GB1569479A

GB1569479A - Sterile artifical kidney dialyzer package

Info

Publication number: GB1569479A
Application number: GB15154/77A
Authority: GB
Original assignee: Cordis Dow Corp
Current assignee: Althin Medical Inc
Priority date: 1976-04-13
Filing date: 1977-04-12
Publication date: 1980-06-18
Also published as: IT1115942B; DE2716178A1; ES468608A1; NL7703779A; JPS52126387A; AU512892B2; CA1142893A; FR2348109B1; ES457663A1; BE853500A; FR2348109A1; CH613422A5; AU2414277A

Abstract

The dialyser package comprises a sterile dialyser (2) in a gas-impermeable casing (9). The inside of the casing (9) and the dialyser (2) are free of sterilising medium and have an air-free CO2 gas atmosphere. For production, the dialyser (2) is arranged in an inner casing (7), which has a gas-permeable zone (10). This arrangement is sterilised and arranged in the casing (9). By evacuation the gas atmosphere is removed from the dialyser (2) and the gas-permeable, inner casing (7) and is then replaced by a CO2 gas atmosphere. The casing (9) is then sealed in a gastight manner. The dialyser package enables the dialyser (2) to be used without problems, and it is possible to dispense with the previously necessary CO2 flushing procedure. <IMAGE>

Description

(54) STERILE ARTIFICAL KIDNEY DIALYZER PACKAGE (71) We, CORDIS Dow CORPORATION, a Corporation organised and existing under the laws of the State of Delaware, United States of America, of 999 Brickell Avenue, Miami, County of Dade, State of Florida, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to a sterile package containing an artificial kidney dialyzer in controlled atmosphere.

Articles such as dry type artificial kidney dialyzers utilizing permeable hollow fibre membranes are typically sterilized with ethylene oxide and, after sterilization, the ethylene oxide gas in the dialyzer is completely replaced with aseptic air during an outgassing period. Prior to dialysis, the dialyzer must be cleared of air and primed.

In such procedures, the air is flushed from the dialyzer and blood lines by passing a saline solution through the dialyzer. Typically, a dialyzer undergoing priming requires a great deal of sharp rapping on the dialyzer itself, on the drip chambers and on the blood lines to effectively clear tiny air bubbles therefrom. Often, the quantity of saline solution utilized and the attention needed to prime a dialyzer requires a substantial amount of time by skilled personnel and thus substantially increases the time needed for dialvzation of each patient.

Moreover, it is believed that the sharp rappings required to clear any air bubbles from the dialyzer may itself be the cause of damage to the membranes, and the creation of leaks in the dialyzer thereby destroying the useability of the dialyzer.

In another procedure attempted for priming a dry, air-filled dialyzer, the arterial blood line connected to the dialyzer is connected to a CO2 cylinder and the dialyzer flushed for 4-5 minutes with CO2 to clear the air from the dialyzer and blood lines.

The dialyzer is then primed in a procedure similar to the one set forth above.

While it has been found that a dialyzer flushed first with CO2 generally can be primed more easily and in a shorter period of time in comparison with an air-filled dialyzer, the above CO2 flush procedure is disadvantageous in certain other respects.

Thus, even though the priming time with a saline rinse solution can be decreased, additional time and hence expense is required for the individual or clinic technician to connect and flush the dialyzer with CO2.

Extra space for cylinders of CO2 must also be provided and an adequate supply of CO2 kept on hand. Additionally, this priming procedure increases the risk of contamination of the dialyzer because of the extra connections necessary to complete the priming of the dialyzer. These factors all clearly negate whatever advantage may have been gained in priming ease and time.

According to the present invention there is provided a package comprising an artificial kidney dialyzer having a plurality of permeable hollow fibers and a gas-impermeable enclosure, said dialyzer being sterile and enclosed in said enclosure, said dialyzer and said enclosure being free of sterilant and containing a controlled atmosphere therein.

Such a package can be produced by (a) placing an artificial kidney dialyzer having a plurality of permeable hollow fibers within an open enclosure comprising a gasimpermeable material, (b) sterilizing said dialyzer and said enclosure, (c) evacuating the atmosphere from said dialyzer and said enclosure, (d) passing a controlled atmosphere into said dialyzer and said enclosure, and (e) sealing said enclosure thereby forming a gas-impermeable package.

In an alternative method a dialyzer which has previously been sterilized is placed in the open enclosure, and accordingly step (b) is omitted.

