Harlan Laboratories. Contract Research Services

Transcription

1 Harlan Laboratories Contract Research Services

2 Table of Contents Overview 2 General Services General Toxicology 3 Reproductive Toxicology in Rats and Rabbits 3 Pathology and Histopathology 4 Genotoxicity and Cell Biology 4 Metabolism 5-6 Environmental Sciences 7 Regulatory Affairs 7 Pharmaceutical Services Special Services for Pharmaceuticals 8 9 Medical Device Services Special Services for Medical Devices 10 Chemical Services Special Services for Chemicals 11 Agrochemicals and Biocides Special Services for Agrochemicals and Biocides 12 Alternative Methods Special Services in Alternative Methods Screening Assays 15 Global Availability and Support

3 Harlan Laboratories Contract Research Services is a leading provider of essential, non-clinical contract research and services to the chemical, pharmaceutical, biotech, medical device and agrochemical industries. Our focus is providing the services you need to optimize the discovery and safety of new medicines and chemicals. Our CRS division has nearly 1,300 employees in 7 countries, but we act locally, understanding the value of close relationships and collaboration with our clients. As important as good customer service and relationships are, it s really all about scientific excellence. Today, research is outsourced more than ever, and researchers need to have confidence in their supplier partners. Stability, reliability, consistency, and quality are all essential. That s what Harlan Laboratories offers with our passion for science and decades of proven expertise, both in research models and services and in contract research services. Our Expertise throughout our European facilities offers a full range of non-clinical services to the Pharmaceutical, Chemical and Agrochemical industries: Toxicology and Pathology Genotoxicology and Cytotoxicity testing Analytical Chemistry Physico-chemical Analysis Bionanalytics, including Pharmaco/Toxicokinetic evaluation Protein Analytics Immunology Animal Metabolism Pharmacodynamic models Screening in early product development Predictive and Mechanistic Toxicology Pharmaceutical Quality Control Ecotoxicology Environmental Fate Plant Metabolism Regulatory Affairs and Consulting Program Management Contract Archiving Quality Assurance 2

4 General Toxicology Harlan Laboratories performs a full range of toxicology studies to support the pharmaceutical, chemical, and agrochemical industries. These studies are performed to fulfil global regulatory guidelines and in accordance with good laboratory practice regulations. We offer: Single dose and repeat dose studies through to 2 year carcinogenicity studies in rodents and chronic studies in non-rodents Rodents, rabbits, dogs, minipigs and primates Transgenic mice including transgenic carcinogenicity studies Routes of administration include oral (manual or semi-automated gavage, capsule and feeding), dermal, intraperitoneal, intravenous (bolus and short infusion manually and by continuous infusion in catheterized rats and dogs), intramuscular, subcutaneous, intratrachaeal, intranasal and inhalation Neurotoxicity In Vivo Micro-CT evaluation especially for bones General Services Reproductive Toxicology in Rats and Rabbits Our experienced toxicologists, fetal pathologist and technical staff have extensive expertise and offer a complete range of developmental and reproductive toxicology studies, including: Fertility Embryo-fetal development Pre and postnatal development Maternal Function Routes of administration include oral, dermal, intraperitoneal, intravenous (bolus and infusion), intramuscular, subcutaneous and infusion, intrachaeal and inhalation. 3

5 Pathology and Histopathology The Pathology department is highly experienced in the performance of all general study types including cancer studies and neurotoxicity, medical devices and exotic animals. It s our goal to always finish your studies on time and to your complete satisfaction. Necropsy of all general animal species routinely used in regulatory toxicology General Services Routine tissue trimming, embedding, cutting and staining including Special stains Special techniques - Cryomicrotome - Plastic embedding and ultrathin sections - Diamond saw and grinding Automated immunostaining In situ hybridization Fish and snail pathology Microscopy - Stereomicroscopy - Fluorescence - Image analysis Genotoxicity and Cell Biology Our study directors are recognized experts in the fields of cell biology, genetic toxicology and biocompatibility. They are members of both national and international scientific working groups and are actively engaged in research projects sponsored by the national and EU authorities. As such, our clients benefit from advice based on the latest scientific and regulatory thinking. Their expertise in the areas of immunology, molecular biology and in vitro metabolism is also available to our clients. Our services include: Ames, HPRT, mouse lymphoma test Chromosome Abberation test in vitro and in vivo, both bone marrow and mouse spermatogonia Photomutagenicity Micronucleus test in vitro and in vivo UDS assay in vitro and in vivo COMET assay in vitro and in vivo DNA binding/adducts 4

