A library of well-characterized, first- and second-generation low-toxicity ADC surrogates available at multi-gram scales will provide manufacturers, vendors and academics with access to materials for ADC process, formulation and analytical research and development efforts as well as for the training of personnel in the safe handling of ADCs without the severe exposure risk and containment burden. For manufacturers, this will permit faster process development and validation in less expensive development suites, outsourcing of process development efforts, greater experimentation and optimization, performance comparisons/validation among global manufacturing sites and/or CROs/CMOs and development of process and analytical performance standards for ADC regulatory filings.
A significant amount of preliminary work was completed in PC2.2-109, where two linker-fluorheads conjugates (LFCs) were successfully synthesized and showed good agreement with the physical properties of their linker-drug counterparts. In the process of completing these tasks, we were able to assess supply chain issues, identify hazardous materials, evaluate costs to manufacture sADCs. The assays we propose to use here are taken directly from the literature. (Liu et al. 1996; Xu et al. 2011; Valliere-Douglass et al. 2012; Wagh et al. 2018; Procopio-Melino et al. 2022) Additionally, there are literature reports of other non-toxic sADCs, including one using he NISTmAb as a substrate for linkers and surrogate payloads. (Agnew et al. 2021) This published report, along with our Final Report for PC 2.2-109, provides independent verification of the sADC synthetic approach.
A library of well-characterized, first- and second-generation low-toxicity ADC surrogates available.
For manufacturers, faster process development and validation.
The library will open new markets to vendors and permit academics to contribute to this important field of biomanufacturing.
The project addresses a major bottleneck in ADC development: safe, scalable, and standardized surrogate materials. It accelerates innovation while reducing cost and risk, and it lays the foundation for data-driven process optimization in biomanufacturing. Few of the benefits for organizations using these well-characterized, first- and second-generation low-toxicity ADC surrogates include,
The project aims to develop and characterize a set of non-toxic surrogate ADCs that captures the diversity and processing behaviors of first-generation and second-generation ADCs without the associated toxicity. These sADCs will use industrially relevant antibodies, linker chemistries, and coupling methods with low-toxicity fluorescent molecules, or “fluorheads”, in place of anti-cancer cytotoxins, or warheads, in current use in ADCs. They will characterize the processing behaviors and the critical quality attributes of the sADCs by using conventional detailed analytical technologies based on chromatography, mass spectrometry, and rapid analytical technologies based on capillary electrophoresis.
The project aims to prepare the business case and reference standards pathway necessary to make sADCs broadly available. Work with NIST to define preparation and characterization protocols for sADCs derived from NISTmAb
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Rensselaer Polytechnic Institute
Carnegie Mellon University
EMD Millipore Corporation
Pfizer, Inc.