A package in accordance with the present invention can also be produced by (a) sealing an artificial kidney dialyzer having à plurality of permeable hollow fibers in an enclosure comprising a gas-impermeable material and having a gas-permeable zone, (b) sterilizing said dialyzer and said enclosure, (c) evacuating the atmosphere from said dialyzer and said enclosure, (d) passing a controlled atmosphere into said dialyzer and said enclosure, and (e) sealingly dividing the package into a first section containing the gas-permeable zone and a second section containing the dialyzer, and optionally (f) separating said first section from said second section. If the first section is not separated from the second section the gas-impermeable enclosure in the package will be sealingly divided from the enclosure comprising the gas-permeable zone. Such a package forms a further aspect of the present invention.

According to yet a further aspect of the present invention there is provided a package comprising an outer gas-impermeable enclosure, an inner enclosure comprising a gas-permeable material and enclosed within said outer enclosure, and an artificial kidney dialyzer having a plurality of permeable hollow fibers and enclosed within said inner enclosure, each of said dialyzer, said inner enclosure and said outer enclosure being free of sterilant and containing a controlled atmosphere therein.

Such a package can be produced by (a) sealing an artificial kidney dialyzer having a plurality of permeable hollow fibers in a first enclosure which is permeable to gas, (b) sterilizing said dialyzer and said first enclosure, (c) enclosing said sealed dialyzer within a second enclosure which when sealed is impermeable to gas, (d) evacuating the atmosphere from said dialyzer, said first enclosure and said second enclosure, (e) passing a controlled atmosphere into said second enclosure, said first enclosure and said dialyzer, and (f) sealing said second enclosure, thereby forming a gas-impermeable package.

In an alternative method steps (a), (b) and (c) are replaced by the single step of placing a previously sterilized dialyzer enclosed in a gas-permeable first enclosure in a second enclosure which when sealed is impermeable to gas.

The present invention will be further described by way of specific example and with reference to the accompanying drawings in which: Figure 1 is a plan view of a sealed, gasimpermeable artificial kidney dialyzer package showing in phantom lines a dialyzer retained therein.

Figure 2 is a plan view of a sealed, gasimpermeable artificial kidney dialyzer package showing in phantom lines a dialyzer contained therein.

Figure 3 is a flow diagram illustrating the method steps in preparing a single package artificial kidney dialyzer.

Figure 4 is a flow diagram illustrating the method steps in preparing a double package dialyzer as illustrated in Figure 2.

fn each drawing the dialyzer shown is one having a plurality of permeable hollow fibres.

By preferred methods of this invention there are obtained an artificial kidney dialyzer packaged in a material which is impermeable to gas. The package, including the dialyzer, contains a controlled atmosphere which enables the priming of the dialyzer to be commenced without the need for pre-flushing procedures and which greatly increases the ease of dialyzer prim ing. In a particular embodiment a dialyzer is enclosed in a first gas-permeable enclosure or gas-impermeable enclosure bearing a zone of gas-permeability, which in turn is enclosed in a second outer gas-impermeable package.

Figure 1 illustrates a packaged and sealed dialyzer (1) which comprises a hollow fibre kidney dialyzer (2) having dialysate inlet and outlet ports (3) and (4) and blood inlet and outlet ports (5) and (6) which is enclosed in a gas-impermeable enclosure (7).

The package, i.e., the enclosure and dialyzer, is sealed and contains a controlled atmosphere therein. This particular package is also referred to as a "single package" dialyzer.

Figure 2 illustrates a sealed packaged dialyzer (8) comprising in combination an outer enclosure (9) of a gas-impermeable material and an inner sealed enclosure (7) having a dialyzer (2) placed therein. The inner enclosure is permeable to gas or, as illustrated, is made of gas-impermeable material containing a gas-permeable zone (10). The package, i.e., the outer and inner enclosures and dialyzer, contains a controlled atmosphere. Such packaging is also referred to as a "double packed" dialyzer.

A method of preparing a package dialyzer is illustrated in the flow diagram of Figure 3, where a gas-impermeable package containing a dialyzer and a controlled atmosphere, is prepared by the following steps: (a) sealing a dialyzer (2) in an enclosure (7) comprising a material which is impermeable to gas and is provided with a gas-permeable zone (10), (b) sterilizing the dialyzer (2) and the enclosure (7), (c) evacuating the atmosphere from the dialyzer (2) and the enclosure (7), (d) passing a controlled atmosphere into the dialyzer (2) and the enclosure (7), and (e) sealing dividing the package (11) along line 12-12 into a first section (13) containing the gas-per meable zone (10) and a second section containing the dialyzer. If desired, the first section (13) can be separated from the second section, thereby forming a gas-impermeable package (1) containing the dialyzer (2) and a controlled atmosphere.

