GB2264936A - Sterilising container head - Google Patents

Abstract

The maintenance of sterility of sterile liquids e.g. drugs in containers during supply/removal of liquid to/from the containers, in particular by a transseptual technique, is enhanced by housing the head only of the container in an internal chamber 11 of a sterilisation body 10 to which sterilisation agent e.g. vapour followed by rinsing water and air is supplied. This sterilisation technique can be extended to tubes and/or needles utilised in supply/removal of such liquid to/from the container. When the liquid is toxic, a neutralising agent for a toxin may be subsequently supplied to the closed region. A sample needle 16 gains access through valved aperture 33 and advances through self sealing head 14 into container 15. A plurality of sterilisation bodies 10 may be mounted on the external side of a wall of a common sterilised chamber (41, Figure 4), access to the chamber being through an access panel (51, Figure 3). Each sample needle may be robotically controlled. Alternatively the sterilisation bodies may form part of an isolation unit consisting of two chambers (210, 220 Figure 6) within which liquid, eg from xoma nuts, may be dispensed into a container 290 through tube 270, the container centrifuged to separate out liquid phases and the desired phase withdrawn through needle 71. The container after removal from the chamber (220, Figure 6) may pass to a container washing chamber (320, Figure 7). <IMAGE>

Description

STERILISATION UNIT This invention relates to a sterilisation unit for sterilising containers, and particularly, but not exclusively, to a sterilisation unit for sterilising bottles for use in the pharmaceutical industry.

A necessary stage in the manufacture of drugs and other compositions in the pharmaceutical industry is the testing of the drug or composition to ensure the required level of sterility.

It is known to test, the sterility of a drug or other compound by placing the compound in a sterilised bottle, which is then sealed. In order to test the compound within the sealed bottle, a sample of the compound is removed transseptually, i.e. a needle is caused to enter through the sealed lid of the bottle in order to draw out a sample of the compound contained therein. The lid of the bottle is self sealing in that when the needle is removed from the bottle after taking the sample, the lid re-seals.

In order to ensure that the correct sterility reading is obtained, it is necessary to ensure that the outside surfaces of the bottle, particularly the area where the needle comes into contact with the bottle, are themselves thoroughly sterilised. If the outside of the bottle contains contaminants, these may give a misleading reading when a sample is analysed.

Typically, so called intravenous bottles are used to contain the samples of compounds. This is the type of bottle which is used in hospitals for the administration of intravenous drugs to patients.

It is known to sterilise the bottles by placing a plurality of bottles on a tray, and then placing trays of bottles into a sterilisation chamber.

A disadvantage of this known method of sterilising sample bottles is that particularly when intravenous bottles are used, the bottles are not capable of standing up on their own and so have to be supported by adjacent bottles. This means that adjacent bottles are in contact with one another, and this contact makes it more difficult to ensure thorough sterilisation.

In addition, the bottles are placed in a large chamber and a long dwell time is necessary in order to ensure sufficient sterilisation.

Further, high concentrations of sterilisation agent cannot be used due to the long dwell time, as polymerisation of the agent would occur.

Equally stringent requirements are associated with the handling of toxic liquids such as may be encountered in the pharmaceutical industry and whose existence outside a closed environment cannot be tolerated. The deactivation of any such material such as is likely to occur on the exterior of a container therefor which is to be handled is generally to be desired. The term "neutralisation" is used herein to denote such deactivation.

According to a first aspect of the present invention there is provided a sterilisation unit for use in the sterilisation of a container, the unit comprising a sterilisation body, an internal chamber within said body and having a container head receiving portion such that entry of the container head thereinto causes the container head to act as a closure to the internal chamber; and entry means to and exit means from the internal chamber for through passage of sterilisation agent to contact the container head therein.

The sterilisation unit according to the invention may also be used in connection with the handling of toxic materials.

The applicant has realised that it is necessary to sterilise only the head of a bottle from which a sample is to be taken, as this is the only area with which the sample needle will come into contact with the bottle.

