METHODS FOR DETECTING LEAKS FOR PHARMACEUTICAL PACKAGES SUCH AS PARENTERAL PACKAGES AND BULK PHARMACEUTICAL BAGS

Abstract

A method for leak detection of a packaged sealed product according to the steps: feeding liquid nitrogen to a vaporizer thereby forming gaseous nitrogen; mixing the gaseous nitrogen with multifunctional particles; feeding the mixture of gaseous nitrogen and multifunctional particles to a chamber wherein a packaged sealed product is present in the chamber; and transmitting a signal when the multifunctional particles contact a component leaking from the packaged sealed product. Typically, the packaged sealed product is a pharmaceutical or other medicinal product.

Claims

1. A method for leak detection comprising the steps: a) Feeding liquid nitrogen to a vaporizer thereby forming gaseous nitrogen wherein either the liquid nitrogen or gaseous nitrogen is sterilized; b) Mixing the gaseous nitrogen with multifunctional particles; c) Feeding the mixture of gaseous nitrogen and multifunctional particles to a chamber wherein a packaged sealed product is present in the chamber; and d) Transmitting a signal when the multifunctional particles contact a component leaking from the packaged sealed product.

2. The method as claimed in claim 1 wherein the liquid nitrogen or gaseous nitrogen is fed through a sterile filtration system.

3. The method as claimed in claim 1 wherein the multifunctional particles are selected from the group consisting of luminescent nano-particles, electro-conductive polymer based nano-particles and color sensitive polymer nano-particles.

4. The method as claimed in claim 1 wherein the multifunctional particles switch their state when they contact a component leaking from the packaged sealed product.

5. The method as claimed in claim 1 wherein the switch state is selected from the group consisting of optical, electrical and color change.

6. The method as claimed in claim 5 wherein the optical switch state is on and off.

7. The method as claimed in claim 5 wherein the electrical switch state is electrical conductivity.

8. The method as claim in claim 5 wherein the color switch state is induced color change.

9. The method as claimed in claim 1 wherein the signal is received by a receiver which is in electronic communication with a programmable logic controller.

10. The method as claimed in claim 1 wherein a detector measures the switch state of a multifunctional particle.

11. The method as claimed in claim 1 wherein the detector is selected from the group of detectors that measure optical, electrical and magnetic switch signals.

12. The method as claimed in claim 1 wherein a location of the leak can be detected.

13. The method as claimed in claim 1 wherein magnitude of the leak can be detected.

14. The method as claimed in claim 1 wherein the detector issues an alert to an operator.

15. The method as claimed in claim 1 wherein the leak is detected at a threshold of 0.3 to 10 microns in size.

16. The method as claimed in claim 1 wherein the packaged sealed product is selected from the group consisting of ampoules, syringes, pouches, pads and bulk pharmaceutical bags.

17. The method as claimed in claim 16 wherein the packaged sealed product is removed from the chamber when a leak condition is detected.

18. The method as claimed in claim 17 wherein the component is selected from the group consisting of injectable, bulk drug solutions, sterile products, solid dosage forms and biopharmaceuticals.

19. The method as claimed in claim 1 wherein the chamber contains 1 to 10,000 sealed product packages.

20. A method for leak detection of a component from a packaged sealed product comprising the steps: a) Feeding liquid nitrogen to a vaporizer thereby forming gaseous nitrogen wherein either the liquid nitrogen or gaseous nitrogen is sterilized; b) Mixing the gaseous nitrogen with multifunctional particles; c) Feeding the mixture of gaseous nitrogen and multifunctional particles to a chamber wherein the packaged sealed product is present in the chamber; and d) Transmitting a signal when the multifunctional particles contact the component leaking from the packaged sealed product.

21. The method as claimed in claim 20 wherein the liquid nitrogen or gaseous nitrogen is fed through a sterile filtration system.

22. The method as claimed in claim 20 wherein the multifunctional particles are selected from the group consisting of luminescent nano-particles, electro-conductive polymer based nano-particles and color sensitive polymer nano-particles.

23. The method as claimed in claim 20 wherein the multifunctional particles switch their state when they contact a component leaking from the packaged sealed product.

24. The method as claimed in claim 20 wherein the switch state is selected from the group consisting of optical, electrical and color change.

25. The method as claimed in claim 24 wherein the optical switch state is on and off.

26. The method as claimed in claim 24 wherein the electrical switch state is electrical conductivity.

27. The method as claim in claim 24 wherein the color switch state is induced color change.

28. The method as claimed in claim 19 wherein the signal is received by a receiver which is in electronic communication with a programmable logic controller.

