As antibody-drug conjugates (ADCs) gain more attention and clinical/commercial success as a form of targeted cancer therapy, the demand for technologies which widen the therapeutic windows for ADCs has increased. Multiple site-specific conjugation methods have emerged in response to this need but developing strong and scalable processes remains a consistent challenge. Here we report the establishment and application of a good manufacturing practice (GMP) strategy to produce site-specific ADCs through the implementation of AJICAP technology, a chemical conjugation platform that employs IgG Fc-affinity peptides.
The ADCs that are currently on the market have a stochastic distribution of drugs attached to the antibody, which can lead to decreased efficacy and/or increased toxicity compared to a site-specific ADC. First generation AJICAP-ADCs showed scalability and high efficacy, prompting us to pursue the application of the site-specific technology to generate material suitable for good laboratory practice (GLP) toxicity studies. To do so, we constructed a GMP strategy to transition from research and process development stages to clinical and commercial manufacturing stages.
Although regulatory agencies enforce strict policies on the manufacture of late-phase clinical and commercial pharmaceutical products, less guidelines exist for the manufacture of preclinical products suitable for GLP studies. Challenges are likely to arise when attempting to transfer these processes to full cGMP manufacturing scales. Therefore, it’s important to establish regulatory guidelines and utilize a Quality Management System (QMS) early on during development.