ADC Safety Assessment

The complex nature of antibody-drug conjugates (ADCs) has raised significant safety concerns. Each component of an ADC, being the monoclonal antibody, the small chemical linker, or the toxic payload drug, contributes uniquely to the overall ADC toxicity profile in clinical tests, making it more challenging to evaluate than that of conventional drugs. As a part of our ADC development service package, Creative Biolabs offers comprehensive yet highly customizable safety assessments services for ADC products. With our diverse animal models (both rodent and non-rodent), state-of-the-art facilities, and experienced pathologists, Creative Biolabs is committed to providing top-quality services and products for every project in a timely and cost efficient manner.

Toxicological Screening

Major in vivo toxicological studies include acute- and repeat-dose toxicity tests, chronic toxicity tests, and additional assessments such as safety pharmacology and tissue cross-reactivity. Given the multiple constituents of an ADC, the toxicology assessment program in Creative Biolabs can be customized to fit the needs of different projects. ADCs can either be tested as one single entity or each of its components can be tested separately. In Creative Biolabs, serum/plasma concentration of ADCs will be measured in:

• Antibody drug conjugate ELISA
• Total antibody ELISA
• Unconjugated drug LC-MS/MS assay
• Immunogenicity, anti-drug antibody, bridging ELISA

We offer various toxicity evaluation programs and specimens to meet the needs of every client:

Tissue Cross-Reactivity Studies

To evaluate potential targeting properties of ADCs, Creative Biolabs offers tissue cross-reactivity (TCR) services in a wide variety of animal or human bio-specimens. Creative Biolabs has established a complete tissue bank of human, non-human primate, dog, rabbit and small rodents. All animal tissues are sourced with full consent for commercial research and in compliance with FDA guideline. Immunohistochemical staining (IHS) is one of most common assays used in TCR studies. Creative Biolabs provides both immunofluorescence and immunoenzymological staining and our service items include but not limited to:

• Providing specific protocols and method development for each project
• Optimal specificity and staining condition determination
• Preliminary tissue cross reactivity screening
• Full tissue cross reactivity screening
• Result evaluation by certified pathologists
• Formal report and photographic image

Immunohistochemical staining (IHS) analysis of ADC. Left: cross reactivity of ADC in ovarian and breast tissue from healthy and carcinomatous donors. Right: amplified image of cross reactivity in breast tissue.

According to FDA guideline and recommendations, monoclonal antibody products designated for human applications shall be tested against 33 human tissue types with triplicate replications based on GLP compliant protocols. To accelerate this process, Creative Biolabs provides cost-effective preliminary screening services, including immunohistochemical analysis of one specimen for each tissue sample. Comprehensive assessments can be proceeded based on preliminary results. Available human tissue types are:

Clinical Observation

Animals that receive ADCs treatments will be monitored under Institutional Animal Care and Use Committee (IACUC) supervision. Basic parameters collected from clinical observation include body weight, feed consumption, behavior and pathologic characteristics. Additional observations such as ophthalmological feature, urine/Feces, and respiration also can be conduct as request.

Histopathological Analysis

Creative Biolabs offers a complete set of postmortem analyses. Preliminary assessments include organ weight and microscopic examinations. All pathological signs and changes will be identified and recorded by experienced pathologists. Further tests such as immunohistochemical staining will be conduct when necessary or as request and bio-specimens/tissue slides can be provided as well.

Creative Biolabs fully understands the time, cost, and devotion in ADC development projects. To meet an accelerated timeline and limited budget, Creative Biolabs has adopted our services to different standards including non-GLP and GLP-compliant test services. For more detail information, please contact our customer service or review our case studies for ADC safety assessment.