design and conduct safety pharmacology & toxicology study for pharmaceuticals dr. basavaraj k....
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Design and Conduct Safety Pharmacology &
Toxicology Study for PharmaceuticalsDr. Basavaraj K. Nanjwade M.Pharm., Ph.D
Professor of PharmaceuticsDepartment of Pharmaceutics, KLE University,
BELGAUM – 590010, Karnataka, IndiaE-mail: bknanjwade@yahoo.co.in
Cell No: +919742431000
R & D Pharmacology and ToxicologyR & D Pharmacology and Toxicology
PHARMACOLOGY• Oncology•Pain & Inflammation• Metabolic Disorders•Respiratory Diseases• Psychopharmacology models
IN-VIVO TOXICOLOGY• General toxicology• In-vivo Genotoxicity studies• Carcinogenicity• Development and reproductive studies• Special toxicity studies
IN-VITRO TOXICOLOGY
• In-vitro toxicity assays•In-vitro genotoxicity assays
SAFETY PHARMACOLOGY
• CNS studies• CVS studies• Respiratory evaluations/ system
DRUG METABOLISM & PHARMACOKINETICS STUDIES
• In-Vivo DMPK studies• In-vitro DMPK studies• Plasma Protein Binding studies• Drug – Drug interaction studies• Bioanalysis• Special Analytical studies
HISTOPATHOLOGICAL AND BIOCHEMISTRY STUDIES
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Birgunj, Nepal.
PHARMACOLOGY
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Birgunj, Nepal.
Oncology
i. Xenograft modelThis model provides consistent and reproducible cell growth and permits easy access to the tumor for treatment and calliper measurement
Cell implant subcutaneously into immuno-compromised animals
Tumors measured during growth phase Animals treated with vehicle, test article and positive
control Various protocol-specified parameters/markers assessed
ex vivo or in vivo assays Report preparation
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Birgunj, Nepal.
Oncology
ii. In vivo targeted inhibition model In PK/PD studies the tumors are from the test
article treated mice group along with respective control groups.
Then the effect of test article at molecular level is investigated in different cell based assays
The MTD of the compound is also analysed
30/12/2009 5Nepal Research Foundation.,
Birgunj, Nepal.
Pain and Inflammation
1. Chemical Induced Capsaicin induced Hyperalgesia in rats FCA induced Hyperalgesia Carrageenan induced paw edema Acetic acid/Formalin induced pain in mice Mouse Ear Edema Adjuvant-Induced Arthritis (AIA) Collagen-Induced Arthritis (CIA)
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Birgunj, Nepal.
Pain and Inflammation
2. Thermal & Mechanical Induced Hyperalgesia Tail flick model of Hyperalgesia Hot plate model of Hyperalgesia Neuropathic Pain (PSL and CCI induced
PAIN) Diabetic neuropathic pain model (DNP) Post operative pain model
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Birgunj, Nepal.
Pain and Inflammation
3. Miscellaneous Novel technique to quantitatively assess
Inflammatory mediators-In Vitro assay measuring cytokine production/inhibition in rat/mice
Mouse LPS model-LPS-stimulated inflammation in mice
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Birgunj, Nepal.
Metabolic Disorder
1. Acute Model OGITT/IPGTT Model
2. Chronic Model STZ induced Diabetes in mice/rats STZ induced Diabetes in neonatal rats Sucrose Fed Diet induced Diabetes High-Fat/carbohydrate Fed Diet and STZ treated Mice
model for Diabetes Glucose and Insulin estimation ob/ob mouse db/db mouse ZDF rats
30/12/2009 9Nepal Research Foundation.,
Birgunj, Nepal.
Respiratory Diseases
Antigen-induced Airway Hyper responsiveness in mice/rats
Antigent-induced Pulmonary eosinophilia in mice/rats
Passive Cutaneous Anaphylaxis Active Cutaneous Anaphylaxis LPS-induced Meutrophilia in rats/mice
30/12/2009 10Nepal Research Foundation.,
Birgunj, Nepal.
Psychopharmacology Models
1. Muscle Relaxation Rota-rod test Inclined screen test Grip Strength test
2. Behavioral test Irwin test
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Birgunj, Nepal.
IN-VIVO TOXICOLOGY
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Birgunj, Nepal.