Likewise, this is the only part of a bottle on which toxic fluid, which is likely to need to be treated with a neutralisation medium, is likely to be found.

Since it is only the head of the bottle which must now be sterilised optionally with there also being neutralisation of the toxic liquid which may be undergoing transfer, the bottle does not have to be placed in a large chamber. In addition, the time necessary for sterilising the head is very short, for example, a few minutes or less.

By means of the present invention therefore, it is possible to use highly concentrated sterilisation agent, because the problems of polymerisation do not occur, since the whole sterilisation process is achieved very quickly. In addition, the fact that the process is so very much shorter reduces the cost of the process.

Preferably, the sterilisation unit further comprises second entry and exit means for allowing entry and exit of a rinse solution through the chamber.

After the bottle head has been sterilised by the sterilisation agent, the rinse agent serves to rinse and remove remaining traces of the sterilisation agent from the head of the bottle.

Advantageously, the sterilisation unit further comprises third entry and exit means for allowing air to pass through the chamber. Preferably the air enters as blasts of air, and serves to dry the head of the bottle.

The sterilisation unit may further comprise fourth entry and exit means for allowing a neutralising agent as aforesaid to pass through the unit.

The second exit means may comprise the first exit means. In other words, the sterilisation agent and the rinse solution may exit the sterilisation unit via the same exit means.

According to a second aspect of the invention, there is provided a sterilisation and testing station comprising: a sterilisable chamber; at least one sterilisation unit according to the first aspect of the invention, the or each sterilisation unit being mounted to the outer surface of the wall of the sterilisable chamber ; and access means in said wall to said at least one sterilisation unit from within the sterilisation chamber.

The access means will generally be sufficient, at least, to allow a sample needle to enter the head of the bottle to remove liquid therefrom and even, as when handling toxic liquids, to supply liquid thereto in a transseptual filling operation.

In use, the head of a bottle is inserted into the container head receiving portion of the sterilisation unit. When the bottle head is in place, it is sealingly engaged with the bottle head receiving portion of the sterilisation unit. The bottle head is then sterilised by first of all passing the sterilisation agent through the internal chamber of the sterilisation unit,via the first entry and exit means.

The head of the bottle may then subsequently be rinsed and dried. A needle is then arranged to pass through the access means in the wall of the sterilisable chamber, and enters the head of the bottle. The sample may then be drawn from the bottle and the needle may be removed.

Advantageously, the head of the bottle is self sealing, in that after the needle has been removed from the head the bottle is re-sealed.

Advantageously, the access means comprises a valve, and control means for controlling the opening and closing of the valve.

Preferably, the control means comprises a solenoid which causes the access means to open when the sample needle is close to the access means and to close when the sample needle is being removed from the access means.

Advantageously, the sterilisation and testing station comprises a plurality of sterilisation units according to the first aspect of the invention. A plurality of bottles may thus be sterilised simultaneously.

Advantageously, the sample needle is a robotically controlled needle. The robot controlling the needle is preferably an xyz robot. The process of sterilisation and sample testing may thus be automated, which leads to further improvements in the efficiency of the process.

According to a third aspect of this invention, there is provided a method of sterilising an apparatus element associated with a liquid medium which is to be kept sterile, the element being the head of a container for the medium or means for introducing to or removing from the container a said liquid medium, which comprises carrying out introduction to or removal from the container of said liquid medium while the head of the container is located within the container head receiving portion of a sterilisation unit according to the first aspect of this inventionand, before and/or after said introducing or removing, exposing the apparatus element to a sterilisation agent while it is within the container head receiving portion.

