US20170349313A1 - Methods for manufacturing non-glass prefilled syringes - Google Patents
Methods for manufacturing non-glass prefilled syringes Download PDFInfo
- Publication number
- US20170349313A1 US20170349313A1 US15/169,962 US201615169962A US2017349313A1 US 20170349313 A1 US20170349313 A1 US 20170349313A1 US 201615169962 A US201615169962 A US 201615169962A US 2017349313 A1 US2017349313 A1 US 2017349313A1
- Authority
- US
- United States
- Prior art keywords
- sterilization
- eto
- range
- barrel
- inhga
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 183
- 239000011521 glass Substances 0.000 title claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 title description 11
- 230000001954 sterilising effect Effects 0.000 claims abstract description 208
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 203
- 239000000463 material Substances 0.000 claims abstract description 79
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 68
- 238000007781 pre-processing Methods 0.000 claims abstract description 41
- 230000003750 conditioning effect Effects 0.000 claims abstract description 38
- 238000012414 sterilization procedure Methods 0.000 claims abstract description 27
- 238000011049 filling Methods 0.000 claims abstract description 8
- 229940071643 prefilled syringe Drugs 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims description 77
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 36
- 239000007789 gas Substances 0.000 claims description 33
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 24
- 239000011780 sodium chloride Substances 0.000 claims description 22
- 238000012360 testing method Methods 0.000 claims description 22
- 229920000089 Cyclic olefin copolymer Polymers 0.000 claims description 21
- 239000007924 injection Substances 0.000 claims description 18
- 238000002347 injection Methods 0.000 claims description 18
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 17
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 238000005273 aeration Methods 0.000 claims description 13
- 230000004888 barrier function Effects 0.000 claims description 11
- 239000004713 Cyclic olefin copolymer Substances 0.000 claims description 10
- 238000004806 packaging method and process Methods 0.000 claims description 9
- -1 bromobutyl Chemical group 0.000 claims description 8
- 244000005700 microbiome Species 0.000 claims description 6
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 5
- 229960004194 lidocaine Drugs 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 5
- 229920005557 bromobutyl Polymers 0.000 claims description 2
- 229920005556 chlorobutyl Polymers 0.000 claims description 2
- 230000000977 initiatory effect Effects 0.000 claims 2
- 239000000243 solution Substances 0.000 description 30
- 239000004033 plastic Substances 0.000 description 25
- 229920003023 plastic Polymers 0.000 description 25
- 239000012530 fluid Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 19
- 238000005406 washing Methods 0.000 description 17
- 230000000712 assembly Effects 0.000 description 14
- 238000000429 assembly Methods 0.000 description 14
- 239000006227 byproduct Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 231100000331 toxic Toxicity 0.000 description 7
- 230000002588 toxic effect Effects 0.000 description 7
- 229920005549 butyl rubber Polymers 0.000 description 6
- 239000011888 foil Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000002411 adverse Effects 0.000 description 4
- 229920000515 polycarbonate Polymers 0.000 description 4
- 239000004417 polycarbonate Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 230000008859 change Effects 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000013011 mating Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 231100000703 Maximum Residue Limit Toxicity 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 229920002725 thermoplastic elastomer Polymers 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 238000012371 Aseptic Filling Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- VXAUWWUXCIMFIM-UHFFFAOYSA-M aluminum;oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Al+3] VXAUWWUXCIMFIM-UHFFFAOYSA-M 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000003562 lightweight material Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229920000379 polypropylene carbonate Polymers 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B55/00—Preserving, protecting or purifying packages or package contents in association with packaging
- B65B55/02—Sterilising, e.g. of complete packages
- B65B55/04—Sterilising wrappers or receptacles prior to, or during, packaging
- B65B55/10—Sterilising wrappers or receptacles prior to, or during, packaging by liquids or gases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/10—Ultraviolet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/20—Gaseous substances, e.g. vapours
- A61L2/206—Ethylene oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/001—Apparatus specially adapted for cleaning or sterilising syringes or needles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/002—Packages specially adapted therefor, e.g. for syringes or needles, kits for diabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/3129—Syringe barrels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31501—Means for blocking or restricting the movement of the rod or piston
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B3/00—Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B3/003—Filling medical containers such as ampoules, vials, syringes or the like
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B55/00—Preserving, protecting or purifying packages or package contents in association with packaging
- B65B55/02—Sterilising, e.g. of complete packages
- B65B55/027—Packaging in aseptic chambers
Definitions
- the present disclosure relates to ethylene oxide (“EtO”) gas sterilization methods for sterilizing non-glass containers that are at least partially prefilled with material that is sensitive to sterilization techniques including, but not limited to, containers prefilled with saline (0.9% NaCl saline, heparinized saline, or lidocaine), without causing EtO ingress gas ingress into the prefilled container.
- EtO ethylene oxide
- Syringes have been in use for many years. However, syringes were typically made of glass. Gradually with the discovery of plastic materials, some syringes began to be offered in plastic. In recent history, a number of plastic syringe manufacturers, medical device manufacturers and/or drug companies began offering prefilled plastic containers, including vials and syringes, with fluid material, such as saline, heparinized saline or lidocaine. However, as discovered by the syringe manufacturers these materials are sensitive to certain sterilization techniques.
- IV flush solutions, drugs, vaccines or other fluid materials that contain saline solution may experience a change in their respective composition or properties, such as an undesirable pH shift of the saline solution, when saline contents in the plastic container is exposed to ethylene oxide (“EtO”) gas sterilization.
- EtO ethylene oxide
- the potency of heparinized saline and/or lidocaine may be adversely affected, and EtO gas residual, and/or residual toxic byproducts may be created when the solution is exposed to certain sterilization techniques after filling is accomplished.
- Pre-filled syringes manufactured from plastic materials, such as polypropylene have been found to lead to various complications.
- USP United States Pharmacopeia
- normal saline solution i.e. 0.9% NaCl
- prefilled syringes may only possess a pH between 4.5 and 7.0 to be suitable for human use.
- EtO ethylene oxide gas
- PH has been identified as an indicator of EO ingress, such that if the pH of the fluid within the syringe had shifted (usually +, or higher) outside of accepted USP standards limits, one or more of the other parameters indicative of suitable for human use (as discussed in further detail below), were also exceeded.
- prefilled syringes containing sterilization-sensitive fluid material with other medical procedural tools and/or equipment requiring sterilization in a medical procedural tray, kit, pouch or other packaging.
- collectively packaged convenience kits such as surgical or procedural kits may include prefilled syringes, as well as surgical instruments, gloves, dressings, aseptic wipes, etc.—all requiring EtO sterilization, which are necessary to perform a given medical procedure.
- prefilled syringes that include sterilization-sensitive fluid material are incorporated in such convenience kits
- one known way to avoid the problems created by the use of plastic pre-filled syringes is to utilize glass containers and glass syringes due to the barrier properties of glass, as glass effectively prevents the above identified undesirable effects of EtO ingress to the fluid material.
- glass containers have proven to be a suitable barrier for enabling EtO sterilization
- glass containers have certain limitations that leave this choice of material undesirable.
- glass containers are fragile.
- microcracks in the glass may permit penetration of EO and/or the glass container may explode during deep sterilization cycle vacuums.
- Other issues caused by the fragility of the glass include breakage of the syringe if the syringe is dropped.
- While broken glass may be cleaned up, if the syringe is dropped during a procedure in the operating room, such clean-up might require shutting the operating room down (at significant financial cost to the facility) to recreate a sterile field, as well as delaying patient care.
- glass is much more costly to manufacture as compared to plastic, and has inherent limitations relating to geometry, size and intricacy of the container. Transporting glass, including with sterilization sensitive material therein and transporting used glass syringes after use, is much more expensive than plastic due to the weight of the material, in addition to the extra care that must be taken to avoid breakage.
- glass syringes have additional issues, in that an integrated medical industry standard luer tip cannot be created for a glass syringe. Instead, an adapter must also be provided to incorporate a luer fitting, thereby increasing costs.
- One method of addressing the known EtO sterilization limits inherent to plastic containers is to sterilize an empty plastic syringe and then fill the plastic syringe with sterile fluid (introducing the sterile fluid in a clean room or aseptic environment). The filled syringe is then packaged in a non-sterile pouch.
- This method provides a “sterile fluid pathway” but the syringe exterior itself is not sterile. More specifically, the outside of the syringe is not sterile. As a result, the syringe must be separately packaged from the rest of the procedure kit, thereby creating two different SKU numbers, which may complicate inventory tracking and create end clinical user inconvenience and inefficiency.
- the non-sterile, prefilled container is attached to the exterior of a sterile kit post-sterilization of the kit, sometimes referred to as a “sidecar” package, thereby creating a secondary non-sterile kit comprised of a non-sterile prefilled container and a sterile kit.
- a sidecar sterile kit post-sterilization of the kit
- this combination kit may reduce inventory tracking, the added step of separately packaging plastic containers and attaching them to sterilized kits makes manufacturing and assembly more time consuming and expensive.
- the syringe components are not inside the wrapped assemblies. Instead, these syringe components must be separately unpackaged and loaded onto the surgical wrap/drape, after the wrap/drape is opened within the sterile field.
- Another known method to address known EtO sterilization limits inherent to plastic containers is to fill an empty plastic syringe with fluid material, which may be introduced as sterile fluid in a clean room or aseptic environment, as discussed above.
- the filled plastic syringe may then be autoclaved, which will ensure that a sterile fluid and fluid pathway results.
- the outside of the syringe still remains non-sterile and may be packaged as described above.
- maintaining sterile technique during a clinical procedure becomes more challenging when a separately packaged, non-sterile component must be handled. This may affect the sequence of actions required to complete a given procedure; or, in some cases, the number of physicians needed to complete a procedure. For example, during a procedure, a nurse must open the non-sterile package outside of the sterile field and once the Doctor touches the syringe, the procedure must be adjusted to maintain the sterile technique.