General Toxicology
Single dose studies Repeated dose sub-acute and sub-chronic
studies (14, 28 & 90 days) Chronic toxicology studies (6, 9 & 12 months) Carcinogenicity studies Toxicokinetics Pathology
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Birgunj, Nepal.
In-Vivo Genotoxicity Studies
Micronucleus test in mouse or rat bone marrow (OECD 474)
Mammalian bone marrow chromosome aberration test in rats or mice (OECD)
Unscheduled DNA synthesis (UDS) with rat hepatocytes (OECD 486)
30/12/2009 14Nepal Research Foundation.,
Birgunj, Nepal.
Development & Reproduction toxicology
Fertility (Segment I) Embryo-fetal development (Segment II) Perinatal and postnatal development, including maternal function
(Segment III) Multigenerational studies Endocrine disruptors Selected neurobehavioral tests Juvenile dosing studies (rodent, dog) Sample collection (TK/PK and absorption analysis, maternal and
fetal blood, amniotic fluid, milk) Spermatogenesis evaluations of cellular endpoint (morphology,
motility, spermatid head count) via the IVOS system Vaginal cytology evaluations
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Birgunj, Nepal.
Special Toxicity Studies
The potential, adverse effects of human pharmaceuticals and biotech products on the immune system is acknowledged as an important issue.
According to the FDA, evaluation of potential immunotoxic effects should be incorporated into standard drug development
It incorporates immunotoxicology assays using standard rodent species (Wistar rat and CD-1 mouse)
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Birgunj, Nepal.
IN – VITRO TOXICOLOGY
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Birgunj, Nepal.
In – Vitro Toxicology
Human skin corrosion assay (OECD 431) Human skin irritation assay (draft proposal for
a new guideline OECD) Hen’ Egg Test-Chorioallantoic Membrane
(HET-CAM) test
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Birgunj, Nepal.
In-Vitro Genotoxicity Studies
Bacterial reverse mutation (Ames) test with salmonella typhimurium and Escherichia coli (OECD 471)
Chromosome aberration test (CAT) with human lymphocytes (OECD 473)
Mammalian gene mutation test (MLA) with mouse lymphoma cells (TK-locus) (OECD 476)
Unscheduled DNA synthesis (UDS) with isolated rat hepatocytes (OECD 482)
Micronucleus test with human lymphocytes (draft OECD 487)
Single cell gel electrophoresis (COMET) Assay
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Birgunj, Nepal.
SAFETY PHARMACOLOGY
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Birgunj, Nepal.
29/12/2009Nepal Pharmaceuticals Ltd.,
Birgunj, Nepal. 21
Scope and Principle Design and conduct safety pharmacology study can be
applied to marketed pharmaceuticals when appropriate
e.g.
1. When adverse clinical events
2. A new patient population
3. A new route of administration raises concerns not previously addressed.
Some safety pharmacology endpoint can be incorporated in the design of toxicology, kinetic and clinical studies
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Birgunj, Nepal.
30/12/2009 22
Definition of Safety Pharmacology
Pharmacology studies can be divided into three categories:
1. Primary pharmacodynamic
2. Secondary pharmacodynamic
3. Safety Pharmacology studies
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 23
Objectives of Studies To identify undesirable pharmacodynamic
properties of a substance that may have relevance to its human safety
To evaluate adverse pharmacodynamic and/or pathophysiological effects of a substance observed in toxicology and /or clinical studies
To investigate the mechanism of the adverse pharmacodynamic effects observed and/or suspected
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30/12/2009 24
General Considerations in Selection and Design of Safety Pharmacology
Effects related to the therapeutic class of the test substance, since the mechanism of action may suggest specific adverse effects
Adverse effects associated with members of the chemical or therapeutic class, but independent of the primary pharmacodynamics effects
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30/12/2009 25
General Considerations in Selection and Design of Safety Pharmacology
Ligand binding or enzyme assay data suggesting a potential for adverse effects
Results from previous safety pharmacology studies, from secondary pharmacodynamic studies, from toxicology studies, or from human use that warrant further investigation to establish and characterize the relevance of these findings to potential adverse effects in humans.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 26
Test Systems
1. General Considerations on Test Systems
2. Use of In Vivo and In Vitro Studies
3. Experimental Design
a. Sample Size and Use of Controls
b. Route of Administration
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 27
General Considerations on Test Systems
Consideration should be given to the selection of relevant animal model or other test systems so that scientifically valid information can be derived.
