Preclinical Services

The preclinical division of Vimta Labs is driven by a mission to develop reliable and reproducible scientific data while maintaining a healthy balance between animal ethics, welfare and experimentation.

Vimta provides the following core services for domestic and global pharmaceutical, biotech, and medical device companies:

  • PHARMACOLOGY

  • DMPK/ADME

  • SAFETY PHARMACOLOGY

  • TOXICOLOGY

  • BIOANALYTICAL


Experiments are designed to generate adequate and robust data in exploratory and regulatory areas using both in vitro and in vivo models. Preclinical evaluation studies are conducted in different modules per the sponsor requirements and in accordance with national and international guidelines (ICH and US FDA, OECD)

NCEs are screened using in vitro systems to facilitate lead optimization and lead identification and in vivo models like mice, rats, guinea pigs, rabbits and beagle dogs through different routes for proof of principle, fast track kinetics and safety assessment, all with GLP compliance.

VIMTA TOXICOLOGY - TRACK RECORD
  • The Toxicology division was initiated in 1992 at Vimta’s Cherlapally facility.

  • This facility was certified for GLP by Standard Australia Quality Assurance Services (SAQAS) in the year 1997.

  • Our initial focus was on agricultural & industrial chemicals. Beginning in 2000, the focus shifted to pharma and biotech industries.

  • To meet the current requirements in the area of drug discovery research, activities at the Cherlapally facility were suspended in the year 2005 while a new facility was being designed and built.

  • The present facility was started in the year 2008 at S.P. Biotech Park, Genome Valley, Turkapally.

  • The new 33, 000 sq. ft., state-of-the-art facility was inaugurated in August 2009, delivering a full set of preclinical services.

Invitro Cytotoxicity - ISO 10993 Part 5

Test for local effects after Implantation - ISO 10993 Part 6

Primary Skin irritation Test - ISO 10993 Part 10

Intracutaneous irritation test - ISO 10993 Part 10

Other Irritation studies - ISO 10993 Part 10

  • Vaginal Irritation

  • Penile irritation

  • Skin irritation

  • Eye irritation

Guinea Pig Skin sensitization test - ISO 10993 Part 10

Systemic toxicity Study

  • Acute & Long TermISO 10993 Part 11

Genotox

  • AMES - ISO 10993 Part 3

  • Chromosomal Aberration - ISO 10993 Part 3

  • Micronucleus Test - ISO 10993 Part 3

  • Mouse Lymphoma - ISO 10993 Part 3

Haemolysis - ISO 10993 Part 3

In Vivo pharmacology efficacy studies provide critical “proof of concept” for advancing an NCE.

At present, Vimta has the requisite expertise to deliver on the following efficacy models across therapeutic areas.

Pain and Inflammatory models
  • CFA/Carrageenan induced hyperalgesia in rats

  • Carrageenan and LPS induced paw edema in rats

  • LPS (i.p) induced TNF α release in rats

  • Acetic acid induced writhing in mice

  • Oxazolone induced ear edema in mice

  • TNBS - induced colitis in rats

  • Ova sensitized model of asthma in Guinea pigs

Thermal & Mechanical Hyperalgesia

Assessment of thermal hyperalgesia is carried out in rats and or mice using the following methods: Hot plate or radiant heat in the Tail Flick model, or in the Plantar test using Hargreaves method. Mechanical hyperalgesia is assessed using Randall-Selitto apparatus for measuring paw pressure. Tactile allodynia is measured using the Electronic Von Frey filaments.

Neuropathic pain models
  • PSNL induced neuropathic pain in rats

  • Diabetic Neuropathic Pain (DNP) in rats

STZ induced Type I diabetes in SD rats.

Appetite Suppression in SD rats.

