U.S. patent application number 11/038377 was filed with the patent office on 2005-12-08 for package of sensitive articles.
This patent application is currently assigned to Avantec Vascular Corporation. Invention is credited to Yan, John.
Application Number | 20050268573 11/038377 |
Document ID | / |
Family ID | 34831057 |
Filed Date | 2005-12-08 |
United States Patent
Application |
20050268573 |
Kind Code |
A1 |
Yan, John |
December 8, 2005 |
Package of sensitive articles
Abstract
The invention is directed to the treating, e.g. sterilizing and
packaging of medical devices and other articles, particularly such
devices and articles which are reactive to oxygen or moisture
containing atmospheres. The sterilized package has a container
which includes at least one portion which is gas permeable and at
least one portion which is gas impermeable and an interior in fluid
communication with the gas permeable portion. The container may be
sealed by applying an impermeable patch to the permeable portion
thereof or by disposing the container in an enclosure formed of
impermeable material and sealing the enclosure. After exposing the
container to a sterilizing gas, the gas permeable portion may be
removed or sealed off from the gas impermeable portion of the
container in order to provide a package which is gas impermeable
and can protect one or more articles within the interior of the
container against environmental gases and moisture.
Inventors: |
Yan, John; (Los Gatos,
CA) |
Correspondence
Address: |
Edward J. Lynch
Duane Morris LLP
20th Floor
One Market, Spear Tower
San Francisco
CA
94105
US
|
Assignee: |
Avantec Vascular
Corporation
Sunnyvale
CA
|
Family ID: |
34831057 |
Appl. No.: |
11/038377 |
Filed: |
January 19, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60540828 |
Jan 29, 2004 |
|
|
|
60537972 |
Jan 20, 2004 |
|
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Current U.S.
Class: |
53/425 ; 206/439;
422/28; 422/34; 422/37 |
Current CPC
Class: |
A61B 50/30 20160201;
A61B 2050/314 20160201; A61L 2/208 20130101; A61L 2202/181
20130101; A61F 2/86 20130101; A61L 2/206 20130101; B65D 75/38
20130101; B65D 81/2084 20130101; B65B 55/19 20130101; A61L 2202/24
20130101; A61L 2/26 20130101; B65D 81/266 20130101; B65B 55/18
20130101; A61F 2/0095 20130101 |
Class at
Publication: |
053/425 ;
422/028; 422/034; 422/037; 206/439 |
International
Class: |
B65B 055/02 |
Claims
What is claimed is:
1. A method for packaging a sterile article, comprising: a.
providing a container which has a wall defining at least in part an
interior and which has at least one portion permeable to
sterilizing gas; b. placing an article into the interior of the
container; c. exposing at least one permeable portion of the
container to an exterior environment which includes a sterilizing
gas under conditions such that the sterilizing gas permeates
through at least one permeable portion of the container into the
interior of the container; and d. removing sterilizing gas from the
interior of the container after the articles therein are
sterilized.
2. The method of claim 1 wherein the at least one permeable region
of the container is sealed after the sterilizing gas is removed
from the interior to prevent gas permeation while the article
remains in the interior.
3. A method as in claim 1, wherein the sterilizing gas is at least
in part ethylene oxide.
4. A method as in claim 1, wherein the sterilizing gas is removed
from the interior of the container by applying a vacuum to the
interior.
5. A method as in claim 1, wherein the sterilized gas is removed
from the interior of the container by purging the interior of the
container with a non-active gas.
6. A method as in claim 1, wherein sealing comprises partitioning
the container to isolate the article within an impermeable portion
of the container interior.
7. A method as in claim 6, further comprising removing the gas
permeable portion of the container.
8. A method as in claim 1, wherein sealing comprises deploying the
container into an impermeable enclosure.
9. A method as in claim 1, wherein the container is sealed by
applying a gas impermeable barrier over the gas permeable portion
of the container.
10. A method as in claim 1, wherein the article within the interior
of the container is a medical device.
11. A method as in claim 10, wherein the medical device is formed
at least in part of a labile material which is degradable in an
atmosphere containing oxygen and/or water vapor.
12. A method as in claim 10, wherein the medical device is a stent
coated with a therapeutic or diagnostic agent.
13. A method as in claim 12 wherein the interior of the container
has less than about 150 ppm sterilizing gas or residuals.
14. A method as in claim 12 wherein the container interior has
about 10 ppm to about 50 ppm sterilizing gas or residuals.
15. A method as in claim 1 wherein the sterilizing gas is selected
from the group consisting of ethylene oxide, ethylene oxide and
nitrogen, ethylene oxide and carbon dioxide, ethylene oxide with
one or more chlorofluorocarbon diluents, Oxyfume 2000 series of
sterilant, ozone, hydrogen peroxide gas plasma, chlorine dioxide
and mixtures thereof.
16. A sterile packaging system for one or more sterile articles,
comprising: a. a container which has a wall, an interior defined at
least in part by the container wall and configured to receive at
least one article and at least one portion that is permeable to
sterilizing gas and is in fluid communication with the interior,
and b. a patch of impermeable material on the permeable portions to
prevent permeation of gas into the interior through the permeable
portions.
17. The sterile packaging system as in claim 16 wherein the
container interior is essentially free of sterilizing gas.
18. The sterile packaging system as in claim 16 wherein the
container interior has less than about 150 ppm sterilizing gas or
residuals.
