When choosing the form of filling pump, not only should we consider the accuracy of filling mentioned in the previous article, but more importantly, evaluate the impact on product quality. When it comes to this, the shear force of the pump becomes an unavoidable topic. Because in all known low volume aseptic filling processes, biological products are subject to shear stress, in other words, both plunger pumps and peristaltic pumps have shear force.

In industrial production, peristaltic pumps are commonly used, often due to the high shear force of rotary piston pumps, which poses a risk of damaging the product. And there is also literature that clearly indicates that plunger pumps do have a tendency to damage biological product formulations.

Here is an experiment that first studies the filling of monoclonal antibodies. Two different mAb formulations are filled, and to simulate a bad situation, these two monoclonal antibody preparations are cycled 15 times to amplify any particle formation caused by protein degradation or material detachment during the filling process. The experimental results were not unexpected. The number of particles generated in the piston pump was much larger than that in the peristaltic pump, indicating that the plunger pump did indeed cause damage to the experimental sample.

Is this directly caused by shear force?

To verify this point, the experiment also chose to test a liposome design that is sensitive to mechanical stress, in which a fluorescent label carboxyfluorescein is encapsulated to directly quantify the shear rate. The experimental results were somewhat unexpected, as the peristaltic pump triggered the release of fluorescein, and compared to the hydraulic plunger pump used in the study, the shear rate level of the peristaltic pump seemed to be about 20 times higher.

In order to obtain more theoretical verification and CFD simulation analysis, it is technically difficult to obtain information about the internal fluid dynamics of the filling system. Although CFD cannot provide direct data, it can be used to support further investigation and interpretation. Similarly, verifying the results with experimental data based on research can avoid misunderstandings of numerical simulation data. CFD analysis shows that the shear rate of peristaltic pumps is also higher than that of hydraulic piston pumps.

But research on mAb formulations does show sub visible particle counts after plunger pump operation. What exactly causes this phenomenon?

The filling process of hydraulic piston pump can be basically divided into four different steps. Lifting the piston in position will cause a decrease in pressure in the system, and liquid will be "sucked" into the reservoir cylinder. The piston has a single-sided notch in the direction of liquid entry. Then, the piston rotates 180 ° and the notch turns towards the direction of the cylinder outlet. In one step, the piston moves downwards and delivers the liquid from the pump to the filling needle.

Obviously, liquid flow is mainly determined by the rotation and vertical movement of the piston inside the cylinder.

In fact, in the biopharmaceutical industry, the small gap between the piston and cylinder and its impact on protein damage have been extensively discussed. And this tiny gap has not been analyzed by previous CFD simulations.

The above:Technological progress of gear pumps in China