Having a DHC team continually engaged as the technical operations lead allowed for support of everything downstream of research: from process development to CMC and regulatory support to manufacturing support, etc. Dark Horse provided certainty that each step was being done to the highest levels of technical proficiency along with the long-range consideration, planning, and analytical awareness that characterize successful therapies. Dark Horse cannot, of course, guarantee the success of any therapy, but our teams can guarantee an optimized process and a 360° technical and strategic viewpoint to give therapies the best possible chance at successful commercialization.
Besides the need to translate their research achievements into a commercially viable product, the client’s manufacturing process would have sufficed for Phase 1…but wasn’t scalable (or at an appropriate quality level) beyond that. DHC provided support for all elements of CMC: building a manufacturing process that would prove strong enough to translate into industrialization.
Preclinical proof-of-concept studies by the academic partner included two transgenes and two plasmid systems. DHC consultants re-sequenced the plasmids, transferred to a three-plasmid system to align with current best practices for regulatory compliant AAV production, and led the vendor selection process for plasmid synthesis, cell banking, and production.
After redesigning and manufacturing the plasmids, Dark Horse went through an RFP process to identify a contract manufacturing partner for the vector that would meet the long-term needs of the developer. Particular consideration was given to use of GMP-grade raw materials and a scalable manufacturing platform to limit the degree of comparability testing that would be necessary as development progressed.
Many pieces of the process were happening in parallel, such as working to get sufficient research grade plasmid, while simultaneously beginning the manufacturing of a GMP-grade plasmid to be used later in development. Regulatory needs were also a consideration in this project. DHC experts wrote the CMC section for the pre-IND and participated in accompanying regulatory discussions.
On the process development side, identifying and testing cell lines was top of mind, as was the need for process parameter optimization and demonstration of scalability. The DHC-chosen manufacturer made materials to support preclinical studies at the same time as working through the process development.
Documentation is critical at each stage, particularly when proceeding from development to manufacturing. Dark Horse took point on every GMP document, every batch record, and every analytical qualification, representing the Quality function for the client in review and approval of all manufacturing and test method qualification documents.
Any remediation needs were addressed via technical troubleshooting during development.