19. The sterile packaging system as in claim 16 wherein the
sterilizing gas is selected from the group consisting of ethylene
oxide, ethylene oxide and nitrogen, ethylene oxide and carbon
dioxide, ethylene oxide with one or more chlorofluorocarbon
diluents, Oxyfume 2000 series of sterilant, ozone, hydrogen
peroxide gas plasma, chlorine dioxide and mixtures thereof.
20. A system as in claim 16, wherein the at least one gas permeable
portion is formed of material which is impermeable to liquid.
21. A system as in claim 16, wherein the at least one gas permeable
portion is at least in part formed of a spun olefin.
22. A system as in claim 16, wherein the patch sealing the
permeable portion is formed of a material which is moisture and gas
impermeable and is non-transmissive for light and UV radiation.
23. A system as in claim 16, wherein the sealing patch is part of a
gas impermeable enclosure which receives the container.
24. The system of claim 23 wherein the impermeable enclosure is
sealed about the container to isolate the container from an
atmosphere containing oxygen and moisture.
25. A system as in claim 23, wherein the enclosure is formed of a
polymer film which is impermeable to oxygen and moisture.
26. A system as in claim 16, wherein the container has a first
portion which is impermeable to gas and a second portion which is
permeable to gas, and wherein the first portion impermeable to gas
contains the one or more articles and the second portion permeable
to gas is sealed from the first portion by a partition line which
can be selectively adhered to isolate the portion of the interior
of the container within the gas impermeable portion from the inner
portion of the gas permeable portion.
27. A system as in claim 16, wherein the enclosure receiving the
container is a pouch having a sealable open end and a receptacle
portion formed from a non-gas permeable material and wherein the
gas permeable portion lies between the receptacle portion and the
open end and a partition line lies between the gas permeable
portion and the receptacle portion.
28. The system of claim 16 wherein the container has oxygen
absorbers or scavengers.
29. The system of claim 28 wherein oxygen absorbers or scavengers
are provided in fluid communication with the interior of the
container.
30. The system of claim 28 wherein the oxygen absorbers or
scavengers are inside the permeable portion of the container.
31. The system of claim 28 wherein an oxygen absorber is
incorporated into or coated on the permeable portion of the
container.
32. The system of claim 28 wherein an oxygen absorber is
incorporated into or coated on the impermeable portion of the
container.
33. The system of claim 28 wherein the oxygen absorber is coated
onto an interior surface of the container.
34. The system of claim 28 wherein the oxygen absorber is coated
onto an exterior surface of the container.
35. The system of claim 28 wherein the oxygen absorber is selected
from the group consisting of ethylene-cyclohexenylmethyl acrylate
copolymer and ethylene-methylacrylate-cyclohexeneylmethyl acrylate
terpolymer.
36. The system of claim 28 wherein the oxygen scavenger is selected
from the group of materials consisting of ethylenically unsaturated
polymers, ferrous oxide, titanium oxide, activated carbon with
sodium ascorbate, diethylhydroxylamine, carbohydrazide,
combinations of these materials.
37. The system of claim 28 wherein the oxygen absorbers or
scavengers are packaged in a packet made from oxygen permeable
material that has an oxygen permeability coefficient greater than
30 cm.sup.3/100 in.sup.2/day-atm.
38. The system of claim 28 wherein the oxygen absorbers or
scavengers are packaged in a packet made from oxygen permeable
material that has an oxygen Permeability Coefficient greater than
100 cm.sup.3/100 in.sup.2/day-atm.
39. The system of claim 28 wherein the oxygen absorbers or
scavengers are packaged in a packet made from oxygen permeable
material that has an oxygen permeability coefficient greater than
about 300 cm.sup.3/100 in.sup.2/day-atm.
40. The system of claim 28 wherein the oxygen absorbers or
scavengers are incorporated into a protective sheath that is
disposed proximate to the sterilized medical device.
41. A sterilized package, comprising: a. a sealed container which
has an interior defined at least in part by a wall, which has at
least a portion permeable to sterilizing gas and which has at least
one sterilized article within the interior; and b. an atmosphere
within the interior of the container which is substantially free of
sterilizing gas.
42. The sterilized package of claim 41 wherein the container
portion permeable to sterilizing gas is sealed to prevent
penetration of non-sterilizing gas exterior to the container into
the interior of the container.
43. The sterilized package of claim 41 wherein an oxygen scavenger
is maintained in fluid communication with the interior of the
container.
44. The sterilized package of claim 43 wherein the oxygen scavenger
is in particulate form.
45. The sterilized package of claim 43 wherein the oxygen scavenger
is incorporated within at least part of a wall defining the
interior of the container.
46. The sterilized package of claim 41 wherein the container is
sealed by disposing the container in a gas impermeable
enclosure.
47. The sterilized package of claim 46 wherein the gas impermeable
enclosure is formed at least in part of a polymer which is
impermeable to vapor and moisture.
48. The sterilized package of claim 41 wherein the at least one
article is a drug eluting stent.
49. The sterilized package of claim 48 wherein the stent is coated
with a drug that is degraded by oxygen and/or water vapor.
50. The sterilized package of claim 48 wherein the stent is mounted
on a balloon of a delivery catheter.
51. The sterilized package of claim 41 wherein the atmosphere
within the container interior has less than about 150 ppm
sterilizing gas or residuals.
