ADC Analytical Development & Quality Control

ADCs are complicated therapeutics composed of large biomolecules (antibodies) and small molecule drugs. This combination leverages the advantages of both biologics and small molecule drugs, providing powerful targeted therapy. However, the complexity of their structure presents significant challenges in ADC analysis and characterization.

With extensive experience and advanced analytical technologies, ChemExpress is committed to offering complete ADC analysis services for ADC drug development，covering key aspects like structural characterization, impurity analysis, microbial safety control , and stability study.

Partner with ChemExpress to tackle your R&D challenges, gain a competitive edge, and accelerate your path to clinical success and market approval.

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One-Stop ADC
CDMO Service

ChemExpress offers integrated services spanning from Payload-Linker to ADC DS&DP, enabling efficient scale-up and seamless technology transfer, effectively reducing management and transition costs.

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Extensive Project Experience
& Comprehensive Inventory

Over 160 ADC projects have been delivered, including over 60 CMC projects, 5 BLA projects, and 1 commercial project. 15 ADC payloads and related intermediates are registered with the FDA as DMFs.

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Expert Scientific
Team

Our team of over 500 scientists provides comprehensive support from R&D to commercialization, ensuring high-quality, scalable solutions for your ADC pipeline.

Our Services

ChemExpress’ analytical services platform offers comprehensive ADC analysis, covering structural characterization, impurity analysis, microbial safety control , and stability study——to accelerate drug development and regulatory submissions across both preclinical and clinical stages.

Our Service Scope Includes

Structural Characterization — Comprehensive analysis from sequence to modification to ensure declaration no need supplementary submissions

Based on cutting-edge equipment such as Thermo Q Exactive high-resolution mass spectrometry, Waters Xevo G3 Q-TOF high-resolution mass spectrometry, PA800 PLUS, and Maurice capillary electrophoresis systems ADC Structural Characterization Platform of ChemExpress provides comprehensive structural characterization services that meet ICH Q6B and FDA/EMA submission requirements, including:

  • Linker-Payload Structural Characterization: a Variety of Methods Including 1H NMR, 13C NMR, 2D NMR, MS, IR, etc. for Identification and Analysis: Structural Characterization of API
  • Primary Structure Analysis: Intact/Reduced/Deglycosylated Molecular Weight (error <5 ppm), N/C-Terminal Sequence Verification, Peptide Map Coverage ≥99%
  • ADC Specificity Projects: DAR Value (HIC/RP, LC-MS), Conjugation Site Identification (LC-MS), Payload Distribution (SEC-MS)
  • Post-Translational Modifications: Deamidation, Oxidation, Glycosylation, Disulfide Bond Mismatch (MS/MS Fragment Ion Confirmation)
  • Advanced Structure: DSC Thermal Stability (Tm Value Deviation ±0.5°C), CD Secondary Structure, FT-IR Fingerprint Spectrum

ADC impurity analysis — Systematic Control Strategies from Genotoxicity to Free Drug

ChemExpress follows ICH Q3A-Q3D and EMA ADC guidelines to establish differentiated control strategies for process-related and product-related impurities:

  • Process-Related Impurities

    · TCEP Residuals (HPLC-UV，LOD≤10ppm)

    · Residual Solvents (DMSO) (GC-MS，USP<467>)

    · Defoaming Agent/Tween 80 (HPLC-CAD/ELSD, Exclusive Method Development)

  • Product-Related Impurities:

    · Genotoxic Impurity (LC-MS/MS, Compliant with ICH M7, PDE ≤ 10 µg/day)

    · Elemental Impurities

    · Free Drug and Related Impurities (RP-HPLC，LOQ≤0.1%）

    · Unconjugated Protein (HIC≤1%）

ADC Microbial Safety Control — Management throughout Lifecycle from Testing to Isolators

ChemExpress Laboratory is CNAS-certified, equipped with Lonza Elx808 endotoxin analyzers and isolator sterile filling systems, providing:

  • Bacterial Endotoxin: Gel Method (ChP General 1143) and Dynamic Colorimetric method (LOD ≤ 0.01 EU/mL)
  • Microbial Limit: Membrane Filtration Method (Detects Aerobic Bacteria, Molds, And Yeasts)
  • Sterility Testing: Isolator Technology
  • Container Integrity Testing: Vacuum Decay Method (MD-750, Sensitivity ≥ 1 µm leak)

ADC Stability Study — Forced Degradation and Real-Time Release Strategy Based on QbD

Stability studies comply with ICH Q1A-Q1E and are designed in accordance with QbD principles:

  • Forced Degradation: Oxidation (H₂O₂ 0.1%-1%), High Temperature (40-60°C), pH (3-9), Light Exposure (1.2 M lux•hr)
  • The Freeze-Thaw Cycle (-80°C ↔ 25°C, 5 cycles) Simulates Clinical Usage Scenarios
  • Real-Time Stability / Long-Term Stability (2-8°C, 24 months)

Why Partner with ChemExpress

Compliance: Not just “compliant with regulations”, but “compliant with future regulations in advance”
Industry Pain Points ChemExpress Advantages
The FDA/EMA's requirements for ADC structure characterization are becoming increasingly stringent each year (e.g., the addition of MS validation requirements for payload distribution in 2023)
 勾选