6 Metabolism Harlan Laboratories supports our clients with ADME studies and programs in all phases of the discovery and development pipeline. These include Lead Optimization programs by in vitro and in vivo PK screening as well as PK or toxicokinetic profiling, mass balance and distribution studies for development projects. Metabolite profiling and identification provides a rationale for the selection of animal species in toxicology studies. Harlan also provides solutions for occupational and consumer studies of chemicals, agrochemical products and veterinary pharmaceuticals. General Services 14 C, 3 H and 125 I radiolabelled materials All relevant species All routes of administration CYP interaction, inhibition, induction Metabolic stability with liver S9 preparation Phase II reactions such as conjugation Protein binding Dermal penetration HPLC, GC, CE, TLC LC-MS/MS and GC-MS QWBA Real time QPCR ICP-MS Analytics and Bioanalytics The analytical departments of Harlan Laboratories feature state of the art instrumentation and methodology. Techniques routinely available for new chemical entities include HPLC, HPLC-MS/MS, High-Resolution-MS, GC, GC-MS, GPC, UV/Vis, FTIR, AAS, NMR. For biologicals ELISA, RIA, electrophoresis, capillary electrophoresis, real-time QPCR and in vivo bioassays are routinely available. 5

7 General Services Analytical data and results will be provided to support toxicological and ecotoxicological studies such as: Development of analytical methods and method validation Analysis of dose preparations for toxicity studies Bioanalysis in plasma, urine and tissues Biochemical analysis of biologics In vivo bioassays In addition, we have extensive experience and expertise in the testing of physico-chemical properties for agrochemical and chemical notifications and can offer the complete package of physico-chemical tests required for REACH. Services include: Physico-chemical properties Hazardous properties Pharmacopoeial and other physicochemical testing Quality control of drugs and API under GMP Establishment of specification for API drug development Stability testing (according to ICH guideline) Product characterization Identification and characterization of active ingredients and formulations Testing of containers and packaging materials Certification of reference material Polymer Analysis Migration studies and modeling Extraction studies Identification of unknown contaminants, metabolites and degradation products Workplace exposure monitoring Residue analysis 5-batch analysis Storage stability to EU/OPPTS US EPA guidelines Client-defined, custom-designed analytical studies 6

8 Environmental Sciences Harlan Laboratories offers extensive expertise in the conduct of aquatic and terrestrial ecotoxicological studies on industrial chemicals, agrochemicals, biocides, and more recently on veterinary medicines and pharmaceutical products. The studies are performed according to the international test guidelines of OECD, EU, EPA/OPPTS, ISO and JMAFF. For a refined risk assessment, higher-tier studies under more realistic environmental conditions are available, such as studies in water sediment systems in laboratories or outdoor mesocosm pond studies. Our ecotoxicity team has extensive expertise in the evaluation of difficult substances with challenging physio-chemical properties (e.g. low water solubility, instability, volatility, strong adsorption or colouration). The ecotoxicology team is supported by the modern analytical laboratories of Harlan Laboratories which offer analytical techniques suitable for use in all biophysical matrices encountered in ecotoxicological studies. Services include: Acute and chronic Daphnia toxicity Algal growth test Acute and chronic toxicity in fish Fish early-life-stage tests Fish bioaccumulation Earthworm toxicity Activated sludge respiration inhibition Ready and inherent biodegradation Hydrolysis tests Adsorption/desorption screening and full studies Soil sediment simulation tests Effects on soil microorganisms Effect on non-target arthropods including honeybees Soil litterbag studies Short term plant toxicity Field Trials and plant metabolism Environmental fate and modeling Avian studies Mesocosm studies General Services Regulatory Affairs Our regulatory affairs managers and risk assessment experts provide seamless development and execution of regulatory strategies. We maintain close contact with major authorities and thus remain on top of the latest developments in regulatory requirements. Our vast experience and in-depth knowledge ensures that your projects are managed by true experts who enable you to bring your product to market in a rapid and cost-effective manner. Further details on our regulatory affairs services are presented in the industry specific special services sections. 7