52. A method of packaging and treating an article, comprising: a.
providing a container which has an interior defined at least in
part by a wall, which has a portion permeable to treating gas and
which has a article to be treated disposed within the interior of
the container; b. surrounding the permeable portion of the
container with a treating gas under conditions which facilitate
permeation of the treating gas through the permeable portion of the
container into the container interior to treat the article disposed
therein; and c. removing treating gas from the inner chamber after
the article has been treated.
53. The method of claim 52 wherein treating gas is removed from the
interior of the container by purging the interior with innocuous
gas.
54. The method of claim 53 wherein the container interior is purged
with innocuous gas until substantially free of treating gas.
55. The method of claim 53 wherein the container interior has less
than about 150 ppm treating gas or residuals.
56. The method of claim 54 wherein the permeable portion is sealed
after the container interior is purged with innocuous gas.
57. The method of claim 52 wherein the article is a medical
device.
58. The method of claim 57 wherein the medical device is a delivery
catheter with an inflatable balloon and a drug eluting stent
mounted on the balloon.
59. The method of packaging and sterilizing a medical device as in
claim 52 wherein the sterilizing gas is removed from the container
interior until essentially free of sterilizing gas.
60. The method of packaging and sterilizing a medical device as in
claim 52 wherein the sterilizing gas is removed from the container
interior until the interior has less than about 150 ppm sterilizing
gas or residuals.
61. A method of packaging and sterilizing a medical device as in
claim 52 wherein the sterilizing gas is selected from the group
consisting of ethylene oxide, ethylene oxide and nitrogen, ethylene
oxide and carbon dioxide, ethylene oxide with one or more
chlorofluorocarbon diluents, Oxyfume 2000 series of sterilant,
ozone, hydrogen peroxide gas plasma, chlorine dioxide and mixtures
thereof.
62. A treated package, comprising: a. a sealed container which has
an interior defined at least in part by a wall, which has at least
a portion permeable to treating gas and which has at least one
treated article within the interior; and b. an atmosphere within
the interior of the container which is substantially free of
treating gas.
63. A method for packaging one or more treated articles,
comprising: a. providing a container which has a wall defining at
least in part an interior and which has at least one portion
permeable to treating gas; b. placing one or more articles into the
interior of the container; c. exposing at least one permeable
portion of the container to an exterior environment which includes
a treating gas under conditions such that the treating gas
permeates through at least one permeable portion of the container
into the interior of the container; and d. removing treating gas
from the interior of the container after the articles therein are
treated.
64. A packaging system for one or more treated articles, comprising
a container which has a wall, an interior defined at least in part
by the container wall and configured to receive at least one
article and a treating gas permeable means in fluid communication
with the interior.
65. The packaging system of claim 64 wherein a patch of impermeable
material covers at least part of the permeable means to prevent
permeation of gas into the interior.
66. A method for packaging one or more treated articles,
comprising: a. a step of providing a container which has a wall
defining at least in part an interior and which has at least one
portion permeable to treating gas; b. a step of placing one or more
articles into the interior of the container; and c. a step of
exposing at least one permeable portion of the container to an
exterior environment which includes a treating gas under conditions
such that the treating gas permeates through at least one permeable
portion of the container into the interior of the container.
67. The method of claim 66 including the step of removing treating
gas from the interior of the container after the articles therein
are treated.
Description
RELATED APPLICATIONS
[0001] This application is based upon and claims priority to
Provisional Application Ser. No. 60/537,972, filed on Jan. 20, 2004
and Provisional Application Ser. No. 60/540,828, filed on Jan. 29,
2004. Both applications are incorporated herein by reference in
their entireties.
BACKGROUND OF THE INVENTION
[0002] The present invention relates generally to sterilized
medical devices and packaging for sterilized medical devices. In
particular, the present invention relates to the packaging of
sterilized environmentally sensitive medical devices, such as
drug-coated stents.
[0003] Most, if not all, disposable medical devices require
sterilization prior to or concurrent with packaging. The packaging,
which may be in the form of a pouch, bag, tube, box, or other
sealed container, will maintain the sterility of the product until
it is withdrawn from the packaging for use. A particularly
successful system and method for sterile packaging of medical
devices relies on use of high-density polyethylene (HDPE) pouches
which are used to contain the medical device or other product. The
device may be placed in the package prior to sterilization.
Sterilization is then effected by placing the package in an
environment including a sterilant gas, such as ethylene oxide
(EtO), ethylene oxide with nitrogen, various blends of ethylene
oxide and carbon dioxide, ethylene oxide with chlorofluorocarbon
diluent(s), Oxyfume 2000 series of sterilant, ozone, hydrogen
peroxide, chlorine dioxide, or others. The spun HDPE material, such
as Tyvek.RTM. which is available from Medical Packaging Division of
E. I. DuPont de Nemours and Company (DuPont), permits passage of
the small molecule sterilant gas while remaining a barrier to
bacteria, viruses, and other larger substances which might
compromise sterility. It also acts as a barrier to water and other
fluids which might detrimentally affect the sterilized
contents.
