NAb Assays – Clinical Trial Support

NAb assays, or neutralizing antibody assays, are often a required component of a clinical trial if immunogenicity is observed in patients. If the patient produces anti-drug antibodies, those antibodies have the potential to neutralize the effects of the drug. In a clinical trial it is important to determine not only if the patient is producing antibodies against the drug (anti-drug antibodies or ADAs), but if those antibodies are neutralizing the drug. This neutralizing effect can lead to altered pharmacokinetics and reduced efficacy. To do this, a NAb Assay must be developed and validated.

In Vitro Cell Based NAb Assays

Most NAb assays are custom designed in vitro cell based assays. PBL scientists will work with your team to design a cell based assay that can detect the presence of neutralizing antibodies. The drug’s mechanism of action that occurs in the patient could also be present in a cell culture environment. By understanding the pathway that allows the drug to work, scientists can design a cell based assay that is specific for a particular drug product, target and mechanism of action.  Often potency bioassays are cell based assays and the same assay which determines the drug’s biological activity may be used to determine if antibodies produced by the patient are inhibiting the activity of the drug product, however matrix effects (caused by serum of plasma) can create complications requiring optimization of the assay to be minimally effected by other proteins or molecules found in serum or plasma.

NAb Assays Using the MSD Platform

Pacific BioLabs (PBL) operates a MesoScale Discovery (MSD) instrument, the MESO QuickPlex SQ 120. With MSD’s QuickPlex, the PBL team can help clients develop NAb assays with decreased matrix affects, increased dynamic range and sensitivity while using less sample amount and reagents. If the biological activity of a biotherapuetic drug product is limited to ligand/receptor binding or protein-protein binding, an MSD NAb assay can be used to detect the presence of neutralizing antibodies. For more information see our MSD Immunogenicity and NAb Assay Page.

Available NAb Assay Services

  • Assay Development and Validation
  • Cell Based Assays
  • Ligand Binding Assays (MSD and ELISA)
  • Enzymatic assays
  • Bridging ELISA
  • Direct ELISA
  • Competitive ELISA

Instrumentation and Platforms Available

  • Enzyme Linked Immuno Sorbent Assay (ELISA)
  • MesoScale Discovery (MSD) QuickPlex SQ 120
  • Fluorescent Plate Readers
  • Laser Light Scattering – Static (LLS)
  • High Performance Liquid Chromatography (HPLC)
  • Mass Spec Instruments – GC-MS, LC-MS/MS, TOF-MS and ICP-MS
  • Instrumentation Details

Importance of NAb Assays

Most large molecule drug products administered to the patients can potentially elicit an immune response. Antibodies can be produced by the patient’s B-cells which can bind to the pharmacological active sites of the drug rendering the drug ineffective of less effective.   These antibodies are called neutralizing antibodies.

Because the presence of neutralizing antibodies impacts a drug’s safety and efficacy, the FDA and EMA require biotherapeutic manufacturers to determine if the presence of neutralizing antibodies in all clinical trial patients that are shown to have anti-drug antibodies. By designing cell based assays or ligand binding assays for identifying the presence of neutralizing antibodies, it is possible to gather predictive data about the strength and type of immune response that a drug may produce in humans. Therefore, performing a NAb assay on all clinical trial patients that are positive for immunogenicity is crucial aspect of biotherapeutic drug development.

Read More About NAb Assays

 

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