Scale Up and Process Controls

Once a target formulation is achieved during the feasibility study and confirmed with an in vivo animal study, the next step is scaling up the formulation while achieving the same critical product attributes. The charts below show two of the critical product attributes that Oakwood focuses on maintaining during the scale-up process. The first is an example of a particle size distribution maintained from a 5 gram batch size through a 1 kilogram batch size. The second is an example of achieving a tight but differentiable in vitro release profile. Through the use of our technology we have demonstrated control over these attributes, which leads to successful scale-up.

Example of Particle Size Distribution throughout Scale-Up:

Example of In Vitro Release throughout Scale-Up:

A key advantage of the Oakwood process is that it is a continuous flow process. The equipment used to manufacture prototype formulations is the same as is used to manufacture full scale lots. The scale-up is accomplished by running the process longer, and by controlling the downstream processing, such that the product is not changed over the course of the run. We have demonstrated scale-up of prototype formulations to batch sizes of 1, 2, and 8 kg.

We validate our process prior to manufacture of clinical trial materials, and set specifications of process parameters such as flow rates, mixing speeds, hold times, etc. We use Quality by Design (QbD) principles and develop specific Design of Experiments (DoE) to increase our success of scale-up. For setting many of these specifications, it is an advantage of the Oakwood process that small batches can be made to determine ranges of the process parameters, instead of needing to manufacture full scale batches, thus saving time and expense.

While controlling the process and optimizing the formulation during scale up, Oakwood provides all necessary CMC documentation for regulatory filings, and has successfully passed CMC reviews by regulatory authorities.