[0004] While this packaging system has been highly successful for
conventional medical devices, such as catheters, stents, surgical
instruments, probes, and the like, it is frequently not suitable
for "hybrid" devices which contain coatings or components which are
subject to oxygen degradation. For example, the use of drug-eluting
stents is promising to revolutionize interventional cardiology. The
stents are coated with drug at a central fabrication facility and
must be distributed to the end user in sterile packaging. While at
least some drugs presently contemplated for use will remain stable
during ethylene oxide sterilization, exposure to oxygen during
lengthy distribution and storage periods can adversely affect the
drug.
[0005] For these reasons, it would be desirable to provide improved
methods and systems for sterilizing and packaging medical
devices.
SUMMARY OF THE INVENTION
[0006] The present invention is directed to packages of articles
such as medical devices, methods of packaging such articles and is
particularly directed to packaging articles which are labile when
exposed to ambient oxygen concentrations or oxygen containing
materials over prolonged periods of time. The present invention
provides convenient, effective, and economical approaches for such
packaging. The method of packaging, the packages and the packaging
systems are particularly suitable for drug-device combinations,
such as drug-eluting stents and other drug-coated medical articles.
The packaging, the system and method may be utilized for
sterilizing articles such as medical devices which are reactive to
an ambient environment.
[0007] The sterilized packaging embodying features of the invention
generally includes a container which has a wall defining at least
part of an interior configured to receive one or more articles or
products for sterilization. The container has a portion, such as
part of a wall forming the container, which is permeable to
sterilizing gas, e.g. EtO, ethylene oxide with nitrogen, various
blends of ethylene oxide and carbon dioxide, ethylene oxide with
chlorofluorocarbon diluent(s), Oxyfume 2000 series of sterilant
(from Honeywell Chemicals, Morristown, N.J.), ozone, hydrogen
peroxide, chlorine dioxide, or others. The permeable portion allows
the article or articles to be placed in the interior, the container
sealed, a vacuum applied to the container interior and an
environment of sterilizing gas in contact with the permeable
portion of the container under conditions which drives the
sterilizing gas through the gas permeable portion into the inner
chamber to sterilize the one or more products disposed within the
chamber.
[0008] The container interior is evacuated to about 15 psia to
about 0.1 psia preferably 7 psia to about 0.5 psia for the purpose
of aspirating the sterilizing gas through the permeable portion of
the container. During this time, the container interior can be
partially or totally evacuated of oxygen and replaced totally or
partially with a non-reactive gas such as nitrogen. This is
followed by a steam injection slightly increasing the vacuum to
about 0.1 psia to about 5 psia higher than the container interior,
preferably to about 1 psia to about 3 psia higher than the
container interior. Sterilizing gas maintained about the exterior
of the permeable portion of the container is drawn into the
container interior through the permeable portion thereof. The
pressure of the sterilizing gas within the container interior for
effective sterilization is about 20 psia to about 2 psia,
preferably about 15 psia to about 5 psia. The dwell time of the
sterilizing gas within the container interior at that pressure is
about 1 to about 24 hours preferably about 6 to about 18 hours.
[0009] After the sterilization, essentially all of the sterilizing
gas is removed from the container interior, either by exposing the
interior to a vacuum, by flushing or purging the container interior
with air or a non reactive gas such as nitrogen, or some
combination thereof or both. Usually, after the sterilizing gas is
removed from the container interior, the sterilized package is left
at room temperature for several days to ensure that the interior is
essentially free of sterilizing gas, i.e. less than about 150 ppm,
preferably about 10 to about 50 ppm, and typically about 25
ppm.
[0010] At this point, at least the permeable portion of the
container is sealed to prevent permeation of undesirable gas into
the container interior while the one or more articles remain within
the interior. The sealing of the container may comprise, for
example, sealing the permeable portion of the container with a
impermeable patch or partitioning the container to isolate or seal
off the portion of the container interior which contains the
article(s) from the portion of the container interior in fluid
communication with the gas permeable portion of the container.
Optionally, the gas permeable portion of the container may be
separated, e.g. severed, from the non-gas permeable portion.
Another approach is to place the sterilized container inside a
impermeable enclosure in order to prevent subsequent gas permeation
into the container interior containing the sterilized article(s)
through the permeable portion of the container. In the latter
instance, any atmosphere within the impermeable enclosure would
have to be non-detrimental to the articles disposed in the interior
of the container within the enclosure. It would of course also be
possible to combine two or more of these approaches, although that
will usually not be necessary.
[0011] The gas permeable portion of the container will typically be
composed of a material which is permeable to the sterilizing gas
and impermeable to liquids. Suitable gas permeable materials
include high-density polyethylene (HDPE), typically a spun HDPE or
other spun olefin. Commercially available materials such as
Tyvek.RTM. (2FS, 1059B, 1073B or others) are specifically designed
for packaging medical devices. Typically, the available materials
are coated partially or totally with an adhesive for the purpose of
sealing the material to itself or to adjacent materials.
[0012] The permeability required for the sterilizing gas to
permeate into the interior of the container and contact the one or
more articles therein, can vary depending upon the pressure
differential, the temperature and the time available for permeation
of the sterilizing gas into the interior.
[0013] In one embodiment, the container has both a gas permeable
portion, as described above, and a gas impermeable portion,
typically formed from a metal or polymer film or a metal-polymer
composite which is impermeable to gases. By "impermeable to gases,"
it is meant that the permeation of oxygen is below about 30
cm.sup.3/100 in.sup.2/day-atm, preferably below about 2
cm.sup.3/100 in.sup.2/day-atm. Exemplary suitable material for the
gas impermeable portion include metal foils such as aluminum;
polymer films such as polyethylene, polyester, polyester
(PET)/modified low density polyethylene (LDPE) laminated film; or
any combination thereof (e.g., metalized PET).