- a filled “sterile fluid path” syringe may be steam sterilized.
- the syringe Upon steam sterilization, the syringe is then placed in an EtO gas impermeable foil package, which is then introduced into a procedural kit, with the kit and foil package being EtO sterilized together.
- the foil package prevents the EtO gas inside the procedural kit from getting through the foil package, and thus prevents EtO gas from interacting with the fluid material within the syringe.
- this process is also time consuming and expensive, as it requires two separate sterilization processes.
- it then requires a clinician to open multiple packages during a procedure and move it to the appropriate location in the sterile field, as well as requiring proper disposal of the packaging components without compromising the integrity of the sterile field.
- the prefilled syringes containing sterile solution (though the exterior of the syringe was not sterile), is packaged in a sleeve that may be attached to lidding or a pouch of the kit. Once packaged, the sleeve may be autoclaved so that the packaged syringe is sterile field ready.
- this arrangement then requires an extra person to open the packaging to drop the syringe within the sterile field. This arrangement does not permit having the syringe in an EtO sterilizable procedure kit.
- FIG. 1 illustrates a side view of an exemplary syringe assembly
- FIG. 2 illustrates a cross-sectional view of the syringe assembly of FIG. 1 , taken along lines 2 - 2 ;
- FIG. 3A illustrates side view of an exemplary plunger assembly for use with the syringe assembly of FIG. 1 ;
- FIG. 3B illustrates a side view of an exemplary plunger tip for use with the plunger of FIG. 3A .
- FIG. 4A illustrates a side view of a barrel of the exemplary syringe assembly of FIG. 1 ;
- FIG. 4B illustrates an enlarged view of an exemplary barrel neck of the barrel of FIG. 4A ;
- FIG. 4 C illustrates an enlarged view of an alternative arrangement of a proximal end of the barrel of FIG. 4A ;
- FIG. 5 illustrates a side view of an exemplary vial
- FIG. 6A illustrates a perspective view of a tip cap assembly
- FIG. 6B illustrates a perspective view of a tip cap insert of the tip cap assembly of FIG. 6A ;
- FIG. 7A is a cross-sectional view of the tip cap assembly of FIG. 6A ;
- FIG. 7B is a plan view of the tip cap assembly of FIG. 7A ;
- FIG. 8 is a flow chart illustrating various product flow paths for groups of EtO sterilization processes.
- a prefilled container system may include a syringe assembly having a barrel, plunger and tip cap.
- a chamber may be formed within the barrel between the plunger and tip cap and may be configured to hold sterilization sensitive materials such as saline or heparinized saline.
- the syringe assembly may be formed of various materials and/or solutions that permit the syringe assembly to be packaged with a surgical kit containing other items necessary to perform a medical procedure and sterilized together.
- a surgical kit containing other items necessary to perform a medical procedure and sterilized together.
- such kits may be tailored to particular procedures and may include items such as instruments, drugs, antiseptics, dressings that are appropriate and needed for the particular procedure.
- providing a sterile convenience kit permits operating room staff to maintain established sterile techniques in performing surgical operations, such that there is no need to separately remove the syringe from separate packaging and locate the syringe in the sterile field.
- the items within the kit may be sterilized to eliminate live bacteria or other microorganisms present on the inside or outside of the kit, and inside and outside of any component item within the sterile kit.
- Known sterilization methods may include EtO sterilization, autoclaving, or other methods such as irradiation.
- terminal sterilization is used as the sole sterilization step in the assembling and manufacturing of the packaged kits.
- the EtO gases used during terminal sterilization may alter the composition of sterilization sensitive material within a syringe.
- a syringe assembly 100 may include a barrel 105 , a plunger 110 and a tip cap 115 (shown in FIG. 6A ).
- the interior of the barrel 105 may cooperate with a distal end 113 of the plunger 110 and the tip cap 115 , when assembled to the barrel 105 , to define a chamber 230 (best seen in FIG. 4A ).
- Any number of solutions i.e., material may be included in the chamber 230 .
- Examples of preferred solutions include, but are not limited to, sodium chloride (such as 0.9% NaCl saline), heparinized saline (various amounts of heparin content), lidocaine or other liquid medication for infusion, or catheter lumen line flushing.
- the solution may also include active ingredients such as vaccines, drugs, probiotics, diagnostic compositions, etc.
- the chamber contents are a liquid solution that is sterile; either by an aseptic filling process or post filling terminal sterilization that provides a sterile fluid path.
- These solutions when included in a procedural kit, may be adversely affected by the terminal kit sterilization process, such as EtO sterilization as explained above. However, the kit sterilization is necessary to ensure all the contents of the finished procedural kit are sterile.
- EtO sterilization may include subjecting the filled syringe assembly 100 to EtO gas.
- EtO gas is effective and an accepted procedure to kill any micro-organisms and ensure that the assembly 100 is sterilized prior to use.
- FDA Federal Drug Administration
- the EtO gases may alter the composition of the sterilization sensitive solution.
- Ethylene Oxide, Ethylene Chlorohydrin, and Ethylene Glycol—Proposed Maximum Residue Limits and Maximum Levels of Exposure the contents of which are incorporated by reference in its entirety, the amount of residual Ethylene Oxide (EO) gas, Ethylene Chlorohydrin (ECH) and Ethylene Glycol (EG) toxic by-products present in an injectable drug must be tightly controlled.
- Ethylene Oxide (EO) gas, Ethylene Chlorohydrin (ECH) and Ethylene Glycol (EG) toxic by-products present in an injectable drug must be tightly controlled.
- the FDA guidance document suggests that the residual EO and ECH shall not exceed 10 ppm and the residual EG shall not exceed 20 ppm.
- the FDA guidelines also set maximum daily exposure level requirements.
- the maximum daily exposure level is 30 ⁇ g/kg/day up to 30 days.
- the maximum daily exposure level is 15 ⁇ g/kg/day up to 30 days.
- the maximum daily exposure level is 2.5 mg/kg/day up to 30 days.
- the U.S. Pharmacopeia (USP)—National Formulary has provided a test standard for an acceptable pH in such solutions. More specifically, the pH should be in the range of 4.5-7.0 (test no. 791). The inventors of the present application have determined that a pH shift outside of this range is an indicator for undesirable EO ingress in a chamber 230 of a syringe. For example, as set forth in the background, testing of samples prior to undergoing a EtO sterilization process, yielded a baseline pH, well within the USP range of 4.5-7.0. However, once those prior art samples were subjected to prior art EtO sterilization techniques, the pH shifted outside the UPS range, thereby revealing that the solution within the syringes had been altered.
- the USP also sets forth an acceptable pH range for other injectable solutions that are contemplated by this disclosure, such as lidocaine hydrochloride and epinephrine injections (pH in the range of 3.3-5.5), lidocaine hydrochloride injections (pH in the range of 5.0-7.0), and heparin lock flush solutions (pH in the range of 5.0-7.0).
- the syringe assembly 100 itself also is subject to maximum residue limits. More specifically, the syringe is classified as a medical device and is subject to ANSI/AAMI/ISO 10993-7:2012 “Biological Evaluation of Medical Devices—Part 7: ETO Sterilization Residuals. For those medical devices subject to EtO Sterilization techniques, the residual EO gas in the device must be less than or equal to 4 mg per device, while the residual ECH toxic by product must be less than or equal to 9 mg/device. Currently there is no standard for residual EG toxic byproduct.
- the syringe assembly 100 provides that the chamber 230 is capable of creating an effective barrier between sterilization gases and the solution so that the solution remains substantially unchanged within the chamber 230 during and after sterilization.
- the pH of the solution stays with the range of about 4.5-7.0.
- the inventors of the present application have determined that small shifts of the pH of the solution that results in a post-sterilization pH still within the range of about 4.5-7.0 is indicative that the sterilization technique has not caused ingress of EtO gas into the solution via any known entry points and pathways (through the barrel, any rubber interfaces, any silicone lubricant, interface areas (tip cap)) of the assembly 100 and has therefore not adversely affected the solution contained within the chamber 230 .
- the solution remains within acceptable specifications for the manufacture, sale, and use of the device.
- the inventors have discovered these unexpected results after numerous experiments with different plastic material for assembly 100 , in combination with variations of sterilization cycle parameters, which will be discussed below in further detail.
- the device and solution still meets the regulatory requirements for the manufacture, sale, and use of that drug, i.e., is also has residual EO gas and ECH toxic byproduct that does not exceed 10 ppm and the residual EG toxic byproduct that does not exceed 20 ppm.
- the plunger 110 may include a plunger body 130 extending along an axis A and having a base 120 at one end and a stopper mount 125 disposed at the opposite end of the plunger body 130 .
- the stopper mount 125 is configured to receive a plunger stopper 127 .
- the plunger body 130 may be made of a light-weight material.
- the plunger body 103 may be fabricated from polypropylene, which is low in cost, as well as being lightweight.
- the stopper mount 125 comprises an extension element 131 that extends distally from the plunger body 130 .
- Extension element 131 has a diameter that is slightly smaller than the diameter of the plunger body 130 .
- a mounting flange 133 is secured to the distal end of the extension element 131 .
- This configuration provides a mounting channel 135 between the mounting flange 133 and the distal end of the plunger body 130 .
- Mounting channel 135 is configured to receive an annular retainer 155 of the stopper 127 , as shown in FIG. 2 , for example.
- the stopper 127 may include a cylindrical portion 140 and an end portion 145 , which may have a conical shape.
- the cylindrical portion 140 may also include at least one wiper 150 extending radially around the cylindrical portion 140 .
- the stopper 125 may be connected to the extension element 131 of the plunger body 130 via a retainer 155 .
- the attachment mechanism 155 includes an annular retainer 155 that extends inwardly from an outside surface and is configured to be frictionally engaged within the mounting channel 135 of the extension element 131 .
- FIG. 3B includes an annular retainer 155 that extends inwardly from an outside surface and is configured to be frictionally engaged within the mounting channel 135 of the extension element 131 .