In a further embodiment (not illustrated), a packaged dialyzer may be prepared by the steps of: (a) placing a sterilized dialyzer, having inlet and outlet ports which are capped with a permeable material to constitute gas-permeable zones within an open enclosure comprising a gas-impermeable material, (b) evacuating the atmosphere from the dialyzer and enclosure, (c) passing a controlled atmosphere into the dialyzer and enclosure, and (d) sealing the enclosure, thereby forming a gas-impermeable package containing the dialyzer and a controlled atmosphere.

As illustrated in the flow diagram of Figure 4, a packaged dialyzer is prepared by the steps of: (a) sealing the dialyzer (2) in a first enclosure (7) comprising a gas-impermeable material and having a gas-permeable zone (10), (b) sterilizing the dialyzer and the first enclosure, (c) enclosing the sealed dialyzer (11) within a second sealable gas-impermeable enclosure (14) thereby forming an outer, open enclosure housing the sealed dialyzer, (d) evacuating the atmosphere from the gas-permeable enclosure, dialyzer and from the outer enclosure, (e) passing a controlled atmosphere into the outer enclosure and into the housed sealed dialyzer, and (f) sealing the outer enclosure (14), thereby forming a gas-impermeable package (15) containing the dialyzer and a controlled atmosphere In yet another embodiment (not illustrated), a packaged dialyzer may be prepared by the steps of: (a) placing a previously sterilized dialyzer enclosed in a first enclosure which is permeable to gas, in a second outer sealable enclosure which is gas-impermeable, (b) evacuating the atmosphere from the permeable enclosure, the dialyzer and from the outer enclosure, (c) passing a controlled atmosphere into the outer enclosure and into the permeable enclosure, and (d) sealing the outer enclosure, thereby forming a gas-impermeable package containing the dialyzer and a controlled atmosphere.

Dialyzers which are packaged according to the present invention can be any one of the dry type units. Multiple units can, of course, be contained within a single package, if desired.

By the term "dialyzer" as used herein is meant those devices useful for the dialyzation of blood. By the term "package" is meant a complete packaged dialyzer and the controlled atmosphere contained within the single or double enclosure and the dialyzer.

The term "controlled atmosphere" is used and is intended as a generic term to cover different gaseous substances which may be introduced into the dialyzer to create an aseptic atmosphere and which are acceptable for use in priming procedures for artificial kidney dialyzers. The controlled atmosphere contained in the package is preferably carbon dioxide.

By the term "gas-impermeable" is meant materials which are impermeable to the controlled atmosphere whilst by the term "gas-permeable" is meant enclosure materials which are permeable to the controlled atmosphere and sterilant.

The dry type dialyzers used herein are typically sterilized according to well-known procedures with a sterilizing agent such as ethylene oxide gas. The sterilization can take place with the single enclosure having a permeable zone or, in the double enclosure package concept, the inner packaged unit can be placed inside the outer open enclosure and the unit then sterilized. After sterilization, the ethylene oxide gas in the dialyzer unit is completely replaced, usually with aseptic air, during an "outgassing period". Typically, the artificial kidney dialyzers are outgassed for several days, e.g., as long as about 15-20 days, to insure that all ethylene oxide residues are removed.

Hence, as used herein, the term "sterilization" or "sterilizing" refers to the initial act of sterilization as well as any following period necessary to remove any toxic residues of sterilization material before the dialyzer and enclosure(s) are subsequently subjected to the evacuation step herein. Additionally, the atmosphere evacuated from the dialyzer and enclosure(s) in the methods claimed herein can be the sterilant gas and/or air. Radiation sterilization techniques which do not affect the dialyzer membranes may also be utilized and evacuation carried out without a waiting period or the controlled atmosphere directly passed into the dialyzer and enclosure(s). Dry type dialyzers sterilized by ethylene oxide, radiation or other means and having the inlet and outlet ports covered with a gas-permeable material, e.g., insert, cap, etc., can be placed in an open enclosure of a gasimpermeable material and the dialyzer and enclosure evacuated (or first sterilized if desired), filled with a controlled atmosphere and then the enclosure sealed.