The invention will now be further described by way of example only, with reference to the accompanying drawings in which: Figure 1 is a schematic diagram of a sterilisation unit according to a first aspect of the invention; Figure 2 is a cross-sectional representation of the sterilisation unit of Figure 1 at II-II therein; Figure 3 is a sterilisation and testing station according to a second aspect of the invention; and Figure 4 is a cross-sectional representation of the station of Figure 3 at IV-IV therein; Figure 5 is a schematic diagram of a method which may be carried out using a sterilisation unit according to the present invention; Figure 6 is a schematic representation of an isolation unit used to carry out the method of Figure 5 in an extracting mode; and Figure 7 is a schematic representation of the isolation unit of Figure 6 in a dispensing mode.

Referring to Figure 1 and 2, a sterilisation unit according to the first aspect of the invention is designated generally by the reference numeral 10. The unit 10 comprises an internal chamber 11 having a bottle head receiving portion 12. The bottle head receiving portion 12 is adapted to receive the head of an intravenous bottle, such that when the bottle is in place, the internal chamber 11 is sealed from the external environment. To effect the seal, a washer 13 is positioned in the bottle head receiving portion.

The unit 10 also comprises entry means 21 (Figure 2) through which a sterilisation agent such as peracetic acid may enter into the chamber 11. The sterilisation agent passes through the chamber and out via exit means 22. In passing through the chamber, the sterilisation agent sterilises the head 14 of the bottle 15. After the head 14 has been sterilised, water enters through second entry means 23 and passes out through exit means 22, in order to rinse the bottle head 14. Finally, blasts of air enter through third entry means 24 and exit via exit mean 25. The blasts of air serve to dry the head 14 of the bottle 15. The washing and drying procedures may be repeated. Once the bottle head 14 has been sterilised, a sample needle 16 is passed through the self sealing head 14, for example of the multipore type, of the bottle 15 in a manner which will be more fully described hereinbelow.The needle is used to draw out a sample of the compound, contained in the bottle in order that the sterility of the compound may be tested. Because the lid 14 of the bottle 15 has been completely sterilised, the chances of contaminants from the external surface of the bottle giving misleading test results, is reduced.

The sterilisation unit 10 may be used in a sterilisation and testing station, as shown in Figures 3 and 4 and designated generally by the reference numeral 30. The station 30 is mounted on a workbench 50 and comprises a plurality of units 10, each of which is mounted on the external side of a wall 31 of a sterilised chamber 41 having a common supply 25 for sterilising vapour. Ducts 21' to the right hand side of each unit 10 are for sterilising vapour, ducts 23' to the left hand side of each unit 10 are for washing water and ducts 22' from the bottom of each unit 10 lead to a drain for receiving sterilising vapour and washing water. Access to the interior of the chamber 41 is through a clamped-on access panel 51. The station includes environmental control equipment 52.

Associated with each unit 10 is a sample needle 16.

Each of the sample needles 16 is robotically controlled by an xyz robot 42 on a frame 43. Once the bottles 15 have been sterilised the needles 16 are caused to advance towards the units 10. The needle 16 can gain access to the units 10 through the wall 31, by means of an aperture 32 and a spring loaded valve 33 (see Figure 1). The spring of valve 33 is controlled by a solenoid 34 which acts on the spring and thus causes the valve to open when the needle 16 comes within a certain distance of the wall 31. The needle thus gains entry into the chamber 11 of the unit 10, and continues to advance through the self sealing head 14 of the bottle 15 in order to draw out a sample of the compound contained therein. The needle 16 is then caused to retreat back into the sterilised chamber 41.The self sealing head 14 of the bottle 15 re-seals, and the solenoid 34 causes the valve 33 to close once the needle 16 is clear of the unit 10.

Thus, by means of the present invention it is possible to automatically sterilise sample bottles 15, and then to draw a sample from the bottle. This results in a very efficient process.

It is known, for example, that drugs which are important in the treatment of cancer may be obtained from a naturally occurring berry known as the xoma nut.

The xoma nut contains a substance which is one of the most highly toxic naturally occurring substances known to man. It is thus highly important that the toxic liquid is treated with appropriate care. A flow scheme to illustrate the extraction of such drugs is shown in Figure 5.