- a suitable attachment member may include a male and female connection mechanism, whereby the stopper 125 may define an opening (not shown) configured to receive a post (not shown) extending outwardly along the axis A of the plunger body 130 so as to frictionally engage the stopper 125 .
- a suitable attachment mechanism 155 may also include an adhesive such as glue may be used. Additionally or alternatively other mechanisms may be used such as a screw mechanism, hook and eye mechanism, etc.
- the stopper 125 may have relatively a stiff elastic modulus and be formed from one or more materials, including high barrier thermoplastic elastomers. Exemplary elastomers may include, but are not limited to, butyl rubber or bromobutyl rubber.
- the stopper 125 may also be coated for increased barrier properties to EO ingress, such as, for example, with silicone lubricant of appropriately selected centistokes viscosity.
- a suitable coating may provide smooth operating/slide friction, with no unintended plunger movement during the many environmental pressure changes imparted on the assembly 100 during the various EtO sterilization cycle parameters.
- the base 120 of the plunger 110 may be formed so as to be co-extensive with the plunger body 130 and thus include similar materials.
- the plunger body 130 is configured to angle inwardly from a first diameter D 1 to a second D 2 to a second diameter at the proximal end 129 of the plunger body 130 . This configuration serves to limit movement of the plunger body 130 within the barrel 105 .
- the base 120 is sized to be greater than the first diameter D 1 so as to provide a land area for activating movement of the plunger 130 within the barrel 105 during use.
- the base 120 , and at least a portion of the plunger body 130 may be exposed to EtO gases.
- the plunger body 130 and base 120 does not come into contact with the sterilization sensitive material within the chamber 230 .
- at least one of the base 120 and plunger body 130 may be formed of less expensive plastics such as polypropylene or polycarbonate.
- the barrel 105 includes a first end 180 , a second end 185 and a barrel body 190 extending therebetween.
- the barrel body 190 may form a cylindrical shape extending along the axis A.
- the first end 180 may be an open end configured to receive the plunger 110 so as to provide a fluid tight seal.
- the second end 185 may include a barrel neck 195 .
- the neck 195 may include a male luer 200 defining an opening 205 .
- the barrel 105 may also include a mechanical engagement system, or barrel flange 210 , extending radially inwardly of an inner surface of the barrel 105 adjacent the first end 180 . More specifically, as shown in FIG. 4A , the inner surface of the barrel 105 adjacent the first end 180 of the barrel 105 may have a cross-sectional thickness that is greater to as to extend toward a central axis extending through the barrel 105 . With this arrangement, a barrel flange 210 is formed. During EtO sterilization, a positive pressure differential may be created within the barrel 105 (relative to the pressure outside the barrel, which may be negative).
- the barrel flange 210 may be configured to engage the outer periphery of a plunger flange 170 and/or the wipers 150 of the stopper 125 to prevent the plunger 110 from complete expulsion from the barrel 105 .
- Other exemplary mechanical engagements may include one or more protrusions on an inner surface of the barrel 105 that are sufficient to prevent expulsion of the plunger 115 .
- the interior surface of barrel 105 may further include an inwardly extending annular detent 210 ′.
- the stopper 125 has an outer diameter that is slightly larger than the interior diameter of the barrel 105 . While stopper 125 will compress when introduced into the barrel 105 , the barrel flange 210 or annular detent 210 ′ will prevent stopper 125 from being extracted from the barrel 105 , as portion of the annular retainer 155 will come into contact with the barrel flange 210 and annular detent 210 ′.
- an air bubble is intentionally left within the barrel after filling the chamber 230 with solution.
- the air bubble facilitates a large pressure differential and outward force of the plunger 110 during sterilization as an EtO sterilization cycle uses a deep draw vacuum.
- the chamber 230 is free of air bubbles.
- choice of silicone lubricant parameters may also affect plunger motion.
- the gripping flange 235 extends radially outwardly around the open first end 180 so as to be sized to be greater than a diameter of the barrel 105 . In one exemplary arrangement, the gripping flange 235 extends all the way around the open first end 180 . In another exemplary arrangement, the gripping flange 235 is configured with gaps between land areas. Both configurations allow a user to grip the barrel 105 while the plunger 130 is being moved inwardly within the chamber 230 .
- the barrel 105 may be manufactured with one or more plastic materials.
- barrel 105 is formed of cyclic olefin polymer (COP) and/or cyclic olefin copolymer (COC) materials. These polymers are similar to glass in that they have high gas impermeability, high moisture barrier and low absorption rate properties. However, unlike glass, COC and COP materials are not fragile and do not have the weight and transport issues associated with glass.
- the barrel 105 may be coated with materials for increased barrier properties, such as silicone dioxide or aluminum dioxide. In another embodiment, the barrel 105 may be uncoated. Additionally or alternatively, the barrel 105 may be formed from materials having high clarity so that contents of the barrel may be visibly inspected.
- the barrel 105 may also be formed from materials having at least one of low water vapor permeability (in one example, less than about 0.5 g/m 2 per day per 330 micron thickness at atm to minimize moisture transmission across walls of the container), low oxygen permeability (in one example, less than about 500 cm 3 /m 2 per day per 80 micron thickness at atm to minimize gas transmission across walls of the container), high heat resistance to withstand temperatures of autoclaving (in one example, the heat resistance is effective to standard autoclaving temperatures), and minimal leaching, elution, extraction, absorption or adsorption.
- low water vapor permeability in one example, less than about 0.5 g/m 2 per day per 330 micron thickness at atm to minimize moisture transmission across walls of the container
- low oxygen permeability in one example, less than about 500 cm 3 /m 2 per day per 80 micron thickness at atm to minimize gas transmission across walls of the container
- high heat resistance to withstand temperatures of autoclaving in one example, the heat resistance is effective to standard auto
- the barrel 105 may be configured to receive the plunger 110 at the barrel first end 180 .
- the stopper 125 of the plunger 110 may be inserted at the first end 180 .
- the stopper 125 along with the tip cap 115 , may be configured to create the chamber 230 within the barrel 105 .
- the stopper 125 may have a relatively stiff elastic modulus and the wipers 150 may create a mating surface with the inside of the barrel 105 .
- the stopper 125 may permit the plunger 110 to move along axis A within the barrel 105 and also create a seal within the barrel 105 to prevent any material from leaving the chamber 230 .
- the mating conical surfaces between the barrel 105 and the stopper 125 may also serve to prevent blood uptake after the prefilled syringe has been administered to a patient by preventing the plunger assembly 110 from recoiling upward after administration.
- the tip cap 115 may be configured as a female luer 220 configured to receive the mating male luer 200 extending from the barrel 105 .
- the tip cap 115 may be configured to seal the syringe assembly 100 to assist in creating the chamber 230 within the barrel 105 .
- the tip cap 115 includes an insert 300 that is disposed in a housing member 302 .
- the housing member 302 may be constructed of a substantially rigid material, such as polycarbonate or other suitable plastic, as the housing member 302 does not contact the material disposed within the chamber 230 .
- the insert 300 includes a base member 304 and a neck 306 .
- the base member 304 is disposed within a cavity 308 formed by inner flanges 310 that extend inwardly from an inner surface 312 of the housing member 302 .
- the inner flange 310 has an upwardly extending lip 314 that extends annularly around the insert 300 so as to lock the insert 300 into the housing member 302 .
- the inner flanges 310 are separated from one another such that a void area 316 is created between adjacent flanges 310 . While not shown, in one exemplary arrangement inner surface 312 may include threads.
- the insert 300 is manipulated such that the base member 304 is disposed within the cavity 308 and retained within the housing member 302 by the inner flanges 310 .
- the housing With the insert 300 mechanically fixed to the housing member 302 , the housing is disposed over the barrel neck 195 , such that the insert 300 is inserted into the barrel neck 195 with the male luer 200 being received within a channel 318 of the insert with an interference fit.
- a locating member 320 is disposed within an opening formed within the male luer 200 .
- the base member 304 fits against and seals a top surface of the barrel neck 195 .
- the inner surface 312 may include threads that cooperate with corresponding threads disposed on an exterior surface of the barrel neck 195 to lock the tip cap 115 onto the barrel 105 .
- the chamber 230 may be configured to hold the sterilization-sensitive material.
- a portion of the tip cap 115 may come in contact with the material during sterilization, shipping and storage of the syringe.
- a needle for insertion into the barrel neck 195 may also be included in the kit.
- the tip cap 115 may be made of any number of materials. Exemplary materials may include polycarbonates that possess adequate barrier properties. For example, plastics such as polypropylene coated with a high-barrier material (e.g., butyl rubber) on at least a portion of the tip cap 115 may be used. The surface area of the tip cap 115 exposed to the material in the chamber 230 is relatively small compared to that of the barrel 105 and stopper 125 . Thus, the portion exposed to the material may be coated, while the remaining portions of the tip cap 115 may not.
- a high-barrier material e.g., butyl rubber
- the tip cap may be constructed entirely of butyl rubber and include a neck and a base member.
- the base member is configured with an outer diameter that is larger than an outer diameter of the neck area.
- Disposed within the neck area is a channel, similar to channel 318 .
- the channel is also defined by an open end and a closed end.
- a locating element similar to locating member 320 and may be fixedly disposed on the closed end of the channel.
- the neck area is inserted into the barrel neck with the male luer being received within the channel with an interference fit.
- the locating member is disposed within an opening formed within the male luer 200 .
- the base member fits against and seals a top surface of the barrel neck 195 .
- the tip cap 115 ′′ includes a butyl rubber insert 300 that is disposed in a housing member 302 .
- the housing member 302 may be constructed of a substantially rigid material, such as polycarbonate or other suitable plastic, as the housing member 302 does not contact the material disposed within the chamber 230 .
- the insert 300 includes a base member 304 and a neck 306 .
- the base member 304 is disposed within a cavity 308 formed by inner flanges 310 that extend inwardly from an inner surface 312 of the housing member 302 .
