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![J.U. & TAAB
February 20, 2010
Protocol
Protocol
Objective
Study Design
Details of Test and Reference samples
Washout period
Inclusion criteria and Exclusion criteria of volunteers
Blood sampling schedule
Plasma Analysis (By HPLC or LCMS/MS)
In-vitro Dissolution Study
Statistical Analysis [ Evaluation of pharmacokinetic parameters (Cmax , Tmax , AUC 0-t & AUC 0-, )]
Compilation](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-3-320.jpg)
![J.U. & TAAB
February 20, 2010
Adverse Event Sheet
Adverse Event Sheet for BA/BE Study Cont….
for BA/BE Study Cont….
SERIOUS ADVERSE EVENT REPORTING
Record all adverse events or any new illness developing during the study
period whether related to the study drug or not. Also record worsening of
preexisting illness, if any. If adverse event is a diagnostic entity, state its
name and NOT individual symptoms. Use one column for each adverse
event. Tick [√] as appropriate.
Adverse event (describe)………………………………………………………………………………………………………………………
Date of onset. (dd/mm/yy) …………………………
Time of onset after the consumption of the drug……
Intensity : Mild Moderate Severe
Outcome of
Adverse Event :
Unknown Still Present Cleared Permanentdisability Death](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-9-320.jpg)
![J.U. & TAAB
February 20, 2010
Informed Consent form
Informed Consent form
INFORMED CONSENT FORM TO PARTICIPATE IN A
INFORMED CONSENT FORM TO PARTICIPATE IN A
BIOEQUIVALENCE / BIOAVAILABILITY STUDY
BIOEQUIVALENCE / BIOAVAILABILITY STUDY
Study Title:………………………………………………………………………………………………………...
Study Number:……………………
Subject’s Initials: …………………. Subject’s Name…………………………………………………………..
Date of Birth / Age: ………………
1
I confirm that I have read and understood the information sheet dated ___
for the above study and have had the opportunity to ask questions.
[ ]
2
I understand that my participation in the study is voluntary and that I am
free to withdraw at any time, without giving any reason, without my
medical care or legal rights being affected.
[ ]](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-15-320.jpg)
![J.U. & TAAB
February 20, 2010
3
I understand that the Sponsor of the study, others working on the
Sponsor’s behalf, the Ethics Committee and the regulatory authorities
will not need my permission to look at my health records both in respect
of the current study and any further research that may be conducted in
relation to it, even if I withdraw from the trial. I agree to this access.
However, I understand that my identity will not be revealed in any
information released to third parties or published.
[ ]
4
I agree not to restrict the use of any data or results that arise from this
study provided such a use is only for scientific purpose(s)
[ ]
5 I agree to take part in the above study. [ ]
6
I…………………………………………………………………………………………
………………….………….. the undersigned voluntarily agree to take part
in, the study: titled as: Bioequivalence of
…………………………………………………………………………………………
……………………...……………….I understand tat the investigation will
involve the oral administration of …………………………..……… X …..….
on ……… study days in …....... dosing sessions at the interval of …….
days.
[ ]
7
I have been given a full explanation by the member of the study team, of
the nature, purpose and likely duration of the study and what I will be
expected to do and I have been advised about my discomfort and
possible ill effects on any health or well being which he believes may
result.
[ ]
Informed Consent form cont…….
Informed Consent form cont…….](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-16-320.jpg)
![J.U. & TAAB
February 20, 2010
8
I further understand that 10 – 14 nos. blood samples of 5ml each will
be withdrawal during the study period of Phase I and Phase II.
[ ]
9
I understand that compensation/or treatment (s) available to me in the
event of trial related injury / adverse effects
[ ]
10
I am happy with the arrangement and compensation for participating
in this study.
[ ]
Informed Consent form cont…….
Informed Consent form cont…….
Signature (or Thumb impression) of the Subject/Legally Acceptable Representative:____________
Date: _____/_____/____
Signatory’s Name: ____________________________________
Signature of the Investigator: ____________________________ Date: _____/_____/____
Study Investigator’s Name: __________________________________________________
Signature of the Witness ______________________ Date:_____/_____/_____
Name of the Witness: _______________________________________________________](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-17-320.jpg)
![J.U. & TAAB
February 20, 2010
Clinical Pharmacology Unit (CPU)
Clinical Pharmacology Unit (CPU)
Clinical pharmacological unit having requisite infrastructural facilities as well as the state-of-the art instrumental support.
