Introduction to Preclinical Toxicological Pathology
Over 50 Years Scientific Excellence AAALAC GLP Chicago CRO
1. Over 50 years of Scientific Excellence
AAALAC Accredited
GLP Service Provider
Chicago, IL
2. US based research institute and nonclinical CRO, Chicago, IL
Over 110 full-time staff, greater than one third with advanced degrees
Staff tenure averages 10.4 years
Study director tenure averages 18+ years
Highly experienced, skilled and tenured animal technicians
Published team of experts in their respective fields
Onsite veterinary, clinical pathology, histopathology
Comprehensive nonclinical services portfolio with niche expertise
High volume of repeat work
3. Government, academic, and commercial sponsors
◦ Internal grant and contract writing team
◦ Grant writing support and collaborations
Complete nonclinical testing and development services
Drugs, vaccines, biologics, nutraceuticals, biopesticides
Regulatory expertise in EPA and FDA guidelines
◦ Regulatory support
Extensive capabilities in inhalation and aerosol sciences
Multiple species capabilities and experience
◦ Rodent, rabbit, guinea pig, ferret, nonhuman primate, canine, mini-pig
Specialized animal models
o Oncology, infectious disease, respiratory, wound
Robust bioanalytical capabilities, preclinical-clinical
Complete micro and molecular biology capabilities
4. Located in Chicago, IL
Over 125,000 square feet
ABSL/BSL 2-3
Small and Large Animal Facilities
Surgical Suites
Xenograft Isolation Facilities
Inhalation Suites for small and large animals
Analytical Chemistry Laboratories
Micro-Molecular Biology Laboratories
Over $20 million invested in last 7 years
5. AAALAC Accredited
OLAW Assured
Good Laboratory Practice
ICH/OECD Compliant
Select Agent Registered
DoD Security Clearance
Active US Army Biosurety Program
ABSL-BSL 2/3
6. In Vivo Pharmacokinetics and ADME , including radiolabeled
◦ Method development and validation
Genetic Toxicology : mutagenesis, cytotoxicity, chromosomal damage
◦ Ames Assay
◦ Micronucleus Assays, in vitro and in vivo
◦ Comet Assays
◦ Neutral Red Cytotoxicity Assay
◦ Mouse Lymphoma Assay
◦ Structural Chromosome Aberration Assay
Cell Lines: CHO, HPBL, CHL, V-79
Safety Pharmacology: Core Battery Assessment
◦ Cardiovascular Physiology: Telemetry
◦ CNS Function: Neurobehavioral Assessment
◦ Respiratory Physiology: Plesmography
◦ Rodent, Canine, Guinea pig, Nonhuman Primate
Systemic Toxicology including Aerosol Dosing
◦ Experience with a wide range of administration routes and methods
◦ All technicians have 5 or more years experience and BS/MS degrees
◦ Rodent, rabbit, guinea pig, canine, nonhuman primate, mini-pig
7. Immunotoxicology
◦ ELISA Development
◦ Detection of Cytokines
◦ Plaque Forming Cell Assay
◦ Natural Killer Assay
◦ In Vivo Host Defense Models
◦ Murine Local Lymph Node Assay
◦ Lymphocyte Blastogenesis Assay
◦ Cytotoxic T-lymphocyte Assay
Complete Analytical Chemistry Services
Complete Molecular and Microbiology Services
Smooth transition to Phase I
◦ method cross-validation and early clinical PK-TK analysis
9. Nonclinical: Complete Assay Development and Validation
◦ Pharmacokinetics and ADME
◦ Drug metabolite profiles
◦ Biomarker identification
◦ Protein binding
◦ Tissue and fluid drug concentrations
◦ Drug-drug interactions
◦ In vitro metabolism
◦ Extractables and leachables
Extensive expertise in small molecule trace level analysis
◦ Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS)
Extensive expertise in elemental trace level analysis
◦ Inductively coupled plasma -mass spectrometry (ICP-MS)
Clinical: Smooth transition from pre-IND to Phase I: 30 days
◦ Cross validation of preclinical PK methods for clinical use
◦ Early clinical PK-TK sample analysis
Biographies and publications available
10. Types of Studies
PK and ADME
Toxicology
Pulmonary sensitization
Sensory irritation
Lung inflammatory studies
Expertise
Generation of complex mixtures of vapor/particulate atmospheres
Generation and monitoring of nanoparticles
Generation of viable aerosols
Modeling of pulmonary deposition
Custom designs for dispersion of powders, liquids and mixtures
Pulmonary function measurements
11. Aerosol Generation Systems
Nebulizers, Spray nozzles, Powder dispersion
