Isolator for sterile applications comprising a supply system for a nebulized decontaminating substance
Patent Information
- Application Number
- EP2024720878
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-03-28
- Filing Date
- 2024-03-27
- Publication Date
- 2026-02-11
AI Technical Summary
The existing methods for decontaminating pharmaceutical isolator work chambers using nebulized hydrogen peroxide face issues with non-uniform concentration and high-speed particle jets, leading to condensation and potential disruption of products, making the decontamination process longer and more difficult.
A pharmaceutical isolator design with a nebulizer nozzle positioned in an interspace separate from the work chamber, generating a nebulized decontaminating substance jet at reduced speed, which enters the chamber through a delivery opening, minimizing condensation and product disturbance, and an air extraction system for efficient ventilation.
This approach ensures uniform diffusion and reduced condensation of the decontaminating substance within the work chamber, preventing product displacement and simplifying the ventilation process, thereby enhancing the efficiency and effectiveness of the decontamination method.
Smart Images
Figure IB2024052971_03102024_PF_FP_ABST
Abstract
Description
[0001] " ISOLATOR FOR STERILE APPLICATIONS COMPRISING A SUPPLY SYSTEM FOR A NEBULIZED DECONTAMINATING SUBSTANCE"
[0002] Cross-Reference to Related Applications
[0003] This Patent Application claims priority from Italian Patent Application No . 102023000005967 filed on March 28 , 2023 , the entire disclosure of which is incorporated herein by reference .
[0004] Technical Field
[0005] The present invention concerns an isolator for sterile applications , in particular a pharmaceutical isolator, comprising a supply system for a nebuli zed decontaminating substance to be di f fused in the isolator work chamber .
[0006] In particular, the present invention is advantageously but not exclusively applied in decontamination, by means of nebuli zed hydrogen peroxide , of the work chamber of a pharmaceutical isolator used for handling a sterile inj ectable pharmaceutical product inside a protective casing that preserves the sterility thereof , to which the following description will explicitly refer without loss of generality .
[0007] Background
[0008] Hydrogen peroxide is the decontaminating substance and in particular disinfecting substance most widely used in the pharmaceutical sector and is used in the form of highly concentrated aqueous solutions . The handling of sterile inj ectable drugs in a pharmaceutical isolator normally comprises a decontamination phase , during which the hydrogen peroxide is inj ected into the work chamber of the pharmaceutical isolator in the form of vapour, hence the term vapori zed hydrogen peroxide or hydrogen peroxide vapour, or in the form of nebuli zed substance , hence the term nebuli zed hydrogen peroxide , also known as dry fog . In particular, the vapori zed or nebuli zed hydrogen peroxide is inj ected into the work chamber of the isolator before opening the protective casing that preserves the sterility of the injectable drug so as to decontaminate the work chamber and the protective casing.
[0009] It is common practice to introduce nebulized hydrogen peroxide into the work chamber by arranging an atomizer nozzle or nebulizer in the work chamber. The most widely used nebulizer nozzle is the mist nozzle. Said nebulizer nozzle is supplied with liquid hydrogen peroxide pressurized by a compressed air flow. The force exerted by the compressed air on the liquid hydrogen peroxide supplied to the mist nozzle allows the cohesion force between the molecules of the substance in liquid form to be overcome, thus nebulizing the substance. The injection phase of the nebulized hydrogen peroxide is always followed by a ventilation phase to remove the hydrogen peroxide from the work chamber at the end of the decontamination process.
[0010] However, the jet of nebulized hydrogen peroxide is not immediately uniform in terms of volumetric concentration in the air, namely the concentration of the nebulized substance is higher in the vicinity of the nebulizer nozzle than in zones farther from the nozzle. Furthermore, the high speed at which the particles of nebulized decontaminating substance come out of the nebulizer nozzle increases the probability of condensation of the decontaminating substance on the surfaces nearest the nozzle and said condensation is undesired because the decontaminating substance in liquid form is more difficult to remove during the ventilation phase. In other words, the condensation of a greater quantity of decontaminating substance increases the difficulty and duration of the ventilation phase and therefore of the entire decontamination process. Furthermore, the parts of the product load in the work chamber nearest the nebulizer nozzle could be moved or overturned by the pressure of the jet of nebulized hydrogen peroxide.
