Systems and methods for producing a mixer

Patent metadata

Field	Value
Publication number	US-12226957-B2
Application number	US-202117395176-A
Country	US
Kind code	B2
Filing date	Aug 5, 2021
Priority date	Aug 6, 2020
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

Systems and method for producing a small-scale mixer are provided. In some implementations, a method for includes obtaining dimensions of an at-scale mixer. The method also includes determining first dimensions of the small-scale mixer based on respective dimensions of the at-scale mixer. The method further includes determining second dimensions of the small-scale mixer independent of the dimensions of the at-scale mixer. Additionally, the method includes generating the small-scale mixer using the first dimensions and the second dimensions using a three-dimensional printer.

First claim

The invention claimed is:

1. A system for producing a first mixer for mixing biopharmaceutical proteins into an aqueous formulation, the system comprising:
a first plurality of dimensions based on a respective plurality of dimensions of a second mixer;
a second plurality of dimensions independent of the respective plurality of dimensions of the second mixer, wherein the second plurality of dimensions is generated by a computational fluid dynamic technique simulating physical forces on an impeller and shear forces on the biopharmaceutical proteins in the aqueous formulation by the impeller over various rotational velocities, fluid densities, and temperatures, and wherein the second plurality of dimensions are calculated to prevent degradation of the biopharmaceutical proteins in the aqueous formulation;
a three-dimensional printer configured to receive the first plurality of dimensions and the second plurality of dimensions and produce the first mixer, wherein the first mixer has a plurality of dimensions based on a combination of the first plurality of dimensions and the second plurality of dimensions; and
a smoothing apparatus configured to smooth a surface of the first mixer, wherein smoothing the surface of the first mixer prevents degradation of the biopharmaceutical proteins in the aqueous formulation.

2. The system of claim 1 , wherein a scaling factor relates the first plurality of dimensions of the first mixer to the respective plurality of dimensions of the second mixer.

3. The system of claim 1 , wherein the first plurality of dimensions of the first mixer and the respective plurality of dimensions of the second mixer comprise impeller clearance off bottom of mixer (C), impeller diameter (D), liquid level (H), rotational speed (N), tank diameter (T), blade width (W), blade height (BH), and baffle width (WB).

4. The system of claim 1 , wherein the second plurality of dimensions correspond to dimensions of an impeller of the first mixer.

5. The system of claim 1 , wherein the three-dimensional printer is configured to produce the first mixer using one of the following: PC (polycarbonate), ABS (acrylonitrile butadiene styrene), PLA (polylactic acid), PET (polyethylene terephthalate), nylon, metal, and glass/PET.

6. The system of claim 1 , wherein the smoothing apparatus is configured to mechanically smooth the surface of the first mixer.

7. The system of claim 1 , wherein the smoothing apparatus is configured to chemically smooth the surface of the first mixer using a volatile solvent bath.

8. The system of claim 7 , wherein the volatile solvent bath includes acetone or dichloromethane.

9. A method for producing a first mixer for mixing biopharmaceutical proteins into an aqueous formulation, the method comprising:
obtaining a respective plurality of dimensions of a second mixer;
determining a first plurality of dimensions of the first mixer based on the respective plurality of dimensions of the second mixer;
determining, by simulating physical forces on an impeller and shear forces on the biopharmaceutical proteins in the aqueous formulation by the impeller over various rotational velocities, fluid densities, and temperatures generated by the first mixer using a computational fluid dynamics technique, a second plurality of dimensions independent of the plurality of dimensions of the second mixer, wherein the second plurality of dimensions are calculated to prevent degradation of the biopharmaceutical proteins in the aqueous formulation; and
generating, using a three-dimensional printer, the first mixer having a plurality of dimensions based on a combination of the first plurality of dimensions and the second plurality of dimensions.

10. The method of claim 9 , further comprising: smoothing a surface of the first mixer, wherein smoothing the surface of the first mixer prevents degradation of the biopharmaceutical proteins in the aqueous formulation.

11. The method of claim 10 , wherein smoothing comprises mechanically abrading the surface of the first mixer.

12. The method of claim 10 , wherein smoothing comprises chemically polishing the surface of the first mixer using a volatile solvent.

13. The method of claim 9 , wherein the first plurality of dimensions of the first mixer and the dimensions of the second mixer comprise impeller clearance off bottom of mixer (C), impeller diameter (D), liquid level (H), rotational speed (N), tank diameter (T), blade width (W), blade height (BH), and baffle width (WB).

14. The method of claim 9 , wherein determining the second plurality of dimensions of the first mixer comprises determining physical forces on an impeller of the first mixer during mixing of the biopharmaceutical proteins in the aqueous formulation.

15. The method of claim 9 , wherein generating the first mixer comprises fused filament fabrication of the first mixer.

16. The method of claim 9 , wherein generating the first mixer comprises producing the first mixer using one of the following: PC (polycarbonate), ABS (acrylonitrile butadiene styrene), PLA (polylactic acid), PET (polyethylene terephthalate), nylon, metal, and glass/PET.

17. The method of claim 9 , further comprising generating a first volume of a first product using the second mixer; generating a second volume of the first product using the first mixer; and comparing one or more physical parameters of the first volume and the second volume.

18. The method of claim 17 , further comprising: comparing shear stress of generating the first volume with shear stress of generating the second volume.

19. The method of claim 18 , wherein the shear stress comprises shear stress imparted on an impeller of the first mixer.

20. The method of claim 17 , wherein the physical parameters include one or more of visual inspection, pH, protein concentration, turbidity, purity, and particulate density.

Assignees

• Regeneron Pharma

Inventors

• Vo Trinh
• Chen Huyun
• Bhupender Bhalla Amardeep Singh

Classifications

• B29C64/30

  Auxiliary operations or equipment · CPC title

• B29C64/10

  Processes of additive manufacturing · CPC title

• B29C64/00

  Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering · CPC title

• B01F2101/22

  Mixing of ingredients for pharmaceutical or medical compositions · CPC title

• B01F35/5312

  with vertical baffles mounted on the walls · CPC title