Medica Innova Siriporn Nonenoy, B.N.S. Kingkamol Kaenkratoke, M.Sc. Pharm Promporn Jumnongtanachot, M.Sc. Pharm Ariya Khunvichai, Ph.D. May 21 st, 2008

Medica Innova is the First Thai Own “Contract Research Organization (CRO)” providing services to Thai and International pharmaceutical industries in 1.Pharmaceutical Product Development 2.Pharmaceutical Product Testing. 3.Clinical Trials/Clinical Research especially in Bioavailability/Bioequivalence studies. Medica Innova

Overview: Clinical Research Development  Strong management team with Full Service of Clinical Trials  A highly understanding of the requirements of the design, conduct, analysis and protocol/report writing for regulatory submissions  Licensed and well equipped laboratories in accordance with GLP practices  Studies are performed according to the GCP guidelines  Valuable Databases: clincal trial sites, investigators, and participants  Fast enrollment of subjects  Services with confidentiality and credibility  Accountability and accurate results  Favorable price/quality ratio and timeline

3. Bioanalytical Manager Ms. Kingkamol Kaenkratoke, B.Sc. Pharm., M. Sc. Pharm, Experiences – M. Sc. Pharm. :Pharmaceutical Chemistry, Chulalongkorn University QC manager : Chew Brother Co., Ltd. QC manager : Nakorn Pattana Pharm Co., Ltd. 1. Clinical Pharmacology Manager Dr. Ariya Khunvichai, B. Sc. Pharm, Ph.D. Experiences – Ph. D. :Pharmaceutics (Pharmacokinetics/Pharmacodynamics), University of Florida Pharmacokineticist in drug discovery & preclinical: Hoffmann-La Roche Inc, Nutley, NJ Senior Clinical Pharmacokineticist : Vertex Pharmaceuticals Inc, Cambridge, MA 2. Senior Clinical Research Associate Ms. Siriporn Nonenoy, B. S.N. Experiences – B. S.N. :Thai Red Cross College of nursing, Chulalongkorn university, Bangkok, Thailand Clinical Trial Monitor of HIV-NAT, Bangkok Clinical Research Associate, Novartis (Thailand) Limited. Key Management Personnel

4. Quality Assurance Manager Ms. Promporn Jamnongtanachot, B.Sc. Pharm., M. Sc. Pharm Experiences - M. Sc. Pharm. :Pharmaceutical Chemistry, Chulalongkorn University Analyst in Division of Drug Stability : Department of Medical Sciences, Ministry of Public Health Plant Manager QA & QC Manager : V. S. Pharma (1971) Co., Ltd. Key Management Personnel

Full Time Staffs in Clinical Research There are 19 staffs in Clinical Research Development:  3 CRAs  6 Bioanalysts  2 Medical writers, 1 Pharmacometrician (PK/Statistician)  3 QAs  2 ITs  2 Officers

- Area : 1,200 sq m. facility (will be sq. m. in mid 2008, 3 floors) - More than “80 million Baht” investment in analytical and bioanalytical laboratory facilities and equipments - Laboratory -“State of the Art” equipments and facilities “OECD-GLP” - Clinical Study -“ICH-GCP” **** Bioequivalence Center must get GLP Certified and GCP monitoring by the beginning of 2009 Our Facilities and Standards

 Controlled and secured logistic storage room  Investigation products storage room (for clinical study)  Controlled specimens storage room (such as plasma or urine)  Weighing room  Biological sample preparation room  Instrumentation room State of the Art Facilities: Analytical Site

Instruments: Analytical and Bioanalytical Laboratories  18 HPLC Systems (UV, Fluorescence, ECD, ELSD)  LC/MS/MS (Applied Biosystems)  UPLC/MS/MS (Micromass, Waters)  -80°C/-20°C Freezer (with online monitoring )  Stability chamber (with online monitoring )

Instruments: Analytical and Bioanalytical Laboratories  6 Dissolution apparatus with autosampler (Distek and Vankel)  15 stations Franz cell apparatus  MilliQ DI water treatment (Waters)  Power generator Software:  WinNonlin (Version 5.2)

Bioequivalence 4 Clinical Sites (ICH-GCP) Subject service room for 24 persons Overnight stay rooms for 24 persons Sampling collection room Controlled sample storage room Physical examination and consultation rooms Qualified clinical staffs Medica Innova Clinical Operating Department (CRA) Clinical Pharmacology Department Bioanalytical Department Sponsor Good Clinical Practice (GCP) Protocol Healthy Volunteers/ Enrollment Good Laboratory Practice (GLP) Biological Samples Bioanalytic al Analysis Report

1.Conduct Clinical Trials From Phase I-III Bioavailability and Bioequivalence Studies Dose Escalation, First-in-Human and Food Effect Studies Drug-Drug Interaction Studies Special Population Studies Efficacy/Proof of Concept Studies Development & Validation of New Assays Analysis of Drug in Biological Fluid using HPLC (UV, Fluorescence), UPLC/MS, LC- MS/MS Investigative Site Audit Study Documentation Audit Preparation for Regulatory Inspection 2.Bioanalysis 3.Quality Assurance Services: Clinical Reserch

Bioequivalence Studies: we provide Protocol Development Study design, sample size, and power calculation Case report form Informed consent form Study Management Regulatory Document Collection Preparing Clinical Supplies Site management IRB and regulatory Submissions Regulatory Document Processing Clinical Monitoring Pre-study & initiation visits Monitoring visits Close out visits Bioanalysis Development & Validation of Assays Analysis of Drug in Biological Fluid Clinical Pharmacology and Safety Data Analysis Statistical analysis Pharmacokinetic (PK) analysis Data management Clinical Study Report Development PK and evaluations Efficacy evalutaions Safety evaluations

Bioequivalence study: Timeline writing, review, sign-off preparation for FDA submission 6 weeks (Develop a final protocol, CRF, and ICF) Set up committee Approval and comment 8-12 weeks (EC submission) Subject screening, enrollment, and follow up Dose administration and Monitoring visits Sample collection, preparation, and analysis 5-8weeks (Study conducted) Data entry and QC check Validate database 2 weeks (Data management ) PK and statistical analysis with locked data QC & QA check 2 weeks (Data analysis) Writing, review, and sign-off QC & QA check 2 weeks (Development of Clinical study report ) Case 1: No protocol (s) Time line = 25– 32 Weeks (7-8 months) months (FDA submission) Case 2:Standard protocol Time line = 19 – 26 Weeks (5-7 months)

Our current activities Projects o8 bioequivalence studies (PK) in human o3 efficacy /clinical studies (PD, DMPK) o1 bioequivalence study for veterinary product

“To be Trusted and Recognized by Our Clients as an Innovator in the Development of Novel Drugs and to Accelerate our Clients’ Molecules to Market Efficiently” Our Vision Contact Ariya Khunvichai, Ph.D. Tel – 4 ext

A list of Protocols oCetirizine oLoratadine oTiclopidine oGabapentin oCandesartan oValsartan oAzithromycin oAmlodipine oFinasteride oAmlodipine oMeloxicam oDonepezil HCL oFexofenadine oFelodipine oRisedronate oRabeprazole oOlanzapine oRivastigmine oSertaline