Eurofins | Advinus provides a one stop solution for biologics/ biosimilar testing which includes Toxicology, TK and Immunogenicity assessment. Eurofins | Advinus has evaluated more than a dozen biologics/ biosimilar for toxicology studies.

Eurofins | Advinus offers following Biologics/Biosimilar services.

  • Exploratory studies (Non-GLP)
    • Mini Ames
    • Mini hERG (hERG screening)
    • Dose range finding studies
    • CVS function screening in telemetered dogs
    • Genotoxicity (GLP)
    • Ames Test
    • In vitro chromosomal aberration test in Human Peripheral Blood Lymphocytes (MUT-CHAB/HPBL)
    • Micronucleus test (MNT) in mice/rats
  • Safety Pharmacology (GLP)
    • hERG assay
    • Pulmonary functions(Rats)
    • Modified Irwin Test/Functional Observation Battery in rats(FOB-Rats)
    • CVS function assessment using telemetered dogs.
    • Toxicology studies (GLP)
    • Maximum Tolerated Dose (MTD) followed by 10 day repeat dose range finding(DRF) in Rat
    • Maximum Tolerated Dose (MTD) followed by 10 day repeat dose range finding(DRF) in Dog
    • 28-Day Repeat dose toxicity study in Rats
    • 28 Day Repeat dose toxicity study Dogs
  • Toxicology studies (GLP)
    • Sub Chronic Toxicology Studies in Rodents and dogs
    • Chronic Toxicology Studies in Rodents and Dogs
    • Carcinogenicity studies– Study Protocols approved by the CARC Committee of the USFDA, (58 Carci Studies performed over the 20 years history )
    • Eurofins | Advinus has demonstrated higher level of consistency and expertise required for long term studies
    • Peer review pathology services offered from Overseas pathologists
    • Availability of 8-9 study directors with 12-15 years of experience in conducting Carcinogenicity studies in Rodents
    • Transgenic Carcinogenicity studies in mice
    • Juvenile toxicity studies in rodents
  • Reproduction studies (GLP)
    • Fertility and Early Emryonic Development to Implantation (SEG-I)
    • Prenatal Developmental Study (SEG-II)
    • Peri-natal and Post-natal Developmental study (SEG-III)
    • Male Fertility Study
    • Female Fertility study
  • In vivo efficacy assays
  • In vivo assessment of pharmacokinetic and pharmacodynamics parameters for biosimilar and comparison with innovator molecule.
  • In vivo immunogenicity assessment for biosimilar and innovator molecule by multi tired approach-
    • Anti-drug antibody screening assay
    • Confirmatory assay
    • Titer estimation
    • Neutralizing antibody assay by ELISA or cell based assays
    • Antibody isotyping
  • Biomarker analysis

Strategy: Bioanalytical Testing of Biosimilars

PK/ TK  Strategies Immunogenicity Testing Strategies
Type of ELISASandwich ELISA preferredBridging ELISA preferred
Biosimilar comparabilityDemonstration of equivalence with referenceDemonstration of equivalence with reference
Assay requirementAssay with high sensitivity to cover the Cmin and CmaxHigh sensitivity to detect very low levels of low affinity ADAs
Challenges with the AssayDemonstrate dilution linearity  and parallelismDetect ADA in presence of high circulating drug concentrations and Drug–ADA complex
  • Ligand binding assays or Enzyme Linked Immunosorbent Assays (ELISA)
    • Sandwich ELISA
    • Bridging ELISA
    • Direct/Indirect ELISA
    • Competition ELISA
  • Meso Scale Discovery (MSD)
  • Radioimmunoassay (RIA)
  • Cell based assays

Quantification of Biological Molecules by LC-MS/MS

  • Assays can be developed and validated on LC-MS/MS platform like API-6500+
  • Method development & optimization for the compound using, immuno pool down, tryptic digestion and signature peptide identification approach
  • Pre-study method validation
  • Analysis of study samples for pharmacokinetics (PK), toxicokinetics (TK), pharmacodynamics (PD) and vaccine efficacy studies for quantification of proteins, peptides and monoclonal antibody based drugs