[0014] In one embodiment, the impermeable portions of the container
may be incorporated with suitable oxygen scavenger materials or
have adjacent thereto a partial or complete film of suitable oxygen
absorbers or scavengers, such as ethylene-cyclohexenylmethyl
acrylate copolymer (ECHA) and
ethylene-methylacrylate-cyclohexeneylmethyl acrylate terpolymer
(EMCM) described in Ching et al. (2001), referenced above. Other
oxygen scavengers include ethylenically unsaturated polymer,
ferrous oxide (partially oxygenated iron), titanium oxide,
activated carbon with sodium ascorbate, diethylhydroxylamine
(DEHA), carbohydrazide, combination of above, or other chemicals
which are readily reactive or combine with oxygen gas. When
suitable oxygen scavenger materials are incorporated or lie
adjacent to the impermeable portion, oxygen within the interior of
the container can be removed to very low levels. Suitable oxygen
levels in the container interior in most instances will be below 5%
oxygen, preferably below 1%, more preferably below 0.1%.
[0015] The permeable portion or portions of the container may be
incorporated with suitable oxygen scavenger materials or may be
positioned adjacent to a partial or complete film of suitable
oxygen scavengers. Not only oxygen is removed from the package,
oxygen gas trying to permeate through the permeable portion will be
limited from entering the package.
[0016] Oxygen scavengers can be placed inside the package, such as
inside a permeable packet that is placed within the interior of the
container or within the interior of an enclosure surrounding the
container. Oxygen scavengers can be embedded in a protective sheath
over or adjacent to the article within the inner chamber. The
sheath can be a polymer incorporated with suitable oxygen
scavenger, or it can be formed of a polymer fully or partially
coated with a suitable oxygen scavenger, or it can be made from
suitable oxygen scavenger.
[0017] Another approach for sealing the gas permeable enclosure is
to place a patch, cover, or other gas impermeable barrier over that
portion of the enclosure which is initially gas permeable. For
example, a window or other area of the enclosure, typically a
portion of a pouch, may be formed from gas permeable Tyvek or other
material, while the remaining portion of the pouch or other
enclosure is formed from a gas impermeable foil, polymer, or other
material. A patch sized to cover the gas permeable window may be
provided to be sealed over the window after the initial
sterilization has been completed.
[0018] Another approach for sealing the gas permeable enclosure is
to place the enclosure inside of a separate gas impermeable
enclosure after the initial sterilization has been performed.
[0019] Preferred gas impermeable materials will also be
non-transmissive for light, UV radiation, heat, and the like. The
gas impermeable materials will also be impermeable to moisture.
[0020] In some cases, it will be further desirable to provide
desiccant materials in or over a portion of the impermeable
enclosure in order to sequester any moisture which may remain
within the pouch after final sealing. The desiccant may be coated
over or laminated within the polymer or metal film which comprises
the gas impermeable enclosure. Alternatively, a small inserter
canister of the desiccant material may be provided within the
enclosure, similar to the desiccant placed in conventional
pharmaceutical packaging.
[0021] These and other advantages of the invention will become more
apparent from the following detailed description of the invention
when taken in conjunction with the accompanying exemplary
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 schematically illustrates a container embodying
features of the present invention which includes both gas permeable
and gas impermeable portions.
[0023] FIG. 2 schematically illustrates an alternate design of a
container embodying features of the present invention which
includes a gas impermeable portions, a gas permeable portion or
window and a separate impermeable patch or cover for sealing the
window.
[0024] FIG. 3 schematically illustrates an alternate design of a
container having features of the present invention which includes
gas permeable portions and a gas impermeable outer pouch or
enclosure to seal the container.
[0025] FIGS. 4A-4E schematically illustrate use of the container
shown in FIG. 1 for packaging and sterilizing an article in a
manner embodying features of the present invention.
[0026] FIG. 5 schematically illustrates one embodiment of the
container constructed with an impermeable portion having a film
adjacent thereto, the film comprising oxygen absorber or scavenger
(in pure, composite, or matrix form).
[0027] FIGS. 6A-6C schematically illustrate use of one embodiment
of a container constructed with a permeable portion incorporated
with or has a film adjacent to made from oxygen scavenger
material.
[0028] FIG. 7 schematically illustrates use of one embodiment of a
container with an oxygen scavenger packet or material.
[0029] FIG. 8 schematically illustrates use of one embodiment of a
container with a sheath made from oxygen scavenger material.
[0030] FIG. 9 schematically illustrates use of one embodiment of a
container within another enclosure that also contains oxygen
scavenger material.
DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0031] Referring now to FIG. 1, a container 10 embodying features
of the invention has a portion 12 which is not permeable to gas and
a portion 14 which is permeable to gas, particularly to sterilizing
gas such as EtO, ethylene oxide with nitrogen, various blends of
ethylene oxide and carbon dioxide, ethylene oxide with
chlorofluorocarbon diluent(s), Oxyfume 2000 series of sterilant,
ozone, hydrogen peroxide gas plasma, chlorine dioxide, or others.
