Evreux, France: Safety Assessment

Geographically located near Paris, our Evreux, France facility performs general toxicology and specialized studies which include ocular, DART, musculoskeletal toxicology, as well as gene and cell therapy. The facility also supports safety pharmacology programs and laboratory sciences services for both preclinical and clinical samples analyses.

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Charles River provides safety assessment services in Evreux, France

Safety Assessment Services

With more than 85 animal rooms and 450 staff, our safety assessment facility in Evreux, France has been providing services to the pharmaceutical, biopharmaceutical, chemical, and agrochemical industries for more than five decades. The site includes BSL1 and BSL2 capabilities and is well placed to support studies for a range of modalities including:

  • Small molecules
  • Peptides and proteins
  • Antibodies
  • Vaccines
  • Antisense oligonucleotides
  • Gene therapies
  • Cell therapies
  • Controlled-release formulations
  • Radiotherapy or imaging agents

Our Scientific Advisory Services group (SAS) can assist you with inquiries pertaining to your customized study design and drug development project. In addition, our Innovation group is available to listen to your needs and anticipate developments in our industry.

General Toxicology: Acute to Chronic Toxicology

Our General Toxicology portfolio includes a comprehensive range of standard and specialist study designs and can support both rodent and non-rodent studies associated with safety pharmacology in all major laboratory models.

Standard and non-standard studies in rodent and non-rodent species with strong and comprehensive analytical capabilities are available, allowing assessment of immunotoxicity, immune responses, or biodistribution of gene and cell therapies.

Ranging from acute to carcinogenicity studies, including the transgenic animal's experience, the expert team at Evreux, France conducts studies via all standard and some non-standard routes of administration. These routes include:

• Subcutaneous infusion
• Intravitreal
• Intrathecal/intracerebral
• Intraarticular

• Intranasal
• Intravesical
• Intraperitoneal

The Experts at Evreux, France Have Extensive Knowledge of:

Safety Pharmacology studies including stand-alone and integrated safety pharmacology endpoints in rodent and non-rodent regulatory toxicology studies. Robust and tailored cardiovascular, respiratory, and central nervous system study designs (cross-over design or parallel groups) are provided in males and/or females for each drug candidate, including small and large molecules, biotechnology-derived pharmaceuticals, vaccines, and anti-cancer pharmaceuticals, in agreement with the ICH recommendations: ICH S7A, ICH S7B, ICH E14/S7B Q&A, ICH S6, ICH S9, and ICH M3 (R2).

• Core Battery Safety Pharmacology Studies
• Continuous telemetry recording (24-hour post-dosing) in fully implanted animal models,
• Continuous analysis of cardiovascular parameters including arterial blood pressure and qualitative and quantitative ECG parameters,
• Pharmacokinetic/Pharmacodynamic (PK/PD) data analysis and reporting,
• Least Significant Difference (LSD) for each parameter, especially QTc.
• Respiratory system in rat and mouse (whole-body plethysmography)
• Central nervous system in rodents (functional observational battery)
• Integrated Safety Pharmacology Endpoints in Toxicology Studies
• Cardiovascular system in non-rodents (Jacketed External Telemetry, minimally invasive telemetry (PA-C10 implants) or fully implanted telemetry (M11 implants)
• Respiratory system in rodents (whole-body plethysmography) and non-rodents (Respiratory inductive plethysmography (RIP), JET)
• Central Nervous System in rodents and non-rodents (functional observational battery)
• Follow-up Studies/Supplemental Studies
• Renal/Urinary:
• Clinical chemistry
• Gastrointestinal
• Gastric emptying
• Intestinal motility

Ocular toxicology studies have been conducted via route including topical instillation, intravitreal, subretinal, and subconjunctival. The team includes board certified veterinary ophthalmologists and their study designs leverage techniques which include:

• Split lamp biomicroscopy
• Indirect ophthalmoscopy
• Ocular imaging
• Schirmer test (lachrymal secretion)
• Tonometry
• Electroretinography (qualitative/quantitative assessment of retinal function)
• Optical coherence tomography (high-resolution imaging of eye anatomy and structure)

Musculoskeletal toxicology has been performed at the Evreux, France facility using a range of models and study designs including osteoporosis, osteoarthritis, fracture healing, biomechanical testing, histomorphometry, and skeletal development.

In vivo and ex vivo services are available for evaluation of pharmacological and toxicological effects of products on the skeleton, which include:

• DXA for bone mineral density measurements
• Radiology
• A full panel of validated bone biomarkers
• In-house histomorphometry for static and dynamic parameters

Carcinogenicity studies have been conducted at the Evreux facility, more than 100 studies have been conducted via oral gavage, dietary admixture, dermal, and parenteral administration.

Developmental and Reproductive Toxicology (DART)
The DART team at Evreux provides developmental and reproductive toxicology (DART) program planning and individual study design. These expert scientists conduct fertility, early embryonic development, and implantation.

• Embryo-fetal development (EFD)
• Pre and post-natal development (PPND)
• Juvenile studies

Therapeutic and Prophylactic Vaccines

We have comprehensive experience in conducting developmental toxicity as well as local and repeated dose toxicity studies in rodent and non-rodent species with a variety of vaccine types, including:

• Inactivated vaccines
• Adjuvanted proteins
• Live attenuated vaccines
• Viral vectors (eg. Measles, adenoviruses, yellow fever, up to BSL2)
• Plasmids
• RNA

In addition to the in vivo phases, proof of exposure can be performed by measuring the humoral as well as cellular immune responses.

