SERVICES

Service Overview

• Over 30 years of experience in toxicology and related fields for the testing of chemically and biologically derived pharmaceuticals, veterinary products and agricultural and industrial chemicals
• Experimental Protocols drawn up according to international guidelines (OECD, EMA, FDA, EPA, etc.)
• International acceptability of reports by major regulatory authorities and pharmaceutical companies
• Full in-house support by means of bioanalytics as well as clinical diagnostics and pathology services
• Ability to customize studies in order to meet specific needs

AnaPath Research offers services in the areas listed below:

Safety Assessment

General Toxicology Capabilities

• Full range of classical general toxicology studies
• Acute, single administration, PK, maximum tolerated dose, repeated dose administration and 2, 4,13, 26 or 52 week duration studies
• Vaccine and immunotoxicity studies
• Daily administration or cyclical dosing
• iv (bolus and infusion), oral, sc, ip, dermal
• A team of Senior Study Directors with an average of 10+ years of experience, with knowledge of current regulatory guidelines
• Collaborative and interdisciplinary exchange of information, ideas, results and scientific discussion between departments and sites
• Significant experience with biologicals
• Capacity, capabilities and expertise to provide meaningful and compliant results within study plan driven and accelerated timelines
• Broad NCE experience

Developmental & Reproductive Toxicology

Broad experience on:

• Combined repeat dose/reproductive toxicity screening: OECD 422
• Multigenerational studies: OECD 416
• Reproduction/Developmental Toxicity Screening Test: OECD 421
• Embryo toxicity studies: OECD 414

Test effects on:

• Fertility (Segment I) in males, females, both sexes
• Embryo fetal development (Segment II) with visceral and skeletal examination
• Embryo fetal development assessment (including fetal TK)
• Pre- and post-natal development (Segment III)
• Maternal function

Core competence: dedicated Study Directors and technical staff

Fetal pathology done in-house

Veterinary Medicinal Drug Development

• Tolerance in target species (TAS)
• Residue depletion
• Pharmacokinetics
• Vaccine efficacy studies

Duration of immunity and challenge

• Screening services
• Others

Safety Pharmacology and PD models

• Safety Pharmacology performed since 1995
• Core battery studies to support Phase I clinical trials
• Designed as standalone investigations or included on toxicology studies
• Includes Cardiovascular (CV) assessment

Anaesthetized and Telemetry (implanted and non-invasive)

• Irwin test
• Functional Observational Battery (FOB)
• Supplementary studies: renal function, GI transit/emptying time
• Research models
  CNS, CV, respiratory, GI, renal, inflammation, metabolism

Analytical & Bioanalytical Capabilities

Dose Formulation Preparation

Scientific experience in the preparation of formulations (solutions, emulsions, suspensions, capsules and patches) to support in vivo studies in multiple species.

Ability to work under Aseptic conditions, pH and Osmosis monitoring

Dose Formulation Analysis

Feasibility, method Development, Transfer, Validation and Dose Formulation Analysis for small and large molecules by LC-UV, LC-Fluorescence, LC-MS/MS.

Platforms: HPLC Alliance 2695 (Waters), UV2487/2489 (Waters), Fluorescence 2475 (Waters)

Bioanalysis of Large Molecules by ImmunoAssay

We offer ImmunoAssay experience in PK/TK method transfer, development and validation for the determination of biotherapeutic products to support regulated and non-regulated preclinical programs for a variety of species and biological matrices. We work to ensure the assay design is fit-for-purpose, understanding the bioanalytical challenge of first-in-class products, biosimilars and biobetters while working with biologics such as recombinant proteins, monoclonal antibodies and vaccines as well as gene therapy based products for which we study the targeted expression of specific transgenes.

ADA method development and validation

The immunogenicity of a biological drug can affect drug exposure interfering in the interpretation of the toxicity and safety data in non-clinical programs. We offer experience in method transfer, development and validation for specific anti-drug antibody measurement through screening and confirmatory of samples as standard characterization. Titering and Neutralization assays such as competitive enzymatic or cell-based assays are additional services offered at preclinical stage as per customer-oriented decision.

Biomarkers determination

Biomarker concentrations in biological matrices provide key information on therapeutic effect. We offer advice on the best analytical approach for biomarker measurement and interpretation applying fit-for-purpose basis within drug development program to implement development and validation of methods.

Immunophenotyping and Cellular Response Assays

Flow cytometry is a powerful tool to provide valuable insights in immune-related responses derived from the effect of biological drugs or vaccines. Immunophenotyping allows the study and characterization of cell populations within immune system and we offer standard and uncommon population panels for the most relevant preclinical species. Functional assays allow the study of cellular responses against specific stimulus such as T cell responses against viral vectors used in gene therapy. We are currently offering both assessments at non-regulated level although our challenge is to fit flow cytometry into the current regulatory landscape.

Platforms: Canto II (BD)

Bioanalysis of Large Molecules by LC-MS/MS

Method Development/Feasibility, fit-for purpose validation, validation and sample analysis of Peptides, Oligonucleotides (SiRNA, DNA) and Proteins by LC-MS/MS detection in multiple species and matrices.

Platforms: UPL Acquity (Waters), API4000 (Sciex), API5000 (Sciex), Triple Quad 6500+ (Sciex)

Pesticides, Phytosanitary Residue studies (Validations and ILV)

Development and Validation or Intra-Laboratory Validation (ILV) method for residue in feed, food and environmental matrices by LC-MS/MS

Clinical Sciences

Biochemistry Area

AnaPath Research S.A.U. offers a Standard Biochemistry panel for the different species used in the Pre-clinical studies and have a wide panel of biomarkers to meet our sponsor’s needs.