9 Special Services for Pharmaceuticals The first administration of a new investigational medicinal product in human beings is a very important step in the development of a new drug. The transition from non-clinical to early clinical development marks a milestone in the destiny of the compound. Pharmaceutical Services Based on our extensive and globally recognized expertise, the multidisciplinary team of specialists in Harlan Laboratories provides a truly integrated service for new chemical entities, biologicals and phytopharmaceuticals from strategic development planning, through project performance, up to dossier preparation for clinical trial authorization or product registration. Pharmacokinetics (PK) and Bioanalytics The early screening of several lead substances to select candidates for a pre-clinical test program is one of the most critical points in the drug development. Harlan Laboratories has established a range of rapid and cost effective of techniques to make drug discovery more successful. Single and multiple administration via oral, dermal, intraperitoneal, intravenous (bolus and infusion), intramuscular, subcutaneous and infusion, intrachaeal, intranasal and inhalation. Rodent, Rabbit, Dog, Minipig and Primate Automated blood sampling Bioanalytics including LC-MS/MS, High-Resolution-MS, GC-MS, RIA, Elisa, CE and RT-PCR Bioanalytics and toxicokinetics (TK) in toxicity studies PK evaluation using WinNonLin or PK Solutions Pharmacodynamic and efficacy models for central and peripheral nervous system, cardiovascular and respiratory system, gastrointestinal and renal system and specialized efficacy studies Safety Pharmacology Safety pharmacology studies contribute to the risk assessment of NCEs in pharmaceutical development by identifying undesirable pharmacodynamic properties before the first administration to man (Phase I). These studies can also be used to evaluate adverse effects observed in toxicology or early clinical trials and to investigate the mechanism(s) underlying them. Safety pharmacology studies should be performed in accordance with the ICH S7A and S7B guidelines and to GLP. Harlan Laboratories has over 14 years of experience in performing safety pharmacology studies in compliance with GLP and our services include: Central Nervous System - Modified Irwin Screen - Functional Observation Battery Cardiovascular system - Telemetered animals - Anaesthetized animals - In vitro HERG-1 assay - Guinea Pig papillary muscle Wide range of disease models 8

10 Special development programs Our experienced program managers offer specialized, tailor made programs of toxicological studies fulfilling all requirements which are necessary for taking a new active pharmaceutical ingredient first time in man. These Fast-intoman study packages benefit from comprehensive program management in very close cooperation with the client and provide a time- and cost-effective way to initiate clinical phase I studies. Regulatory Affairs Our regulatory affairs managers and risk assessment experts work together to provide seamless development and execution of regulatory strategies. We stay in close contact with major authorities and thus remain on top of the latest developments in regulatory requirements Advice on regulatory requirements and testing strategies Negotiation with authorities Preparation of registration dossiers Compilation of dossiers including CTD Follow up on submissions Dealing with deficiency lists and variations Preparation of drug master files Applications for certificates of suitability Expert opinions, reviews Pharmaceutical Services 9

11 Medical Device Services Special Services for Medical Devices Harlan Laboratories knows the special regulations for the assessment of efficacy and safety for medical devises. Our deep expertise can assist with the regulatory requirements, testing and reporting required for approval. Our Services include: In vitro assessment of cytotoxicity and genotoxicity In vitro and in vivo assessment of efficacy / feasibility of intended application In vivo safety assessment according to standard guideline procedures Toxicological profiling of materials for Medical Devices Material characterization by biological and toxicological evaluation with acute, subacute, subchronic and chronic toxicological studies. Biocompatibility testing of Medical Devices according to ISO Strategic planning of study program Genotoxicity, carcinogenicity, reproductive toxicity Hemocompatiblity, static and dynamic systems Cytotoxicity Implantation, e.g. vascular stents Vascular grafts, bioresorbable polymers, histopathology Osseous implantation (rabbit and sheep) with CT-/MRI-monitoring Intracranial implantation Determination of ethylene oxide sterilization residuals Determination of material degradation, irritation and sensitization 10

12 Special Services for Chemicals REACH offers the opportunity to reduce costs, perform the appropriate testing according to regulations, and provides guidance on producing quality Technical Dossiers and Chemical Safety Reports. Harlan Laboratories has vast experience in the worldwide regulatory process for substances and our experts assess data requirements, ensure that the correct tests are performed, and achieve acceptance in the regulatory community. Services include: Strategic planning of test programs and registration strategies Project Management and study monitoring of test programs in toxicology, analytics and ecotoxicology Data analysis and interpretation Data compensation appraisals Liaison with regulatory authorities and scientific bodies Expert reports Risk assessments Product safety evaluations Dossier compilation and submission Literature searches/inventory checks Product defense Regulatory compliance check and certification Chemical Services Task force and consortia management REACH Services Client representation and consortia management SIEF negotiations Portfolio examination Development of intelligent testing strategies Preparation of Technical dossiers and chemical safety assessments Seminars and training 11