Selection factors can include the pharmacodynamic responsiveness of the model, pharmacokinetic profile, species, strain, gender and age of the experimental animals, the susceptibility, sensitivity, and reproducibility of the test system and available background data on the substance.
Nepal Research Foundation., Birgunj, Nepal.
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Use of In Vivo and in Vitro Studies
Animal models as well as ex vivo and in citro preparations can be used as test systems.
Ex vivo and vitro systems can include, but are not limited to: isolated organs and tissues, cell cultures, cellular fragments, subcellular organelles, receptors, ion channels, transporters and enzymes.
In vitro systems can be used in supportive studies
In conducting in vivo studies, it is preferable to use anaesthetized
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30/12/2009 29
Sample Size and Use of Controls
The sample size should take into consideration the size of the biological effect that is of concern for humans
Appropriate negative and positive control group should be included in the experimental design
In well-characterized in vivo test systems, positive controls may not be necessary.
The exclusion of control from studies should be justified
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 30
Route of Administration
In general, the expected clinical route of administration should be used when feasible.
Regardless of the route of administration, exposure to the parent substance and its major metabolites should be similar to or greater than that achieved in humans hen such information is available.
Assessment of effects by more than one route may be appropriate if the test substance is intended for clinical use by more than one route of administration
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 31
Dose Levels or Concentrations of test Substance
In Vivo Studies
In Vitro Studies
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30/12/2009 32
In Vivo Studies
In vivo safety pharmacology studies should be designed to define the dose-response relationship of the adverse effect observed.
The time course of the adverse effect should be investigated, when feasible.
Generally, the doses eliciting the adverse effect should be compared to the doses eliciting the primary pharmacodynamic effect in the test species or the proposed therapeutic effect in humans, if feasible.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 33
In Vitro Studies In vitro studies should be designed to establish a
concentration-effect relationship.
The range of concentrations used should be selected to increase the likelihood of detecting an effect on the test system.
The upper limit of this range may be influenced by physico-chemical properties of the test substance and other assay specific factors.
In the absence of an effect, the range of concentrations selected should be justified.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 34
Duration of Studies
Safety pharmacology studies are generally performed by single-dose administration
When pharmacodynamic effects occur only after a certain duration of treatment, or when results from repeat dose non-clinical studies or results from use in humans give rise to concerns about safety pharmacological effects, the duration of the safety pharmacology studies to address these effects should be rationally based.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 35
Studies on Metabolites, Isomers and Finished Products
Metabolites from humans are known to substantially contribute to the pharmacological actions of the therapeutic agent, it could be important to test such active metabolites.
When the in vivo studies on the parent compound have not adequately assessed metabolites, as discussed above, the tests of metabolites can use in vitro systems based on practical considerations.
Nepal Research Foundation., Birgunj, Nepal.
Studies on Metabolites, Isomers and Finished Products
In vitro or in vivo testing of the individual isomers should also be considered when the product contains an isomeric mixture
Finished product formulations should be conducted only for formulations that substantially alter the pharmacokinetics and/or pharmacodynamics of the active substance in comparison to formulations previously tested
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30/12/2009 37
Safety Pharmacology Core Battery
1. Central Nervous System
2. Cardiovascular System
3. Respiratory System
Nepal Research Foundation., Birgunj, Nepal.
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Central Nervous System
Effects of the test substance on the central nervous system should be assessed appropriately.
Motor activity, behavioral changes, coordination, sensory/motor reflex responses and body temperature should be evaluated.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 39
Cardiovascular System
Effect of the test substance on the cardiovascular system should be assessed appropriately.
Blood pressure, heart rate and the electrocardiogram should be evaluated
In vivo, in vitro and /or ex vivo evaluations, including methods for repolarzation and conductance abnormalities, should also be considered.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 40
Respiratory System
Effects of the test substance on the respiratory system should be assessed appropriately
Respiratory rate and other measures of respiratory function should be evaluated.
Clinical observation of animals is generally not adequate to assess respiratory function, and thus these parameters should be quantified by using appropriate methodologies.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 41
Follow-up and Supplemental Safety Pharmacology Studies
1. Follow-up Studies For Safety Pharmacology Core Battery
a. Central Nervous System
b. Cardiovascular System
c. Respiratory System
Nepal Research Foundation., Birgunj, Nepal.