- the inner flange 310 has an upwardly extending lip 314 that extends annularly around the insert 300 so as to lock the insert 300 into the housing member 302 .
- the inner flanges 310 are separated from one another such that a void area 316 is created between adjacent flanges 310 .
- inner surface 312 may include threads.
- FIG. 5 shows an exemplary vial 240 including a stopper 245 and a cap 250 .
- the vial 240 may be formed from COC or COP and the stopper 245 may include a region formed of a thermoplastic elastomer such as a butyl rubber.
- the stopper 245 may be fitted within a neck of the vial 240 .
- the cap 250 may surround the top of the vial 240 .
- the vial 240 may include sterilization sensitive material, similar to the syringe assembly 100 above.
- pressure may build within the vial and the cap 250 may be configured to abut at least a portion of the stopper 245 at the top of the vial to prevent the stopper 245 from being ejected from the vial 240 during pressure increases.
- the outside of the syringe assembly 100 and/or the vial 240 may be sterilized along with the other items within a surgical kit via a variety of sterilization techniques such as EtO sterilization and/or autoclaving.
- the separate components of the syringe assembly 100 and the vial 240 e.g., the barrel 105 , plunger 110 , tip cap 115 , etc.
- each component may be sterilized prior to assembly.
- the chamber 230 may be filled with the material.
- the stopper 125 of the plunger 110 may be inserted at the first end 180 of the barrel 105 and prior to attaching the tip cap 115 to the barrel neck 195 , the material may be filled at the opening 205 .
- the tip cap 115 may then be attached to the barrel 105 at the barrel neck 195 , thus sealing the material within the chamber 230 .
- the tip cap 115 may first be connected to the barrel neck 195 via the luer fitting and the material may be filled at the first end 180 prior to the plunger 110 being inserted into the barrel 105 . Once the chamber 230 has been filled, and the plunger 110 inserted, the syringe assembly 100 may be sterilized.
- the assembly 100 may be placed in an autoclave. By subjecting the syringe assembly 100 to highly saturated steam, the exterior of the assembly may be sterilized. Further, the interior of the components, which will not be exposed to the steam, will also be sterilized due to high temperature of the container's solution therein. Once the syringe assembly 100 is removed from the autoclave, the outside of the assembly 100 may become non-sterile; however, the fluid and fluid path remain sterile.
- the syringe assembly 100 may be individually packaged (as single dose syringes or multiple syringes in a single package) or be combined with the remaining kit contents. The individual packages or the entire kit may then be sterilized via EtO sterilization.
- the outside of the assembly 100 is sterilized.
- the outside of the assembly 100 may be sterilized simultaneously with the other kit components. Due to the specific properties of the barrel 105 , plunger 110 , stopper 125 , and tip cap 115 , the material within the chamber 230 is not altered or affected by the sterilization process.
- the syringe assemblies 100 may be placed in its own pouch with one or more vials 240 containing sterilization sensitive material.
- the packaged combination syringe assembly 100 and vial 240 may then be subjected to an EtO sterilization procedure.
- vials such as vial 240 , that are constructed of COP or COC material with a suitable butyl rubber boundary, may be individually packaged (or included in a surgical kit) and subjected to an EtO sterilization process without adversely affecting sterilization sensitive material.
- prefilled container systems may be packaged together with other materials requiring terminal sterilization as part of the manufacturing process and need not be separately packaged with materials having high barrier properties such as sealed, foil wrapping.
- the inventors have found that by using COP or COC for the barrel of the syringe and employing a suitable sterilization protocol, no undesirable pH shift of the solution disposed within the chamber 230 after undergoing a suitable terminal sterilization procedure was experienced. More specifically, the inventors have developed a series of sterilization protocols that were tested on an exemplary arrangement of prototypes manufactured with a COP barrel and a tip cap manufactured from polypropylene with a chlorobutyl rubber insert.
- One exemplary EtO sterilization cycle that the inventors have developed for successfully EtO sterilizing prefilled syringes has many processes, but generally can be classified into four basic groups of processes and/or parameters: 1) preprocessing or preconditioning; 2) chamber washes and conditioning; 3) sterilization and 4) evacuation.
- a first embodiment of the preprocessing group of processes/parameters for an exemplary EtO sterilization cycle is set forth in Table 1 below:
- the preprocessing group of processes is designed to precondition the syringes to get any bacteria “active” or “excited” so as to make any bacteria/microorganisms grow and be more susceptible to EtO gas.
- the preprocessing group of processes seeks to raise the temperature and humidity to precondition the syringes and their contents.
- the preprocessing group of processes starts by placing the syringes in a preconditioning area, such as, for example, a room or chamber, which is set at a minimum temperature.
- the preprocessing step may also be done in a sterilization chamber, which is used for other of the parameters of the sterilization cycles, as will be explained in further detail below.
- the minimum initial starting temperature may be within the range of 40-125° F.
- the initial starting temperature may be room temperature, i.e., approximately 70° F.
- the temperature in the preprocessing area is then raised to a preconditioning temperature.
- the range of temperatures is within about 90-130° F.
- the range of preconditioning temperatures may be within the range of 90-110° F.
- the preprocessing temperature is set to 100° F.
- the humidity is also raised in the preprocessing group of processes. More specifically, the preconditioning humidity in the preprocessing area is raised to be in the range of 45-85% relative humidity. In another exemplary arrangement, the preconditioning humidity is raised in the range of 45-95%. In one particular example, the preconditioning humidity is set to be 60%.
- the syringes remain in the preprocessing area/chamber for a preprocessing time period.
- the time period is dependent upon the temperature of the product and the humidity of the product reaching the approximate temperature and humidity of the room/chamber.
- the range of time for the syringes to remain in the preprocessing room/chamber is between 6 hours and 96 hours. In another exemplary arrangement, the range of time for the syringes to remain in the preprocessing room/chamber is between 18-96 hours.
- the temperature of the syringes is in the range of 45-125° F. In another exemplary configuration, after preconditioning, the syringes are ⁇ in the range of 90-110° F.
- the relative humidity of the syringes is within the range of 45-85%. In another exemplary arrangement, the relative humidity of the syringes is within the range of 45-95%.
- the washing/conditioning group of processes/parameters is performed to remove most (in one exemplary arrangement >97%) of the air from the chamber so the EO gas/air mixture is not explosive.
- the washing/conditioning group of processes/parameters is performed to add both moisture and heat to the area/chamber so when EO gas is injected into the chamber, the bacteria/microorganisms exposed in the preprocessing step above will be eradicated.
- the temperature with the area/chamber is raised to a sterilization temperature.
- the sterilization temperature is raised within the range of 85-130° F.
- the sterilization temperature is raised within the range of 105-125° F.
- a target temperature for the sterilization temperature is 115° F.
- the sterilization area is subjected to an evacuation process to remove air from the syringes.
- the evacuation process applies vacuum pressure within a range of 1-24 inHgA.
- the initial evacuation process applies vacuum pressure of approximately 6 inHgA.
- the initial evacuation process applies vacuum pressure of approximately 10 inHgA.
- An acceptable tolerance for vacuum pressure is 0.5 inHgA.
- the vacuum may be turned off and a leak test is performed to verify that the that the sterilization area is properly sealed. If the evacuation pressure remains at the set point, within an acceptable tolerance for the duration of the leak test, then the washing/conditioning process proceeds to a pressure injection step. However, if the leak test fails, the sterilization area must be inspected for any failed seals and preprocessing procedure must be repeated for the syringes. In one exemplary arrangement, the leak test is performed within the range of 5-60 minutes. In one particular example, the leak test is performed for 5 minutes.
- moisture may be introduced into the syringes, such as by raising the relative humidity of the sterilization area until pressure within the sterilization area is raised to a predetermined pressure limit or the desired relative humidity set point is reached from direct measure (i.e., if the sterilization area includes one or more sensors to indicate the relative humidity). If the pressure injection step is omitted, the next step in the process is injecting Nitrogen gas into the sterilization area, discussed below.
- the sterilization area (including the syringes) is injected with moisture to a target range of relative humidity of 0.5-3.0 inHgA to achieve a predetermined dwell pressure.
- the dwell pressure may be within the range of 2.3-14.0 inHgA.
- the relative humidity level is maintained for a predetermined dwell time.
- the dwell time is within the range of 15-120 minutes. Once the dwell time has expired, the relative humidity of the sterilization area is confirmed. A relative humidity within the range of 47.6-91.9% has been determined by the inventors to be acceptable. If pressure injection fails, the cycle will be aborted.
- Nitrogen gas is injected into the sterilization area under pressure.
- Nitrogen gas is injected up to 30.5 inHgA.
- Nitrogen gas is injected at approximately 28 inHgA.
- Nitrogen gas is injected with a range of 26-27 inHgA.
- the sterilization area undergoes another evacuation process.
- the sterilization area is subjected to vacuum pressure within the range of 1-24 inHgA.
- the sterilization chamber is subjected to a vacuum pressure set point of approximately 6 inHgA.
- the sterilization area is subjected to a vacuum pressure set point of approximately 10 inHgA.
- the inventors have determined that a tolerance of 0.5 inHgA is acceptable for the second evacuation process.
- the Nitrogen pressure/evacuation process outlined above may be repeated, though not required.
- the Nitrogen pressure/evacuation process is repeated within the range of 1-4 times.
- the Nitrogen pressure/evacuation process is repeated approximately 2 times.
- the Nitrogen pressure/evacuation process is repeated is repeated 3 times.
- the sterilization area (including the syringes) is injected with moisture to a target range of relative humidity of 0.5-3.0 inHgA.
- the sterilization area is injected with moisture to a target humidity of 1.5 inHgA, to achieve a predetermined dwell pressure.
- the dwell pressure may be within the range of 2.3-14.0 inHgA.
- a target dwell pressure may be within the range of 10-14 inHgA.
- a target dwell pressure may be 6.5 or 11.5.