13 Special Services for Agrochemicals and Biocides Agrochemicals and Biocides Our vast experience and in-depth knowledge ensures that your projects are managed by experts who help bring your product to market quickly and cost-effectively. Services include: Test programs Strategic planning of intelligent test programs Project Management and study monitoring of test programs Data analysis and interpretation Design and protocol development of higher-tier studies Residue studies Development and Registration Regulatory compliance review Dossier preparation (OECD/BPD) and submission Electronic submissions (CADDY, IUCLID, R4BP) Regulatory Support Data compensation appraisals Liaison with regulatory authorities and scientific bodies Expert reports Literature searches/inventory checks Risk assessment across all scientific disciplines Regulatory strategies Liaison with regulatory agencies Product defense Product safety evaluations Issue management Partnership Task force management and technical advice, client representation Management of global registrations Management of development programs Global logistics Seminars and training 12

14 Special Services in Alternative Methods Harlan is committed to the principle of the 3R s of Replacement, Reduction and Refinement and few companies can match our range of services and depth of experience in non-animal alternative methods. Harlan is pro-active in the development and use of in vitro and ex vivo methods. We partner with researchers and clients in pre-validation and formal validation studies to achieve your testing needs. Alternative Methods Immunology Lymphocyte blastogenesis Analysis of natural killer cell activity Analysis of macrophage function Reproductive Toxicology Embryonic mouse stem cell test Toxicity Assessment of starting dose for acute systemic toxicity using neutral red uptake Target organ toxicity with primary cells and cell lines from various organs Balb/3T3 neutral red uptake for phototoxicity evaluation Eye Irritancy Bovine corneal opacity and permeability test (BCOP) Hens egg chorionallantoic membrane test (HET-CAM) Reconstructed human corneal epithelial models (e.g. EpiOcular) Rabbit and chicken enucleated eye tests (REET and CEET) Skin Corrosivity Reconstructed human skin equivalents for assessment of skin corrosivity (OECD 431) Transcutaneous electrical resistance assay (TER; OECD 430) Corrositex membrane barrier test (OECD 435) 13

15 Skin Irritancy Reconstructed human skin equivalents for assessment of skin irritancy (EU B 46) Barrier Systems Dermal Penetration using flow-through diffusion cells and human and pig isolated skin systems Intestinal uptake using CaC0-2 absorption models Blood brain barrier systems using pig brain microvascular endothelial cells Alternative Methods In vitro metabolism Interspecies comparative metabolism Selective human cytochrome P450 metabolism Human cytochrome P450 inhibition MDR (P-glycoprotein) interaction assays Carcinogenicity Cell transformation assays for detecting initiators and promotors: Balb/c3T3 assay and Syrian hamster embryo (SHE) cell assayselective In silico Safety Modelling Structure activity relationship by computerized models (TOPKAT and DERE) 14

16 Screening Assays Harlan Laboratories knows assay development, early screening and drug development. Compounds at early research stages are screened to gain data on safety and efficacy. Tests include in vitro screening of adsorption, distribution, metabolism, excretion, and toxicity and genotoxicity. Alternative Methods Comet assay DNA binding/adducts Screening Ames, micronucleus, mouse lymphoma and Comet assays Cell-based assays Phototoxicity Cytotoxicity Cell line characterization Cell transformation assay (SHE, Balb/c 3T3) Biochemical analysis Virus safety Prion Safety Other endpoints PK screen with automated blood sampling QT prolongation (HERG)/other ion channels Oxidative stress Endocrine toxicology Enzymology 15

17 Global availability and support At Harlan Laboratories, we have a passion for science and for developing solutions to help you achieve your goals. With contract research services, research models, and laboratory animal diets, we can support your global research needs. Contract Research Services Our locations in 7 countries across Europe and Asia can assist with non clinical research needs for the pharmaceutical, biotech, medical device, chemical, and agrochemical industries. Research Models and Services Harlan Laboratories is committed to the welfare and quality of our animal models. Our veterinary, scientific and quality staffs are committed to ensuring our company mission helping you do research better. Our global line of research models includes mice, rats, rabbits, dogs and primates. Teklad Global Diets Harlan Laboratories Teklad Diets have grown to be an industry leader by concentrating on reducing research variables through quality and consistency. Our nutritionists provide support and technical advice to help with your diet selection. Our diets are available world-wide. 16

18 Find out more We re Harlan Laboratories. And we re here to help you do research better. Contact your sales representative or visit us on the Web at Corporate Headquarters Harlan Laboratories, Inc Allison Pointe Blvd., Suite 400 Indianapolis, IN Harlan, Harlan Laboratories, the Harlan logo and Teklad Global Diets are trademarks of Harlan Laboratories, Inc Harlan Laboratories, Inc.