Central Nervous System, Cardiovascular System& Respiratory System
Behavioral pharmacology, learning and memory, ligand-specific binding, neurochemistry, visual, auditory, and/or electrophysiology examination
Cardiac output, ventricular contractility, vascular resistant, the effects of endogenous and/or exogenous substances on the cardiovascular responses
Airway resistance, compliance, pulmonary arterial pressure, blood gases, blood pH
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Birgunj, Nepal.
30/12/2009 43
Follow-up and Supplemental Safety Pharmacology Studies
2. Supplemental Safety Pharmacology Studies
a. Renal/Urinary System
b. Autonomic Nervous System
c. Gastrointestinal System
d. Other Organ Systems
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 44
Renal/Urinary System
Effect of the test substance on renal parameters should be assessed.
e.g
Urinary volume, specific gravity, osmolality, pH, fluid/electrolyte balance, protein, cytology, and blood chemistry determinations such as blood urea nitrogen, creatinine, and plasma proteins can be used
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 45
Autonomic Nervous System
Effects of the test substance on the autonomic nervous system should be assessed.
e.g
Binding to receptors relevant for the autonomic nervous system, functional responses to agonists or antagonists in vivo or in vitro, direct stimulation of autonomic nerves and measurement of cardiovascular responses, baroreflex testing, and heart rate variability can be used.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 46
Gastrointestinal System
Effects of the test substance on the gastrointestinal system should be assessed.
e.g
Gastric secretion, gastrointestinal injury potential, bile secretion, transit time in vivo, ileal contraction in vitro, gastric pH measurement and pooling can be used
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 47
Other Organ Systems
Effects of the test substance on organ systems not investigated elsewhere should be assessed when there is a reason for concern.
e.g.
Dependency potential or skeletal muscle, immune and endocrine functions can be investigated.
Nepal Research Foundation., Birgunj, Nepal.
30/12/2009 48
Conditions Under Which Studies are Not Necessary
Safety pharmacology studies may not be needed for locally applied
Safety pharmacology studies prior to the first administration in human may not be needed for cytotoxic agents for treatment of end-stage cancer patients.
There may be additional exceptions where safety pharmacology testing is not needed
e.gCase of a new salt having similar pharmacokinetics and pharmacodynamics
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Timing of Safety Pharmacology Studies in Relation to Clinical
Development1. Studies Prior to First Administration in Humans
2. Studies During Clinical Development
3. Studies Before Approval
Nepal Research Foundation., Birgunj, Nepal.
Studies prior to First Administration in Human
The effects of a test substance on the functions listed in the safety pharmacology core battery should be investigated prior to first administration in humans
Any follow-up or supplemental studies identified as appropriate, based on a cause for concern, should also be conducted.
Information from toxicology studies adequately designed and conducted to address safety pharmacology endpoint can result in reduction or elimination of separate safety pharmacology studies.
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Birgunj, Nepal.
Studies During Clinical Development
Additional studies may be warranted to clarify observed or suspected adverse effects in animals and humans during clinical development
30/12/2009 51Nepal Research Foundation.,
Birgunj, Nepal.
Studies Before Approval
Safety pharmacology effects should be assessed prior to product approval, unless not warranted, in which case this should be justified.
Available information from toxicology studies adequately designed and conducted to address safety pharmacology endpoint, or information from clinical studies, can support this assessment and replace safety pharmacology studies
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30/12/2009 53
Application of Good Laboratory Practice (GLP)
This is normally accomplished through the conduct of the studies in compliance with GLP.
Due to the unique design of and practical considerations for, some safety pharmacology studies, it may not be feasible to conduct these in compliance with GLP
The safety pharmacology core battery should ordinarily be conducted in compliance with GLP
Nepal Research Foundation., Birgunj, Nepal.
Application of Good Laboratory Practice (GLP)
Follow-up and supplemental studies should be conducted in compliance with GLP to the greatest extent feasible.
Safety pharmacology investigations can be part of toxicology studies; in such cases, these studies would be conducted in compliance with GLP
Primary pharmacodynamic studies do not need to be conducted in compliance with GLP
30/12/2009 54Nepal Research Foundation.,
Birgunj, Nepal.