- the EtO sterilization group of processes begins by introduction of EtO gas into the sterilization area until reaching a predetermined pressure level.
- the pressure level is within the range of approximately 10.7-29.9 inHgA.
- a target pressure level is 20 inHgA.
- a target pressure level is 19 inHgA.
- the EtO concentration within the sterilization area is verified to be with a preset target level after EtO injection.
- a suitable target range is 150-800 mg/L.
- a set target of 421.7 mg/L is desirable.
- a biologic indicator may be used to verify the EtO concentration within the sterilization chamber.
- a nitrogen blanket may be introduced.
- the nitrogen blanket target range is up to 30 inHgA.
- a suitable target range may be between 25.5-27.0 inHgA.
- the EtO concentration within the sterilization area is maintained at a set temperature for a suitable dwell time.
- the dwell temperature is within the range 102-140° F.
- the dwell temperature may be within the range of 110-125° F.
- the dwell time may be within the range of 1-24 hours.
- the dwell time may be within the range of 4-8 hours.
- a dwell time of 4 hours is utilized.
- EtO injections may be employed up to 10 times during an EtO sterilization procedure.
- the wash/exposure group of processes/parameters begins by evacuating EtO gas and Nitrogen from the sterilization area to remove EtO gas from the sterilization area.
- a vacuum pressure is applied to the sterilization area within the range of 1-24 inHgA.
- a vacuum pressure of 6 inHgA has been found to be a suitable vacuum level by the inventors of the present application.
- the evacuation pressure is applied between 1 and 30 minutes.
- Nitrogen gas is injected into the sterilization chamber under pressure.
- Nitrogen gas is injected up to 30.5 inHgA.
- Nitrogen gas is injected at approximately 27 inHgA.
- Nitrogen gas is injected with a range of 27-28 inHgA.
- the nitrogen gas injection is performed for 1 to 30 minutes. This process may be repeated up to 4 times. In one exemplary arrangement, the Nitrogen gas injection is repeated three times.
- the sterilization area is evacuated to an evacuation pressure.
- a vacuum pressure of approximately 1-24 inHgA is applied.
- a vacuum pressure of 6 inHgA has been found to be acceptable.
- a vacuum pressure of 10 inHgA has been found to be acceptable.
- the sterilization area undergoes an air wash step.
- Air is injected under pressure between up to 30.5 inHgA.
- the pressure range for the air wash is between 27-28 inHgA.
- the sterilization area is subjected to the air wash for 1 to 30 minutes.
- the air washes may be repeated up to 6 times.
- the air wash may be repeated 3 times.
- the air wash process may be repeated 4 times.
- the sterilization area is opened to the atmosphere and product pallets containing the prefilled syringes may be removed and taken to an aeration facility within the manufacturing facility, as well be explained in further detail below.
- the product pallets may remain the sterilization area.
- the aeration temperature within the aeration area of the facility may be within the range of 95-120° F.
- the product pallets may be aerated within the range of 24-120 hours.
- FIG. 8 configurations of the sterilization protocols will now be discussed. More specifically, the flow chart in FIG. 8 represents alternative product flow (i.e., syringes, vials or other items) for sterilization protocols discussed herein.
- product flow will be described in the context of EtO sterilization of a syringe.
- the preprocessing/preconditioning group of processes begins with the syringe (or group of syringes) being placed in a preconditioning area within a facility.
- the preprocessing/preconditioning group of processes are then all performed in the preconditioning area.
- the syringes are then moved to a sterilization chamber/area. Once in the sterilization chamber/area, in product flow A, the syringes are subjected to the chamber washes/conditioning, sterilization and evacuation group of processes. Finally, the syringes may then be moved to an aeration area to aerate the syringes.
- all of the group of processes i.e., preprocessing/preconditioning, chamber washes/conditioning, sterilization and evacuation, (including aeration) may be done as an “all-in-one” process in a single area or chamber.
- This product flow is represented by element B in FIG. 8 .
- the product flow comprises the preprocess/preconditioning group of processes being performed in a preprocessing area/chamber.
- the syringes are moved to a sterilization chamber/area, where the remaining groups of processes are conducted (i.e, the chamber washes/conditioning, sterilization and evacuation, including aeration).
- the syringes undergo the preprocessing/preconditioning group of processes and the chamber washes/conditioning and sterilization group of processes in the same location, such as in a sterilization chamber/area. Once evacuation of the chamber/area is completed, the syringes are then moved to an aeration area in a facility.
- Product flow arrangements represented by product flow paths E-H involves repeating certain aspects of the groups of processes. More specifically, product flow path represented by a dot alternating with a dash line E involves, first subjecting the syringes to the preprocessing group of steps in the preconditioning area. Next, the syringes are moved to sterilization chamber where the preconditioning group of processes are repeated and the chamber washes/conditioning, sterilization and evacuation (including aeration) group of processes are completed. The syringes are then moved to the aeration area in the facility and may be aerated again.
- the syringes are first subjected to the preprocessing group of steps in a preconditioning area. Next, the syringes are moved to a sterilization chamber where chamber washes/conditioning, sterilization and evacuation groups of processes are conducted. The syringes are then moved to the aeration area in the facility and may be aerated again.
- the product flow arrangement represented by long dashed lines G involves first subjecting the syringes to the preprocessing group of steps in a preconditioning area. Next, the syringes are moved to a sterilization chamber/area, where the preprocessing group of steps of repeated, and where the chamber washes/conditioning, sterilization and evacuation groups of processes are conducted. The syringes are then moved to the aeration facility and may be aerated.
- An additional alternative product flow arrangement is represented by double dot dashed line H.
- the syringes are subjected to the preprocessing group of steps in a preconditioning area.
- the syringes are moved to a sterilization chamber whereby the syringes then undergo another preprocessing/preconditioning step, as well as subjecting the syringes to the chamber washes/conditioning, sterilization and evacuation group of steps, including aeration.
- a series of test samples were prepared for verifying the effectiveness of the sterilization procedures described above.
- the sample size for testing included 60 total prefilled syringe assemblies 100 , divided into six groups of 10 syringe assemblies 100 .
- Each chamber 230 of the respective syringe assemblies 100 includes a chamber 230 of the barrel 105 filed with 5 mL of saline and the tip cap 115 is secured at the end of the barrel 105 .
- One set of 10 syringe assemblies 100 was selected as being the Control Samples (identified as Group 1) and set aside, without performing any sterilization procedure.
- a second set of 10 syringe assemblies 100 was designated as Group 2.
- the Group 2 syringes were exposed to two EtO sterilization cycles (as discussed in further detail below).
- a third set of 10 syringe assemblies 100 was designated as Group 3.
- the Group 3 syringe assemblies 100 were exposed to steam sterilization only.
- a fourth set of 10 syringe assemblies 100 was designated as Group 4.
- the Group 4 syringe assemblies 100 were exposed to steam sterilization and two EtO sterilization cycles (set forth below).
- a fifth set of 10 syringe assemblies 100 was designated as Group 5.
- the Group 5 syringe assemblies 100 were exposed to one EtO sterilization cycle (set forth below).
- a final set of 10 syringe assemblies 100 was designated as Group 6.
- the Group 6 was exposed to steam sterilization and one EtO sterilization cycle (set forth below).
- the NaCl saline solution from each syringe in Groups 1-6 were tested for pH using an acceptable testing protocol for determining pH readings with an accuracy level of ⁇ 0.02 pH.
- the NaCl saline solution from each syringe in the Control Group (Group 1) and Groups 2, 4, and 6 were tested for EO and ECH residuals using an acceptable testing protocol, such as one using gas chromatography with a flame ionization detector.
- the average results of the testing for each group are set forth in Table 5 table below:
- the pH shift is within acceptable ranges resulting pH levels well within the USP requirements. More specifically, the pH for the solution in Groups 2-6 all fall within the range of 4.5-7.0. Moreover, the residual EO and ECH are also well within the FDA requirements. More specifically, the EO residual results are below the limit of 4 mg/device and the ECH residual results are below the limit of 9 mg/device.
- the present disclosure provides a manufacturing methods, EtO sterilization processes and cycles, parameters, and ranges, for regulatory compliant production and EtO gas sterilization (post filling and autoclaving) of polymer prefilled containers, such as syringes, as well as vials.
- Suitable materials for such prefilled containers include 0.9% NaCl normal saline, heparinized saline, or other liquids. Correct application of the above complex methods create resultant sterile prefilled container without EtO gas ingress to EtO sensitive fluid within the container.
- the methods disclosed herein do not create the many possible unacceptable side effects of EtO gas ingress, such as pH shift outside the range of 4.5 to 7.0; toxic byproducts like EO-EC-EG residuals; 0.9% NaCl potency shift more than ⁇ 5%; alteration of contents (mL) due to plunger motion and leakage caused by an inappropriate selection of the nominal value of one or more of 30+ EtO sterilization process cycle parameters.