With respect to the gas-impermeable packaging materials from which the enclosures herein are prepared, sealable flexible or rigid materials, also generally impermeable to moisture, are utilized. Suit able gas-impermeable materials include, for example, synthetic plastic laminates, metal foils, or laminates or films having barrier layers of metal, e.g., foils. MYLAR (registered Trade Mark) is a well-known polyester film which can be conventionally coated with a metal foil barrier. Other materials, such as, for example, laminations of polyesters and poly ethylene and a co-extrusion of nylon and SURLYN (registered Trade Mark) are also available. Enclosures comprising a laminated polyethylene and SURLYN material constitute a preferred embodiment. Also, other materials such as polyethylene, could be employed as gas-impermeable materials provided sufficient thicknesses thereof are utilized. However, these generally are disadvantageous from a coat viewpoint and relatively inexpensive, thin laminates are available. A laminate material of MYLAR, low density polyethylene and SURLYU containing a metal foil barrier is particularly preferred.

Gas-impermeable enclosures can also be prepared with some of the above mentioned materials which are thermo-formable and other materials such as, for example, polypropylene or styrene. The thermo-formed enclosure can typically have a suitable barrier coating which is impermeable to the controlled atmosphere, if necessary. These and various other materials which can be used as the gas-impermeable enclosure, as well as techniques for varying enclosure thicknesses or barrier coatings to control permeability, will be readily apparent to those skilled in the art.

The inner enclosure of the double-packaged dialyzer and the gas-permeable material covering the ports of the dialyzer can be prepared from the same materials as the gas-permeable zone. Such materials should be permeable to sterilizing gases and the controlled atmosphere, and can be formed of materials such as permeable papers or plastics. The inner enclosure can also be prepared from the same gas-impermeable material as the outer enclosure as long as a gas-permeable zone is provided on the inner enclosure. Preferably, a gas-impermeable enclosure provided with a gaspermeable zone is utilized as the inner enclosure.

The gas-permeable materials, e.g., gaspermeable zones, are typically prepared from papers or synthetic plastic materials having a controlled porosity and being permeable to the sterilization gases and controlled atmosphere. Such papers or plastic materials also serve as microbial barriers to maintain the sterility or aseptic condition of the dialyzer. Materials of this type are available and include spun-bound polyolefins such as TYVEK (registered Trade Mark), and various controlled porosity papers. Those skilled in the art will recognize these and other materials which can be utilized for the purpose.

The gas-impermeable enclosure having a gas-permeables zone which is employed in preparing a single enclosure packaged dialyzer has the permeable zones located in an area where it can be readily sealed off and subsequently removed, if desired.

The size and shape of the inner or outer enclosures is not critical. They can take the shape of flexible bags, wraps, pouches, or rigid or semi-rigid canisters, or tubs. Flexible bags are preferably employed for ease in assembly and savings in cost. Relatively rigid, thermo-formed enclosures having a gas-permeable lidding may be desirable for protective purposes or for forming convenient, readily storable rigid containers. Where thermo-formed enclosures having a permeable zone are employed, flexible or thermo-formed, gas -impermeable materials can also be placed over the permeable zone in a sealing relationship with the gas-impermeable package containing therein a dialyzer and a controlled atmosphere. All of the enclosures are readily sealable and typically have means provided in the package for ease in opening the sealed package. The enclosures are preferably of sufficient strength to resist abrasive ripping, puncturing or the like.

Typically, an artificial kidney dialyzer utilizing hollow fibre membranes is packaged in an inner enclosure comprising a bag (prepared from a laminate material of low density polyethylene and SURLYN) being about 36 cm. long and about 17 cm. wide. The bag contains a gas-permeable zone of spun polyolefin material (TYVEK) of about 7.60 cm. in diameter. The outer gas-impermeable enclosure is of the same material and is slightly larger (about 40 cm. by about 19.5 cm.) to accommodate the dialyzer within the inner package.

Where the dialyzer is to be enclosed within a single enclosure, a bag about 48 cm. long and having a 7.60 cm, diameter gas-permeable zone (TYVEK) so located that it can be sealed off from the rest of the package containing the dialyzer, can be utilized. The gas-permeable area is preferably located at one end of the enclosure, an excess enclosure area of about 12.70 cm. is provided for the permeable zone. Once the bag is sealed, the steps of sterilization, evacuation and filling of the bag with the controlled atmosphere are carried out through the permeable zone. Once the controlled atmosphere is introduced into the package, a second seal dividing the package into two sections is made across the bag between the dialyzer and the area containing the permeable zone so that the permeable zone is completely sealed off from the rest of the package containing the dialyzer, which is thus isolated within a gasimpermeable bag. The section containing the permeable zone can be removed from the packaged dialyzer if desired but this is not necessary.

