Process and apparatus for removal of DNA and viruses

• US 5,076,933 A
• Filed: 06/29/1990
• Issued: 12/31/1991
• Est. Priority Date: 06/29/1990
• Status: Expired due to Term

• Current Assignee: Coulter International Corp. (Danaher Corporation)
• Original Assignee: Coulter Corporation (Danaher Corporation)
• Inventors: Smariga, Paulette, O'Connell, Edward, Glenn, Stephan D., Butchko, Gregory
• Primary Examiner(s): Jones, W. Gary
• Application Number:
  US07/546,011
• Time in Patent Office: 550 Days
• Field of Search: 210/641, 210/652, 210/653, 210/655, 210/321.64, 210/321.84, 210/335, 210/446, 210/500.29, 210/506, 210/507, 210/508, 422/1, 422/101, 435/371, 935/19
• US Class Current: 210/641
• CPC Class Codes: A61L 2/0017 Filtration
• CPC Class Codes: B01D 61/146 comprising multiple ultrafiltration steps
• CPC Class Codes: B01D 61/1471 comprising multiple microfiltration steps
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 71/10 Cellulose; Modified cellulose

Abstract

A single filtration device containing coated filter membranes and absolute pore filters is provided in which the membranes and absolute pore filters are present in two sections of the filter device. The filter device will remove viruses, as modeled by type-C Xenotropic retrovirus, with an efficiency of at least 4.6×10⁵ ; remove DNA from levels of 10 μg/sample to levels below 10 picograms per 500 mg sample of monoclonal antibody; and will remove at least 97% of some bacterial endotoxins.

Claims

1. A process for the removal of DNA, endotoxins and viruses from aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions comprising, passing one of said aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions through a first DNA filter section and a second virus filter section, wherein said DNA, viruses and endotoxins are substantially removed;

and collecting said aqueous buffer solutions, aqueous pharmaceutical solutions or aqueous biological pharmaceutical solutions;

said first DNA filter having;

(i) a first absolute pore filter,

(ii) a first and second filter selected from one of (a) a DEAE cellulose filter membrane and (b) an absolute pore filter coated with at least one of DEAE cellulose, quaternary aminoethyl salts and quaternary aminomethyl salts, and

(iii) a second absolute pore filter; and

said second virus filter section having absolute pore filters of smaller pore diameter than the absolute pore filters in the DNA filter section.

2. A process in accordance with claim 1 wherein the yield of pharmaceuticals, or biological pharmaceuticals in the filtered solutions is 90% or higher compared to the starting solution.

3. A process in accordance with claim 1 wherein the virus removal is 99.9999997% or higher when the virus is 0.100 microns or larger, and the yield of pharmaceutical or biological pharmaceutical in the filtered solution of same is 90% or higher compared to the starting solution.

4. A process in accordance with claim 1 wherein said DNA in the filtered solutions is less than 10 picograms per 100 ml of solution.

5. A process in accordance with claim 1 wherein the aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions have a pH in the range of 3 to 9.

6. A process in accordance with claim 1 wherein the aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions each have a specific salt content of less than 0.5 Molar, said specific salt being at least one selected from the group consisting of the lithium, sodium, potassium and ammonium salts of the phosphate, chloride, bromide, iodide, sulfate and acetate anions.

7. A process in accordance with claim 1 wherein said DNA in the filtered solutions is less than 1 picogram per 100 ml of solution.

15. A process in accordance with claim 1 or 8 wherein said aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions are passed through said DNA filter section and said virus filter section by a vacuum means or a pressure means.

8. A process for the removal of DNA and viruses from aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions, comprising passing either one of the solutions through a first DNA filter section and a second virus filter section to obtain a filtered aqueous pharmaceutical solution or a filtered aqueous biological pharmaceutical solution having substantially reduced DNA and virus levels, said solutions passing through:

(a) a first DNA filter section comprising a first 0.2 micron absolute pore filter, a first diethylaminoethyl cellulose filter, a second diethylaminoethyl cellulose filter and a second 0.2 micron absolute pore filter, and

(b) a second virus filter section comprising a first 0.1 micron absolute pore filter, a second 0.1 micron absolute pore filter, a first 0.04 micron absolute pore filter and a second 0.04 micron absolute pore filter; and

collecting the filtered solutions.

9. A process in accordance with claim 8 wherein the yield of the pharmaceutical or biological pharmaceutical, in the filtered solution is 90% or higher.

