State of the Ecosystem

The field of personalized oligonucleotide treatments has evolved rapidly since the pioneering case of Milasen in 2018. A defining characteristic of this landscape is the shift in clinical stewardship; unlike traditional drug development aimed at large cohorts, N-of-1 development is primarily driven by academic institutions and patient organizations.

For many of these organizations, this is their first time dealing with the complex world of oligonucleotide drug development. Consequently, each group is required to navigate regulatory requirements and technical logistics—ranging from producing non-clinical safety batches to the formal manufacturing of Drug Substance (DS) and Drug Product (DP).

While knowledge exchange takes place within the community, a vast amount of critical information and strategies remain inaccessible between institutes. One of the limiting factors is the use of non-disclosure agreements designed to protect the intellectual property of involved commercial partners. As a result, each new research group is often forced to independently develop CMC strategies fit with local regulatory requirements, even when similar oligonucleotide platforms have been used before. These institutional barriers lead to a redundant duplication of effort in defining requirements for drug substance and drug product development.

Our Focus

The CMC Workgroup supports N-of-1 projects in manufacturing-related topics. Its aim is to train scientists and drug developers on manufacturing-related and regulatory (GMP) issues, provide suggestions for processes, analyses, and acceptance criteria, and support communication with regulatory authorities. Based on a generally applicable roadmap, projects should receive guidance to address their specific questions.

By offering a general roadmap for CMC issues, researchers can receive inspiration and suggestions for their own CMC documents, thereby saving time and research effort. Furthermore, the CMC Workgroup provides a network and a platform for partners to discuss problems and specific questions.