The container 10 typically has an open end 16 disposed at one end
of the impermeable portion, while the permeable portion 14 is
formed about another end of the portion 12. As will be described
further with reference to FIGS. 4A-4E below, the container 10 is
utilized by placing the article to be sterilized into the container
interior 18 through the open end 16, sealing the open end 16, so
that the article is fully contained within the gas permeable but
otherwise impermeable structure of the container prior to
sterilization.
[0032] An alternative container 20 is depicted in FIG. 2 which has
an impermeable portion 22 having a opening 24 covered by a gas
permeable layer or wall 25. The article to be sterilized and
packaged may be placed through open-end 26 of the container 20 into
the container interior 27 prior to the sealing of the open end. The
open end 26 sealed and then sterilization performed by evacuating
the interior 27 while maintaining a sterilizing gas at the gas
permeable layer 25. After sterilization, a impermeable sealing
patch 28 is placed over the opening 24 as indicated by the dotted
lines in order to seal the gas permeable layer 25 against
subsequent gas permeation.
[0033] FIG. 3, illustrates a third exemplary system 30 for
sterilizing and packaging articles according to the present
invention. The system 30 includes an inner container 32, at least a
portion of which is formed from a gas permeable material, and an
outer enclosure or pouch 34 which is at least substantially formed
from a gas impermeable material. The one or more articles to be
packaged and sterilized are placed within the interior of container
32 through the open end 33, the open end 33 sealed, and the sealed
container sterilized using a sterilizing gas which passes through
the permeable portion of the container. Residual sterilizing gas
within the pouch may be removed as previously described. After the
sterilization is complete, the container 32 may be placed into the
open end 36 of the outer enclosure 34, and the open end 36 sealed
in order to prevent subsequent gas permeation into the interior of
the outer enclosure 34 and ultimately into the interior of the
container 32.
[0034] FIGS. 4A-4E illustrate the use of the container 10 for
packaging and sterilizing a catheter 40 which carries a drug
eluting stent 42 (or any other environmentally sensitive medical or
non-medical article). The catheter 40 is first placed through the
open end 16 of the container 10 so that it is positioned within the
interior 18 thereof. The container 10 is open at this point so that
the gas impermeable portion 12 generally surrounds the catheter 40
and the gas permeable portion 14 is disposed to one side of the
catheter, as shown in FIG. 4A.
[0035] Open end 16 is sealed, typically by heat sealing, adhesive
sealing, lamination, or the like, along a sealing line 44, as shown
in FIG. 4B, and the EtO is introduced through the gas permeable
portion 14, typically by placing the sealed container 10 within a
conventional gas sterilizer. Other conditions of sterilization will
be chosen to be compatible with the nature of the device and/or
drug or other potentially labile component on the device. After the
sterilization is complete, the EtO will be removed from the
interior of container, typically by vacuum and/or by purging with
air, nitrogen, or other inactive gas. Optionally, as discussed
above, a desiccant may be placed within the interior of the
container and/or a portion of the container, typically the
impermeable portion, may contain or be formed of a laminated or
otherwise coupled oxygen absorbers or scavenger and/or moisture
desiccants.
[0036] As shown in FIG. 4C, after the sterilizing gas has been
removed from the interior 18 of the container 10, the container may
be flattened so that the catheter 40 remains in the impermeable
portion 12, which is isolated from the permeable portion 14 along a
partition line 46. The partition line 46 may then be flattened and
sealed, as shown in FIG. 4D, by conventional methods including heat
sealing, adhesive bonding, ultrasonic welding, and the like.
Preferably, the permeable portion 14 is then severed from the
impermeable portion 12, as shown in FIG. 4E. The impermeable
portion 12 is then ready for transportation and storage prior to
use. The impermeable portion 12 itself may be placed in further
packaging, such as boxes, trays, or the like.
[0037] Referring to FIG. 5, the impermeable portion 12 of the
container 10 can be made from a material with oxygen absorbers or
scavengers incorporated therein as well as being coated, including
lamination or layer 48 partially or completely with suitable oxygen
absorbers or scavengers. The presence of the oxygen absorbers or
scavengers can remove oxygen gas as it permeates into the container
interior 18 containing the sterilized articles (not shown) during
processing and during storage.
[0038] Referring to FIGS. 6A, 6B, and 6C, the permeable portion 14
of container 10 can be made from a material incorporated with
oxygen absorbers or scavengers 50 as well as being coated partially
or fully on the interior or exterior surface with a layer (or
matrix of oxygen absorbers, scavenger, and/or permeable polymers)
50 or 52 of suitable oxygen absorbers or scavengers. The presence
of the oxygen absorbers or scavengers can remove oxygen gas within
the interior 18 as the gas permeates into the interior during
sterilization and during storage. Even if the permeable portion of
the enclosure is not eliminated from the path between outside and
the drug device, oxygen can be limited from entering the interior
18.
[0039] Referring to FIG. 7, the container 10 contains oxygen
absorbers or scavengers within the interior 18 that may be packaged
in its own packet 54 made from oxygen permeable material such as
silicone rubber, polystyrene or any polymer that has an oxygen
permeability coefficient greater than about 30 cm.sup.3/100
in.sup.2/day-atm, matrix into a oxygen permeable polymer, or in its
original form with or without a oxygen permeable coating. The
oxygen absorbers or scavengers inside the packet 54 absorbs any
oxygen gas that may enter the interior 18 during sterilization and
storage.