10. A process in accordance with claim 8 wherein the virus removal is 99.99999997% or when the virus is 0.100 microns or larger, and the yield of the pharmaceutical or biological pharmaceutical in the filtered solution is 90% or higher.

11. A process in accordance with claim 8 wherein the DNA in the filtered pharmaceutical or biological pharmaceutical solution is reduced to less than 10 picograms per 100 ml of solution.

12. A process in accordance with claim 8 wherein the pharmaceutical solution or biological solution has a pH in the range of 6 to 8.

13. A process in accordance with claim 8 wherein the pharmaceutical or biological pharmaceutical has a specific salt content, excluding salts of pharmaceuticals or biological pharmaceuticals, of less than 0.5 Molar, said specific salts being at least one selected from the group consisting the lithium, sodium, potassium and ammonium salts of the phosphate, chloride, bromide, iodide, sulfate and acetate anions.

14. A process in accordance with claim 8 wherein the DNA in the filtered pharmaceutical or biological pharmaceutical solution is reduced to less than 1 picogram per 100 ml of solution.

24. The improved apparatus in accordance with claim 14, wherein said apparatus is capable of removing DNA to a level of less than 1 picogram per ml of solution.

16. An improved apparatus for the removal of DNA, endotoxins and viruses from aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions, said apparatus having a housing with suitable inlet/outlet means internal gaskets and filter supports, and internal filters wherein the improvement comprises a first DNA filter section having, from inflow to outflow, a first 0.2 micron filter, a first diethylaminoethyl cellulose filter, a second diethylaminoethyl cellulose filter and a second 0.2 micron filter, the filters having face-to-face contact;

and a second virus filter section having, from inflow to outflow, a first 0.1 micron filter, a second 0.1 micron filter, a first 0.04 micron filter and a second 0.04 micron filter, said filters having face-to-face contact.

17. An improved apparatus in accordance with claim 16 wherein said 0.2, 0.1 and 0.04 filters are absolute pore filters.

18. The improved apparatus in accordance with claim 16 wherein said apparatus is capable of removing DNA to a level of less than 10 picograms per 100 ml of solution.

19. The improved apparatus of claim 16 wherein said apparatus is capable of removing 99.9999997% of virus when the virus is 0.100 microns or larger.

20. The improved apparatus of claim 16 wherein the apparatus gives a yield of pharmaceutical or biological pharmaceutical in the filtered solution of 90% or higher compared to the unfiltered solution.

21. The improved apparatus of claim 16 where the solution to be filtered is passed through said apparatus by pressure or vacuum means.

22. The improved apparatus of claim 16 wherein said apparatus is a means of administration of said aqueous buffer solution, aqueous pharmaceutical solution or aqueous biological pharmaceutical solution to a patient which means contains said DNA and virus filter sections.

23. The improved apparatus of claim 16 wherein said apparatus is a syringe filtration device containing said DNA and virus removal filters.

25. An improved apparatus for the removal of DNA, endotoxins and viruses from aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions, said apparatus having a housing with suitable inlet/outlet means, internal gaskets and filter supports, and internal filters wherein the improvement comprises a first DNA filter section having, from inflow to outflow, a first 0.2 micron filter, a second 0.2 micron filter, the filters having face-to-face contact;

and a second virus filter section having, from inflow to outflow, a first 0.1 micron filter, a second 0.1 micron filter, a first 0.04 micron filter and a second 0.04 micron filter, said filters having face-to-face contact;

wherein at least one of the absolute pore filters is coated with at least one of the group consisting of DEAE, QAE, QAM and other quaternary ammonium salts.

26. An improved apparatus for the removal of DNA, endotoxins and viruses from aqueous buffer solutions, aqueous pharmaceutical solutions and aqueous biological pharmaceutical solutions, said apparatus having a housing with suitable inlet/outlet means, internal gaskets and filter supports, and internal filters wherein the improvement comprises a first DNA filter section having, from inflow to outflow, a first 0.2 micron filter, first and second absolute pore filters coated with at least one selected from the group consisting of DEAE cellulose, QAE, QAM and other quaternary ammonium salts, a second 0.2 micron filter, the filters having face-to-face contact;

and a second virus filter section having, from inflow to outflow, a first 0.1 micron filter, a second 0.1 micron filter, a first 0.04 micron filter and a second 0.04 micron filter, said filters having face-to-face contact.