Application of Good Laboratory Practice (GLP)
Generally, secondary pharmacodynamic studies do not need to be conduct in compliance with GLP
In some circumstances, results of secondary pharmacodynamics studies may make a pivotal contribution to the safety evaluation for potential adverse effects in humans, and these are normally conducted in compliance with GLP
30/12/2009 55Nepal Research Foundation.,
Birgunj, Nepal.
DRUG METABOLISM & PHARMACOKINETIC STUDIES
30/12/2009 56Nepal Research Foundation.,
Birgunj, Nepal.
In-vivo DMPK Studies
In vivo preclinical ADME studies are routinely performed in rat and dog with radiolabeled compounds usually using carbon-14 or tritium isotopes
However, all other animal species or isotopes can be considered
These studies are performed using all common routes of administration
This includes mass balance, tissue distribution, bile cannulation and dermal absorption studies
Pharmacokinetic evaluation using validated WinNonLin software is performed in house
30/12/2009 57Nepal Research Foundation.,
Birgunj, Nepal.
In-vitro DMPK Studies
Cytochrome P450 studies Metabolite Profiling metabolite Identification
& Metabolic Stability Studies Blood Distribution Studies Drug Transport Using Caco-2 cell and skin
Absortion, transport and Metabolism studies
30/12/2009 58Nepal Research Foundation.,
Birgunj, Nepal.
Plasma Protein Binding
The plasma protein binding of a drug is determined in plasma of different species (including human) using either equilibrium dialysis or ultrafiltration
In addition, the stability of the drug in plasma is investigated
These studies are performed using radiolabeled and non-labeled compounds
30/12/2009 59Nepal Research Foundation.,
Birgunj, Nepal.
Drug –Drug Interaction Studies
Using pooled human liver microsomes or other in vitro metabolism models
The interaction of a drug on the metabolism of another drug is determined
30/12/2009 60Nepal Research Foundation.,
Birgunj, Nepal.
Special Analytical Studies
Metabolite Identification/Elucidation This provides metabolite identification in sample
available from in vitro and in vivo studies, as well as from environmental fate studies
The method is then adapted for the specific compound
Generally method development is finished within three days
Data are generated using LC-PDA-MS analysis with data-dependent MS-MS
Additional MS analysis is possible, as well as accurate mass determination
30/12/2009 61Nepal Research Foundation.,
Birgunj, Nepal.
HISTOPATHOLOGICAL & BIOCHEMISTRY STUDIES
30/12/2009 62Nepal Research Foundation.,
Birgunj, Nepal.
Hematology
Complete Blood Count (CBC) with no Differential (WBC, RBC, HCT, HGB, MCV, MCH, MCHC, MPV, RDW, CHCM)
Platelet (automated count), Reticulocytes Differential Count Complete Blood Count (CBC) with
Differential
30/12/2009 63Nepal Research Foundation.,
Birgunj, Nepal.
Clinical Chemistry Alanine Aminotransferase Albumin Alkaline Phosphatase Aspartate Aminotrasferase Calcium Chloride Cholesterol Creatinine Glucose Prealbumin A/G/ Ratio
Globulin, Phosphorous Potassium Sodium Total Bilirubin Total Protein Triglycerides Urea Nitrogen Osmolality Anion Gap
30/12/2009 64Nepal Research Foundation.,
Birgunj, Nepal.
BiomarkersAdvanced Lipid biomarkers
HDL-C LDL-C VLDL Cardiac risk ratio Apo A1 Apo B FFA
Cardiac biomarkers
BNP Troponin I Myoglobin CK CK-MB Homocysteine Hs-CRP D-Dimer
30/12/2009 65Nepal Research Foundation.,
Birgunj, Nepal.
LIST OF EQUIPMENTS
30/12/2009 66Nepal Research Foundation.,
Birgunj, Nepal.
General Pharmacology Equipments
Auto analyzer (semi-automated) Blood cell counter UV Spectrophotometer HPLC CO2 incubator with air jacket ELISA microplate reader Inverted microscopes Non Invasive BP Measurements (Tail cuff) Physiograph Polygraph
30/12/2009 67Nepal Research Foundation.,
Birgunj, Nepal.
General Pharmacology Equipments
Deep freezer (420 L) Electrophoresis Cooling microcentrifuge CNS Pharmacology related instruments Student kymographs Respiratory pumps Langendorff’s apparatus UGO Basile plethysmometer UGO Basile analgesiometer UGO Basile ECT
30/12/2009 68Nepal Research Foundation.,
Birgunj, Nepal.
