, Chennai. The clinical parts of the studies of
product HA 403 and HA 411 where performed there.

This Prequalification Programme inspection was the 8th inspection conducted by WHO at a Lotus
Labs facility in relation with the prequalification program (WHOPIR published).
Lotus is regularly inspected by the Indian competent regulatory authority and was inspected several
times by the French (AFSSAPS) , the Brazilian (ANVISA), the South Africa (MCC) National Drug
Regulatory Authorities as well as by the FDA.
The Chennai facility was last inspected by USFDA in March 2008.

The purpose of the inspection was to evaluate whether the bioequivalence studies performed for
the following products were conducted in compliance with the protocols, WHO Good Clinical
Practices (GCP) and Good Laboratory Practices (GLP) where applicable :

HA 403 Efavirenz 600 mg Tablets manufactured by Matrix Laboratories Limited, India

The study was conducted at the following settings:

Clinical Facility (last physically inspected in 2005)
Lotus Labs Pvt. Ltd.,
#56, Ragas building,
Dr. Radhakrishnan Salai,
Opp. CSI Kalyani Hospital,
Mylapore, Chennai–600 004
India

Analytical Laboratories (site were the present inspection was performed)
Lotus Labs Pvt. Ltd.,
7/1, Millers Tank Bed Area,
Opp. Gurunanak Bhavan, Vasanthnagar,
Bangalore-560 052
India

The study was already accepted at the time of the inspection.

WHOPIR Page 3 of 5
Lotus Lab, Bangalore , India
June 2008

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HA 411 Lopinavir/Ritonavir 200/50 mg tablets, manufactured by Matrix Laboratories Limited,

India

The clinical part of the study was conducted at the following settings:

Clinical Facility (last physically inspected in 2005)
Lotus Labs Pvt. Ltd.,
#56, Ragas building,
Dr. Radhakrishnan Salai,
Opp. CSI Kalyani Hospital,
Mylapore, Chennai–600 004
India

The analytical part was conducted at a different CRO

The study was already accepted at the time of the inspection.

The facilities for the bio analytical parts, procedures and documentation for the studies were
reviewed. Various staff members were interviewed in relation to the conduct of the study.
Documentation reviewed for all studies included:

Clinical part

• Independent ethics committee review procedures
• Screening, and study consent forms
• Source data and results
• Master lists for subjects
• Documentation and SOPs relating to study drugs accountability and dispensing records, and study

drug labels
• Randomization schedule
• Study drug administration
• Blood sample collection
• Lists of staff present during the study
• Master list of signatures of volunteers
• Monitoring reports
• QA audit reports

Bioanalytical part

Various documents were reviewed. This included method validation for : stock solution preparation,
weighing, working standards and COA, source data, chromatograms (short term, long term, freeze
thaw), validation and qualification. The concentrations indicated on chromatograms were checked
against the reported tabulated data and dossier report.

Documentation reviewed included for several subjects: Page 4 of 5
• Repeat analysis record
• Chromatograms for subjects for different periods

WHOPIR
Lotus Lab, Bangalore , India
June 2008

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• Results of calibration curves, and quality controls were reviewed for all runs of the study

Part 3: Conclusion

HA 403

Based on the people met and the documents reviewed, and considering the findings of the inspection,
reflected in the observations listed in the inspection report, the clinical parts and bio-analytical
parts of the study of product HA 403 inspected can be considered to have been conducted at an
acceptable level of compliance with WHO Good Clinical Practices (GCP) and Good Laboratory
Practices (GLP), by Lotus Labs Pvt. Ltd located in Chennai and Bangalore , India.

HA 411

Based on the people met and the documents reviewed, and considering the findings of the inspection,
reflected in the observations listed in the inspection report, the clinical part of the studies of product
HA 411 inspected, can be considered to have been conducted at an acceptable level of compliance
with WHO Good Clinical Practices (GCP) and Good Laboratory Practices (GLP), by Lotus Labs Pvt.
Ltd located in Chennai, India.

WHOPIR Page 5 of 5
Lotus Lab, Bangalore , India
June 2008