Advinus provides a one stop solution for biologics/ biosimilar testing which includes Toxicology, TK and Immunogenicity assessment. Advinus has evaluated more than a dozen biologics/ biosimilar for toxicology studies.
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 )
- 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 ELISA | Sandwich ELISA preferred | Bridging ELISA preferred |
| Biosimilar comparability | Demonstration of equivalence with reference | Demonstration of equivalence with reference |
| Assay requirement | Assay with high sensitivity to cover the Cmin and Cmax | High sensitivity to detect very low levels of low affinity ADAs |
| Challenges with the Assay | Demonstrate dilution linearity and parallelism | Detect 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