From QTPP 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.

Circular dichroism has been used/proposed in 96% of biosimilar applications involving mAbs and other biotherapeutics

Regulatory consideration for characterization of HOS in biotechnology products, M. T. Gutierrez Lugo, Ph. D., OBP/CDER/FDA. 5th International Symposium on HOS of Protein Therapeutics 2016

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 biosimilar, 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 HOS, 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.

  • Determine innovator HOS characteristics for the Quality Target Product Profile (QTPP)
  • Run effective comparability programs
    • Evaluate similarities and differences supported by statistically-validated data
    • Quantify and evaluate the significance of minor changes under native and stressed conditions
  • Monitor change throughout development and scale-up
  • Define acceptable range for HOS variability within a control strategy
  • Strengthen totality of evidence for regulatory submissions

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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