Those skilled in the art will recognize that many variations in the bags or enclosures and location, type and size of the permeable zone on the bag or enclosure can be made in providing the various embodiments of dialyzers containing a controlled atmosphere disclosed herein. The steps of initially sealing, sterilizing, evacuating, filling with a controlled atmosphere and subsequent sealing for either the single or double enclosed dialyzers and variations thereof will also be readily apparent and can be carried out by those skilled in the art of packaging.

While these steps can be manually carried out with each unit, semi-automated procedures can also be utilized. For example, multiple packaged units (e.g., single or double packaged sterilized dialyzers) can readily be evacuated, filled with a controlled atmosphere and sealed to form a gas-impermeable package by use of a vacuum and gas backfill packaging machine. In typical operations, three sterilized dialyzers individually packaged in an inner bag of a gas impermeable material and bearing a gas-permeable zone and an outer open bag of a gas-impermeable material are placed within the vacuum chamber of the machine and the bags and dialyzers are evacuated under a reduced pressure of about 29 inches of mercury. The evacuation period is usualy about 60 seconds but shorter or longer periods may be necessary depending upon conditions such as dialyzer sizes and configurations. Carbon dioxide gas is then injected into the chamber, completely flooding the dialyzers and inner and outer bags. The pressure of the CO, is maintained at about atmospheric. Once the chamber is completely flooded with CO, the outer open bags are sealed with an impulse sealing mechanism contained in the chamber. The chamber is then vented to remove excess CO, before the sealed gas-impermeable packaged dialyzers containing the CO, are removed therefrom.

More particularly, the present invention provides a new, packaged kidney dialyzer containing a controlled atmosphere which will enable the priming of the dialyzer, e.g., with a saline solution rinse, to be instituted and completed in a quick, convenient manner without increasing the risks of contamination.

WHAT WE CLAIM IS: - 1. A package comprising an artificial kidney dialyzer having a plurality of permeable hollow fibers and a gas-impermeable enclosure, said dialyzer being sterile and enclosed in said enclosure, said dialyzer and said enclosure being free of sterilant and containing a controlled atmosphere therein.

2. A package as claimed in claim 1 in which said enclosure is sealingly divided from an enclosure comprising a gas-impermeable material and containing a gas-permeable zone.

3. A package comprising an outer gasimpermeable enclosure, an inner enclosure comprising a gas-permeable material and enclosed within said outer enclosure, and an artificial kidney dialyzer having a plurality of permeable hollow fibers and enclosed within said inner enclosure, each of said dialyzer, said inner enclosure and said outer enclosure being free of sterilant and containing a controlled atmosphere therein.

4. A package as claimed in claim 3 in which said inner enclosure consists of a gas-permeable material.

5. A package as claimed in claim 3 in which said inner enclosure comprises a gasimpermeable material and contains a gaspermeable zone.

6. A package as claimed in any one of the preceding claims in which the gas-impermeable material is a sealable, and flexible or rigid material.

7. A package as claimed in claim 6 in which the gas-impermeable material is a thermo-formable synthetic resinous material or a laminate comprising a thermoplastic synthetic resinous material layer and a metal barrier layer.

8. A package as claimed in claim 7 in which the gas-impermeable material is a laminate comprising a polyester film layer, a low density polyethylene layer, a metal barrier layer, and a layer of a polymeric resin ionomer of ethylene.

9. A package as claimed in claim 1 in which said dialyzer has inlet and outlet ports capped with a gas-permeable material.

10. A package as claimed in claim 3 in which the inner enclosure is formed from a thermo-formed base bearing a gas-permeable lid.

11. A package as claimed in any one of claims 2 to 9 in which the gas-permeable material, when present, is a controlled porosity paper or plastics material which serves as a microbial barrier.

12. A package as claimed in any one of the preceding claims in which the controlled atmosphere is carbon dioxide.

13. A package as claimed in claim 1 substantially as hereinbefore described with reference to and as illustrated in Figure 1 or Figure 2 of the accompanying drawings.

