抗体药物偶联物的关键质量属性

Originally published by Crystal Bio Solutions. Republished with company attribution. Original technical perspectives, references and source links are retained.

Antibody Drug Conjugate (ADC) Components

Antibody-drug conjugates (ADCs) consist of three main components:

• Antibody: engineered to target specific antigen(s), mainly as mAb but can be bi-specific.
• Linker: conjugated between a cytotoxic drug and an antibody at Cys or Lys residue, mainly as cleavable but can be non-cleavable.
• Drug: synthetical small molecule functioning as cytotoxin (warhead or payload).

Figure 1: ADC structure (adopted from Signal Transduction and Targeted Therapy).

Heterogeneities of CQAs are anticipated in consideration of the 3 components in ADC. The influences in potency, stability, and toxicity will be discussed with evaluation of risk assessment.

Table 1: Summary of ADC-related CQA.

Read more about critical quality attribute D0 impact in ADC modality.

ADC-Related CQA

Many of these quality attributes are expected to be crucial for ADCs; nonetheless, experimental validation is necessary to ascertain their criticality for a specific ADC.

As per regulatory ICH guidelines Q8 R(2), a risk assessment for each quality attribute must be evaluated for potential impact on the patient. This involves employing a scoring system that considers the impact and uncertainty of each attribute.

#### 3-Part Series: Assessment of Critical Quality Attributes for Relevant Modalities

In this series, we will assess Critical Quality Attributes (CQAs) relevant to 3 modalities:

• mRNA-LNP (Lipid Nano Particle)
• Antibody-Drug Conjugate (ADC)
• Monoclonal Antibody (mAb)

Capabilities at Crystal Bio Solutions

Crystal Bio Solutions is a leading Contract Research Organization (CRO) specializing in comprehensive analytical services for biotherapeutics. Our expertise covers many modalities, including Antibody Drug Conjugates, Monoclonal Antibodies, Fusion Proteins, and mRNA-LNP Therapeutics with our strategic partner CATUG. We provide all necessary analytical tools to measure the related CQAs, comprising High-resolution LC-MS, liquid-based chromatography (HIC, IEX, SEC, RPLC, CE, and cIEF), along with comprehensive bio-analytical tool comprising various binding and cell-based assays, effector function-based assays like surrogate cytotoxicity assays and direct ADCC, ADCP and CDC assays, anti-ADC-antibody assays, qPCR, ELISA, Endotoxin, Sterility, Bioburden, and Cell-based Bioassay, etc.

Our capabilities also extend to method development and analytical characterization of biotherapeutics. This holistic approach ensures compliance with stringent regulatory requirements outlined in the CMC section, making us a valuable partner for pre-IND, Phase I, and subsequent submissions.

Read the original article and source figures