Biologics is a leading growth area in the Pharmaceutical industry with growth rates 2 -3 times as fast as chemical entities. All large Pharmaceutical companies have a pipeline of biologics (either through acquisition or internal development) and the share of those in their portfolios is quickly increasing.
In the drug development process for the biopharmaceutical market, the challenges are different to those from traditional chemical entities. Not only is the discovery, process development and manufacturing more sophisticated using bacterial or mammalian cell culture, the safety testing requires completely different tools than for chemical entities. Adverse drug effects are driven by the fact that protein based therapeutics like antibodies can induce an immune reaction. This could lead to loss in drug potency or potentially dangerous physiological reactions and therefore has the potential to be a significant obstacle in the successful development of new biological medications.
Immunogenicity assays are technically very challenging, particularly when the therapeutic molecule is an antibody. The administered antibody which caused an immune reaction has to be detected in serum samples which are rich in immunoglobulin and there are bound by their ADA (anti-drug-antibodies). That means the drug/anti-drug complex needs to be dissociated and subsequently accurately measured by the test system’s antibody.
For each drug binding affinities and concentrations vary significantly, therefore the assay needs to be developed and optimized carefully for each molecule.
PerkinElmer offers two platforms to set up immunogenicity assays, AlphaLISA and DELFIA.
AlphaLISA is a homogenous, a “No-Wash” assay which can measure ADA’s in a bridging assay with excellent sensitivity and reproducibility. For those customers who prefer a wash assay to remove antibodies which could mask the ADA, DELFIA is the platform of choice. DELFIA works similar to an ELISA assay, however being significantly more sensitive than standard ELISA.
AlphaLISA has also very successfully been used for other steps of the development of biologics drugs, namely clone selection, biomarker profiling and in process contaminant determination (i.e. host cell proteins, protein A). While clone selection requires high throughput brought by the homogenous nature of the AlphaLISA assays, its excellent sensitivity is an advantage for the detection of low level process contaminants.
While off the shelf kits are available for biomarkers and in-process contaminants, PerkinElmer offer expert services by partnering with the customer for the set-up of immunogenicity tests.