Roadmap for the development and GMP translation of optical tracers cetuximab-800CW and trastuzumab-800CW.

Optical molecular imaging using fluorescently labeled monoclonal antibodies is of significant added value to guide surgical or endoscopic procedures. However, development of tracers for clinical trials is complex, and therefore implementation in the clinic is slow. We present a roadmap for development and translation of monoclonal antibody tracers into a current Good Manufacturing Process (cGMP) compliant drug product. Methods: The production process of cetuximab-800CW and trastuzumab-800CW was optimized with regard to dye to protein label ratio and formulation buffer. Promising formulations were produced under cGMP conditions and advanced to full-scale stability study. Tracers were analyzed for stability by SE-HPLC, pH-measurement, osmolality, visual inspection and sterility, as required by the European Pharmacopeia and cGMP guidelines. Results: For cetuximab-800CW, 7 formulations were investigated and for trastuzumab-800CW 10 formulations were investigated. Based on the formulation study results, we chose 2 formulations per antibody for investigation during full-scale stability study. These formulations all performed well, showing good compliance with the acceptance criteria set for each product. Conclusion: We designed a roadmap to standardize the development, formulation and cGMP translation of molecular fluorescent tracers. Using our standardized approach, we developed two stable antibody-based tracers for clinical use. When developing tracers, the proposed roadmap can be used to efficiently develop a cGMP compliant formulation and improve translation of newly developed optical tracers to first in human use.