There are provisions to accommodate 24 healthy human volunteers at a time in the cozy air-conditioned CPU.
Composition of Clinical Pharmacology Unit
Name Qualification Training and Experience Responsibility
Prof. (Dr.) T.K.Pal MChE, PhD, DAAD Fellow
(Germany), VDI Germany,
Director, Bioequivalence
Study Centre
33 yrs experience as a
Professor of Pharm Tech, J.U.
& 6 yrs Experience in BA/BE
Study
[1]. Scheduling of Study & co-
ordination with
industry/overall monitoring of
CPU
[2]. Documentation and
storage of drugs
Dr. T.K.Chattaraj MBBS, MD (Pharmacology) 6 yrs experience in CT &
BA/BE Study
[1]. Overall supervision
[2]. Clinical Management &
informed consent
[3]. Supervision of blood
withdrawal
[4]. Adverse effect
management
Dr. Balaram Ghosh MBBS, MD, Dip. In Clinical
Research
3 yrs experience in CT &
BA/BE Study
[1]. Physical Check up
[2]. Volunteers screening
[3]. Supervision of BA/BE
study](https://image.slidesharecdn.com/seminaronbioequivalencestudy-251124055732-f880c27c/85/Seminar-on-Bioequivalence-Study-ppt-19-320.jpg)
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- 1. J.U. & TAAB February20, 2010 Prof. (Dr.) Tapan Kumar Pal Prof. (Dr.) Tapan Kumar Pal Director Director Bioequivalence Study Centre Bioequivalence Study Centre Jadavpur University, Kolkata-32 Jadavpur University, Kolkata-32 In collaboration with TAAB Biostudy Services In collaboration with TAAB Biostudy Services
- 2. J.U. & TAAB February20, 2010 Main requirements Main requirements Protocol. Institutional Ethical Commeittee Clearance. No objection certificate from DCGI/or Regulators body. Volunteers. Clinical Pharmacology Unit (CPU). Analytical Unit. Data handling and interpretation. Quality assurance of all operations in the centre. Documented standard operating procedure.
- 3. J.U. & TAAB February20, 2010 Protocol Protocol Objective Study Design Details of Test and Reference samples Washout period Inclusion criteria and Exclusion criteria of volunteers Blood sampling schedule Plasma Analysis (By HPLC or LCMS/MS) In-vitro Dissolution Study Statistical Analysis [ Evaluation of pharmacokinetic parameters (Cmax , Tmax , AUC 0-t & AUC 0-, )] Compilation
- 4. J.U. & TAAB February20, 2010 Pre Study Data for BA/BE Study Pre Study Data for BA/BE Study BIOEQUIVALENCE / BIOAVAILABILITY STUDY Volunteer’s Name: ………………………………………………… Volunteer’s No. ………..…. Age (yrs) Sex M Height (cms) Weight (Kg) VITAL SIGNS Pulse (bpm) Systolic Blood Pressure (Mm Hg) Diastolic Blood Pressure (Mm Hg) Temperature (o f) Respiratory Rate (per minute) PEFR (L) PRE STUDY DATA
- 5. J.U. & TAAB February20, 2010 Pre Study Data for BA/BE Study Cont… Pre Study Data for BA/BE Study Cont… MEDICAL HISTORY: SURGICAL HISTORY: H/O ALLERY: FAMILY HISTORY: Has the volunteer participated in any drug trail before? Yes No If yes, Date on which volunteer last participated in study: 90 day clearance since last study: Have any problem occurred in previous study: If yes, specify: PHYSICAL EXAMINATION GENERAL APPEARANCE CARDIOVASCULAR SYSTEM RESPIRATORY SYSTEM GASTROINTESTINAL SYSTEM PRE STUDY DATA Cont…
- 6. J.U. & TAAB February20, 2010 CENTRAL NERVOUS SYSTEM MUSCULOSKELETAL SYSTEM ECG CHEST X-RAY HIV TEST Negative Positive AUSTRALIA ANTIGEN Negative Positive PHYSICAL EXAMINATION Pre Study Data for BA/BE Study Cont… Pre Study Data for BA/BE Study Cont… Signature
- 7. J.U. & TAAB February20, 2010 Adverse Event Sheet Adverse Event Sheet for BA/BE Study for BA/BE Study BIOEQUIVALENCE / BIOAVAILABILITY STUDY Volunteer’s Name: …………………………………………………Volunteer’s No. ………..…. ADVERSE EVENT SHEET (TO BE FILLED IN BY THE VOLUNTEER) ADVERSE EVENT ADVERSE EVENT ADVERSE EVENT GIDDINESS DOUBLE VISION REDNESS OF EYES DROWISINESS DISCOLORED VISION HEARING IMPAIRMENT FAINTING DARK SPOTS RINGING IN EARS LIGHT HEADEDNESS LIGHT INTOLERANCE VERTIGO HEADACHE WATERING OF EYES SNEEZING BLURRING ITCHING IN EYES NASAL CONGESTION COLORED VISION DRYNESS OF EYES COLD