14. A method of producing a package

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. the rest of the package containing the dialyzer, which is thus isolated within a gasimpermeable bag. The section containing the permeable zone can be removed from the packaged dialyzer if desired but this is not necessary. Those skilled in the art will recognize that many variations in the bags or enclosures and location, type and size of the permeable zone on the bag or enclosure can be made in providing the various embodiments of dialyzers containing a controlled atmosphere disclosed herein. The steps of initially sealing, sterilizing, evacuating, filling with a controlled atmosphere and subsequent sealing for either the single or double enclosed dialyzers and variations thereof will also be readily apparent and can be carried out by those skilled in the art of packaging. While these steps can be manually carried out with each unit, semi-automated procedures can also be utilized. For example, multiple packaged units (e.g., single or double packaged sterilized dialyzers) can readily be evacuated, filled with a controlled atmosphere and sealed to form a gas-impermeable package by use of a vacuum and gas backfill packaging machine. In typical operations, three sterilized dialyzers individually packaged in an inner bag of a gas impermeable material and bearing a gas-permeable zone and an outer open bag of a gas-impermeable material are placed within the vacuum chamber of the machine and the bags and dialyzers are evacuated under a reduced pressure of about 29 inches of mercury. The evacuation period is usualy about 60 seconds but shorter or longer periods may be necessary depending upon conditions such as dialyzer sizes and configurations. Carbon dioxide gas is then injected into the chamber, completely flooding the dialyzers and inner and outer bags. The pressure of the CO, is maintained at about atmospheric. Once the chamber is completely flooded with CO, the outer open bags are sealed with an impulse sealing mechanism contained in the chamber. The chamber is then vented to remove excess CO, before the sealed gas-impermeable packaged dialyzers containing the CO, are removed therefrom. More particularly, the present invention provides a new, packaged kidney dialyzer containing a controlled atmosphere which will enable the priming of the dialyzer, e.g., with a saline solution rinse, to be instituted and completed in a quick, convenient manner without increasing the risks of contamination. WHAT WE CLAIM IS: -

1. A package comprising an artificial kidney dialyzer having a plurality of permeable hollow fibers and a gas-impermeable enclosure, said dialyzer being sterile and enclosed in said enclosure, said dialyzer and said enclosure being free of sterilant and containing a controlled atmosphere therein.

14. A method of producing a package

as claimed in claim 1, which method comprises (a) placing an artificial kidney dialyzer having a plurality of permeable hollow fibers within an open enclosure comprising a gas-impermeable material, (b) sterilizing said dialyzer and said enclosure (c) evacuating the atmosphere from said dialyzer and said enclosure, (d) passing a controlled atmosphere into said dialyzer and said enclosure, and (e) sealing said enclosure, thereby forming a gas-impermeable package.

15. A modification of the method as claimed in claim 14 in which said dialyzer is sterilized prior to its being placed in said open enclosure, and accordingly step (b) is omitted.

16. A method of producing a package as claimed in claim 1 or claim 2, which method comprises (a) sealing an artificial kidney dialyzer having a plurality of permeable hollow fibers in an enclosure comprising a gas-impermeable material and having a gas-permeable zone, (b) sterilizing said dialyzer and said enclosure, (c) evacuating the atmosphere from said dialyzer and said enclosure, (d) passing a controlled atmosphere into said dialyzer and said enclosure, and (e) sealingly dividing the package into a first section containing the gaspermeable zone and a second section containing the dialyzer, and optionally (f) separating said first section from said second section.

17. A method of producing a package as claimed in claim 3, which method comprises (a) sealing an artificial kidney dialyzer having a plurality of permeable hollow fibers in a first enclosure which is permeable to gas, (b) sterilizing said dialyzer and said first enclosure, (c) enclosing said sealed dialyzer within a second enclosure which when sealed is impermeable to gas, (d) evacuating the atmosphere from said dialyzer, said first enclosure and said second enclosure, (e) passing a controlled atmosphere into said second enclosure, said first enclosure and said dialyzer, and (f) sealing said second enclosure, thereby forming a gas-impermeable package.

18. A modification of the method as claimed in claim 17 in which steps (a), (b) and (c) are replaced by the single step of placing a previously sterilized dialyzer enclosed in a gas-permeable first enclosure in a second enclosure which when sealed is impermeable to gas.

19. A method as claimed in any one of claims 14 to 18 in which sterilization is effected with ethylene oxide.

20. A method as claimed in any one of claims 14 to 19 in which the controlled atmosphere is carbon dioxide.

21. A method as claimed in claim 16 substantially as hereinbefore described with reference to and as illustrated in Figure 3 of the accompanying drawings.

22. A method as claimed in claim 17 substantially as hereinbefore described with reference to and as illustrated in Figure 4 of the accompanying drawings.

23. A package which has been produced by a method as claimed in any one of claims 14 to 22.