received by the International Bureau on 18 April 2019 (18.04.2019)

CLAIMS:

1 . An ophthalmic drug in a pre-filled pharmaceutical package comprising:

• a vessel, for example a syringe barrel, cartridge, or vial, comprising a thermoplastic wall having an interior surface enclosing at least a portion of a lumen, an exterior surface, and a coating set on at least one of the interior surface and the exterior surface of the wall, the coating set comprising: o a tie coating or layer on the interior surface or the exterior surface comprising SiO_xC_yH_z in which x is from about 0.5 to about 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is from about 0.6 to about 3 as measured by XPS, and z is from about 2 to about 9 as measured by at least one of Rutherford backscattering spectrometry (RBS) or hydrogen forward scattering (HFS), the tie coating or layer having a facing surface facing toward the wall, the tie coating or layer also having an opposed surface facing away from the wall; o a barrier coating or layer of SiO_x, in which x is from about 1.5 to about 2.9 as measured by XPS, the barrier coating or layer having a facing surface facing toward the opposed surface of the tie coating or layer and an opposed surface facing away from the tie coating or layer; o optionally, a pH protective coating or layer of SiO_xC_yH_z, in which x is from about 0.5 to about 2.4 as measured by XPS, y is from about 0.6 to about 3 as measured by XPS, and z is from about 2 to about 9 as measured by at least one of RBS or HFS, the pH protective coating or layer, if present, having a facing surface facing toward the opposed surface of the barrier layer and an opposed surface facing away from the barrier layer;

• in the lumen, a liquid formulation of an ophthalmic drug suitable for intravitreal injection;

• a closure, for example a plunger or stopper, seated in the lumen having a front face facing the liquid formulation;

177 wherein the pre-filled pharmaceutical package comprising the ophthalmic drug is suitable for sterilization with gases; the gas residuals are minimal and/or lower than required by ISO 10993- 7.

2. The ophthalmic drug in a pre-filled pharmaceutical package according to Claim 1, wherein the stability of the ophthalmic drug is maintained, during a prolonged time period following the sterilization.

3. An ophthalmic drug in a pre-filled pharmaceutical package comprising:

• a vessel, for example a syringe barrel, cartridge, or vial, comprising a thermoplastic wall having an interior surface enclosing at least a portion of a lumen, an exterior surface, and a coating set on the exterior surface of the wall, the coating set comprising: o PECVD trilayer or quadlayer coatings;

o Amorphous carbon (CH);

o Aluminum oxide (A1203);

o Silicon nitride (Si3N4);

o Titanium oxide (Ti02);

o Indium tin oxide (In205Sn);

o Silicon oxide (Si02); and/or

one or more of the above; which may all be deposited by the following deposition technologies:

• Plasma enhanced chemical vapor deposition;

• Electron beam evaporation;

• Thermal evaporation;

Magnetron sputtering; and/or

Atomic layer deposition;

178 wherein the pre-filled pharmaceutical package comprising the ophthalmic drug is suitable for sterilization with gases; the gas residuals are minimal and/or lower than required by ISO 10993- 7; and/or the stability of the ophthalmic drug is maintained, during a prolonged time period following the sterilization.

4. An ophthalmic drug in a pre-filled pharmaceutical package comprising:

• a vessel, for example a syringe barrel, cartridge, or vial, comprising a thermoplastic wall having an interior surface enclosing at least a portion of a lumen, an exterior surface, and a coating set on at least one of the interior surface and the exterior surface of the wall, the coating set comprising: o a pH protective coating or layer of SiO_xC_yH_z, in which x is from about 0.5 to about 2.4 as measured by XPS, y is from about 0.6 to about 3 as measured by XPS, and z is from about 2 to about 9 as measured by at least one of RBS or HFS;

• in the lumen, a liquid formulation of a VEGF antagonist comprising an anti-VEGF antibody or an antigen-binding fragment of such antibody, such liquid formulation being suitable for intravitreal injection; and

• a closure, for example a plunger or stopper, seated in the lumen having a front face facing the liquid formulation; wherein the pre-filled pharmaceutical package comprising the ophthalmic drug is suitable for sterilization with gases; the gas residuals are minimal and/or lower than required by ISO 10993-7 and/or the stability of the ophthalmic drug is maintained, during a prolonged time period following the sterilization.

5. A method of sterilizing an ophthalmic drug in a pre-filled pharmaceutical package comprising:

• a vessel, for example a syringe barrel, cartridge, or vial, comprising a thermoplastic wall having an interior surface enclosing at least a portion of a lumen, an exterior

179 surface, and a coating set on at least one of the interior surface and the exterior surface of the wall, the coating set comprising: o a pH protective coating or layer of SiO_xC_yH_z, in which x is from about 0.5 to about 2.4 as measured by XPS, y is from about 0.6 to about 3 as measured by XPS, and z is from about 2 to about 9 as measured by at least one of RBS or HFS;

• in the lumen, a liquid formulation of an ophthalmic drug suitable for intravitreal injection;

• a closure, for example a plunger or stopper, seated in the lumen having a front face facing the liquid formulation; wherein the sterilization uses a gas or gases selecting from the group consisting of EO, propylene oxide, chlorine dioxide, nitrogen dioxide, vaporized hydrogen peroxide (VHP), peracetic acid, formaldehyde, paraformaldehyde, glutaraldehyde, ozone, gas plasma, seeded gas plasma, and beta-propiolactone; preferably EO, nitrogen dioxide or hydrogen peroxide; and four process variables, gas concentration, humidity level, temperature and gas exposure time, are determined for the sterilization.