- 8. J.U. & TAAB February20, 2010 ADVERSE EVENT ADVERSE EVENT ADVERSE EVENT COUGH URINARY RETENTION MUSCLE CRAMPS DRYNESS OF MOUTH BURNING MICTURATION TREMORS SKIN RASH DARK URINE TWITCHING URTICARIA PAIN IN ABDOMEN WEAKNESS ITCHING NAUSEA JOINT PAIN PALPITATION VOMITTING NO SLEEP DIFFICULTY BREATHING ALTERED TASTE EXCESSIVE SLEEP CHEST PAIN DIARRHEA ANY OTHER FEQUENT URINATION HYPERACIDITY Adverse Event Sheet Adverse Event Sheet for BA/BE Study Cont…. for BA/BE Study Cont…. ADVERSE EVENT SHEET Cont….
- 9. J.U. & TAAB February20, 2010 Adverse Event Sheet Adverse Event Sheet for BA/BE Study Cont…. for BA/BE Study Cont…. SERIOUS ADVERSE EVENT REPORTING Record all adverse events or any new illness developing during the study period whether related to the study drug or not. Also record worsening of preexisting illness, if any. If adverse event is a diagnostic entity, state its name and NOT individual symptoms. Use one column for each adverse event. Tick [√] as appropriate. Adverse event (describe)……………………………………………………………………………………………………………………… Date of onset. (dd/mm/yy) ………………………… Time of onset after the consumption of the drug…… Intensity : Mild Moderate Severe Outcome of Adverse Event : Unknown Still Present Cleared Permanentdisability Death
- 10. J.U. & TAAB February20, 2010 Adverse Event Sheet Adverse Event Sheet for BA/BE Study Cont…. for BA/BE Study Cont…. Most likely cause of even Uncertain Study drug Disease under study New illness Pre-existing illness Concomitant drugs Fatal or permanently disabling Required in patient hospitalization Or prolongation in hospitalization Life threatening Involved a congenital anomaly Cancer or overdose If adverse event is one of the following (tick box), notify immediately.
- 11. J.U. & TAAB February20, 2010 Clinical Examination Data Clinical Examination Data for BA/BE Study for BA/BE Study BIOEQUIVALENCE / BIOAVAILABILITY STUDY CLINICAL EXAMINATION DATA Volunteer’s Name: …………………………………………………Volunteer’s No. ………..…. Total Count W.B.C. Normal: 4500-11000/C mm Differential Count Neutrophils Normal: 60-70 % Monocytes Normal: 3-6 % Basophil Normal: 0-1 % Lymphocytes Normal: 20-35 % Eosinophil Normal: 1-4 % Hemoglobin % Normal for male: 14-18 G/ml Blood Sugar Normal fasting: 76-110 mg/dl Urea Normal serum/plasma: 14-50 mg/dl Total Protein Normal:6-8 g/dl Bilirubin Direct Normal: upto 0.2 mg/dl Total Normal: upto 1.0 mg/dl
- 12. J.U. & TAAB February20, 2010 SGPT Normal: upto 40IU/L at 37ºC Plasma Protein Albulin Normal: 3.7 to 5.3 g/dl Globulin Normal: 2.3 to 3.6 g/dl A/G Ratio Normal: 1 to 2.3 Alkaline Phosphate Normal : 100 to 250 IU/L Australian Antigen (Hbs AG) Normal : Negative HIV Normal : Negative VDRL Normal: Non reactive Creatinine Cholesterol Na+ K+ Urine R/E Clinical Examination Data for BA/BE Study Cont….. Clinical Examination Data for BA/BE Study Cont….. CLINICAL EXAMINATION DATA
- 13. J.U. & TAAB February20, 2010 Composition of Institutional Ethical Committee (IEC) Composition of Institutional Ethical Committee (IEC) SL.NO. Name Status 1. Prof. (Dr.) S. Dutta, Pro-Vice Chancellor Jadavpur University; Kolkata – 700 032. Chairman 2. Prof. Subrata Pal, School of Bioscience & Engineering, Jadavpur University; Kolkata – 700 032. Convener 3. Prof. (Dr.) T.K. Pal, Professor, Pharmaceutical Technology, Jadavpur University; Kolkata – 700 032 Joint Convener 4. Prof. (Dr.) Sujata Ghosh Dastidar, Ex-Prof. Pharmaceutical Technology, Jadavpur University, Kolkata – 700 032. Member 5. Prof. H.K. Deb, Orthopedic Surgeon 91, Ekdalia Road, Kolkata – 700 019 Member 6. Prof. (Dr.) S.N. Banerjee, Special Secretary (Medical Education), Department of Health & Family Welfare, Govt of West Bengal, Swastha Bhavan, GN – 29, Salt Lake City, Sector – V; Kolkata –91 Member 7. Mr. Shovan Lal Hazra Retained Lawyer, Law Cell, Jadavpur University; Kolkata – 700 032. Law Officer 8. Prof. (Dr.) Suchita Ghosh Professor, International Relations, Jadavpur University, Kolkata – 700 032. Social Worker 9. Prof. (Dr.) Krishnangshu Ray Director, School of Tropical Medicine, C.R.Avenue, Kolkata – 700 073 Clinical Pharmacologist
- 14. J.U. & TAAB February20, 2010 No objection certificate from DCGI/or Regulators body No objection certificate from DCGI/or Regulators body