- non-glass pre-filled containers such as syringes and vials
- a standard breathable medical procedure sterile tray i.e., convenience tray
- kit pouch or package with other components, or individually package the containers and be subjected to EtO sterilization and directly ready for infusion when it is extracted from its packaging or lifted out of the sterile procedure tray by the operating technician.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Mechanical Engineering (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/169,962 US20170349313A1 (en) | 2016-06-01 | 2016-06-01 | Methods for manufacturing non-glass prefilled syringes |
AU2017273335A AU2017273335B2 (en) | 2016-06-01 | 2017-05-22 | Methods for manufacturing non-glass prefilled containers |
BR112018074925-7A BR112018074925B1 (pt) | 2016-06-01 | 2017-05-22 | Método de empregar óxido de etileno (eto) para esterilizar uma montagem de seringa pré- preenchida |
CA3026404A CA3026404A1 (en) | 2016-06-01 | 2017-05-22 | Methods for manufacturing non-glass prefilled containers |
NZ748836A NZ748836A (en) | 2016-06-01 | 2017-05-22 | Methods for manufacturing non-glass prefilled containers |
EP17807234.4A EP3463490B1 (en) | 2016-06-01 | 2017-05-22 | Methods for manufacturing non-glass prefilled containers |
CN201780033848.6A CN109414518A (zh) | 2016-06-01 | 2017-05-22 | 制造非玻璃预填充容器的方法 |
PCT/US2017/033719 WO2017209998A1 (en) | 2016-06-01 | 2017-05-22 | Methods for manufacturing non-glass prefilled containers |
JP2018563068A JP7187321B2 (ja) | 2016-06-01 | 2017-05-22 | 予め充填された非ガラスの容器を製造するための方法 |
MX2018014633A MX2018014633A (es) | 2016-06-01 | 2017-05-22 | Métodos para la fabricación de envases llenados de antemano no de vidrio. |
AU2022204394A AU2022204394B2 (en) | 2016-06-01 | 2022-06-22 | Methods for manufacturing non-glass prefilled containers |
US17/855,912 US11958647B2 (en) | 2016-06-01 | 2022-07-01 | Methods for manufacturing non-glass prefilled syringes |
US18/613,254 US20240262554A1 (en) | 2016-06-01 | 2024-03-22 | Methods for manufacturing non-glass prefilled syringes |
AU2024203424A AU2024203424A1 (en) | 2016-06-01 | 2024-05-22 | Methods for manufacturing non-glass prefilled containers |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/169,962 US20170349313A1 (en) | 2016-06-01 | 2016-06-01 | Methods for manufacturing non-glass prefilled syringes |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/855,912 Continuation US11958647B2 (en) | 2016-06-01 | 2022-07-01 | Methods for manufacturing non-glass prefilled syringes |
Publications (1)
Publication Number | Publication Date |
---|---|
US20170349313A1 true US20170349313A1 (en) | 2017-12-07 |
Family
ID=60477844
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/169,962 Abandoned US20170349313A1 (en) | 2016-06-01 | 2016-06-01 | Methods for manufacturing non-glass prefilled syringes |
US17/855,912 Active US11958647B2 (en) | 2016-06-01 | 2022-07-01 | Methods for manufacturing non-glass prefilled syringes |
US18/613,254 Pending US20240262554A1 (en) | 2016-06-01 | 2024-03-22 | Methods for manufacturing non-glass prefilled syringes |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/855,912 Active US11958647B2 (en) | 2016-06-01 | 2022-07-01 | Methods for manufacturing non-glass prefilled syringes |
US18/613,254 Pending US20240262554A1 (en) | 2016-06-01 | 2024-03-22 | Methods for manufacturing non-glass prefilled syringes |
Country Status (10)
Country | Link |
---|---|
US (3) | US20170349313A1 (pt) |
EP (1) | EP3463490B1 (pt) |
JP (1) | JP7187321B2 (pt) |
CN (1) | CN109414518A (pt) |
AU (3) | AU2017273335B2 (pt) |
BR (1) | BR112018074925B1 (pt) |
CA (1) | CA3026404A1 (pt) |
MX (1) | MX2018014633A (pt) |
NZ (1) | NZ748836A (pt) |
WO (1) | WO2017209998A1 (pt) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10780228B2 (en) | 2012-05-07 | 2020-09-22 | Medline Industries, Inc. | Prefilled container systems |
CN112773918A (zh) * | 2020-12-23 | 2021-05-11 | 北京伏尔特技术有限公司 | 一种环氧乙烷灭菌后快速解析工艺 |
CN113491784A (zh) * | 2020-04-03 | 2021-10-12 | 清华大学 | 一种利用环氧乙烷对医疗防护用品进行高效灭菌及强化解析的方法 |
WO2023113842A1 (en) * | 2021-12-13 | 2023-06-22 | Thorne Intellectual Property Holdings, Llc | Closed convenience kits for sterilized medicine preparation |
JP7510952B2 (ja) | 2019-04-24 | 2024-07-04 | アムジエン・インコーポレーテツド | シリンジ滅菌確認アセンブリ及び方法 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110025850A (zh) * | 2019-05-07 | 2019-07-19 | 中国人民解放军第四军医大学 | 一种预充式冲管注射器 |
CN113306880A (zh) * | 2020-08-25 | 2021-08-27 | 美昕医疗器械(昆山)有限公司 | 一种组合包装及其灭菌方法 |
CN112999388B (zh) * | 2021-02-08 | 2023-02-10 | 厦门博创中安医疗技术有限公司 | 一种可吸收植入物及配套器械组合产品的灭菌方法 |
Citations (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3630665A (en) * | 1966-06-30 | 1971-12-28 | Andersen Prod H W | Method of sterilization |
US3878664A (en) * | 1972-11-27 | 1975-04-22 | Cybersol | Process for producing a therapeutic composition |
US3993751A (en) * | 1972-11-27 | 1976-11-23 | Cybersol, Inc. | Process for stabilizing therapeutic compositions and article |
US4018222A (en) * | 1975-02-10 | 1977-04-19 | Merck & Co., Inc. | Syringe containing frozen vaccine |
US4739881A (en) * | 1986-08-14 | 1988-04-26 | Beckton, Dickinson And Company | Quick open syringe |
US5061281A (en) * | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US5342673A (en) * | 1993-02-23 | 1994-08-30 | W. L. Gore & Associates, Inc. | Sterilizable packaging material |
US5358475A (en) * | 1985-12-17 | 1994-10-25 | United States Surgical Corporation | High molecular weight bioresorbable polymers and implantable devices thereof |
US5382406A (en) * | 1990-04-17 | 1995-01-17 | Abbott Laboratories | Sterile filling method |
US5597530A (en) * | 1994-08-18 | 1997-01-28 | Abbott Laboratories | Process for prefilling and terminally sterilizing syringes |
US5620425A (en) * | 1993-11-03 | 1997-04-15 | Bracco International B.V. | Method for the preparation of pre-filled plastic syringes |
US6164044A (en) * | 1998-03-13 | 2000-12-26 | Becton Dickinson And Company | Method and apparatus for assembling and packaging medical devices |
US6189195B1 (en) * | 1995-08-22 | 2001-02-20 | Medrad, Inc. | Manufacture of prefilled syringes |
US6231810B1 (en) * | 1999-04-21 | 2001-05-15 | Stryker Technologies Corporation | Special cycle for ethylene oxide sterilization |
US20020051730A1 (en) * | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
US6475140B1 (en) * | 1998-05-29 | 2002-11-05 | Acmi Corporation | Flexible pressure resistant cover for the articulation system of a medical instrument |
US20020172615A1 (en) * | 2001-03-08 | 2002-11-21 | Archie Woodworth | Apparatus for and method of manufacturing a prefilled sterile container |
US6488890B1 (en) * | 1999-08-05 | 2002-12-03 | 3M Innovative Properties Company | Machine readable sterilization indicator for monitoring articles to be sterilized |
US20030159969A1 (en) * | 2002-02-28 | 2003-08-28 | Kimberly-Clark Worldwide, Inc. | Surgical kit with multiple planar recess surfaces |
US20040187438A1 (en) * | 2003-03-25 | 2004-09-30 | Frank Clarke | Packaging for stents and stent delivery system |
US20060260967A1 (en) * | 2003-01-27 | 2006-11-23 | Frank Clarke | Packaging for stent delivery systems |
US20070048251A1 (en) * | 2005-08-24 | 2007-03-01 | Arthur Samuel D | Methods for sealing an orifice in tissue using an aldol-crosslinked polymeric hydrogel adhesive |
US20070048337A1 (en) * | 2005-08-24 | 2007-03-01 | Arthur Samuel D | Aldol-crosslinked polymeric hydrogel adhesives |
US20070082859A1 (en) * | 2005-10-07 | 2007-04-12 | Stover Richard R | Formulations of AICA riboside |
US20080081763A1 (en) * | 2006-09-28 | 2008-04-03 | Swetlin Brian J | Polyester Compositions, Methods of Manufacturing Said Compositions, and Articles Made Therefrom |
US20100112063A1 (en) * | 2007-06-28 | 2010-05-06 | Figuly Garret D | Method for preparing a hydrogel adhesive having extended gelation time and decreased degradation time |
US20100313962A1 (en) * | 2006-09-29 | 2010-12-16 | Tyco Healthcare Group Lp | System and method for recycling sterilant gas |
US20100331864A1 (en) * | 2009-06-30 | 2010-12-30 | Shetty Dhanuraj S | Device for Repair of Urological Structures |
US20120035129A1 (en) * | 2009-04-09 | 2012-02-09 | Actamax Surgical Materials Llc | Hydrogel tissue adhesive having reduced degradation time |
US20120094955A1 (en) * | 2009-04-09 | 2012-04-19 | Actamax Surgical Materials Llc | Method of dissolving an oxidized polysaccharide in an aqueous solution |
