Process for manufacturing glatiramer acetate product

Patent metadata

Field	Value
Publication number	US-9763993-B2
Application number	US-201514860053-A
Country	US
Kind code	B2
Filing date	Sep 21, 2015
Priority date	Jan 28, 2015
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

The patent provides a process of preparing a pharmaceutical preparation of glatiramer acetate and mannitol in a suitable container comprising the steps of:
(i) obtaining an aqueous pharmaceutical solution of glatiramer acetate and mannitol; (ii) filtering the aqueous pharmaceutical solution at a temperature of from above 0° C. up to 17.5° C. to produce a filtrate; and (iii) filling the suitable container with the filtrate obtained after performing step (ii), so as to thereby prepare the pharmaceutical preparation of glatiramer acetate and mannitol in the suitable container.

This patent further provides an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol, wherein the aqueous pharmaceutical solution
a) has a viscosity in the range of 2.0-3.5 cPa; or b) has an osmolality in the range of 275-325 mosmol/Kg.

This patent also provides a prefilled syringe, an automated injector and a method of treatment of a human patient.

First claim

What is claimed:

1. A process of preparing a pharmaceutical preparation of glatiramer acetate and mannitol in a suitable container comprising the steps of:
(i) obtaining an aqueous pharmaceutical solution of glatiramer acetate and mannitol;
(ii) filtering the aqueous pharmaceutical solution through a first filter to produce a first filtrate;
(iii) filtering the first filtrate at a temperature of above 0° C. to 17.5° C. through a second filter to produce a second filtrate; and
(iv) filling the suitable container with the second filtrate obtained after performing step (iii), so as to thereby prepare the pharmaceutical preparation of glatiramer acetate and mannitol in the suitable container.

2. The process of claim 1 further comprising the step of reducing the temperature of the second filter to a temperature of above 0° C. to 17.5° C.

3. The process of claim 1 further comprising the step of reducing the temperature of the aqueous pharmaceutical solution to a temperature of above 0° C. to 17.5° C. before passing through the second filter.

4. The process of claim 1 further comprising the step of receiving the first filtrate in a receiving vessel and reducing the temperature of the first filtrate to a temperature of above 0° C. to 17.5° C. after leaving the receiving vessel and before entering into the second filter.

5. The process of claim 1 further comprising the step of receiving the first filtrate in a receiving vessel and reducing the temperature of the first filtrate to a temperature of above 0° C. to 17.5° C. while in the receiving vessel.

6. The process of claim 1 further comprising the step of reducing the temperature of the first filter to a temperature of above 0° C. to 17.5° C.

7. The process of claim 1 further comprising the step of reducing the temperature of the aqueous pharmaceutical solution to a temperature of above 0° C. to 17.5° C. before passing through the first filter.

8. The process of claim 1 , wherein the obtaining step (i) comprises compounding the aqueous pharmaceutical solution in a compounding vessel.

9. The process of claim 8 further comprising the step of reducing the temperature of the aqueous pharmaceutical solution to a temperature of above 0° C. to 17.5° C. after leaving the compounding vessel and before entering into the first filter.

10. The process of claim 8 further comprising the step of reducing the temperature of the aqueous pharmaceutical solution to a temperature of above 0° C. to 17.5° C. while in the compounding vessel.

11. The process of claim 1 , wherein the first filtrate is passed through the second filter at a rate of 3-25 liters/hour; at a rate of 3-22 liters/hour; at a rate of 3-15 liters/hour; or at a rate of 3-10 liters/hour.

12. The process of claim 1 , wherein the pressure during the filtering of step (iii) and the pressure during the filling of step (iv) is maintained below 2.0 bar.

13. The process of claim 1 , wherein the temperature of the first filtrate in step (iii) is between 0° C. and 14° C., or the temperature of the first filtrate in step (iii) is reduced to a temperature between 0° C. and 14° C.

14. The process of claim 1 , wherein the temperature of the first filtrate in step (iii) is between 0° C. and 12° C., or the temperature of the first filtrate in step (iii) is reduced to a temperature between 0° C. and 12° C.

15. The process of claim 1 , wherein the temperature of the first filtrate in step (iii) is between 2° C. and 12° C., or the temperature of the first filtrate in step (iii) is reduced to a temperature between 2° C. and 12° C.

16. The process of claim 1 , wherein the temperature of the first filtrate in step (iii) is between 4° C. and 12° C., or the temperature of the first filtrate in step (iii) is reduced to a temperature between 4° C. and 12° C.

17. The process of claim 1 , wherein the filtering in step (ii), in step (iii) or both are performed using a sterilizing filter having a pore size of 0.2 μm or less.

18. The process of claim 1 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

19. A process of preparing a pharmaceutical product comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol which comprises the steps of:
(i) obtaining an aqueous pharmaceutical solution of glatiramer acetate and mannitol;
(ii) filtering the aqueous pharmaceutical solution at a temperature of above 0° C. to 17.5° C. to produce a filtrate; and
(iii) filling a suitable container with the filtrate obtained after performing step (ii), so as to thereby prepare the pharmaceutical product comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

20. The process of claim 2 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

21. The process of claim 3 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

22. The process of claim 4 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

23. The process of claim 5 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

24. The process of claim 6 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

25. The process of claim 7 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

26. The process of claim 8 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

27. The process of claim 9 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

28. The process of claim 10 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

29. The process of claim 11 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

30. The process of claim 12 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

31. The process of claim 13 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

32. The process of claim 14 , wherein the pharmaceutical preparation in the suitable container is an aqueous pharmaceutical solution comprising 40 mg/ml glatiramer acetate and 40 mg/ml mannitol.

33. The process of claim 15 , wherein the pharmaceutical p

Assignees

• Teva Pharma
• Teva Pharma

Inventors

• Cohen Rakefet
• Habbah Sasson
• Safadi Muhammad

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title