- 15. J.U. & TAAB February20, 2010 Informed Consent form Informed Consent form INFORMED CONSENT FORM TO PARTICIPATE IN A INFORMED CONSENT FORM TO PARTICIPATE IN A BIOEQUIVALENCE / BIOAVAILABILITY STUDY BIOEQUIVALENCE / BIOAVAILABILITY STUDY Study Title:………………………………………………………………………………………………………... Study Number:…………………… Subject’s Initials: …………………. Subject’s Name………………………………………………………….. Date of Birth / Age: ……………… 1 I confirm that I have read and understood the information sheet dated ___ for the above study and have had the opportunity to ask questions. [ ] 2 I understand that my participation in the study is voluntary and that I am free to withdraw at any time, without giving any reason, without my medical care or legal rights being affected. [ ]
- 16. J.U. & TAAB February20, 2010 3 I understand that the Sponsor of the study, others working on the Sponsor’s behalf, the Ethics Committee and the regulatory authorities will not need my permission to look at my health records both in respect of the current study and any further research that may be conducted in relation to it, even if I withdraw from the trial. I agree to this access. However, I understand that my identity will not be revealed in any information released to third parties or published. [ ] 4 I agree not to restrict the use of any data or results that arise from this study provided such a use is only for scientific purpose(s) [ ] 5 I agree to take part in the above study. [ ] 6 I………………………………………………………………………………………… ………………….………….. the undersigned voluntarily agree to take part in, the study: titled as: Bioequivalence of ………………………………………………………………………………………… ……………………...……………….I understand tat the investigation will involve the oral administration of …………………………..……… X …..…. on ……… study days in …....... dosing sessions at the interval of ……. days. [ ] 7 I have been given a full explanation by the member of the study team, of the nature, purpose and likely duration of the study and what I will be expected to do and I have been advised about my discomfort and possible ill effects on any health or well being which he believes may result. [ ] Informed Consent form cont……. Informed Consent form cont…….
- 17. J.U. & TAAB February20, 2010 8 I further understand that 10 – 14 nos. blood samples of 5ml each will be withdrawal during the study period of Phase I and Phase II. [ ] 9 I understand that compensation/or treatment (s) available to me in the event of trial related injury / adverse effects [ ] 10 I am happy with the arrangement and compensation for participating in this study. [ ] Informed Consent form cont……. Informed Consent form cont……. Signature (or Thumb impression) of the Subject/Legally Acceptable Representative:____________ Date: _____/_____/____ Signatory’s Name: ____________________________________ Signature of the Investigator: ____________________________ Date: _____/_____/____ Study Investigator’s Name: __________________________________________________ Signature of the Witness ______________________ Date:_____/_____/_____ Name of the Witness: _______________________________________________________
- 18. J.U. & TAAB February20, 2010 Volunteers Volunteers VOLUNTEER’S PROFILE Subjects should be adult, human, healthy male volunteers (18 to 40 years of age) selected from the panel of volunteers. Volunteers should be screened for inclusion in the study within 21 days before the commencement of the study. SCREENING TESTS The screening examination includes complete physical and clinical examination, including various biochemical and hematological tests. INCLUSION CRITERIA Normal ECG , Normal blood pressure and heart rate as measured after resting supine for three minutes. Normal B.P is taken to be 100 to 150 mm Hg systolic and 50 to 90 mm Hg diastolic supine. Normal heart rate is taken to be 50 to 90 beats per minute. EXCLUSION CRITERIA Clinically relevant abnormalities in physical and/or the results of the screening tests, Abnormal ECG, History of alcohol / drug abuse / smoking.
