Beruflich Dokumente
Kultur Dokumente
Postal address
Same as above
Telephone number
00 91 22 28306435, 28314611
Fax number
Summary of activities
00 91 22 28304641
Performance of clinical studies, including bioequivalence trials
(clinical and bio-analytical parts)
TB 134
Study : BEQ-002-ETHA-2005
Study Title: An open label, randomized, two-treatment, twosequence, two period, two-way crossover, single dose
bioequivalence study of Ethambutol tablets (containing
Ethambutol 400 mg) manufactured by Macleods
Pharmaceuticals Ltd., India comparing with Myambutol tablets
(containing Ethambutol 400 mg) manufactured by Reimser
Arzneimittel AG (Wyeth Lederle Germany), in healthy, adult,
male, human subjects under fasting conditions.
Reference Products
Principal Investigator
Sponsor
Investigational Products
WHOPIR
Macleods, Mumbai, India
25-26 May 2006
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TB 168
Study : BEQ-005-RIPE(F)-2005
Study Title: An open label, randomised, two treatment, two
sequence, two period, two way, crossover bioequivalence
study of four fixed combination tablets, each containing
rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400mg,
ethambutol 275 mg manufactured by Macleods Pharmaceutical
Ltd, India comparing with separate formulation of 4 capsules
of Rimactane (150 mg rifampicin) of Novartis South Africa
(Pty) Ltd, 3 tablets of Isozid 100 mg (isoniazid 100 mg) of
Fatol Arzneimittel GmbH, Schiffweiler, Germany, 3 tablets of
Rolab-Pyrazinamide 500 (pyrazinamide 500 mg) of Rolab Pvt
Ltd. (Novartis South Africa), 2 tablets of Myambutol 400 mg
(ethambutol dihydrochloride 400 mg) of Riemser Arzneimittel
AG (Germany) and 3 tablets of Myambutol 100 mg
(ethambutol hydrochloride 100 mg) of Patheon Inc Toronto,
Ontario in healthy adult male human subjects under fasting
conditions.
Investigational Products
Reference Products
Principal Investigator
Sponsor
Date of inspection:
Prequalification Programme.
WHOPIR
Macleods, Mumbai, India
25-26 May 2006
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Part 2: Summary
The purpose of the inspection was to assess the bioequivalence study performed at
Macleod Pharmaceuticals Research & Development Centre for the following products:
- TB 134 : Ethambutol Hydrochloride 400 mg, tablet
- TB 168 : Rifampicin Isoniazid Pyrazinamide Ethambutol Hydrochloride
150/75/400/275 mg, tablet
and to evaluate whether the study was conducted in compliance with the protocols, Good
Clinical Practices (GCP) and Good Laboratory Practices (GLP) where applicable.
Macleod Pharmaceuticals, under its R&D centre started clinical and bioanalytical
operations for bioequivalence (BE) studies at this premise on April 2005. There are
currently over 40 staff employed at Macleod BE centre with the following breakdown by
department: 16 in Clinical, 18 in Bioanalytical, 6 in the Quality Assurance, and 2 in
Statistics team.
This Prequalification Programme inspection was the second audit conducted by WHO at
Macleod BE centre.
Documentation reviewed included:
Clinical part
Randomization schedule
QA audit reports
Bioanalytical part
Various documents were reviewed. This included method validation for rifampicin :
stock solution preparation, weighing, working standards and COA, source data,
calculations, chromatograms (short term, long term, freeze thaw), validation and
qualification. Manual calculations were done for the concentrations (chromatograms) and
checked against the reported tabulated data and dossier report.
Documentation reviewed included for several subjects:
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Results of calibration curves, and quality controls were reviewed for all runs of the
two studies
The protocol
In general acceptable.
2.3. Protection of trial subjects
(Including: Declaration of Helsinki, Ethics committee, Informed consent,
Confidentiality)
The chairman of the ethic committee member approved alone the second version of the
protocol. He was not entitled to do that.
2.4. Responsibilities of the investigator
(Including: Medical care of trial subjects, Qualifications, Selection of trial subjects,
Compliance with the protocol, Information for subjects and informed consent, The
investigational product, The trial site, Notification of the trial or submission to the drug
regulatory authority, Review by an ethics committee, Serious adverse events or
reactions, Financing, monitoring, auditing and inspection, Record-keeping and handling
of data, Handling of and accountability for pharmaceutical products for trial,
Termination of trial, Final report, Trials in which the investigator is the sponsor)
In general, besides minor observations, acceptable.
2.5. Responsibilities of the sponsor
(Including: Selection of the Investigator(s), Delegation of responsibilities, Compliance
with the protocol and procedures, Product information, Safety information,
Investigational product, Trial management and handling of data, Standard operating
procedures, Compensation for subjects and investigators, Monitoring, Quality assurance,
Study reports, Handling of adverse events, Termination of trial)
In general acceptable. Nevertheless, the monitoring of the study was inadequate.
2.6. Responsibilities of the monitor
(Including: Qualifications, Assessment of the trial site, Staff education and compliance,
Data management, Case-report forms, Investigational product, Communication,
Notification of the trial or submission to the regulatory authority, Reports)
WHOPIR
Macleods, Mumbai, India
25-26 May2006
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In general, acceptable (nevertheless, some quality controls identified as outlier were not
included in the overall calculation of precision and accuracy. This is considered as a
major deficiency as it can affect the acceptability of the study. Fortunately reintegration
was done during the inspection and the new result found still within the 15% of CV.
WHOPIR
Macleods, Mumbai, India
25-26 May2006
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Part 3: Conclusion
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 studies,
clinical parts and bioanalytical parts, inspected are considered to have been conducted at
an acceptable level of compliance with WHO Good Clinical Practices (GCP) and Good
Laboratory Practices (GLP), by Bioequivalence dept, Macleods Pharmaceuticals located
in Mumbai, India.
WHOPIR
Macleods, Mumbai, India
25-26 May2006
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