In order to obtain the beneficial drug from the xoma nut, the nuts are initially placed in container 100 where they are processed in order to produce a liquid. Once the liquid has been produced within the container 100, the liquid is dispensed into a second container 110. The container 110 is then placed in a centrifuge 120 in order to separate out the beneficial drug from the toxic solution. The beneficial drug 130 is then extracted at 140, and may then be further processed in order to produce the desired drug.

Referring to Figure 6 an isolation unit for carrying out the process of Figure 5 is designated generally by reference number 200. The isolation unit 200 comprises a first isolation chamber 210 and a second isolation chamber 220. The chambers 210, 220 are isolated from the surrounding environment, but are not completely isolated from one another, in that access between the two chamber 210, 220 may be gained by a port 230. The second isolation chamber 220 comprises a pass-in port 240 and a pass-out port 250.

The pass-in port is used to place objects in the second isolation chamber 220 and the pass-out port 250 is used to remove articles from the second isolation chamber 220.

The environment within the isolation unit 200 is controlled by means of HEPA filters 260 and 261 for inflow and out-flow air respectively.

Liquid produced from xoma nuts in dispenser 100 (Figure 5), is dispensed by means of a tube 270 and stop tap 280 into a container 290, which has been placed in the second isolation chamber 220. When the desired amount of liquid has been dispensed into container 290, the tube 270 is withdrawn from the container 290 and sterilised in a sterilisation unit such as unit 10 as illustrated in Figure 1. The container 290 is attached to a centrifuge and once the liquid has been dispensed into the container 290, the container is processed by means of the centrifuge.

This has the effect of separating out liquid phases, one of which contains the desired drug and from which the desired drug will be extracted. The displacement of the tube 270 is controlled by a robotic arm 310.

Prior to and after supply of liquid, the tube 270 is held above a cover dish 291 having an absorbent filler to catch drips of toxic liquid.

Referring to Figure 7, the unit 200 is shown in an extracting mode. Once the toxic liquid has separated out, the desired solution phase may be removed from the container 290 through needle 71 and transfer tube 76 by peristaltic action of a peristaltic pump 78 and collected in container 77. The container 290 and the remaining liquid may then be disposed of in an appropriate manner, before the container 77 is removed from the first chamber 210 for further processing. A bottle wash chamber 320 for bottles removed from chamber 220 is shown.

The container 77 could even be placed in the second chamber 220.

In greater detail, the container 290 is attached to a sterilisation unit 230 according to the present invention. The needle 71 passes through the unit 230 and is sterilised. The needle 71 is lowered to a position just above the interphase level 72, i.e. just within the required liquid 73. The movement of the needle may be controlled in any desirable way, but in this example it is controlled by a sensor which senses the changes in the reflectivity of the different layers of liquid in the container 290.

The needle comprises an outer portion 74 and an inner portion 75 (see details shown in circles to enlarged scale indicating closed and retracted conditions of inner portion). When the needle has been moved to the appropriate level, the inner portion 75 is extended. Liquid 73 is extracted through the needle via a tube 76 and into a container 77. The liquid 73 is drawn out by the action of a peristaltic pump 77.

After extraction, the needle 71 passes through the sterilisation unit and is re-sterilised.

The sterilisation of needle 71 and tube 270 in the foregoing procedure may take place in the sterilisation unit 230 as withdrawal therethrough takes place.

Thus, by means of the present invention the whole process may be carried out within an overall isolation unit 200.

Moreover, in this extraction procedure, there is likely to be contamination of needle 71 and tube 270, as well as of the top of container 290 and the interior of the contamination unit itself by the liquid being treated. This contamination should be neutralised by supply of an appropriate neutralising agent to the exterior of these elements while they are located within the isolation unit. Additional entry and exit means therefor will be present in the isolation unit.

Each application of neutralisation agent will usually be followed by supply of washing agent and drying air in a procedure preferably repeated twice. When this is done, the cap can be safely removed from the container 290. Thus, there is protection of product from the operator and of the operator from the product.