- 19. J.U. & TAAB February20, 2010 Clinical Pharmacology Unit (CPU) Clinical Pharmacology Unit (CPU) Clinical pharmacological unit having requisite infrastructural facilities as well as the state-of-the art instrumental support. There are provisions to accommodate 24 healthy human volunteers at a time in the cozy air-conditioned CPU. Composition of Clinical Pharmacology Unit Name Qualification Training and Experience Responsibility Prof. (Dr.) T.K.Pal MChE, PhD, DAAD Fellow (Germany), VDI Germany, Director, Bioequivalence Study Centre 33 yrs experience as a Professor of Pharm Tech, J.U. & 6 yrs Experience in BA/BE Study [1]. Scheduling of Study & co- ordination with industry/overall monitoring of CPU [2]. Documentation and storage of drugs Dr. T.K.Chattaraj MBBS, MD (Pharmacology) 6 yrs experience in CT & BA/BE Study [1]. Overall supervision [2]. Clinical Management & informed consent [3]. Supervision of blood withdrawal [4]. Adverse effect management Dr. Balaram Ghosh MBBS, MD, Dip. In Clinical Research 3 yrs experience in CT & BA/BE Study [1]. Physical Check up [2]. Volunteers screening [3]. Supervision of BA/BE study
- 20. J.U. & TAAB February20, 2010 Name Qualification Training and Experience Responsibility Mr. Dilip Das Pathological Technician having DMLT certificate 25 yrs experience in different Pathological Labs 1. Blood withdrawal, plasma separation and recording ; 2. Transporting the samples to Analytical Labs Miss Sutapa Adhikary Passed AMN Trained from Krishtio Sevaniketan, (Govt. of West-Bengal) 10 yrs experience as a Nurse 1. Blood withdrawal, nursing support to the volunteers ; 2. Food Management3. Helping Clinical Management Mr. Tapas Pal B.Sc 2 yrs experience in CPU 1. coordinating volunteers, Doctors, Staffs/Record keeping2. Arrangement of sample transportation Mr. Ratan Gupta H.S. 5 yrs experience in CPU 1. Volunteers management ; 2. Physical arrangement3. Collecting, providing and supervising food/accommodation Gurupada Kuila Madhyamik 5 yrs experience in CPU 1. Overall cleaning of CPU Bholanath Maity Madhyamik 3 yrs experience in CPU 1. Helper cum peon Composition of CPU Cont……
- 21. J.U. & TAAB February20, 2010 Instrumental facility in Clinical Pharmacology Unit Instrumental facility in Clinical Pharmacology Unit Sl. No. Name Make /Model / Country 1 Cold centrifuze(-20ºC) Elektrocraft /RC 4100D/Mumbai.India 2 ECG Machine Vega 3 Channel ECG machine/Larson & Toubro Ltd. Cardiart / 108T/ India 3 Microscope National Instruments Ltd./Calcutta, India 4 Colorimeter Systonic/ SD06/India 5 Sphygmomanometer Cardiofonic/ H. Mukherji/India 6 Refrigerator (2 to 8ºC) Electrolus/ India 7 Digital Blood Pressure Monitor Omron MX/ Omron Healthcare Co. Ltd./India 8 Ice Box Milton/India 9 Micro Pipette (100-1000µl) Accupipette/Tarsons/India 10 Micro Pipette (10-100µl) Accupipette/Tarsons/India 11 Oxygen Cylinder India 12 Color TV Onida/21 inch/India 13 DVD LG/India 14 Saline Accessories Not Applicable (NA) 15 Emergency Accessories NA 16 Other Emergency Accessories NA