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Cell and Gene Therapy

We are a single service provider for in vivo studies and laboratory sciences (preclinical and clinical), including evaluation of immune responses against vectors and transgenes, as well as biodistribution and shedding evaluation by qPCR, RT-qPCR and ddPCR. Our site has comprehensive experience with a variety of vectors and cells, including AAVs, adenoviruses, naked nucleic acids, vaccinia viruses, as well as mesenchymal and embryonic stem cells.

View our Cell and Gene Therapy Portfolio

Immunotoxicity

• TDAR assay for immunostimulation or immunosuppression
• Evaluation of the specific immune response (humoral or cellular)
• Immunophenotyping by flow cytometry
• Immunohistochemistry
• TCR
• Humoral (ADA), TDAR (multiple species), Nabs (cell-based assays)
• Cellular (ELISPOT, ICS)

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Biodistribution Studies

Biodistribution studies as well as shedding data are required by regulatory authorities. We combine our extensive experience in toxicology with our expertise in molecular biology to offer you advice and conduct robust biodistribution/shedding studies that meet the expectations of regulatory guidelines. We leverage diverse matrices from the whole panel of animal models and development states to investigate a wide range of compounds (vaccines, cells, plasmids, viruses, etc.) in preclinical as well as clinical settings.

With a suitably qualified detection system (e.g., qPCR or ddPCR) and adapted specific necropsy procedures, we can detect as little as five copies of gene or cell DNA in any tissue or fluid in any species, including humans. Additional expertise in specialty areas such as DART allows us to perform complete investigations covering integration, expression, persistence, and shedding.

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General Toxicology

• OECD 407 Repeated Dose 28-day Oral Toxicity Study in Rodents
• OECD 408 Repeated Dose 90-Day Oral Toxicity Study in Rodents
• OECD 409 Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents
• OECD 410 Repeated Dose Dermal Toxicity: 90-Day

DART

• OECD 414 Rat and rabbit prenatal developmental toxicity studies
• OECD 416 Two generation reproduction toxicity studies
• OECD 421 Reproduction/developmental toxicity screening test
• OECD 422 Combined repeat dose toxicity study with the reproduction/developmental toxicity screening test
• OECD 426 Developmental neurotoxicity study
• OECD 443 Extended one generation reproductive toxicity study
• OPPTS 870-7800 Developmental immunotoxicology & immunotoxicity

In Vivo Studies

• Uterotrophic assay (rat) OPPTS 890-1600 / OECD 440
• Hershberger (rat) OPPTS 890-1400 / OECD 441
• Pubertal female (rat) OPPTS 890-1450
• Pubertal male (rat) OPPTS 890-1500

Analytical Chemistry
Available supporting toxicology studies are provided below:

• Formulation and dietary analysis
• Dose confirmation
• Method development and validation

Bioanalytical services are available for both small and large molecule studies from discovery through to clinical trials in our state-of-the-art laboratory facilities. The scientists leverage the latest techniques, including PCR, flow cytometry, ELISA, and multiplex for large molecule analysis.

Immunology scientists in Evreux support both nonclinical studies and clinical sample analyses using immuno- and cell-based assays as well as flow cytometry. Our team can support the following immunology testing:

• Development and validation of immunological methods
• Immunophenotyping
• Immunotoxicity
• Clinical biomarkers
• Cell-based functional assays
• ADA, nAbs

List of the equipment:
• Flow cytometers
• Beckman Coulter Navios (10 parameters)
• Miltenyi MacsQuant 10 and 16 parameters
• ELISPOT reader
• CTL ImmunoSpot S6
• ELISA
• ECLIA (MSD)
• Bioplex

Genomics
Charles River Evreux provides specialty genomics services to support all phases of drug development, from discovery and preclinical studies, through clinical trials. This includes Gene Expression Profiling and genotyping in usual tox species and human. It also includes Next Gen sequencing library preparation. Sequencing runs (MiSeq, NovaSeq) and data analysis are proposed with preferred partners.

Molecular Biology – PCR

• qPCR,
• RT-qPCR
• Relative-quantitative RT-PCR
• ddPCR: Recent acquisition of the Digital droplet ddPCR cf video Keith Sutton
• Biodistribution, shedding
• NGS
• RNASeq, WGS, WES, targeted sequencing
• Microarrays
• Gene expression profiling, genotyping (incl. DMET), CNV

Scientist using microscope in laboratory

View Our Quick Guide to ddPCR
Key considerations for planning studies and case studies: evaluating multiple vectors
Watch the video

Anatomic and Clinical Pathology
The following pathology-based services are available at our Evreux site:

• Necropsy
• Histology
• Histopathology
• Peer review
• Hematology
• Biochemistry

• Urinalysis
• ROTEM analysis
• Immunohistochemistry
• In-situ hybridization
• Tissue-cross reactivity (TCR)

Speak with our team

Charles River Evreux, France is a full-service site, where we work with all species and dosing routes. We have a particular expertise in ocular, DART, musculoskeletal toxicology, and gene and cell therapy. In addition, we offer full support in pathology, safety pharmacology, and lab sciences with an increased focus on immunology and large molecules.

Innovation paired with a history of delivering clients needs are key factors that bring significant value to your program. Our Evreux experts are engaged in local and global networking to stay up to date with new regulatory guidance and technologies.

Frequently Asked Questions (FAQs) About Evreux, France: Safety Assessment