Claims (20)

CLAIMS:

1. A sterilisation unit for use in the sterilisation of a container, the unit comprising a sterilisation body, an internal chamber within the said body and having a container head receiving portion such that entry of the container head thereinto causes the container head to act as a closure to the internal chamber; and entry means to and exit means from the internal chamber for through-passage of sterilisation agent to contact the container head therein.

2. A sterilisation unit as claimed in Claim 1, additionally comprising a source of sterilisation agent communicable with the said entry means.

3. A sterilisation unit as claimed in Claim 1 or 2, comprising additional entry means for fluid to and additional exit means for fluid from the internal chamber.

4. A sterilisation unit as claimed in Claim 3, additionally comprising a source of rinse solution communicable with additional entry means for fluid to the internal chamber.

5. A sterilisation unit as claimed in Claim 3 or 4, additionally comprising a source of air supply as air blasts to additional entry means to the internal chamber.

6. A sterilisation unit as claimed in Claim 3, 4 or 5, additionally comprising a source of neutralising agent for a toxic reagent communicating with additional entry means to the internal chamber.

7. A sterilisation unit as claimed in Claim 4, wherein entry means for sterilisation fluid and for rinse solution to the internal chamber are associated with common exit means from the internal chamber.

8. A sterilisation unit as claimed in Claim 1, substantially as hereinbefore described with reference to and as shown in Figures 1 and 2 of the accompanying drawings.

9. A sterilisation station comprising: a sterilisable chamber; at least one sterilisation unit according to any one of Claims 1 to 8, the or each sterilisation unit being mounted to the outer surface of a wall of the sterilisable chamber; and access means in said wall to said at least one sterilisation unit from within the sterilisable chamber.

10. A sterilisation station as claimed in Claim 9, which has associated therewith a needle for transseptual transfer of liquid into and/or out of a container whose head is located, in use, in the container head receiving portion.

11. A sterilisation station as claimed in Claim 10, comprising robotically controlled means for driving the needle through a closure in the container head and withdrawing it therefrom after said transfer has taken place.

12. A sterilisation station as claimed in Claim 10 or 11, in combination with at least one said closure, the closure being self re-sealing after removal of the needle therefrom.

13. A sterilisation station as claimed in any one of Claims 9 to 12, wherein the access means comprises a valve and control means for controlling the opening and closing of the valve.

14. A sterilisation station as claimed in Claim 13, wherein the control means comprises a solenoid which causes the access means to open and close on approach and removal respectively of the needle.

15. A sterilisation station, substantially as hereinbefore described with reference to and as shown in Figures 3 and 4 or Figures 6 and 7 of the accompanying drawings.

16. A method of sterilising an apparatus element associated with a liquid medium which is to be kept sterile, the element being the head of a container for the medium or means for introducing to or removing from the container a said liquid medium, which comprises carrying out introduction to or removal from the container of said liquid medium while the head of the container is located within the container head receiving portion of a sterilisation unit as claimed in any one of Claims 1 to 7 and, before and/or after said introducing or removing, exposing the apparatus element to a sterilisation agent while it is within the container head receiving portion.

17. A method as claimed in Claim 16, wherein, following exposure of the apparatus element to the sterilisation agent, the apparatus element is washed to remove residual sterilisation agent.

18. A method as claimed in Claim 16 or 17, which is carried out on a said container following removal from the container of a sterile sample for testing.

19. A method as claimed in Claim 16 or 17, which is carried out on an apparatus element, located in an isolation unit in which liquid transfer and/or phase separation take place of a toxic liquid and wherein after exposure of the apparatus element to sterilisation agent and while the apparatus element is still within the container head receiving portion, the apparatus element is contacted with a neutralisation agent to detoxify it with respect to such toxic liquid.

20. A method of sterilising an apparatus element, substantially as hereinbefore described with reference to Figures 6 and 7 of the accompanying drawings.