our fields of activity
GenoSafe’s services cover all phases of drug candidate development, in compliance with GxPs (GLP, GMP, and GCP). This comprehensive analytical expertise ensures the continuity and consistency you need as you progress in your development.
As a key player in the field for more than 20 years, our services are based on a strong analytical expertise, technical know-how and methodological skills.
The objective of a preclinical evaluation is to demonstrate the in vivo proof of concept of a therapeutic approach and then determine the safety and efficacy of a drug candidate by assessing risks associated with their future use in humans.
Based on a strong analytical expertise, GenoSafe supports its customers in the design, development, validation and implementation of the analytical methods used in this context, in particular to document the in vivo proof of concept, biodistribution / biodissemination and immunogenicity of a drug candidate.
Results generated in this context contribute to promote the transition to clinical trials and anticipate the adaptation of similar methods in humans. GenoSafe is GLP certified by the French Agency (ANSM) since 2008.
Services available
- Transfer and / or development and validation of analytical methods
- Extraction of genetic materials from various tissues / cells from different species
- Biodistribution / biodissemination analyses
- Immunogenicity studies (neutralizing antibodies, total antibodies, cellular and inflammatory responses)
- Detection and quantification of biomarkers
- Gene and protein expression in different tissues
Equipments & platforms
- Spectrophotometry
- Flow cytometry
- Nucleic acid purification and extraction (manual and automated)
- PCR platforms (qPCR / RTqPCR / dPCR)
- Luminometry
- ELISA platform
- Meso Scale Discovery (MSD-ECLA)
- Western blot (traditionnal or capillary)
- ImmunoSpot (ELISpot / FluoroSpot)
Our references
GLP certified since
Involved in more than
Extraction methods available for
FOCUS 1:Â Characterization of the biodistribution / expression profile
Characterizing the biodistribution profile of a drug candidate after in vivo administration is a major component of preclinical development.
Biodistribution studies, as required by regulatory authorities, are intended to determine the presence and/or the persistence of a drug candidate (vector or cellular agent) in targeted biological tissues or fluids. These studies also highlight the biodissemination in non-targeted tissues and fluids, as well as their transmission in germ lines.
Biodistribution data, combined with other preclinical safety indicators, are used to determine whether the presence of the drug candidate or the expression of a gene of interest leads to an adverse effect in the animal.
Through its expertise, GenoSafe is involved in any step of the biodistribution analysis from the extraction of genetic materials to the detection/quantification of DNA/RNA by molecular biology methods (qPCR, RTqPCR). The data generated are used to document the biodistribution and expression profile of the administered product in the different tissues and fluids.
GenoSafe performs biodistribution studies in compliance with Good Laboratory Practices (GLP).
FOCUS 2:Â Immunogenicity assessment
Biotherapies, such as vaccination, seek to activate the immune system, while others, such as gene therapy or cell therapy, seek to prevent the activation of the immune system. It is therefore crucial to evaluate and characterize the immune response. GenoSafe offers tests to monitor the immune response in animals in preclinical studies.
Through its expertise, GenoSafe performs the following studies :
- Measurement of anti-virus/vector neutralizing factors/antibodies: cell-based neutralization assays to quantify neutralizing factors/antibody titer, before and after treatment.
- Detection of total/circulating antibodies: based on ELISA and MSD-ECLA assay, quantification of antigen-specific antibodies.
- Evaluation of cellular immune response: detection and determination of the frequency of cytokine secretory cells (or other proteins) by ELISpot (Enzyme-Linked ImmunoSpot) / flow cytometry.
Several methods are already validated for certain species or can be transposed from generic methods available for clinical testing. Depending on the needs, GenoSafe develops, qualifies and validates custom methods.
Our immunogenicity tests are performed, for a large majority, in accordance with Good Laboratory Practices (GLP).
