Method development (R&D)

Why is method development important?

Analytical method development is the strategic selection and optimization of analytical techniques tailored to quantify a designated attribute of a drug substance or product. This multifaceted exercise employs a systematic framework for assessing and choosing methodologies that exhibit:

• Sensitivity: Designed with a low limit of detection to measure small amounts of analyte
• Specificity: Highly specific for the analyte of interest, distinguishing it from other present materials
• Accuracy:  Yields results that are close to the true value
• Precision: Reproducible method that leads to consistent results
• Robustness: Resilient to small variations leading to method consistency
• Compliance with regulations: Meets the requirements of regulatory bodies such as the USFDA or EMA

In addition to these criteria, the method should also be efficient and cost-effective.

Understanding our method development capabilities

We employ state-of-the-art techniques throughout our method development processes to ensure precise measurement of various critical quality attributes (CQA).

These methods encompass various types of analyses including:

• Product variants
• Content
• Excipient
• Process related impurities

For assessing defined attributes we utilize the following methods:

• Identity

  • Isoform patterns by cIEF, CE-IEF

  • High-performance liquid chromatography (HPLC)
•  Structure
  • Primary structure
    • Intact or reduced mass analysis
    • Peptide mapping
  • Higher-order structure
    • Circular dichroism and
    • Intrinsic flourescence assays
    • Differential scanning calorimetry (DSC)
    • Disulphide bond analysis

• Quantity

  • Total protein content

  • UV absorbance

• Impurity

  • HCP, HCD by RT-PCR

  • Aggregates by SE-HPLC or CE

  • Cell substrate impurities

  • Enzyme-linked immunosorbent assay (ELISA)

  • Reverse transcription-polymerase chain reaction (RT-PCR)

  • Charge variants by cIEF

• Biological Activity

  • Cell based assay

  • Binding assay (Octet® surface plasmon resonance (SPR), and ELISA assays)

• Microbial testing

  • Microbiological tests (sterility etc.)

  • Endotoxin

  • Sterility testing

    • Membrane filtration

    • Direct Inoculation