Formulation development | Flexible phase 1 formulation options enable fast switch
WuXi STA's F2CS package applies our capability, expertise, and advanced technology to deliver effective clinical trial material fast. F2CS stands for "Fast to Clinical Supply" which focuses on "speed, flexibility, and integration" to accelerate our partners' new drug Clinical Trial Materials (CTM) supply. This case will show you a flexible solution to improve compound bioavailability and accelerate the supply of phase I CTM supply and IND submission.
Due to poor bioavailability, a biopharmaceutical company needed to change the formulation for their molecule. Through WuXi STA's comprehensive bioavailability enhancement platform, the formulation was changed from the conventional powder-in-capsule to spray-dried dispersion (SDD). The new formulation demonstrated greatly improved bioavailability. WuXi STA took only 13 weeks to push forward the work from receiving GMP API to completing GMP manufacture and batch release with COA (Certificate of Analysis), enabling the delivery of the project ahead of the original timeline.
The change was requested by the client, only three months before the planned IND submission to the US FDA, so the timeline became a considerable challenge.
WuXi STA Solution
· Continuous and robust supply of API to ensure the smooth progress of formulation development
A flexible and robust API supply is the "cornerstone" to enable efficient and rapid formulation development:
- The close connection of the API production and formulation R&D teams provided the required flexibility of API supply to make formulation development possible without delay and still deliver GMP API on time
- The API production and formulation development are carried out under the same quality system
In order to rapidly accelerate this change, the API team provided a small batch of API to allow the immediate start of formulation development while simultaneously starting the production scale-up of GMP API to ensure sufficient supply for GMP drug product batches in time for the IND submission.
· Selecting spray-dried dispersion to solve solubility problems from the source
The flexibility of the technology platform was also key to accelerating the advancement of the project. Based on the rich experience from the R&D team, the researchers comprehensively considered various solubilization strategies, such as salt form/crystal form screening, nanoparticles, spray drying, and hot-melt extrusion, and conducted a series of studies in parallel within a limited time.
After a comprehensive assessment of crystal form, solubility, and stability, as well as considering the project timeline, spray drying technology was selected to address the solubility challenges of this compound.
· Applying spray drying platform capability and experience, the project team took 13 weeks to complete development and GMP batches for IND submission
In addition to flexibility, speed, and quality, the experience from the team added value to the project. The formulation development team adopted the strategy of "parallel advancement of both spray drying and capsule process development in lab-scale" and finalized the range of process parameters and possible mechanistic models for production-scale spray drying and capsule filling with several iterations of validation.
The spray drying process was then scaled up, followed by encapsulation. The drug product batches met release specifications. The whole process including enabling technology selection, SDD and capsule formulation development, and scale-up from laboratory to production scale was completed in 8 weeks. The close collaboration among API, formulation, and analytical teams enabled efficient troubleshooting, material and time-saving.
Further collaboration with the drug product manufacturing team allowed the completion of the GMP manufacture, packaging, analytical testing, and release in 5 weeks.
In total, the project team took only 13 weeks to deliver an improved formulation.
WuXi STA has an industry-leading integrated API and drug product platform from preclinical to commercial. In this case, stable and reliable API supply, highly flexible and customized bioavailability enhancement technology, and an experienced project team were the keys to ensuring the rapid advancement and seamless delivery of the project.
About F2CS (Fast to Clinical Supply)
WuXi STA's customizable drug product service package: F2CS (Fast to Clinical Supply) shortens the time it takes to develop a formulation and deliver clinical trial material (CTM) for Phase I studies. WuXi STA has 10+ years of experience in the field of CTM development and manufacturing, delivering over 1,250 GMP batches globally in 2021. Our large teams have deep experience and laboratory to commercial scale capacity across a wide range of bioavailability enhancing technologies to enable flexible, fast, and efficient dosage form development and manufacture.
We are committed to making F2CS a "fast-track" connecting clients and patients, and finally enabling the rapid marketing of innovative therapies. Contact us at STA_Info@wuxiapptec.com.