Platforms

Cobas 6000

The Cobas 6000 analyzer series delivers high quality results based on experience, innovation and advanced technologies:

• Reference-traceable results with minimal lot-to-lot variance
• High quality results by ensuring sample and result integrity
• Innovative tests on a standardized, automated platform
• Results standardized to other Cobas serum work area systems

The Cobas 6000 series is a fully automated, random-access, software Indications for controlled system photometric analysis intended for use qualitative and quantitative in vitro determinations using a wide variety of tests. It is optimized for high throughput workloads in the professional environment using a combination of ion selective electrodes (ISE) and a photometric analysis unit.

The module c501 analyzer is a fully automated, discrete clinical chemistry analyzer intended for the in vitro quantitative/ qualitative determination of analytes in body fluids (Serum/Plasma/Urine/LCR and Others).

AnaPath Research S.A.U. offers a Standard Biochemistry panel for the different species used in pre-clinical studies and have a wide panel of biomarkers to accomplish our sponsor’s needs.

Cobas u 411

The Cobas u 411 urinalysis analyzer is a semi-automated, bench top analyzer which is designed to read strips via reflectance photometry. This equipment is designed to measure bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, urobilinogen and color (if selected). These measurements are useful in the evaluation of renal, urinary and metabolic disorders. These measurements are useful in the evaluation of renal, urinary and metabolic disorders.

Hydrasys

Protein electrophoresis is a well-established technique routinely used in clinical laboratories for screening of protein abnormalities in serum and other biological fluids. The semi-automated gel electrophoresis instrument, HYDRASYS, has been developed to provide a complete test panel with high sensitivity and good resolution.

We offer three types of separation for our Sponsors:

• The charge of the proteins, in a specific pH buffer. Serum proteinogram
• The isoelectric point, in a specific pH gradient.  Antibody isotyping
• The molecular weight of the proteins, in an SDS-agarose gel.  Protein characterization

Hematology and Hemostasis Area:

AnaPath Research S.A.U. offers a standard hematology and hemostasis panel for the different species used in pre-clinical studies.

Technology available:

Advia 120 & 2120

The ADVIA 2120 Hematology System was released as a bench-top analyzer designed for medium- to large-volume laboratories. This flow cytometry–based system uses light scatter, differential white blood cell (WBC) lysis, and myeloperoxidase and oxazine 750 staining to provide a complete blood cell count, a WBC differential, and a reticulocyte count. A cyanide-free method is used to measure hemoglobin colorimetrically. In addition to its capability for analyzing peripheral blood specimens, the analyzer is also equipped to analyze cerebrospinal fluid samples.

The instrument uses 5 channels to analyze blood samples: a hemoglobin channel for the colorimetric measurement of hemoglobin concentration, a combined RBC and platelet channel, 2 channels (the peroxidase and lobularity/nuclear density channels) for WBC counts and differentials, and a reticulocyte channel. In the 2 WBC analysis channels, for example, the blood sample is diluted approximately 50-fold so that 1 µL of diluted suspension corresponds to 0.02 µL of the undiluted blood sample. Forty microliters of this suspension are passed through the flow cell for analysis; therefore, 0.8 µL of whole blood is analyzed in each WBC analysis channel

STA Compact Max 2

STA Compact Max® is a fully automatic coagulation analyzer. A central processing unit controls instrument functions such as management of patient results, quality control, support for instrument maintenance, and workload optimization. The instrument utilizes barcoding of test reagents, calibrators and controls that facilitate their use on the system and permits reagent management simple. The proposed device has same fundamental technological characteristics as the predicate device based on Chronometry Measurement Principle and Photometry Measurement Principle.

The detection of chromogenic assays is based on the absorbance (optical density: O.D) of monochromatic light passing through the cuvette as a chromogenic reaction takes place. Incident light entering the cuvette is partially absorbed by the reaction mixture as it passes through. The transmitted light is measured and converted to absorbance. The Beer-Lambert law is applied to convert absorbance to concentration of the substance being measured.

Microscopy evaluation

AnaPath Research S.A.U. offers an extensive experience on microscopy evaluation of hematological and urinary sediment. At our facilities we have different microscopy technologies to cover all our sponsor’s needs on the preclinical and non-clinical evaluations.

Molecular biology area:

At AnaPath Research S.A.U., we offer the full GTMP non-clinical study program to fulfill the proper benefit-risk assessment for the use of such products in humans. AnaPath Research S.A.U. is ready to fully coverage both toxicological investigations and pharmacokinetic studies designing the GTMP non-clinical development on a risk-based approach.

Both the GMTP risk associated and the potential in vivo will directly depend on the transgene or other recombinant nucleic acid sequences, the vector backbone (i.e. viral, bacterial or plasmid derived sequences) and the excipients including any carrier or support medical device employed.

GTMPs are constructed with specific purposes in terms of the biodistribution, cell or tissue specificity and tropism, and gene product expression. In principle, most safety aspects of GTMP might be anticipated when combining knowledge on the components to the biodistribution profile in vivo and at the cellular level where appropriate. The toxicological evaluation of the GTMP will therefore consist mostly of the search for anticipated or predicted toxicities, their characterization, and when possible, their quantification (dose-response relationship) to define the safe conditions of human therapeutic use.

Pathology

• Board-certified pathologist on the site
• In close cooperation with AnaPath pathologists in Switzerland, re-known scientists with up to 35 years of experience

Necropsy and Histology

• Necropsy and Histology

  Surveillance of Board certified pathologist

  ·       Experienced group of technicians

  ·       Technicians cross trained in necropsy and histology techniques on a wide range of rodent and nonrodent species

  Routine histotechnique at site possible

  Larger studies and special technologies in cooperation with AnaPath Services GmbH in Switzerland

Please contact us for more information: info@anapath.ch