DESIGN OF TECHNOLOGY TRANSFER- BASED MANUFACTURING PROCESS
Although a transferred process should ideally remain the same as the original, in practice, the process always undergoes adaptation
at the receiving site, mostly due to the difference in equipment between the sending and receiving sites, as well as the need
for scale-up of the entire process. The adaptation approach is different for different process steps. With an understanding
of the process through the technology transfer document package and direct communication between sending and receiving sites,
the anticipated GMP manufacturing process can be designed in detail.
Prior to the manufacturing process design, the desired scale of the overall process is often decided based on the amount of
bulk drug substance required. The scale of each unit operation at the receiving site is then selected based on the scale-up
factor and expected product recovery in each process step. The anticipated approach of operation and consequently the technical
feasibility of each unit operation can be visualized at this stage. The decision to modify any process step or to split a
part of the process into several runs in parallel or series can also be made. Eventually, a detailed process flow diagram
containing in-depth activities in each unit operation can be generated (see Figure 2).
Figure 2: Schematic workflow route to the design of a manufacturing process based on technology transfer.
The operation of an overall biopharmaceutical manufacturing process is always executed in batch mode. The intermediate process
bulks are stored at certain conditions before using in the next process steps. The required duration of each process step
at the technology receiving site may vary from the sending site, particularly due to the difference in equipment and scale.
This affects the storage duration of the intermediate process bulks. In addition, due to the larger volumes, the actual cooling
and warming rates of intermediate process bulks may not be equal to the original small-scale process when both are stored
at the same temperature. Scheduling of each process step in a biopharmaceutical manufacturing process, therefore, is a significant
part of overall process design.
The selection and design of process conditions and process equipment are interrelated. The process conditions should be kept
the same as the original process at the sending site or should be changed according to the scale-up factor. How to change
different process parameters upon scale-up is not within the scope of this article and can be found in the literature (4).
Critical raw materials, that define the performance of the process, should not be changed at the receiving site. The equipment
selected or designed for executing the process must be compatible with the desired raw materials and must ensure the performance
at the desired process conditions and parameters. In reality, however, the existing equipment often necessitates changes in
process conditions and parameters due to the significant investment required for setting up new equipment for GMP production.