System for long time storage of pharmaceutical compositions at low temperatures
At least one system for storage of pharmaceutical compositions includes: a container including a neck and a crown that includes an upper crown surface; a stopper including a flange and a plug, the flange including a lower flange surface and a flange height; and a holding element configured to exert a force on the crown and the flange to form a horizontal contact area between the upper crown surface and the lower flange surface. The horizontal contact area has a size of 30 mm 2 to 300 mm 2 and the flange height is compressed at least partially in the horizontal contact area by 10% to 40%.
1. At least one system for storage of pharmaceutical compositions, the at least one system comprising:
a container comprising a neck and a crown, the crown comprising an upper crown surface;
a stopper comprising a flange and a plug, the flange comprising a lower flange surface and a flange height; and
a holding element configured to exert a force on the crown and the flange to form a horizontal contact area between the upper crown surface and the lower flange surface, the horizontal contact area having a size of 30 mm 2 to 300 mm 2 and the flange height being compressed at least partially in the horizontal contact area by 10% to 40%, wherein the horizontal contact area and the flange height are configured to maintain tightness at low temperatures, and wherein the container comprises an opening and the flange extends radially away from the opening past the upper crown surface.
2. The at least one system of claim 1 , wherein an angle between a line defined by the upper crown surface and a line defined by a center axis of the container is 75° to 89.99°.
3. The at least one system of claim 2 , wherein the angle is 85.5° to 88.5°.
4. The at least one system of claim 1 , wherein at least one of the following is satisfied:
a ratio [mm/mm] of values of a minimal inner crown diameter and a maximal inner crown diameter is 0.95 to 1.00; or
the upper crown surface has an average surface roughness Ra of 2 nm to 200 nm.
5. The at least one system of claim 1 , wherein at least one of the following is satisfied:
at least one of an inner surface or an outer surface of the container is coated; or
the upper crown surface is uncoated.
6. The at least one system of claim 5 , wherein the container is coated by a coating comprising silicone or a coating obtained by a chemical vapor deposition method.
7. The at least one system of claim 1 , wherein at least one of the following is satisfied:
the stopper comprises a thermoplastic elastomer;
an E Module of the stopper is 1 N/mm 2 to 10 N/mm 2 ; or
a shore hardness A of the stopper is 40 to 80.
8. The at least one system of claim 7 , wherein the thermoplastic elastomer comprises butyl groups and halogen.
9. The at least one system of claim 1 , wherein the horizontal contact area has a size of 50 mm 2 to 250 mm 2 .
10. The at least one system of claim 1 , wherein the horizontal contact area has a width of 0.1 mm to 5 mm.
11. The at least one system of claim 1 , wherein the flange height is compressed by 15% to 30%.
12. The at least one system of claim 1 , wherein the horizontal contact area comprises an upper inner crown edge and the flange height is compressed at the upper inner crown edge by 10% to 40%.
13. The at least one system of claim 12 , wherein a distance between the upper inner crown edge and a lower inner crown edge is 3 mm to 5 mm.
14. The at least one system of claim 1 , wherein the at least one system passes a container closure integrity test according to DIN EN ISO 8871-5:2016; chapter 4.4 in combination with Annex D.
15. The at least one system of claim 1 , wherein the container comprises a pharmaceutical composition at a temperature that is −200° C. or more and less than 0° C.
16. The at least one system of claim 15 , wherein the pharmaceutical composition comprises 50 wt-% to 99 wt-% water.
17. The at least one system of claim 15 , wherein the pharmaceutical composition is at a temperature that is −80° C. or more and −20° C. or less.
18. The at least one system of claim 1 , wherein the at least one system comprises 5 or more systems forming a bundle.
19. At least one system for storage of pharmaceutical compositions, the at least one system comprising:
a container comprising a neck and a crown, the crown comprising an upper crown surface;
a stopper comprising a flange and a plug, the flange comprising a lower flange surface and a flange height; and
a holding element configured to exert a force on the crown and the flange to form a horizontal contact area between the upper crown surface and the lower flange surface, the horizontal contact area having a size of 30 mm 2 to 300 mm 2 and the flange height being compressed at least partially in the horizontal contact area by 10% to 40%, wherein the horizontal contact area and the flange height are configured to maintain tightness at low temperatures, wherein the at least one system passes a modified container closure integrity test, wherein the modified container closure integrity test is a test according to DIN EN ISO 8871-5:2016; chapter 4.4 in combination with Annex D, wherein a pressure in part D.4.2 in Annex D is increased to 2 bar instead of decreased to 27 kPa, and wherein the container comprises an opening and the flange extends radially away from the opening past the upper crown surface.