Method for the reduction of viral titer in pharmaceuticals

Patent metadata

Field	Value
Publication number	US-11034721-B2
Application number	US-201715836683-A
Country	US
Kind code	B2
Filing date	Dec 8, 2017
Priority date	Dec 9, 2016
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Disclosed are methods and devices for the optimization of virus removal from solutions. A method of filtering a process fluid comprising a product includes allowing some of the process fluid to flow from a first reservoir to a viral filter; adding a chase fluid to the process fluid in the first reservoir to form a composite fluid; and allowing the composite fluid to flow from the first reservoir to the viral filter to produce eluent. In some embodiments, flow of fluid across the viral filter is sufficient to avoid significant impairment to viral removal until a preselected event, occurs. In some embodiments, flow of fluid from the first reservoir across the viral filter is maintained in the absence of an interruption or slowing of flow of duration or magnitude sufficient to impair viral removal to a level below a log-reduction value of the viral filter.

First claim

What is claimed is:

1. A method of filtering a process fluid comprising a pharmaceutical product, the method comprising:
a) allowing some of the process fluid in a first reservoir to flow out of the first reservoir, reducing an amount of process fluid remaining in the first reservoir, and pass a size exclusion viral filter to produce a first eluent;
b) adding a chase fluid from a chase fluid reservoir to the process fluid in the first reservoir to form a composite fluid, and wherein a ratio of an amount of chase fluid to an amount of process fluid remaining in the first reservoir when the chase fluid is added is equal to or greater than 1:1; and
c) allowing the composite fluid in the first reservoir to flow out of the first reservoir and pass the size exclusion viral filter to produce a second eluent,
wherein the composite fluid does not include the first or second eluent,
wherein the flow of the process fluid or the composite fluid across the size exclusion viral filter is continuous such that air does not enter the size exclusion viral filter until a preselected event occurs.

2. The method of claim 1 , wherein the pharmaceutical product includes an active pharmaceutical ingredient.

3. The method of claim 1 , wherein adding the chase fluid is performed when the volume of process fluid remaining in the first reservoir is at a reference volume or within a reference volume range.

4. The method of claim 3 , wherein the reference volume is equal to or greater than 0.5 times a volume of components disposed between the first reservoir and a destination reservoir, wherein the volume of components comprises the combined volume of the size exclusion viral filter, a pre-filter conduit, and a post filter conduit.

5. The method of claim 3 , wherein the reference volume is equal to or greater than a volume of components disposed between the first reservoir and a destination reservoir, wherein the volume of components comprises the combined volume of the size exclusion viral filter, a pre-filter conduit, and a post filter conduit.

6. The method of claim 1 , wherein the volume of chase fluid added is less than or equal to a chase fluid reference volume, wherein the chase fluid reference volume is equal to or greater than 0.5 times a volume of components disposed between the first reservoir and a destination reservoir, and wherein the volume of components comprises the combined volume of the size exclusion viral filter, a pre-filter conduit, and a post filter conduit.

7. The method of claim 6 , wherein the chase fluid reference volume is equal to or greater than a volume of components disposed between the first reservoir and the destination reservoir, wherein the volume of components comprises the combined volume of the size exclusion viral filter, a pre-filter conduit, and a post filter conduit.

8. The method of claim 1 , wherein the chase fluid is added to the first reservoir while the first reservoir still contains a predetermined amount of process fluid.

9. The method of claim 1 , wherein a ratio of an amount of chase fluid to an amount of process fluid remaining in the first reservoir when the chase fluid is added is equal to or greater than 1.5:1.

10. The method of claim 1 , wherein a preselected difference in pressure across the size exclusion viral filter is maintained.

11. The method of claim 1 , wherein a differential pressure across the size exclusion viral filter is maintained at or below a preselected maximal value.

12. The method of claim 1 , wherein a preselected difference in pressure, equal to or no greater than 14 psi of differential pressure across the size exclusion viral filter is maintained.

13. The method of claim 1 , wherein a differential pressure across the size exclusion viral filter is maintained at or above a preselected minimal value.

14. The method of claim 1 , wherein a differential pressure across the size exclusion viral filter sufficient that a reduction in viral particles of at least 5 fold is achieved.

15. The method of claim 1 , wherein the preselected event includes reaching the end of a preselected time period.

16. The method of claim 1 , further comprising:
providing a system including
the first reservoir,
the size exclusion viral filter, and
a destination reservoir,
wherein the first reservoir is in fluid connection with the size exclusion viral filter and the size exclusion viral filter is in fluid connection with the destination reservoir.

17. The method of claim 16 , wherein the size exclusion viral filter is disposed between the first reservoir and the destination reservoir.

18. The method of claim 16 , wherein the size exclusion viral filter is disposed between the first reservoir and a conduit.

19. The method of claim 16 , wherein the system includes a pre-filter conduit configured to convey the process fluid or the composite fluid from the first reservoir to the size exclusion viral filter.

20. The method of claim 16 , wherein the system includes a conduit configured to convey the process fluid or the composite fluid to the destination reservoir or a conduit to a destination.

21. The method of claim 16 , wherein the system includes
a first conduit configured to convey the process fluid or the composite fluid from the first reservoir to the size exclusion viral filter, and
a second conduit configured to convey the first or the second eluent from the size exclusion viral filter to the destination reservoir.

22. The method of claim 16 , wherein the system includes a first valve disposed to control the flow of the process fluid or the composite fluid from the first reservoir to the size exclusion viral filter.

23. The method of claim 16 , wherein the system includes a valve disposed to control the flow of the first or the second eluent from the size exclusion viral filter to the destination reservoir.

24. The method of claim 1 , wherein flow of the process fluid or the composite fluid from the first reservoir across the size exclusion viral filter is maintained in the absence of a stoppage of the process fluid or the composite fluid flow.

25. A method of filtering a process fluid comprising a pharmaceutical product, comprising:
a) allowing process fluid in a first reservoir to flow out of the first reservoir and pass a size exclusion viral filter to produce a eluent first and to reduce an amount of process fluid in the first reservoir;
b) determining a value which is a function of the amount of process fluid remaining in the first reservoir and, if the value meets a predetermined reference value, adding chase fluid from a chase fluid reservoir, to the process fluid in the first reservoir to form a composite fluid, wherein the chase fluid is added to the first reservoir while the first reservoir still contains a predetermined amount of process fluid, and wherein a ratio of an amount of chase fluid to an amount of process fluid remaining in the first reservoir when the chase fluid is added is equal to or greater than 1:1;
c) allowing the composite fluid in the first reservoir to flow out of the first reservoir and pass the viral filter to produce a second eluent; and
d) stopping the flow from the size exclusion viral filter,
wherein the composite fluid does not include the first or second eluent,
wherein the flow of the process fluid or the composite fluid from the first reservoir across the viral filter is continuous such that air does not enter the size exclusion viral filte

Assignees

• Lonza Ag

Inventors

• PEASE Paul
• Miller Wilburn
• Cobb Jesse
• Castagnaro Anthony
• Harris Andrew

Classifications

• C07K16/065 Primary

  Purification, fragmentation · CPC title

• B01D63/02

  Hollow fibre modules · CPC title

• B01D61/22

  Controlling or regulating · CPC title

• B01D61/14

  Ultrafiltration; Microfiltration · CPC title

• C07K16/08

  against material from viruses · CPC title