QUANTITATION OF BIOLOGICS USING LIGAND BINDING ASSAYS (LBAS)
QPS is at the forefront of a wide range of LBA technology platforms including ELISA using colorimetric, fluorescent and chemiluminescent detection as well as Gyrolab®, electrochemiluminescence (ECL) on the MSD® platform. Our in-depth technical expertise enables us to offer cost-effective services for pharmacokinetics (PK) and immunogenicity – both anti-drug antibody (ADA) and neutralizing antibodies (NAb) assessments – in various biological matrices.
QUANTITATION OF BIOLOGICS USING UPLC-MS/MS
QPS has analyzed polypeptides and proteins using LC-MS/MS since 2000. The direct approach combines sample extraction from the biological matrix, followed by sample clean up, concentration and UPLC-MS/MS analysis. We also offer a more elegant approach starting with immunoaffinity capture followed by enzymatic digestion and LC MS/MS. Essentially, this method uses an immunoaffinity column or beads to selectively enrich the target protein(s) prior to analysis, resulting in lower total signal complexity and higher specific peptide signal by LC MS/MS. The decision on what methodology to use depends on the individual protein target. Both approaches are non-trivial and utilize the skills of our highly experienced bioanalytical chemists.
The potential of biomarkers to facilitate the development of effective and safe drugs has been well recognized as an integral part of all phases of drug development. As molecular and cell biology science advances, cell-based technologies have become a critical part of biomarker discovery, development and target validation.
At QPS, our scientific team has a wide range of molecular and cell biology experience, working with established cell lines and primary cultures to meet sponsor’s study needs. Since 2002, QPS has supported more than 40 cell-based studies for numerous sponsors. Our expertise ranges from cell banking, cell proliferation assays, on-site cell stimulation followed by cytokine induction analysis and various target specific functional assays. Although cell-based assays do not have current standardized industry guidance, we have developed and validated cell-based assays in good laboratory practice (GLP) environments to assess neutralizing antibody activity in human serum samples in support of the clinical investigation of anti-drug antibodies (ADA) on drug efficacy and safety.
- Endotoxin Stimulation (Cytokine Production)
- Compound Toxicity on Monocytes (Cytokine Induction)
- Uptake Study (33 P) Using Primary Cells
- Toxin Neutralizing Assay (Cell Proliferation)
- Neutralizing Antibody (NAb) Assay (Cell Viability)
- Custom Functional Assay
Our cell culture facility is well equipped with biosafety hoods, incubators, automated cell counters, microscopes with cameras and imaging capability, as well as liquid nitrogen tanks for cell banking.
IMMUNOGENICITY & NEUTRALIZING ANTIBODIES
Immunogenicity refers to a drug-elicited anti-drug immune response. All macromolecules are potentially immunogenic. Sometimes compounds with molecular weights as low as 1,000 Daltons, such as penicillin or sulfonamides, may also elicit an immune response, but all severe immune responses, including immediate hypersensitivity responses and neutralizing antibody responses, must be avoided.
Immunogenicity can be either non-neutralizing or neutralizing. While a non-neutralizing immunogenicity may not have negative effect on the pharmacodynamics of the drug, neutralizing immunogenicity can deactivate drug activity and alter drug clearance, plasma half-life and tissue distribution. Thus, immunogenicity testing is important both to the safety and efficacy of the product.
- Preparation of antigen-protein conjugates for plate coating.
- Method development and validation using ELISA format.
- Screening for positive responses in study samples.
- Confirmation test for samples displaying positive responses during screening.
- Titering of confirmed positive samples to determine the relative degree of antigenicity.
- Detection and determination of various classes of antibodies Neutralizing antibody assays.