From lead characterization to regulatory submission

Make informed decisions,
maintain project momentum

The slightest change in Higher Order Structure (HOS) can significantly impact the efficacy and immunogenicity of a biotherapeutic. HOS analysis is therefore well-established as one of many Critical quality Attributes (CQAs) used to characterize the structure, purity, functionality and stability of a potential biotherapeutic candidate.

Fulfilling the demand for more
stringent HOS analysis

HOS analysis by circular dichroism is currently viewed as a ‘Tier 3’ CQA i.e. simple a graphical comparison.

Although regional regulatory authorities may differ in their specific requirements to gain approval for a biotherapeutic, there is much discussion as to how HOS analysis has the potential to provide more than a subjective comparison of the secondary structure ‘fingerprint’.

The Chirascan Q100 system for CD analysis is designed to support the ‘tiered’ approach to rigorous statistical analysis as recommended by the Office of Biostatistics and Office of Biotechnology Products (CDER/FDA).

Capable of detecting minor differences in secondary and tertiary structure, the system generates high quality raw data to enable quantification of similarities and differences and confirm their statistical significance. Previously subjective HOS comparisons now contribute to objective, informed decision making.

Increase operator productivity: unattended operation 48 sample/buffer pairs in 24h.

  • Characterize higher order structures
    • Confirm structural integrity, gain insight into mechanism and interactions, detect differences between wild type and mutant
  • Compare HOS characteristics of lead candidates
    • Objectively evaluate changes and differences supported by statistically-validated data
    • Quantify differences and similarities, evaluate statistical significance of minor changes under native or stressed conditions
  • Monitor change throughout biotherapeutic development and scale-up
  • Define acceptable range for HOS variability within a control strategy
  • Contribute to the totality of evidence
    • Contribute to characterization profiles to fulfill International Conference of Harmonization demands -ICH Q6B/Q8
    • Apply the most rigorous statistical methods to raw data

Quality by design in brief

A systematic approach to biotherapeutic development, Quality by Design (QbD), begins with two predefined objectives: to define Quality Target Product Profiles (QTPP) and identify Critical Quality Attributes (CQA). These objectives are supported by an understanding of the product and process, an appropriate process control strategy, sound science and quality risk management i.e. risk-based development.

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