6. The method of sterilization according to Claim 5, wherein the gas is EO, optionally wherein the EO gas concentration is between about 400 to about 800 mg/L.

7. The method of sterilization according to Claim 6, wherein the humidity level is between 30%RH to 80%RH; preferably 50%RH to 80%RH.

8. The method of sterilization according to Claim 6, wherein the temperature during sterilization is between about 70°F to about l45°F, (about 21 °C to about 63°C), optionally, about 85°F to about l30°F (about 29°C to about 54°C), preferably about H5°F (about 46°C).

9. The method of sterilization according to Claim 6, wherein the gas exposure time is between about 3 hours to about 40 hours, optionally about 5 hours to about 20 hours, preferably about 10 hours to 15 hours.

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10. The method of sterilization according to Claim 6, wherein the EO and/or ECH residuals after sterilization are analyzed using Water Extraction described in ANSI/A AMI/ISO 10993-7.

11. The method of sterilization according to Claim 6, wherein the EO and/or ECH residues are comparable to the EO and/or ECH residuals of glass vessels after a prolonged time period following the sterilization.

12. The method of sterilization according to Claim 6, wherein the daily dose of EO residual to patient does not exceed 4 mg and the daily dose of ECH residual to patient does not exceed 9 mg after drug administration.

13. The method of sterilization according to Claim 6, wherein the EO and/or ECH residuals are below detection limit after a prolonged time period following the sterilization.

14. The method of sterilization according to Claim 6, wherein the EO and/or ECH residuals are below 0.1 pg/mL, optionally below 0.1 pg/device, after a prolonged time period following the sterilization.

15. The method of sterilization according to Claim 5, wherein the gas is vaporized hydrogen peroxide (VHP).

16. The method of sterilization according to Claim 15, wherein the VHP gas concentration is between about 20% to about 50%, optionally about 30% to about 40%, optionally about 35%.

17. The method of sterilization according to Claim 15, wherein the humidity level is between 3% to 98%; optionally 5% to 95%.

18. The method of sterilization according to Claim 15, wherein the temperature during sterilization is between about 50°F to about l25°F (about l0°C to about 52°C), optionally, about 70°F to about l00°F (about 21 °C to about 38°C), preferably about 85°F (about 29°C).

19. The method of sterilization according to Claim 15, wherein the gas exposure time is between about 10 minutes to about 8 hours, optionally about 20 minutes to about 5 hours, optionally about 30 minutes to 2 hours, optionally about 50 minutes.

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20. The method of sterilization according to Claim 5, wherein the gas is nitrogen dioxide.

21. The method of sterilization according to Claim 20, wherein the nitrogen dioxide gas concentration is between about 3 mg/L to about 40 mg/L, optionally about 5 mg/L to about 20 mg/L, optionally about 10 mg/L.

22. The method of sterilization according to Claim 20, wherein the humidity level is between 3% to 98%; optionally 10% to 90%, optionally 60%-85%, optionally around 75%.

23. The method of sterilization according to Claim 20, wherein the temperature during sterilization is between about 50°F to about l25°F (about l0°C to about 52°C), optionally, about 70°F to about l00°F (about 21 °C to about 38°C), preferably about 85°F (about 29°C)

24. The method of sterilization according to Claim 20, wherein the gas exposure time is between about 10 minutes to about 8 hours, optionally about 20 minutes to about 5 hours, optionally about 30 minutes to 2 hours, optionally about 60 minutes.

25. The method of sterilization according to Claim 5, wherein the coating set further comprises: o a tie coating or layer on the interior surface or the exterior surface comprising SiO_xC_yH_z in which x is from about 0.5 to about 2.4 as measured by X-ray photoelectron spectroscopy (XPS), y is from about 0.6 to about 3 as measured by XPS, and z is from about 2 to about 9 as measured by at least one of Rutherford backscattering spectrometry (RBS) or hydrogen forward scattering (HFS), the tie coating or layer having a facing surface facing toward the wall, the tie coating or layer also having an opposed surface facing away from the wall; and o a barrier coating or layer of SiO_x, in which x is from about 1.5 to about 2.9 as measured by XPS, the barrier coating or layer having a facing surface facing toward the opposed surface of the tie coating or layer and an opposed surface facing away from the tie coating or layer; wherein the pH protective coating or layer of SiO_xC_yH_z has a facing surface facing toward the opposed surface of the barrier layer and an opposed surface facing away from the barrier layer.

26. The method of sterilization according to Claim 25, wherein the coating set further comprises a lubricity coating or layer positioned between the pH protective coating or layer and the lumen.

27. An ophthalmic drug in a pre-filled pharmaceutical package according to Claim 1, wherein the prolonged time period following the sterilization is time zero (TO), optionally 1 month, optionally 2 months, optionally 3 months, optionally 6 months, optionally 9 months, optionally 12 months, optionally 18 months, optionally 24 months, optionally 30 months, optionally 36 months, optionally 42 months, optionally 48 months, optionally 54 months, or optionally 60 months.

28. A kit comprising one or more pre-filled pharmaceutical packages according to Claim 1, contained in a sealed outer package, in which the prefilled pharmaceutical package is sterile, optionally in which the sealed outer package is permeable to ethylene oxide sterilant, optionally in which the lumen is essentially free, preferably free, of ethylene oxide.