- 22. J.U. & TAAB February20, 2010 Analytical Unit Analytical Unit Analytical unit having requisite infrastructural facilities as well as the state-of-the art instrumental support in the cozy air-conditioned lab. Organogram of Analytical Unit ANALYTICAL LABORATORY UNIT Qualification Experience 1 Mr. Amlan Kanti Sarkar, Incharge M.Sc. 5 yrs experience in handling analytical instruments (HPLC, LC-MS/MS) for plasma analysis in BA/BE Study in Jadavpur University 2 Mr. Ayan Das M.Sc. 3 yrs experience in handling HPLC/LCMS/MS in connection with BA/BE Study in Jadavpur University 3 Mr. Bikash Roy M.Pharm., (Clinical Pharmacy) 2 yrs experience in BA/BE Study in Jadavpur University DATA HANDLING& INTERPRETATION Qualification Experience Uday Shankar Chakraborty Incharge M.Pharm. 2 yrs experience in BA/BE Study in Jadavpur University DOCUMENTATION & REPORT PREPERATION Qualification Experience 1 Mrs. Debotri Ghosh, Incharge M.Sc. 5 yrs experience in BA/BE Study in Jadavpur University 2 Mrs. Manashree Mukherjee BCA 3 yrs experience in BA/BE Study in Jadavpur University 3 Mr. Chiranjit Saha B.Sc. 2 yrs experience in BA/BE Study in Jadavpur University QUALITY ASSURANCE OF ALL OPERATIONS IN CENTRE Qualification Experience 1. Dr. (Mrs. ) Sangita Agarwal M.Sc., PhD 5 yrs experience in BA/BE Study in Jadavpur University
- 23. J.U. & TAAB February20, 2010 Instrumental facility in Analytical Unit Instrumental facility in Analytical Unit Sr. No. Name Make /Model / Country 1. LCMS/MS with ESI and APCI Applied Biosystem/API 2000/Canada 2. HPLC with UV detector Shimadzu/LC20AD/japan; Jasco/ Japan, Knauer/Germany 3. Autometic off line Tablet Dissolution Apparatus Electrolab/TDT-06T/ Bombay,India 4. Autometic off line Tablet Dissolution Apparatus with Auto samplar Electrolab/TDT-08L/ Bombay,India 5. Tablet Disintegration Tester Electrolab/ED-2L / Mumbai, India 6. Deep freezer (-20Cº) ICP/India 7. Cold centrifuze Elektrocraft /RC 4100D/Mumbai.India 8. Centrifuge Eltak/TC650S/Mumbai, India 9. Cold Centrifuge (-20° C) 20,000 rpm Eltek /RC-4100F /Mumbai 10. Electronic balance AdairDutta Instrument Pvt.Ltd./AD-50B/India 11 Electronic balance Sartorius /GD-103/Germany 12. pH meter Sartorius /PB-11/Germany 13. pH meter Toshniwal inst. mfg. Pvt. Ltd. /CL-54/ Ajmer, India 14. UV-Vis-Spectrophotometer Chemito/UV 2600/India 15. UV-Vis-Spectrophotometer Jasco/V-630/Japan. 16. Physiopic, 4-channel comp. polygraph ( EEG, ECG, EMG, GSR) Medicaid system/ PC-2004 / Chandigarh, India. 17. Macro element analyzer Medica corporation/Sr. No.32814BNK/Bedford, USA 18. Cell Counter (Animal blood) Medonica/ CA-620 / Loke, Canada 19. Pertical Size Analyser Malvern/2000SM/UK 20. Humidity Chamber Thermolab/Mumbai,India 21. Ultra Sonic Bath ICT/D-Compact/India 22. Water Bath (Digital) ITC/Kolkata, India 23. Vortex Mixture Eltak/VM301/Mumbai, India
- 24. J.U. & TAAB February20, 2010 FLOW CHART OF DRUG SAMPLES FOR BA/BE STUDY FLOW CHART OF DRUG SAMPLES FOR BA/BE STUDY RECEIPT, RECORD & STORAGE OF DRUG SAMPLE Incharge RECEIPT OF DRUG SAMPLES at CPU Incharge RECORD & STORAGE OF DRUG SAMPLES AT CPU Incharge CPU ACTIVITIES CO-ORDINATING DOCTORS, STAFFS, VOLUNTEERS AND RECORD KEEPING DRUG ADMINISTRATION BLOOD WITHDRAWAL & PLASMA SEPARATION TRANSPORTATION OF PLASMA FOOD/LODGING BULK DRUGS/APU Incharge RECEIPT OF DRUG SAMPLES at ANALYTICAL LAB Incharge RECORD & STORAGE OF DRUG SAMPLES at ANALYTICAL LAB Incharge BIOAVAILABILITY METHOD DEVOLOPEMENT and ANALYSIS OF PLASMA by HPLC & LCMS/MS Incharge DATA HANDLING & INTERPRETATION Incharge Transport DOCUMENTATION AND REPORT PREPARATION Transport Transport
- 25. J.U. & TAAB February20, 2010 Bioequivalence Study of Gatifloxacin Bioequivalence Study of Gatifloxacin by HPLC ( A Case Study) by HPLC ( A Case Study)