29. The method as claimed in claim 20 wherein a detector measures the switch state of a multifunctional particle.

30. The method as claimed in claim 20 wherein the detector is selected from the group of detectors that measure optical, electrical and magnetic switch signals.

31. The method as claimed in claim 20 wherein a location of the leak can be detected.

32. The method as claimed in claim 20 wherein magnitude of the leak can be detected.

33. The method as claimed in claim 19 wherein the detector issues an alert to an operator.

34. The method as claimed in claim 20 wherein the leak is detected at a threshold of 0.3 to 10 microns in size.

35. The method as claimed in claim 20 wherein the packaged sealed product is selected from the group consisting of ampoules, syringes, pouches, pads and bulk pharmaceutical bags.

36. The method as claimed in claim 35 wherein the packaged sealed product is removed from the chamber when a leak condition is detected.

37. The method as claimed in claim 20 wherein the component is selected from the group consisting of injectable, bulk drug solutions, sterile products, solid dosage forms and biopharmaceuticals.

38. The method as claimed in claim 19 wherein the chamber contains 1 to 10,000 sealed product packages.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The FIGURE is a schematic of a leak detection process according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0038] The FIGURE shows a schematic of an assembly for the detection of leaks in a packaged sealed product. A source of liquid nitrogen A which can be a cylinder, bulk container or other storage device feeds the liquid nitrogen to a filter B through line 1. Line 1 will transfer the liquid nitrogen through a vaporizer to vaporize the liquid nitrogen which will turn it into gaseous nitrogen. The filter B is typically a 0.2 micron filter and assists in sterilizing the gaseous nitrogen before it contacts the multifunctional particles. The filter B feeds the sterilized gaseous nitrogen through line 3 where it will intersect with line 2 which delivers the multifunctional particles from their storage container C.

[0039] These multifunctional particles are selected from the group consisting of luminescent nano-particles, electro-conductive polymer based nano-particles, and color sensitive polymer or enzymatic biosensors. These multifunctional particles will contact the sterilized gaseous nitrogen in line 3 and will mix with the sterile gaseous nitrogen before entering the testing chamber F.

[0040] This testing chamber F is typically made of glass and is designed to be air tight and hold nitrogen gas under pressure as well as packaged pharmaceutical products.

[0041] Typically, this testing chamber F will be cylindrical in shape and contain either shelves or other holding devices for holding packages. The testing chamber F as noted will be air tight and could be configured to be placed at the end of a filling line. In that situation, there could be two testing chambers with a first chamber being filled with packages, bags or ampoules to be tested, while the second testing chamber could be in testing mode.

[0042] The dimensions of the testing chamber F could vary depending upon the type and size of a batch of the product to be tested but typically, the dimensions would be about 6 to 8 feet (1.8 to 2.4 meters) in length, 4 to 5 feet (1.2 to 1.5 meters) in height and 5 to 6 feet (1.5 to 1.8 meters) deep. The testing chamber could be fabricated from glass or aluminum and would be fitted with sensors to detect the defects in the containers being tested.

[0043] The testing chamber F contains the sealed product packages E which can range in number from 1 to about 10,000 sealed product packages, with preferably 1 to 1000 and 1 to 5000 sealed product packages preferred. These sealed product packages E will contain pharmaceutical products but may also contain bulk drug solutions, buffers or sterile products. The gaseous nitrogen and multifunctional particle mixture will disseminate through the testing chamber F and will in particular come into contact with the sealed packaged products E.

[0044] If these multifunctional particles contact a leak site on the sealed packaged products E, they will activate in the sense that they will change electrically, optically or by color indicating that they have contacted the particular molecule that is being tested for. Accordingly, the multifunctional particles will give off a signal that will be detected by the detectors D present in the testing chamber F.

[0045] These detectors are typically optical detectors and they will receive the data encoded in the signal and forward this data to a process logic controller which will interpret the data and provide the operator with information such as which sealed packaged product is leaking; how big the leak is; how intense or how much volume is leaking; and any related information to allow the operator to determine through its quality control means to remove the leaking sealed packaged products from the testing chamber and prior to packaging for shipment and merchandising.

[0046] While this invention has been described with respect to particular embodiments thereof, it is apparent that numerous other forms and modifications of the invention will be obvious to those skilled in the art. The appended claims in this invention generally should be construed to cover all such obvious forms and modifications which are within the true spirit and scope of the invention.