US20120121532A1 (en) * | 2010-06-01 | 2012-05-17 | Baxter Healthcare S.A. | Process for making dry and stable hemostatic compositions |
US20130032967A1 (en) * | 2010-05-07 | 2013-02-07 | Abbott Cardiovascular Systems Inc. | Cold ethylene oxide sterilization of a biodegradable polymeric stent |
US20130103023A1 (en) * | 2011-10-24 | 2013-04-25 | Ethicon Endo-Surgery, Inc. | Litz wire battery powered device |
US20130110025A1 (en) * | 2010-07-14 | 2013-05-02 | Hemcon Medical Technologies (Ip) Limited | Dressing device for use wtih a cannula or a catheter |
US20130280346A1 (en) * | 2012-04-19 | 2013-10-24 | C. R. Bard, Inc. | Infusates with Enhanced pH Stability Under Ethylene Oxide Sterilization |
US20130296779A1 (en) * | 2012-05-07 | 2013-11-07 | Centurion Medical Products Corporation | Prefilled container systems |
US20140262883A1 (en) * | 2013-03-14 | 2014-09-18 | Becton Dickinson France S.A.S. | Packaging system for oxygen-sensitive drugs |
US20140342954A1 (en) * | 2012-01-10 | 2014-11-20 | President And Fellows Of Harvard College | Modification of surfaces for fluid and solid repellency |
US20150306282A1 (en) * | 2014-04-28 | 2015-10-29 | John James Scanlon | Bioresorbable Stent |
US20160135895A1 (en) * | 2014-11-07 | 2016-05-19 | Corium International, Inc. | Medical device packaging |
US20160200461A1 (en) * | 2013-08-16 | 2016-07-14 | Vanrx Pharmasystems Inc. | Method, device and system for filling pharmaceutical containers |
US20170333641A1 (en) * | 2014-10-30 | 2017-11-23 | Hoffmann-La Roche Inc. | Syringe and method of preparing syringe |
US20180105294A1 (en) * | 2016-10-13 | 2018-04-19 | Bourjois Abboud | Methods and systems for prefilling syringes |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2075845A (en) * | 1933-05-05 | 1937-04-06 | Liggett & Myers Tobacco Compan | Method of sterilizing |
US4474734A (en) * | 1983-07-05 | 1984-10-02 | Microbiological Applications, Inc. | Syringe shield and closure sterilization method |
US5039485A (en) * | 1990-09-26 | 1991-08-13 | Union Carbide Industrial Gases Technology Corporation | Sterilization method |
DE4438360C2 (de) * | 1994-10-27 | 1999-05-20 | Schott Glas | Vorfüllbare partikelarme, sterile Einmalspritze für die Injektion von Präparaten und Verfahren zu ihrer Herstellung |
JP3715026B2 (ja) * | 1996-04-24 | 2005-11-09 | 株式会社アルテ | 容器兼用注射器 |
US20020119074A1 (en) * | 2000-12-28 | 2002-08-29 | Mcgowan, James E. | Medical article sterilization method and device |
US6802828B2 (en) * | 2001-11-23 | 2004-10-12 | Duoject Medical Systems, Inc. | System for filling and assembling pharmaceutical delivery devices |
US6769546B2 (en) * | 2002-07-03 | 2004-08-03 | L. John Busch | Epidural anesthesia kit |
US20050075611A1 (en) * | 2003-10-01 | 2005-04-07 | Hetzler Kevin G. | Low extractable, thermoplastic syringe and tip cap |
US20050089442A1 (en) * | 2003-10-28 | 2005-04-28 | Young William T. | Method for sterilization using ethylene oxide |
US20050268573A1 (en) * | 2004-01-20 | 2005-12-08 | Avantec Vascular Corporation | Package of sensitive articles |
JP2006271461A (ja) * | 2005-03-28 | 2006-10-12 | Terumo Corp | 医療用器具の製造方法 |
JP2006314554A (ja) * | 2005-05-12 | 2006-11-24 | Mitsubishi Pharma Corp | ヘパリン溶液プレフィルドシリンジ包装体 |
WO2007024957A1 (en) * | 2005-08-26 | 2007-03-01 | Becton, Dickinson And Company | Methods of sterilizing elastomeric sealing articles |
WO2008077155A1 (en) * | 2006-12-21 | 2008-06-26 | Genentech, Inc. | Sterilization of objects containing biological molecules |
CA2703017C (en) * | 2007-10-19 | 2017-04-25 | Roseita Esfand | Self-eliminating coatings |
CN101485892B (zh) * | 2009-02-25 | 2012-10-03 | 乐普(北京)医疗器械股份有限公司 | 一种携载基因涂层医疗装置的灭菌处理方法 |
US9956385B2 (en) * | 2012-06-28 | 2018-05-01 | The Spectranetics Corporation | Post-processing of a medical device to control morphology and mechanical properties |
JOP20200175A1 (ar) * | 2012-07-03 | 2017-06-16 | Novartis Ag | حقنة |
AU2013100071C4 (en) * | 2012-07-03 | 2013-05-02 | Novartis Ag | Device |
WO2014041968A1 (ja) * | 2012-09-11 | 2014-03-20 | 株式会社日本触媒 | ポリアクリル酸(塩)系吸水剤の製造方法及びその吸水剤 |
CN103722809A (zh) * | 2012-10-14 | 2014-04-16 | 青岛医防消毒专业技术中心 | 一种新型eo织物灭菌袋 |
EP2974762B1 (en) * | 2013-03-15 | 2021-12-08 | Terumo Kabushiki Kaisha | Syringe assembly, syringe assembly packaging, and pre-filled syringe |
WO2014155562A1 (ja) * | 2013-03-27 | 2014-10-02 | テルモ株式会社 | チャンバー内の減圧方法 |
CN106062652B (zh) * | 2013-12-16 | 2019-06-14 | 3M创新有限公司 | 用于控制湿度的系统和方法 |
CN104707154B (zh) * | 2015-02-13 | 2017-08-08 | 西安交通大学 | 一种干湿法相结合的等离子体消毒灭菌装置和方法 |
DE102015207228A1 (de) * | 2015-04-21 | 2016-10-27 | Vetter Pharma-Fertigung GmbH & Co. KG | Primärpackmittel und Verfahren zur Herstellung eines Primärpackmittels |
-
2016
- 2016-06-01 US US15/169,962 patent/US20170349313A1/en not_active Abandoned
-
2017
- 2017-05-22 BR BR112018074925-7A patent/BR112018074925B1/pt active IP Right Grant
- 2017-05-22 NZ NZ748836A patent/NZ748836A/en unknown
- 2017-05-22 MX MX2018014633A patent/MX2018014633A/es unknown
- 2017-05-22 WO PCT/US2017/033719 patent/WO2017209998A1/en unknown
- 2017-05-22 CA CA3026404A patent/CA3026404A1/en active Pending
- 2017-05-22 CN CN201780033848.6A patent/CN109414518A/zh active Pending
- 2017-05-22 EP EP17807234.4A patent/EP3463490B1/en active Active
- 2017-05-22 AU AU2017273335A patent/AU2017273335B2/en active Active
- 2017-05-22 JP JP2018563068A patent/JP7187321B2/ja active Active
-
2022
- 2022-06-22 AU AU2022204394A patent/AU2022204394B2/en active Active
- 2022-07-01 US US17/855,912 patent/US11958647B2/en active Active
-
2024
- 2024-03-22 US US18/613,254 patent/US20240262554A1/en active Pending
- 2024-05-22 AU AU2024203424A patent/AU2024203424A1/en active Pending
Patent Citations (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3630665A (en) * | 1966-06-30 | 1971-12-28 | Andersen Prod H W | Method of sterilization |
US3878664A (en) * | 1972-11-27 | 1975-04-22 | Cybersol | Process for producing a therapeutic composition |
US3993751A (en) * | 1972-11-27 | 1976-11-23 | Cybersol, Inc. | Process for stabilizing therapeutic compositions and article |
US4018222A (en) * | 1975-02-10 | 1977-04-19 | Merck & Co., Inc. | Syringe containing frozen vaccine |
US5358475A (en) * | 1985-12-17 | 1994-10-25 | United States Surgical Corporation | High molecular weight bioresorbable polymers and implantable devices thereof |
US5061281A (en) * | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US4739881A (en) * | 1986-08-14 | 1988-04-26 | Beckton, Dickinson And Company | Quick open syringe |
US5382406A (en) * | 1990-04-17 | 1995-01-17 | Abbott Laboratories | Sterile filling method |
US5342673A (en) * | 1993-02-23 | 1994-08-30 | W. L. Gore & Associates, Inc. | Sterilizable packaging material |
US5620425A (en) * | 1993-11-03 | 1997-04-15 | Bracco International B.V. | Method for the preparation of pre-filled plastic syringes |
US5597530A (en) * | 1994-08-18 | 1997-01-28 | Abbott Laboratories | Process for prefilling and terminally sterilizing syringes |
US6189195B1 (en) * | 1995-08-22 | 2001-02-20 | Medrad, Inc. | Manufacture of prefilled syringes |
US6164044A (en) * | 1998-03-13 | 2000-12-26 | Becton Dickinson And Company | Method and apparatus for assembling and packaging medical devices |
US6475140B1 (en) * | 1998-05-29 | 2002-11-05 | Acmi Corporation | Flexible pressure resistant cover for the articulation system of a medical instrument |
US6231810B1 (en) * | 1999-04-21 | 2001-05-15 | Stryker Technologies Corporation | Special cycle for ethylene oxide sterilization |
US6488890B1 (en) * | 1999-08-05 | 2002-12-03 | 3M Innovative Properties Company | Machine readable sterilization indicator for monitoring articles to be sterilized |
US20020051730A1 (en) * | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
US20020172615A1 (en) * | 2001-03-08 | 2002-11-21 | Archie Woodworth | Apparatus for and method of manufacturing a prefilled sterile container |
US20030159969A1 (en) * | 2002-02-28 | 2003-08-28 | Kimberly-Clark Worldwide, Inc. | Surgical kit with multiple planar recess surfaces |
US20060260967A1 (en) * | 2003-01-27 | 2006-11-23 | Frank Clarke | Packaging for stent delivery systems |
US20040187438A1 (en) * | 2003-03-25 | 2004-09-30 | Frank Clarke | Packaging for stents and stent delivery system |
US20070048251A1 (en) * | 2005-08-24 | 2007-03-01 | Arthur Samuel D | Methods for sealing an orifice in tissue using an aldol-crosslinked polymeric hydrogel adhesive |
US20070048337A1 (en) * | 2005-08-24 | 2007-03-01 | Arthur Samuel D | Aldol-crosslinked polymeric hydrogel adhesives |