- 26. J.U. & TAAB February20, 2010 Introduction Introduction Gatifloxacin is 8- methoxyfluoroquinolone Active against broad spectrum pathogens Has an elimination half life of about 7-10 hrs. Most of the methods are available by LC-MS
- 27. J.U. & TAAB February20, 2010 Study Design Study Design I. Clinical II. Analytical III. Data Interpretation IV. Documentation
- 28. J.U. & TAAB February20, 2010 Clinical Study Clinical Study (Study was approved by DCGI, New Delhi & IEC of Jadavpur University) Volunteers screening Volunteers screening •Male – 18-30 yrs aged (20.08 + 3.9) 48-69 kg weight (52.75 + 6.48) •Complete Physical & Clinical Examination (biochemical & hematological) •Checked for evidence or history of relevant disease of drug allergy or dependence. •Subjects were informed about the nature of drug & informed consents were signed.
- 29. J.U. & TAAB February20, 2010 Clinical Study (cont.,) Clinical Study (cont.,) Preparations Preparations Test (Gatifloxacin 400 mg from SAGA labs, Ahmedabad) Reference (Gatilox 400mg from SUN Pharmaceuticals) Study Design Study Design 2 way complete cross-over design (7 days wash out period) Drug Administration Drug Administration Tablets given orally with 250 ml water after overnight fasting Dietary Control Dietary Control Standard breakfast, lunch & dinner with non-caffeine drinks Allowed normal activities like watching TV excluding strenuous exercise.
- 30. J.U. & TAAB February20, 2010 Clinical Study (cont.,) Clinical Study (cont.,) Biological Samples Biological Samples 15 blood samples were collected (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 & 48 hrs) in coded tubes with EDTA Samples were centrifuged, plasma separated & frozen at - 200 C.
- 31. J.U. & TAAB February20, 2010 Analytical Study Analytical Study Instrument Instrument HPLC, Shimadzu, Japan (Prominence, LC20AD) Isocratic system with integrating software Eurochrom 2000 Variable UV spectrophotometer Column (Gemini –C18, 150 X 4.6 mm, 5µ particle size) Rheodyne injector (fixed loop) with 20 µl Rhd. loop. HPLC
- 32. J.U. & TAAB February20, 2010 Analytical study (cont.,) Analytical study (cont.,) Analytical Conditions Analytical Conditions Mobile phase (10mM phosphate solution : Acetonitirile 50:50 v/v) UV detector set at 290 nm Flow rate – 1ml / min Calibration curve Calibration curve Concentrations of 0.25-8µg ml-1 were taken in blank plasma 20µl injected Mean drug peak area ratio was plotted against concentration (x)
- 33. J.U. & TAAB February20, 2010 Reconstituted with 1ml mobile phase & injected into HPLC Organic layer (4ml) evaporated to dryness Centrifuged for 5 min (4000 rpm) Extraction with dichloromethane 1ml plasma + 0.1 ml dil. H3PO4 Analytical study (cont.,) Analytical study (cont.,) Plasma Extraction procedure Plasma Extraction procedure Plasma Extraction Unit
- 34. J.U. & TAAB February20, 2010 Analytical study (cont.,) Analytical study (cont.,) Freeze Thaw Recovery Freeze Thaw Recovery Analyte of 0.25 (QCL), 0.75 (QCM) & 1.5 (QCH) mcg/ml of GTX were tested with blank plasma (n=3) Precision & Accuracy Precision & Accuracy Between – run precision & accuracy are determined from low, medium & high QC samples 5 replicates were carried out for each QC samples on day 2 & day 3 Within – run precision & accuracy are determined from 5 replicates of each QC samples on day 1 Pharmacokinetic parameters Pharmacokinetic parameters Pharmacokinetic parameters like AUC, Cmax, Tmax, Kel/hr, t1/2 were studied.