Custom designed systems
Aerosol Atmosphere Monitoring Systems
Aerosol concentration
Particle size distribution
Gas concentration
Chemical analysis
Respiratory Disease Models
Asthma
COPD
Pulmonary fibrosis
Lung cancer
12. IITRI Process and System
Bacterial cells are diluted with PBS to specified concentrations
◦ Osmolarity of cells is maintained
◦ Washing of cells is unnecessary
Six simultaneously firing nebulizers require less pressure
◦ Lower pressure - less cellular shearing = higher viability
◦ Lower pressure - less foaming - no antifoam = higher viability
100% humidified air provided to animals without dilution air
◦ Higher humidity – less desiccation = higher viability
◦ No dilution air – higher humidity = higher viability
Comparison of Spray Factor with
Multiple Concentrations
1e+6 1e+7 1e+8 1e+9
Benefits of IITRI System
1e+0 1e+0
1e-1 1e-1
High-efficiency delivery of viable microorganisms 1e-2 1e-2
High accuracy for delivery of specified doses
1e-3 1e-3
Spray Factor (Fs)
1e-4 1e-4
1e-5 1e-5
Biographies and publications available 1e-6 1e-6
1e-7 1e-7
1e-8 1e-8
1e-9 1e-9
1e-10 1e-10
1e+6 1e+7 1e+8 1e+9
Starting culture concentration (CFU/mL)
13. Infectious Disease Model Development
Vaccines, anti-bacterials, anti-virals
◦ Immunogenicity, Efficacy, PK, Safety-Toxicology
◦ Various dosing routes including aerosol
◦ BSL2-3
Influenza experience specifically
◦ Ferret and guinea pig models, transmission models
◦ Multiple seasonal influenza strains, H3N2 and H1N1
◦ Pandemic H1N1 and H5N1 strains including highly pathogenic H5N1
Extensive Pathogen and Toxin Library
Evaluation of decontamination materials
Validation of bio-detection methods
14. Microbiology
◦ ELISAs
◦ Hemagglutination inhibition assays
◦ Viral neutralization assays
◦ Bacterial/viral extraction and isolation
Molecular Biology
◦ Real-time, quantitative PCR
◦ Microbial forensics
◦ Gene expression, cloning and DNA sequencing
◦ Biomarker identification and detection
Biographies and publications available
15. IITRI is the largest nonclinical contractor to the NCI
◦ Screening
◦ Efficacy
◦ Pharmacokinetics
◦ Full safety testing, toxicology
Cancer Biology: In Vitro and In Vivo Studies
◦ Mechanism of action
◦ Drug-drug interactions
◦ Drug concentration in tissues
◦ Gene expression, cloning and DNA sequencing
◦ Well established xenograft models
◦ Development of new xenograft models
◦ Highly experienced in the testing of natural compounds
◦ Growth initiative: orthotopic model development
Biographies and publications available
16. IITRI and EPA, 1985-1994
◦ Cooperative agreement with EPA
◦ Assessment of toxicity and pathogenicity testing methods and protocols
◦ This work markedly changed FIFRA, now OPPTS guidelines
Well-versed in US and Canadian guidelines
Member of the Biopesticide Industry Alliance
Complete Safety and Pathogenicity Testing
◦ Acute eye irritation
◦ Acute dermal irritation
◦ Skin sensitization
◦ Dermal toxicity and pathogenicity
◦ Injection toxicity and pathogenicity
◦ Pulmonary toxicity and pathogenicity
◦ Oral toxicity and pathogenicity
◦ Reproductive toxicity
◦ Immunotoxicity
◦ Storage stability
Biographies and publications available
17. Incision Site Wound: topical treatment
◦ Models surgical site wounds and cuts, various bacteria
Groin Wound: topical treatment
◦ Models MRSA (or other) SC infection with sepsis
Deep Puncture Thigh Wound: topical, injectable, PO
◦ Models deep puncture wound often leading to sepsis
Peritonitis Wound, two types
◦ Caecal ligature and puncture: to assess direct site treatment
◦ IP injection of bacteria: to assess surgical gels used internally
18. Scientific excellence since 1936
Highly experienced, tenured and published team
Hands on study directors for personalized attention
Technical expertise for a variety of complex and diverse programs
Fully integrated nonclinical developmental services
Many long-standing industry relationships including co-authored work
Applied regulatory expertise in support of full program development
Robust analytical capabilities to support nonclinical and early clinical studies
From grant writing support to development, efficacy and safety testing, IITRI supports all
your nonclinical in vivo and analytical needs at a single US facility.