FOCUS 3:Â Detection / Determination of Biomarkers
Using our ELISA and MSD-ECLA platforms, we can analyze, detect and quantify a wide range of proteins of interest (cytokines, chemokines, growth factors, cardiac biomarkers, etc.) from preclinical samples. Our capabilities include the ability to perform multiplexing analyses and the measurement of a large number of analytes in small volumes.
These services are performed in accordance with Good Laboratory Practices (GLP).
FOCUS 4:Â UshTher Project
This European collaborative project aims at evaluating the safety and efficacy of an innovative gene therapy approach for retinis pigmentosa (USHIB) in humans. As a member of the consortium, GenoSafe contributed to the biodistribution/biodessimination study of the gene therapy candidate and the immunogenicity study.
See also:
GenoSafe supports its customers by developing, validating and performing analytical methods in accordance with Good Manufacturing Practices (GMP), to assess the different quality attributes of innovative therapeutics (safety, strength, identity, in vitro potency/efficacy and purity). Backed by a strong analytical expertise, we offer several standardized test platforms and the development of tailored-made tests, specific to your product.
GenoSafe helps you evolve in a complex and poorly standardized technical and regulatory environment. We promote a flexible approach, tailored to your schedule, and an open communication with our customers.
Services available
- Transfer and/or development and validation of analytical methods
- Physical and infectious titration
- Detection of replication competent viruses
- Identity tests
- Cell characterization
- Cell-based expression assays (RNA/proteins)
- Potency tests
- Detection of impurities: residual DNA and proteins or other impurities from the production process
Equipments & platforms
- Spectrophotometry
- Luminometry
- Automated nucleic acid extraction
- Western blot (traditionnal or capillary)
- PCR platform (qPCR / RTqPCR / dPCR)
- Flow cytometry
Our references
More than
Quality control performed
on any kind of batches
research-grade, preclinical, clinical and commercial batches
Nearly
Customers based in more than
composed of pharmas, biotechs, CMO/CDMO and academic institutions
FOCUS 1: AAV Gene Therapy
GenoSafe offers various tests, generic or custom-made, to evaluate the different quality attributes of AAV vector batches :
- Determination of infectious titre (TCID50) and VG/GI ratio
- Determination of physical titre in viral genome (solid particles / VG qPCR / VG digital PCR) or in AAV capsids (total particles/ELISA)
- Determination of the full/empty capsid ratio
- Detection of impurities, contaminants from the manufacturing processes (residual plasmid and host cell DNA, residual host cell proteins, antibiotics, BSA and other residual reagents…)
- Detection of replicative viruses (rcAAV)
- Determination of purity (% VP1/VP2/VP3)
- Cell-based expression assays and RNA/protein quantification
- Cell-based assays to measure biological activity (potency)
- Stability studies involving physical, infectious titration or expression/potency testing (long-term stability, accelerated, forced degradation, with or without medical device…)
- Identification of relevant cell lines and production/characterization of cell banks
- Extractable volume measurement
Methods are developed and validated in accordance with GMP regulations and ICH guidelines.
FOCUS 2: Lentivirus Gene Therapy
Equipped with BSL3 laboratories, GenoSafe offers a range of tests, generic or custom-made, to evaluate the quality attributes of lentiviral vector batches :
- Detection of replicative viruses (RCL) on the product, producing cells or therapeutic target cells
- Determination of physical titre (DNA or p24 protein)
- Determination of infectious titer (infectious genome, cytometry)
- Determination of the number of copies of lentivirus per cell (VCN)
- Detection of impurities, contaminants from manufacturing processes (residual plasmid and host cell DNA, residual host cell proteins, antibiotics, BSA and other residual reagents…)
- RNA/protein expression and quantification
- Cell-based assays to measure biological activity (potency)
- Stability studies involving physical, infectious titration or expression/potency testing (long-term stability, accelerated, forced degradation, with or without medical device…)
- Identification of relevant cell lines and production/characterization of cell banks
- Extractable volume measurement
These methods are developed and validated in accordance with GMP regulations and ICH guidelines.