In 2024, SEC-MS coupled technology has been deployed in advance, which can resolve payload distribution isomers with DAR=2/4/8
Controversy over PDE limits for genotoxic impurities (such as MMAE) (differences in calculations between regulatory agencies)
 勾选

Build our own PDE database (based on EMA/ICH M7 cases) and dynamically update limits.
Microbial testing is often supplemented due to “insufficient method sensitivity.” 勾选

solator + disposable consumables combination, sensitivity ≥ 1 CFU/vial (traditional clean rooms are 10 CFU/vial)
Technical accuracy: Not just “measurable,” but “accurate” + “fast.”
Industry Pain Points ChemExpress Advantages
High detection limit for free payload (industry standard LOQ = 0.5%), resulting in delayed process optimization
 勾选

Reverse-phase chromatography method development reduced the LOQ to 0.05%
Disulfide bond mismatches need to be indirectly proven using “reduction + alkylation,” which takes two weeks
 勾选

Non-reducing LC-MS/MS direct analysis of mismatched peptide segments, with results available in 3 days
The DAR value measurement error is large (HIC method ±0.5), affecting the formulation of release standards 勾选

HIC+RP-LC-MS dual platform verification, DAR value error controlled within ±0.2
Risk Control: Not “remedial action after the fact,” but “risk avoidance at the design stage.
Industry Pain Points ChemExpress Advantages
Stability study design flaws (such as with no simulation clinical use scenarios) led to OOT investigation failure
 勾选

Forced degradation experiments include freeze-thaw cycles + mechanical shaking (simulating transportation scenarios)
Impurity studies missing “genotoxic impurities” (such as linker degradation products)
 勾选

Impurity spectrum analysis based on QbD principles identifies ≥5 types of potential genotoxic impurities in advance
Cell line contamination (such as mycoplasma) leads to clinical batch rejection 勾选

Cells undergo double testing (mycoplasma + sterility + virus), and non-compliant cells are immediately isolated

Equipment

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Related Services

ADC Payload Linker

We specialize in complex and novel Payload-Linker, offering fully customized synthesis services to meet the specific needs of client projects.

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ADC Conjugation

At ChemExpress，our expert team offers flexible and scalable ADC conjugation solutions covering both site-specific and non-site-specific technologies.

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ADC Manufacturing

We provide cGMP-compliant bioconjugate manufacturing services for R&D, clinical and commercial stages, covering the entire ADC production process.

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Antibody Process Development

ChemExpress can offer comprehensive antibody process development solutions covering cell culture process development, purification process development and formulation process development, enabling rapid, cost-effective, and high-quality antibody production.

Case Study

Payload-Linker Compound Impurity Separation

In the research of a Payload-Linker compound with a molecular weight of over 1000, a homologue impurity with a small fragment was identified. In existing analytical methods, this impurity was not efficiently separated from the main component and known impurities. Through the development of a rapid optimization technique, we successfully developed a method that enables effective separation of this homologue impurity, ensuring higher purity for the final product.

优化前

Before Optimization

优化前

After Optimization

Solution for Charge Heterogeneity Analysis of ADCs

ChemExpress has developed a dedicated solution for ADC charge heterogeneity analysis based on imaged capillary isoelectric focusing (icIEF). Leveraging the principle of isoelectric focusing, icIEF enables high-resolution separation of charge variants. The method’s reliability and separation performance were further validated by the incorporation of pI 5.85 and pI 9.99 internal markers.

In this case study:
·  icIEF clearly distinguished the main peak from charge variants;
·  A comprehensive charge heterogeneity profile was obtained;
·  Internal marker verification ensured reproducibility and accuracy.

优化前

FAQs

Reproducibility is ensured through rigorous standardization of testing protocols, use of validated analytical methods, and maintaining a controlled environment during studies. Regular calibration of instruments and use of well-characterized reference standards also play a key role in ensuring consistency across batches and tests.

We will formulate corresponding chiral control strategies according to the characteristics of the compound itself based on the process situation. At present, most of the chirality of linker-payload is not control at the final step, and there are many step-by-step controls, which can fully meet the needs of application.

In the IND stage, endotoxin testing is generally carried out and specifications are set, and the specific limit is calculated according to the customer's downstream end. Microbiological testing is generally not performed during the IND stage (unless the customer has special needs); Endotoxins and microorganisms are controlled during the BLA phase, and the limits of endotoxins are calculated according to the drug specifications, and the microbial limits are tested according to the requirements of the pharmacopoeia.

Cross-contamination is prevented through a well-defined and stringent control process. After each project, the equipment undergoes thorough cleaning and decontamination, followed by corresponding testing verification to ensure compliance with standards. Before the production of the next product, cleaning validation will be conducted, and a detailed cleaning assessment report for the equipment chain will be generated. These measures ensure traceability and safe production practices.

Drug conjugation uniformity is critical because it ensures that each antibody in the ADC has the same amount of drug attached, which in turn ensures consistent therapeutic activity. Variability in conjugation can lead to inconsistent efficacy and toxicity, so achieving uniform drug-antibody conjugation is essential for optimizing ADC performance.

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