[0040] Referring to FIG. 8, the container 10 contains a protective
sheath 56 made from suitable oxygen absorbers or scavengers that is
adjacent to the drug coated device 58. The sheath 56 can be made
directly from suitable oxygen absorbers or scavengers such as
ferrous oxide or ethylene-cyclohexenylmethyl acrylate copolymer, or
an oxygen permeable polymer matrix with the oxygen absorber or
scavenger. The protective sheath oxygen absorbers or scavengers
inside the enclosure and adjacent to the drug device will locally
absorb any oxygen gas that may enter the inner chamber of the
container 10 during sterilization and storage and minimize oxygen
gas in the vicinity of the drug device.
[0041] FIG. 9 illustrates container 10 that is similar to the
container shown in FIGS. 5 and 6 or has oxygen absorbers or
scavengers similar to that shown in FIG. 7. The container 10 is
disposed within the interior of an outer enclosure 34. Oxygen
absorbers or scavengers are provided in the outer enclosure such as
in a packet 60 as shown to reduce the oxygen level within the
enclosure 34 to prevent penetration into the interior 18 of the
container 10. Moreover, such scavengers can reduce the oxygen level
within the interior 18 through the permeable portion of the
container since oxygen is freely transported through the permeable
portion of the container and that the scavengers attract the oxygen
gas. Optionally, desiccants may be placed inside the interior of
the outer and/or containers to reduce, maintain and/or control the
moisture content of the container.
[0042] The present invention relies upon gas sterilization where
the articles to be sterilized are first placed and sealed within a
container. At least a portion of the container is gas permeable so
that one or more articles within the interior of the container may
be sterilized by placing the container in an environment of the
sterilizing gas, typically an environment of essentially all
ethylene oxide. Once the one or more articles are placed in the
interior of the container, the interior may be evacuated to remove
ambient gases which may be present. Sterilizing gas is introduced
into the container interior through the permeable portion of the
container and maintained within the container interior at
sufficient levels to sterilize the articles therein. After
sterilization is complete, the interior is preferably evacuated to
remove the sterilizing gas, and the container is modified,
partitioned, replaced into a secondary enclosure, or otherwise
placed in a condition so that further gas exchange between the
exterior and interior of the container is inhibited or prevented.
The method and system of the present invention provide for
convenient and effective sterilization of articles using a
conventional gas sterilant, and prevent the degradation of the
sterilized articles or portions thereof by subsequent exposure to
oxygen, water, or other ambient gases.
[0043] EtO sterilization and packaging according to the present
invention usually employs five major steps, including:
pre-sterilization conditioning, sterilization, evacuation, air
wash, and aeration. The conditioning step includes placing the one
or more articles to be sterilized into the interior of the
container, sealing the container and evacuating the gas from the
container interior. The sterilization step includes introducing the
sterilant into the interior of the container by passing a
sterilizing gas through the permeable portion of the container,
establishing the appropriate operating parameters, such as
temperature, pressure, and relative humidity, within the inner
chamber and keeping these conditions in the chamber for a
pre-determined period of time for effective sterilization of the
articles. The container may be placed in a sterilization vessel
with the atmosphere surrounding the container within the vessel
being adjusted to control the procedure. The evacuation step after
sterilization includes the removal of EtO from the container
interior by one or more vacuum washes and/or one or more purges
with air or nitrogen, or combinations thereof. In order to further
remove residual EtO from the inner chamber, the container package
then undergoes aeration which can be performed in either the
sterilization vessel or in a separate aeration chamber.
[0044] The EtO sterilization process embodying features of the
present invention is performed at process parameters which are
particularly useful and effective in the sterilization of an
article which is at least in part formed of a reactive or labile
material, such as a therapeutic agent coated on the device, while
minimizing adverse effects on the integrity of the reactive or
labile material during and post sterilization process. The packaged
device sterilized according to the present invention enables
enhanced product shelf-life and greater confidence in the integrity
and suitability of the sterilized aged device.
[0045] The sterilization step is preferably carried out at a
temperature below 30.degree. C. with a dwell time of about 6 to 18
hours or greater. While ethylene oxide is reactive in both liquid
and gaseous phase, it is preferred to employ EtO in gaseous phase
to increase penetration of the gas into the device/package and its
reactivity. Either or both, higher temperature and lower pressure
as well as relative humidity can increase gas penetration and/or
reactivity.
[0046] The boiling point for ethylene oxide at atmospheric pressure
is about 10.degree. C. (51.degree. F.) where EtO is in gaseous
state. Therefore, this temperature of 1.degree. C. is the preferred
lowest temperature at which to perform the sterilization step at
atmospheric pressure. Alternatively, the temperature of the
container interior can further be reduced below 10.degree. C. by
further reducing the pressure to below atmospheric pressure. By way
of example, the sterilization step can effectively be performed at
a temperature of 0.degree. C. by reducing the pressure within the
container interior to about 4 psi (pounds per square inch).
[0047] The following examples are offered by way of illustration,
not by way of limitation.