FOCUS 3: Cell Therapy
GenoSafe offers tailor-made tests to assess the quality attributes of cell therapy products:
- Cell counting and viability determination
- Cell characterization by cytometry (example: determination of CAR expression, product purity, viability…)
- Identity determination by qPCR (example: identification of expression markers)
- Cytotoxicity test for T-cells and/or CAR T-cells
- Potency tests
- Determination of CAR-T cell transduction efficacy by qPCR
- Determination of the number of viral copies (VCN) and detection of replicative viruses (RCL) for cell therapies resulting from a lentiviral vector
- Detection of replicative viruses (rcAAV) for cell therapies derived from an AAV vector
- Stability studies based on viability measurement or expression/potency (long-term stability, accelerated, forced degradation, with or without medical device…)
These methods are developed and validated in compliance with GMP regulations and ICH guidelines.
See also:
Clinical development of advanced therapy medicinal products (ATMPs) requires, as part of the follow-up/ inclusion of patients, the performance of specific analytical tests to monitor the immunogenicity and shedding of the drug candidate – a process that relies on a strong analytical expertise.
As an expert in the evaluation of ATMPs, GenoSafe supports its customers from the inclusion of patients enrolled in clinical studies to their analytical follow-up, by implementing in-house methods or tailored-made tests, developed and validated in compliance with the FDA/ICH M10 recommendations.
Services available
- Transfer and/or development and validation of analytical methods
- Immunogenicity:
- detection of neutralizing factors/antibodies (titration, screening and confirmatory test)
- detection of total antibodies/anti-drug antibodies (ADA)
- evaluation of the cellular response
- Detection and quantification of biomarkers
- Shedding of the product
- Tissue expression (RNA/protein) – clinical biopsy testing
- Immune cell profile by flow cytometry
Equipments & platforms
- Spectrophotometry (detection of nucleic acids)
- Flow cytometry
- Luminometry
- Nucleic acid purification and extraction (manual and automated)
- PCR platforms (qPCR / RTqPCR / dPCR)
- Western blot (traditionnal or capillary)
- ELISA platform
- Meso Scale Discovery (MSD-ECLA)
- ImmunoSpot (ELISpot / FluoroSpot)
Our references
Since 2015, nearly
Nearly
FOCUS 1: Titration of neutralizing antibodies / factors
A major problem encountered during gene therapy is the immune response directed against the vector and/or against the transgene product.
Neutralizing factors/antibodies block the entry of viruses/vectors into the transduced cells. It is now widely described that there is a high prevalence of AAV vectors in humans and in various species due to exposure to the wild virus. It is therefore recommended to monitor the level of neutralizing antibodies/factors before and after administration of the gene therapy product during the clinical trial.
GenoSafe offers cell-based neutralizing assays to evaluate and quantify the titer of specific neutralizing antibodies/factors of viruses/vectors, before and after treatment. These tests are available and validated in humans for some serotypes, but can be developped to meet the specific needs of clients. These methods are easily adaptable to other species in preclinical studies.
FOCUS 2: Titration of total antibodies / biomakers
GenoSafe offers ELISA or ECLA tests to detect/titer antibodies of interest directed against the therapeutic candidate (gene therapy vector, transgene protein, vaccine, etc.). Among the biomarkers of interest, we propose the detection of a large panel of pro-inflammatory cytokines to document the immune response. We have generic and validated tests in humans that can be easily adapted to other species in preclinical studies.
GenoSafe has the expertise and tools to develop methods that meet the specific requirements of its customers.
FOCUS 3: ARDAT
The ARDAT (Accelerating Research & Development for Advanced Therapies) project is an international consortium of experts and leaders in the field of innovative therapeutics. One of its aims is to develop and provide the necessary tools and data to strengthen knowledge on gene and cell therapies.
GenoSafe is one of the major players of the consortium involved in the standardization and harmonization of detection and titration methods used in gene therapies.
See also: