Biosimilars

AQS3 Support for biosimilarity studies

Sensitive Measurement of secondary structure, allowing biopharma researchers to prove bioequivalence

Effective, orthogonal biophysical characterization is essential for biosimilar development and helps reduce reliance on clinical and animal studies, thereby cutting time to market and development costs. For example, measurements of primary and higher order structure (secondary, tertiary, quaternary) define the active biotherapeutic molecule, a vital element of reverse engineering, and provide evidence of biosimilarity. Comparative testing of a proposed and reference product reveals the extent of structural similarity and helps to elucidate differences in stability and aggregation behavior.

biosimilar development

The AQS3pro is a powerful and flexible system that uses Microfluidic Modulation Spectroscopy to characterize the secondary structure of proteins. Compared to conventional FTIR spectroscopy it offers much greater reproducibility and utility for biosimilar development. Defining features include:

  • High sensitivity, for the confident confirmation of similarity between a proposed and reference product. 
  • Clear and specific measurements that unambiguously inform reverse engineering, aggregation studies, formulation process development.
  • Automated measurement and data processing, that makes it easy to maximize the application of secondary structure measurements in biosimilar development.

Comparability testing with the AQS3pro is simple, efficient, precise. Use it to boost the value of in vitro biophysical testing and minimize dependence on more costly and time-consuming animal and clinical studies.

Demonstrating Biosimilarity: The Value of Better structural analysis

FDA guidance outlines a step wise approach to demonstrating biosimilarity based on data derived from assessing the comparability of "structure, function, animal toxicity, human pharmacokinetics (PK) and pharmacodynamics (PD), [and] clinical immunogenicity".1 These data are subject to a ‘totality of the evidence’ review when it comes to submission assessment and product approval. Stronger more robust data in one area can therefore mitigate requirements for information derived from alternative forms of testing. Crucially, as the guidance notes ‘… rigorous structural and functional comparisons that show minimal or no difference between the proposed product and the reference product will strengthen the scientific justification for a selective and targeted approach to animal and/or clinical testing…’.

Assessing structural and functional comparability calls for the application of orthogonal analytical techniques. This will allow comprehensive assessment of physicochemical and biofunctional characteristics. Generally, such testing is faster, easier and less expensive than animal and clinical studies. Optimizing its application and use is therefore critical. Investing in the instrumentation for more robust structural analysis can directly accelerate development and at the same time help to push down costs.

 

1FDA Guidance for Industry ‘Scientific Considerations in Demonstrating Biosimilarity to a Reference Product’ April 2015

Using measurements of secondary structure in biosimilar development.

Integrating secondary structure measurements in existing biosimilar workflows

Biosimilarity Workflow: Ensure Composition Similarity

Biosimilarity Workflow for Microfluidic Modulation Spectroscopy

Confidently compare the secondary structure of proposed and reference biotherapeutics.

FTIR and AQS3pro measurements for a mAb are highly comparable at a concentration of 10mg/mL. Unlike FTIR, MMS can also measure with high sensitivity at a concentration of 0.5 mg/mL. Acceptable quality data (similarity score >95%) is not possible at 0.5 mg/ml using traditional FTIR.

Comparision of AQS3pro & Traditional FTIR Data

RedShiftBio MMS & FTIR Data Are Highly Comparable

AQS3pro Achieves High Sensitivity with Low Concentration Sample (Similarity Scores >98%)

Redshiftbio MMS Can Be Used At Low Concentration With High Sensitivity (Similarity Scores For 98% )

Summary

The AQS3pro is a powerful analytical instrument that can directly boost the quality and value of structural characterization studies in biosimilar development. It enables precise comparability studies of secondary structure to directly support reverse engineering, process development and the demonstration of biosimilarity. The AQS3pro which offers:

  • Demonstrably higher precision than conventional FTIR instrumentation.
  • Automated data acquisition and processing, for high analytical throughput.
  • The ability to compare structure in clinically representative samples, at high concentration and in the presence of excipients.
  • The complementary detection of differences in excipients and composition.

Better structural characterization provides a foundation for minimizing the use of costly animal and clinical trials in biosimilar development. The AQS3pro delivers improved specificity, reproducibility and sensitivity relative to FTIR, boosting the value of secondary structure measurements. Requiring minimal expert input and offering high analytical throughput, this innovative instrument makes the benefits of better structural characterization widely accessible.