US20070082859A1 (en) * | 2005-10-07 | 2007-04-12 | Stover Richard R | Formulations of AICA riboside |
US20080081763A1 (en) * | 2006-09-28 | 2008-04-03 | Swetlin Brian J | Polyester Compositions, Methods of Manufacturing Said Compositions, and Articles Made Therefrom |
US20100313962A1 (en) * | 2006-09-29 | 2010-12-16 | Tyco Healthcare Group Lp | System and method for recycling sterilant gas |
US20100112063A1 (en) * | 2007-06-28 | 2010-05-06 | Figuly Garret D | Method for preparing a hydrogel adhesive having extended gelation time and decreased degradation time |
US20120035129A1 (en) * | 2009-04-09 | 2012-02-09 | Actamax Surgical Materials Llc | Hydrogel tissue adhesive having reduced degradation time |
US20120094955A1 (en) * | 2009-04-09 | 2012-04-19 | Actamax Surgical Materials Llc | Method of dissolving an oxidized polysaccharide in an aqueous solution |
US20100331864A1 (en) * | 2009-06-30 | 2010-12-30 | Shetty Dhanuraj S | Device for Repair of Urological Structures |
US20130032967A1 (en) * | 2010-05-07 | 2013-02-07 | Abbott Cardiovascular Systems Inc. | Cold ethylene oxide sterilization of a biodegradable polymeric stent |
US20120121532A1 (en) * | 2010-06-01 | 2012-05-17 | Baxter Healthcare S.A. | Process for making dry and stable hemostatic compositions |
US20130110025A1 (en) * | 2010-07-14 | 2013-05-02 | Hemcon Medical Technologies (Ip) Limited | Dressing device for use wtih a cannula or a catheter |
US20130103023A1 (en) * | 2011-10-24 | 2013-04-25 | Ethicon Endo-Surgery, Inc. | Litz wire battery powered device |
US20140342954A1 (en) * | 2012-01-10 | 2014-11-20 | President And Fellows Of Harvard College | Modification of surfaces for fluid and solid repellency |
US20130280346A1 (en) * | 2012-04-19 | 2013-10-24 | C. R. Bard, Inc. | Infusates with Enhanced pH Stability Under Ethylene Oxide Sterilization |
US20130296779A1 (en) * | 2012-05-07 | 2013-11-07 | Centurion Medical Products Corporation | Prefilled container systems |
US20140262883A1 (en) * | 2013-03-14 | 2014-09-18 | Becton Dickinson France S.A.S. | Packaging system for oxygen-sensitive drugs |
US20160200461A1 (en) * | 2013-08-16 | 2016-07-14 | Vanrx Pharmasystems Inc. | Method, device and system for filling pharmaceutical containers |
US20150306282A1 (en) * | 2014-04-28 | 2015-10-29 | John James Scanlon | Bioresorbable Stent |
US20170333641A1 (en) * | 2014-10-30 | 2017-11-23 | Hoffmann-La Roche Inc. | Syringe and method of preparing syringe |
US20160135895A1 (en) * | 2014-11-07 | 2016-05-19 | Corium International, Inc. | Medical device packaging |
US20180105294A1 (en) * | 2016-10-13 | 2018-04-19 | Bourjois Abboud | Methods and systems for prefilling syringes |
Non-Patent Citations (11)
Title |
---|
0.9% Sodium Chloride Injection, USP, June 2014, Hospira Inc. * |
AAMI, AAMI TIR56: 2013 Guidance for the development, validation and routine control of an ethylene oxide sterilization process utilizing flexible bag systems for the sterilization of medical devices, December 27, 2013, Association for the ADvancement of Medical Instrumentation * |
Bateman, Relative Humidity and the Killing of Bacteria, May 10, 1961 * |
Daryl L. Woodman, Determination of Spore Lethality at low Ethylene Oxide Gas Concentrations at Atmospheric Pressure, July 7, 2011, Andersen Scientific Inc. * |
Ernst, Ethylene Oxide Gaseous Sterilization for Industrial Applications, 1972, Duke University Press * |
Federal Register, Vol. 43, NO.122, June 23, 1978, pages 27474-27480 * |
Food Safety and Inspection Service, Food Safety Information, October 2011, USDA * |
Gisela C.C. Mendes, Ethylene oxide sterilization of medical devices: A review, November 2007, AJIC: American Journal of Infection Control, Federal Register, Vol. 43, NO.122 * |
Lucas, REsidual Ethylene Oxide in Medical Devices and Device Material, January 8, 2003 * |
MD+DI, EtO Sterilization: Principles of Process Design, December 1, 1998, Medical Device and Diagnostic Industry, https://www.mddionline.com/eto-sterilization-principles-process-design * |
Office of Air Quality PLanning and Standards, Ethylene Oxide Commercial Sterilization and Funigation Operations Neshap Implementation Document, March 2004, EPA * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10780228B2 (en) | 2012-05-07 | 2020-09-22 | Medline Industries, Inc. | Prefilled container systems |
US11786664B2 (en) | 2012-05-07 | 2023-10-17 | Medline Industries, Lp | Prefilled container systems |
JP7510952B2 (ja) | 2019-04-24 | 2024-07-04 | アムジエン・インコーポレーテツド | シリンジ滅菌確認アセンブリ及び方法 |
CN113491784A (zh) * | 2020-04-03 | 2021-10-12 | 清华大学 | 一种利用环氧乙烷对医疗防护用品进行高效灭菌及强化解析的方法 |
CN112773918A (zh) * | 2020-12-23 | 2021-05-11 | 北京伏尔特技术有限公司 | 一种环氧乙烷灭菌后快速解析工艺 |
WO2023113842A1 (en) * | 2021-12-13 | 2023-06-22 | Thorne Intellectual Property Holdings, Llc | Closed convenience kits for sterilized medicine preparation |
Also Published As
Publication number | Publication date |
---|---|
EP3463490A1 (en) | 2019-04-10 |
US20220332453A1 (en) | 2022-10-20 |
WO2017209998A1 (en) | 2017-12-07 |
NZ748836A (en) | 2024-05-31 |
EP3463490A4 (en) | 2020-10-14 |
JP2019519298A (ja) | 2019-07-11 |
AU2017273335A1 (en) | 2018-12-13 |
US20240262554A1 (en) | 2024-08-08 |
US11958647B2 (en) | 2024-04-16 |
CN109414518A (zh) | 2019-03-01 |
BR112018074925A2 (pt) | 2019-03-12 |
AU2017273335B2 (en) | 2022-03-24 |
AU2022204394A1 (en) | 2022-07-14 |
CA3026404A1 (en) | 2017-12-07 |
AU2022204394B2 (en) | 2024-02-22 |
EP3463490B1 (en) | 2024-10-23 |
AU2024203424A1 (en) | 2024-06-13 |
JP7187321B2 (ja) | 2022-12-12 |
MX2018014633A (es) | 2019-07-18 |
BR112018074925B1 (pt) | 2022-10-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11958647B2 (en) | Methods for manufacturing non-glass prefilled syringes | |
US11786664B2 (en) | Prefilled container systems | |
US20200246533A1 (en) | Medical apparatus and method for sterilizing medical apparatus | |
US20200297919A1 (en) | Prefilled syringe and method of preparing a prefilled syringe | |
US20230310681A1 (en) | Prefilled syringe and method of preparing a prefilled syringe | |
JP2023505488A (ja) | 注射器および気密性の試験方法 | |
JP2021511906A (ja) | プレフィルドシリンジおよびプレフィルドシリンジを滅菌する方法 | |
US20050150855A1 (en) | Medicament container |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: CENTURION MEDICAL PRODUCTS CORPORATION, MICHIGAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KUEHNE, KELLEY;CARPENTER, CURT;LEGINSKI, JESSICA;SIGNING DATES FROM 20160907 TO 20160908;REEL/FRAME:039697/0670 |
|
AS | Assignment |
Owner name: MEDLINE INDUSTRIES, INC., ILLINOIS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CENTURION MEDICAL PRODUCTS COMPANY;REEL/FRAME:048032/0072 Effective date: 20190103 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
AS | Assignment |
Owner name: MEDLINE INDUSTRIES, INC., ILLINOIS Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE CENTURION MEDICAL PRODUCTS COMPANY TO CENTURION MEDICAL PRODUCTS CORPORATION PREVIOUSLY RECORDED ON REEL 048032 FRAME 0072. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT;ASSIGNOR:CENTURION MEDICAL PRODUCTS CORPORATION;REEL/FRAME:051855/0258 Effective date: 20191021 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE AFTER FINAL ACTION FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: AMENDMENT AFTER NOTICE OF APPEAL |
|
STCV | Information on status: appeal procedure |
Free format text: NOTICE OF APPEAL FILED |
|
STCV | Information on status: appeal procedure |
Free format text: APPEAL BRIEF (OR SUPPLEMENTAL BRIEF) ENTERED AND FORWARDED TO EXAMINER |
|
STCV | Information on status: appeal procedure |
Free format text: EXAMINER'S ANSWER TO APPEAL BRIEF MAILED |
|
STCV | Information on status: appeal procedure |
Free format text: ON APPEAL -- AWAITING DECISION BY THE BOARD OF APPEALS |
|
AS | Assignment |
Owner name: MEDLINE INDUSTRIES, LP, ILLINOIS Free format text: CHANGE OF NAME;ASSIGNOR:MEDLINE INDUSTRIES, INC.;REEL/FRAME:057970/0098 Effective date: 20210907 |
|
AS | Assignment |
Owner name: BANK OF AMERICA, N.A., TEXAS Free format text: SECURITY INTEREST;ASSIGNOR:MEDLINE INDUSTRIES, LP;REEL/FRAME:058040/0001 Effective date: 20211021 Owner name: WILMINGTON TRUST, NATIONAL ASSOCIATION, MINNESOTA Free format text: SECURITY INTEREST;ASSIGNOR:MEDLINE INDUSTRIES, LP;REEL/FRAME:057927/0091 Effective date: 20211021 |
|
STCV | Information on status: appeal procedure |
Free format text: BOARD OF APPEALS DECISION RENDERED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- AFTER EXAMINER'S ANSWER OR BOARD OF APPEALS DECISION |