- 35. J.U. & TAAB February20, 2010 Results Chromatogram of Gatifloxacin Chromatogram of Gatifloxacin In Blank Plasma In Human Plasma In Raw Drug
- 36. J.U. & TAAB February20, 2010 Between – run precision & Accuracy (n = 13) Between – run precision & Accuracy (n = 13) QCL 0.25 QCM 0.75 QCH 1.5 Mean µg/ml 0.2470 0.7492 1.54 SD 0.0149 0.0152 0.1204 CV % 3.66 1.87 4.72 Absolute % bias 99.75 99.90 101.92
- 37. J.U. & TAAB February20, 2010 Within – run precision & Accuracy (n = 5) Within – run precision & Accuracy (n = 5) QCL 0.25 QCM 0.75 QCH 1.5 Mean µg/ml 0.2476 0.7364 1.513 SD 0.0116 0.0127 0.0902 CV % 2.93 1.601 3.58 Absolute % bias 99.40 98.95 100.55
- 38. J.U. & TAAB February20, 2010 Freeze thaw recovery determination (n = 3) Freeze thaw recovery determination (n = 3) Conc. µg/ml QCL 0.25 QCM 0.75 QCH 1.5 1st cycle 0.248 0.705 1.43 2nd cycle 0.234 0.729 1.41 3rd cycle 0.239 0.743 1.46
- 39. J.U. & TAAB February20, 2010 Mean Pharmacokinetic parameters obtained in 12 healthy volunteers Mean Pharmacokinetic parameters obtained in 12 healthy volunteers Pharmacokinetic parameters GATIFLOXACIN 400 mg Reference Preparation (A) Test Preparation (B) Cmax (ng./ml.) Mean 463.7 452.3 S.D. 0.383 0.546 tmax (hr.) Mean 1.917 1.917 S.D. 0.195 0.417 AUC 0-t (ng. hr./ml.) Mean 2715.2 2599.1 S.D. 2.061 2.630 AUC 0- (ng. hr./ml.) Mean 3832.9 3437.1 S.D. 2.508 3.089 kel (hr.-1 ) Mean 0.065 0.078 S.D. 0.012 0.016 t1/2 (hr.) Mean 11.015 9.268 S.D. 1.820 1.974 Relative Bioavailability (%) 100 95.72%
- 40. J.U. & TAAB February20, 2010 90% confidence Interval with the Test and Reference Preparation 90% confidence Interval with the Test and Reference Preparation Confidence Interval GATIFLOXACIN Cmax Untransformed Data 0.8343-1.0052 Ln transformed Data 0.8358-1.0014 AUC 0-t Untransformed Data 0.8877-1.0171 Ln transformed Data 0.8844-1.0148 AUC 0- Untransformed Data 0.857-1.0231 Ln transformed Data 0.8566-1.0206
- 41. J.U. & TAAB February20, 2010 Curves of the mean plasma conc. (mcg/ml) Vs time (h) Curves of the mean plasma conc. (mcg/ml) Vs time (h) Test Sample Reference Sample
- 42. J.U. & TAAB February20, 2010 On comparison of AUC0-t the relative bioavailability of test preparation was 93.50 % that of reference preparation The HPLC method here proved to be simple, fast & reliable The present study shows Test preparation was bioequivalent to Standard preparation. Conclusion
- 43. J.U. & TAAB February20, 2010 AN OVERVIEW OF AN OVERVIEW OF BIOEQUIVALENCE STUDY CENTRE BIOEQUIVALENCE STUDY CENTRE Jadavpur University Jadavpur University
- 44. J.U. & TAAB February20, 2010 ABOUT BIOEQUIVALENCE STUDY CENTRE, ABOUT BIOEQUIVALENCE STUDY CENTRE, Jadavpur University Jadavpur University Approved by DCGI Approved by DCGI Certified by ISO 9001:2000 Certified by ISO 9001:2000 Air Conditioned Lab Air Conditioned Lab Well equipped Lab Well equipped Lab Experts from all fields Experts from all fields
- 45. J.U. & TAAB February20, 2010 EXPERTISE EXPERTISE Bioequivalence studies Toxicity studies Clinical Trials Formulation development of Conventional & SR Tablets (Single & Fixed Dose Combinations), Liquid orals, Soft gelatin capsules Analytical method development for drugs Validation of the analytical methods Stability studies
- 46. J.U. & TAAB February20, 2010 Analytical Lab Analytical Lab
- 47. J.U. & TAAB February20, 2010 Bioequivalence Team Bioequivalence Team
- 48. J.U. & TAAB February20, 2010 Thank you Thank you