EXAMPLE 1
[0048] A drug eluting stent mounted onto the balloon of a stent
delivery catheter (a drug eluting stent system) is packaged in a
foil pouch that has a permeable portion or patch formed of
Tyvek.RTM.. The pouch is subjected to a vacuum within the inner
chamber with a surrounding atmosphere of EtO gas at temperatures of
60.degree. C. to sterilize the drug eluting stent and delivery
catheter. After sterilization, the pouch is resealed with the stent
and delivery system within the post seal area and the Tyvek patch
outside the post-seal area. The foil pouch minimizes the light
exposure as well the oxygen and moisture exposure to the sterilized
contents of the container.
EXAMPLE 2
[0049] A drug eluting stent mounted onto the balloon of a stent
delivery catheter is packaged in a Tyvek pouch along with ferrous
oxide as an oxygen absorber and desiccant. The pouch is closed,
subjected to ethylene oxide gas which permeates the pouch. After
sterilization, the Tyvek pouch is evacuated and purged with
nitrogen and air to remove essentially all EtO and then placed
inside a gas impermeable foil pouch. The foil pouch is evacuated by
vacuum to remove the remaining air and nitrogen gas, and then
finally sealed. The foil pouch minimizes the exposure of the
sterilized product within the Tyvek pouch to light and to oxygen
and moisture, thus providing a long shelf life.
EXAMPLE 3
[0050] A drug eluting stent crimped onto a PTCA catheter or a drug
eluting stent system is packaged on Tyvek pouch along with ferrous
oxide oxygen absorbers and desiccant. The pouch is sterilized by
ethylene oxide gas with sterilization temperatures of about
55.degree. C. After sterilization, the sterilized Tyvek pouch with
the stent system sealed inside is inserted inside a foil pouch. The
foil pouch is sealed using a vacuum sealer that first purge the bag
with nitrogen gas which replaces the air inside the foil pouch and
that finally seal the foil pouch. This minimizes the light exposure
as well as limit oxygen and moisture exposure.
EXAMPLE 4
[0051] A drug eluting stent mounted onto the balloon of a stent
delivery catheter is packaged in an essentially gas impermeable
foil container that has a Tyvek patch which allows for gas
permeability through the gas permeable patch. The pouch is exposed
to ethylene oxide gas using the following cycle:
1 Set Point Chamber Temperature 77.degree. F. (25.degree. C.)
Preconditioning Time 3 hrs Initial Evacuation Pressure 1 psia EtO
Dwell Pressure 7 psia EtO Exposure Time 14 hrs Number of Air Wash
after 12 times sterilization Air Wash Time 10 hrs Room Temperature
(20.degree. C.) 3 days Aeration
EXAMPLE 5
[0052] A drug eluting stent mounted onto the balloon of a stent
delivery catheter is packaged on foil pouch that has a Tyvek patch
(i.e., breathable). The pouch is exposed to ethylene oxide gas
using the following cycle:
2 Set Point Chamber Temperature 84.degree. F. (29.degree. C.)
Preconditioning Time 3 hrs Initial Evacuation Pressure 1 psia EtO
Dwell Pressure 7 psia EtO Exposure Time 14 hrs Number of Air Washes
12 times Air Wash Time 10 hrs Room Temperature (20.degree. C.) 3
days Aeration
EXAMPLE 6
[0053] A drug eluting stent is crimped onto the balloon of a stent
delivery catheter. A protective sheath made from
ethylene-cyclohexenylmet- hyl acrylate copolymer (an oxygen
absorber) is inserted over the drug eluting device. The drug
eluting stent and delivery catheter is packaged in a Tyvek pouch,
the pouch is sealed and then sterilized by ethylene oxide gas at
normal sterilization parameters. The protective sheath formed of
oxygen absorbing polymer material minimizes the oxidative
degradation of the drug eluting stent by limiting exposure to
oxygen gas.
[0054] While the invention has been described herein primarily in
terms of packaging medical devices, and in particular to drug
eluting stents, it is also suitable for sterilization and packaging
of other articles, including foods, pharmaceuticals, diagnostic and
assay systems, sensitive electrical components, chemical system
components, and the like, where the ability to sterilize articles
after initial packaging has been completed is desirable. The
methods and systems of the present invention are simple to perform,
require minimum changes from existing packaging practices, and
provide a package to the end user which is as convenient and easy
to use as prior packaging systems.
[0055] Many other alterations and modifications may be made by
those of ordinary skill in this art, without departing from the
spirit and scope of this invention. For example, the method and
packaging may be utilized for packaging articles treated by gases
other than sterilizing gases The illustrated embodiments have been
shown only for purposes of clarity and the examples should not be
taken as limiting the invention as defined in the following claims.
The claims are intended to include all equivalents, whether now or
later devised.
[0056] Moreover, individual features of embodiments of the
invention may be shown in some drawings and not in others, but
those skilled in the art will recognize that individual features of
one embodiment of the invention can be combined with one or more
features of another embodiment. Accordingly, it is not intended
that the invention be limited to the specific embodiments
illustrated or described. It is therefore intended that this
invention to be defined by the scope of the appended claims as
broadly as the prior art will permit.
[0057] Terms such a "element," "member," "component," "device,"
"section," "portion," "means," "steps" and words of similar import
when used herein shall not be construed as invoking the provisions
of 35 U.S.C. .sctn.112(6) unless the following claims expressly use
the term "means" followed by a particular function without specific
structure or expressly use the term "step" followed by a particular
function without specific action. All patents and patent
applications referred to above are hereby incorporated by reference
in their entirety.
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