List of Critical Equipment for Pharmacology
IVC units Boyle’s apparatus Hot plate Plethysmometer Automated cell counter (Mythic 18) Plate reader (Biotech) Plantar Aesthesiometer
30/12/2009 69Nepal Research Foundation.,
Birgunj, Nepal.
List of Critical Equipments for ADME and PK
HPLCs (Water, Agilent) LC/MS/MS (API 3000, Applied Biosciences) Spectramax-Quartz plate reader (Molecular
Devices) Zymark Evaporator (Caliper) Vacuum manifield (Whatman) Apricot Centrifuge (Hettich) Shaker incubator (Jeotech)
30/12/2009 70Nepal Research Foundation.,
Birgunj, Nepal.
List of Critical Equipment for Assay Development
FLIPR (Molecular Devices) Janus Liquid Handaling system
(PerkinElmer) Novostar-single channel robotic plate reader
(BMG Labtech) Fluostar-single channel robotic plate reader
(BMG Labtech) Victor (PerkinElmer) Cell Harvesters (Tomtec, Skatron)30/12/2009 71
Nepal Research Foundation., Birgunj, Nepal.
Wallac Beta and Gamma counter (PerkinElmer) Inverted fluorescence microscope (Nikon TE 200U) CO2 incubator (Thermo) Ultracentrifuge (Beckman coulter) Cold centrifuge (Beckman coulter) Cryopreservation Equipment (Thermo) Hydra (Matrix) Lyophilizer
List of Critical Equipment for Assay Development
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Birgunj, Nepal.
List of Critical Equipments for Molecular Biology and Gene
Expression Gradient PCR machines (Biometra, Applied
Biosciences) Gel Imaging System Bio-Rad) Shaker incubators (VWR, Zhicheng) DNA Electrophoresis system (Owl) UV-Vis Spectrophotometer (Beckman
Coulter) Electroporator (Bio-Rad)
30/12/2009 73Nepal Research Foundation.,
Birgunj, Nepal.
List of Critical Equipments for Molecular Biology and Gene
Expression FPLC (Bio-Rad) Gel dryer (Bio-Rad) Southern/Northern blot chamber (Amersham
Biosciences) Western transfer apparatus (Bio-Rad) Table-top refrigerated centrifuges (Beckman
Coulter, Eppendroff) Protein Electrophoresis (Bio-Rad)
30/12/2009 74Nepal Research Foundation.,
Birgunj, Nepal.
PHARMACOLOGY LAB LAY OUT (ANIMAL PHARMACOLOGY LAB LAY OUT (ANIMAL
HOUSE)HOUSE)
Entra
nce
Sterile room for exchange of clothes,
belongings etc
Restricted Entry
HOD’s
Office
Discussion/Meeting Room
Library
Senior and Junior
Research Officers
Well equipped Sample’s Analysis Room
Restricted Entrance
Quarantine room
Dosing Room
Animal House for MICEAnimal house for RATS
Operation Room for invasive
procedures Animal House for
Rabbits
Animal House
for Guinea
Pigs
Dosing
Room
Mating Room for
Rats and Mice
30/12/2009 75Nepal Research Foundation.,
Birgunj, Nepal.
Rodent Facility
Preclinical research facility encompasses a state-of-art building with a total built up area of 33,000 sq. ft. with 32 Rodent experimental rooms (200 sq. ft) and separate provision of rooms for quarantine of animals and 5 procedure rooms wherein different pharmacological studies are carried out as on need basis
The facility is registered with the CPCSEA (Committee for the Purpose of Control and Supervision of Experiments on Animals)
30/12/2009 76Nepal Research Foundation.,
Birgunj, Nepal.
International Guidelines
ICH www.ich.og International Conference on Harmonization
FDA www.fda.org
Food and Drug Administration
EPA www.epa.org
Environmental Protection Agency
OECD www.oecd.org Organization for Economic Co-operation & Development
CPCSEA www.cpcsea.com Committee for the Purpose of Control and Supervision of Experiments on Animals
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Birgunj, Nepal.
Thanking You
30/12/2009 78Nepal Research Foundation.,
Birgunj, Nepal.
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