HFD/STZ (low dose) induced Type II diabetes in SD rats (Under Validation)

List of Instruments Pharmacology

Instruments Name

Make

Plantar Test

UgoBasile

Digital Plethysmometer

Pan Labs

Tail-Flick Meter

Pan Labs

Paw Pressure Meter

Pan Labs

Electronic von Frey

Pan Labs

Anaesthesia Gas system

Matrix

Multi Mode Reader

Thermo

Incapacitance meter

IITC

Plate washer

Thermo

Auto Track system

Columbus Instruments

Hot plate

Columbus Instruments

Grip Strength Meter

Columbus Instruments

Rota Rod (Rotamex-5)

Columbus Instruments

Startle Responder

Columbus Instruments

Digital Thermometer

Pan Labs

Active and Passive Avoidance System

Pan Labs

Whole body Plethysmography System

EMKA Technologies

Telemetry System for conscious dogs

EMKA Technologies

Nanions Port a patch hERG assay

Nanion Technologies

In vitro ADME screens provide critical information for lead optimization and selection of the appropriate species for conduct of toxicological studies. Elucidation of the interaction of a test substance under investigation using human cytochrome(s) P450 (CYP) and other drug-metabolizing enzymes is important for predicting its potential for interaction with other drugs which is of great relevance in the planning of clinical studies.

At present Vimta has capability to conduct the following studies.

Absorption studies

  • Cell permeability assays (Caco2 and MDCK cells)

  • Parallel Artificial Membrane Permeability Assay (PAMPA)

  • Everted Gut Sac Permeability Assay

Drug – Drug Interaction studies

  • Cytochrome P450 Inhibition

Metabolic stability, metabolic identification and estimation of reactive metabolites using liver microsomes

  • Clearance and half life determination

Physico-chemical Studies

  • Solubility studies for NCE – Kinetic and Equilibrium solubility

  • Determination of Log P and Log D

Plasma / Whole blood studies

  • Plasma Protein Binding – mouse, rat, rabbit, dog and human

  • Plasma / Whole blood stability – mouse, rat, rabbit, dog and human

DMPK studies are conducted to determine the disposition of the drug and its metabolites using suitable animal models. At Vimta we offer the following DMPK services

  • Single or multiple dose (s) – in mice & rats

  • Oral &/or IV or IP (or intended) route

  • 2-6 animals/dose; 5-12 time points / client specific designs

  • PK study in cannulated animals as per client's requirement

  • Tissue distribution studies

  • In -vivo blood – brain barrier penetration studies

End-points

  • Oral BA

  • Elimination half life (t1/2) Clearance (Cl) Volume Distribution (Vd)

  • Metabolite identification

VIMTA provides its customers with high quality analytical data regarding the identity and concentrations of compounds in laboratory animal body fluids and tissues, as well as the concentrations in formulations and test systems. Methods are developed and validated in-house, or are implemented based on available methods with the sponsor, followed by cross-validation. The performance of the method complies with FDA, ICH other international guidelines. We also provide customer specific services.

The salient features of our bio-analytical services include

  • 25 Mass specs covering technologies such as single quadrapole, triple quadrapole, ion trap, LC-MS/MS, GC-MS/TOF, HRGCMS, ICP-MS

  • Multiple HPLCs with PDA and fluorescence detectors

  • Different matrices tested include rat plasma; dog plasma; & monkey plasma

  • Proprietary method development & validation on NCE's & method transfer

  • Metabolite identification

At present Vimta can offer the following bio analytical services

  • Bio-analytical support for in vitro & in vivo DMPK

  • Standalone Bioanalytical services

  • Proprietary method development

  • Method validation

  • Method transfer

  • Sample analysis using HPLC / Mass Specs

Safety Pharmacology is the study of the mechanism by which drugs and new chemical entities (NCEs) act on a living system to provide an assessment of the pharmacological profile in areas other than the intended therapeutic use. These studies will be conducted as identified in the ICH (International Conference on Harmonization) guideline on safety pharmacology studies for human pharmaceuticals (S7A and S7B). At present Vimta has the following expertise.

Respiratory system :

  • Whole body plethysmography in guinea pigs & rats

Central nervous system:

  • Modified Irwin test in rat.

  • Motor activity in rat and mice.

  • Motor in-coordination in rat and mice.

  • Pro-convulsant activity (chemical induced (PZT) and electroshock) in rat.

GI Safety :

  • Gastrointestinal motility test in rat

Vimta has many years of experience and has qualified staff to design and conduct toxicology studies in accordance with international guidelines (ICH, OECD, FDA, and Schedule Y). The studies are conducted in compliance with Good Laboratory Practice (GLP) regulations.

  • Maximum Tolerable Dose(MTD).

  • Dose Range Finding (DRF).

  • Single Dose Toxicity studies.

