A robust platform for oligonucleotide lyophilization

I had the privilege to contribute to a project for one of our customers as external consultant, which aimed at the setup of a robust platform for the lyophilization of oligonucleotide API’s. The project was part of a larger effort to support the early development of clinical oligonucleotide drugs and to enable a faster initiation of clinical studies, which would ultimately lead to a faster time to market. Given the increasing success of oligonucleotide medicines in recent years and the promising potential, the project was an important strategic pillar for our customer to accelerate innovation in the upcoming years.

Manufacturing of oligonucleotide API’s presents unique challenges due to the highly sensitive nature of these molecules. To ensure the stability and consistency of the API’s, it was crucial that a robust lyophilization platform was set up, meeting the stringent compliance requirements of the pharmaceutical industry.

My role focused on ensuring compliance and Quality Assurance throughout the entire project, which came along with number of challenges. The platform needed to be robust enough to support all oligonucleotide APIs which could potentially come through the pipeline in the coming years, while also being flexible enough to accommodate early development where only limited information about the compound is available. Despite these challenges, we were able to establish a structured and coherent Quality strategy that not only met the necessary regulatory requirements, but also ensured the platform’s long-term sustainability and agility.

Through a risk-based approach, we identified an adequate contamination control strategy. The final lyophilized API powder needed to be low bioburden grade to allow the API to be compounded into a sterile drug product afterwards. The contamination control strategy did not only embrace microbial contamination, but also focused on endotoxins. Based on our strategy, we were able to define appropriate specifications for input & packaging materials, adequate controls for equipment with both direct and indirect product contact, and acceptable environmental monitoring controls.

After defining our strategy, we continued with the design of the end-to-end manufacturing process. This included the qualification strategy, but also comprised the set-up of the master batch record, the entire procedural framework, and the required training for the operators.

Meanwhile, the first oligonucleotide API batches were successfully lyophilized, which was a great achievement for the entire team. Speaking for myself, the project was a great learning experience. It allowed me to reflect on the design of an appropriate contamination control strategy within an early clinical development setting, which was pretty challenging to be honest. Apart from that, it was a very nice and pleasant experience to work together with all internal and external stakeholders.

Interested in our services after reading this blog? Contact us today if you are looking for support with the design of a robust Quality framework.