  • Repeated dose sub-acute Toxicity studies (14, 28 days).

  • Sub-chronic and Chronic Toxicity studies.

  • Skin, mucous membrane and eye irritation studies.

  • Skin Sensitization Studies.

  • Biocompatibility studies on medical devices as per ISO 10993.

Other Studies:

  • Pharmacopoeial Bioassays.

  • Cytotoxicity.

Genetic toxicology studies are conducted early in the safety testing program of pharmaceuticals, medical devices, chemicals, food additives, etc., Vimta Labs offers comprehensive range of in vitro and in vivo Genetic toxicology studies in compliance with GLP principles as per OECD, US-EPA (OPPTS), EEC guidelines.

Services - Regulatory Genetic toxicology/Mutagenicity Studies

  • Bacterial Reverse Mutation Test (Ames test) - OECD 471.

  • In Vitro Mammalian Chromosome Aberration Test in Cultured Human Peripheral Blood Lymphocytes/CHO cell line - OECD 473.

  • In Vitro Mammalian Cell Gene Mutation Test (using mouse lymphoma L5178Y tk +/- cells) - OECD 476.

  • In Vitro Micronucleus Test - OECD 487.

  • In Vivo Mammalian Erythrocyte Micronucleus Test - OECD 474.

  • In Vivo Mammalian Bone Marrow Chromosome Aberration Test - OECD 475.

Screening Studies :

In addition, we offer various screening versions of the genotoxicity tests, which are useful during the early development of new products/early stages of drug development. These can be designed to meet the specific requirements of each sponsor.

  • Fluctuation AMES Test/AMES II Test.

  • Mini AMES Test.

  • In Vitro Micronucleus Test - Miniature Version.

Vimta has state of the art pathology facility. Our services include:

Histopathology

  • Routine and specialized necropsy procedures of different species of animals.

  • Tissue processing and slide preparation.

  • Routine (H&E) and special staining techniques.

  • Microscopic evaluation of slides by Veterinary Pathologists.

Clinical Pathology Services:

  • Hematology (multispecies).

  • Serum biochemistry.

  • Urinalysis.

Clinical Pathology Services:

  • Spin Tissue Processor STP 120 (Microm).

  • Embedding Center EC 350 (Microm).

  • Fully Motorized Microtome (Microm).

  • HMS 740 Robotic Strainer (Microm).

  • Advia 2120 hematology Analyzer (Siemens).

  • Coagulometer Start 4, (Diagnostica Stago).

  • Haeraeus Multifuge X3R Centrifuge (Thermo).

  • Uriscan pro II (Merck).

  • Vitros 250 Chemistry Analyser (J&J).

  • BX51-microscope (Olympus).

  • CX41-microscope (Olympus).

  • CX21-microscope (Olympus).

  • Zoom stereo microscope (Olympus).

CPCSEA Registration No. 156/ 1999 (Committee for the Purpose of Control and Supervision of Experiments on Animals Government of India)

VIMTA's Preclinical facility is accredited by AAALAC International

The state-of-the-art barrier-maintained animal facility is designed to conduct experiments using rodents, rabbits and beagle dogs. The facility has been constructed with clean and return corridor concept. The facility is located on 3 floors and has total area of 33, 000 square feet. Service areas and labs are located on the ground floor, animal holding rooms are located on the first floor and 17 AHUs are located on the second floor. The animal holding rooms are constructed of clean panels and the floors have epoxy coating. The small laboratory animal facility has

  • 27 animal holding (200 sq feet and Class 10,000) rooms each with ante room and dynamic pass boxes. 6 procedure rooms (Class 10,000). The animal facility is constructed in the modules of 5,10, 12 experimental rooms to provide dedicated place and services to clients as required

  • Separate facility with IVCs for conducting experiments using immune-deficient mice and ADME studies.

  • The dog facility has 70 SS kennels, [12 sq. ft. each], with a comfortable perch, liberal exercise area, socialization options between the kennels.

  • The preclinical division has achieved Gold level of certification for the Green Building Standards from the Leadership in Energy & Environment Design (LEED), of Indian Green Building Council (IGBC) in January 2010. Currently, this is the only animal facility in India with such certification. This certification substantiates the facility's commitment to saving energy and effective management of bio-hazards.