[0011] Summary
[0012] The object of the present invention is to provide a pharmaceutical isolator able to decontaminate the work chamber thereof so that sterile products can be handled in the work chamber, said isolator being free from the drawbacks described above and, at the same time , easy and inexpensive to produce .
[0013] In accordance with the present invention, a pharmaceutical isolator and a method for decontaminating a work chamber of a pharmaceutical isolator are provided as defined in the attached claims .
[0014] The claims describe preferred embodiments of the present invention which should be considered an integral part of the present description .
[0015] Brief Description of the Drawings
[0016] For a better understanding of the present invention, a preferred embodiment is now described, purely by way of non-limiting example and with reference to the attached drawings , in which :
[0017] - figure 1 schematically illustrates , according to a section view along a vertical plane , the pharmaceutical isolator of the present invention during an operating phase that implements the decontamination method of the present invention; and
[0018] - figure 2 illustrates the pharmaceutical isolator of figure 1 during a further operating phase .
[0019] Description of Embodiments
[0020] In figures 1 and 2 , the number 1 generically indicates , overall , an isolator for sterile applications , in particular a pharmaceutical isolator, comprising a work chamber 2 to house a load of sterile pharmaceutical products (not illustrated) , for example closed within one or more protective casings that preserve the sterility thereof , having at least one access hatch 3 . In the example of figures 1 and 2 , the access hatch 3 is in a vertical wall 4 of the work chamber 2 , hereinafter also called front wall . Typically, the sterile pharmaceutical products are distributed on shelves having a plurality of holes or slits , known per se and not illustrated .
[0021] The isolator 1 comprises a laminar air flow generation system 5, which comprises an inlet duct 6 for the ambient air, a fan 7 for sucking ambient air from the inlet duct 6 and a HEPA filter 8 for filtering the air sucked in . The laminar air flow generation system 5 communicates with a ceiling 9 of the work chamber 2 to introduce clean air into the work chamber 2 according to a laminar flow . The inlet duct 6 is provided with an electrovalve 10 to allow or block the inlet of air .
[0022] The isolator 1 comprises an interspace 11 for return of the air taken into the work chamber 2 . The interspace 11 extends vertically on the outside of the work chamber 2 and communicates with a lower portion 12 of the work chamber 2 through a return opening 13 . In particular, the work chamber 2 comprises a wall 14 located opposite the front wall 4 , namely a rear part , and the interspace 11 extends behind the rear wall 14 . During normal operation of the isolator 1 , the air taken into the work chamber 2 according to the above-mentioned laminar flow leaves the work chamber 2 through the return opening 13 and then travels through the interspace 11 .
[0023] The interspace 11 furthermore communicates with an upper portion
[0024] 15 of the work chamber 2 through a delivery opening 16 . The isolator 1 comprises a hatch 17 , which is applied to the delivery opening 16 and i s movable inside the interspace 11 between an open position, in which the hatch 17 leaves the del ivery opening
[0025] 16 open ( figure 1 ) , and a closed position, in which the hatch
[0026] 17 closes the delivery opening 16 ( figure 2 ) . In the example of figures 1 and 2 , the hatch 17 is hinged on the rear wall 14 to rotate around a substantially hori zontal axis . The hatch 17 is moved by a respective actuator (not illustrated) .
[0027] The delivery opening 16 is provided with an inflatable gasket 18 to achieve an airtight seal with the hatch 17 when the latter is in the closed position . The inf latable gasket 18 is supplied by a pneumatic circuit (not illustrated) .
[0028] The return opening 13 and the delivery opening 16 are provided with respective grilles 19 and 20 to prevent solid parts of products located in the work chamber 2 from entering the interspace 11 .
[0029] The isolator 1 comprises a decontaminating substance supply system 21 for supplying a decontaminating substance , in particular a nebuli zed disinfecting substance , preferably comprising nebuli zed hydrogen peroxide . The decontaminating substance supply system 21 comprises a nebuli zer noz zle 22 arranged in the interspace 11 so that the nebuli zed contaminating substance is inj ected and circulates in the work chamber 2 , entering from the delivery opening 16 and exiting from the return opening 13 , when the hatch 17 is open and the laminar air flow generation system 5 is switched of f ( figure 1 ) .
[0030] In particular, the nebuli zer noz zle 22 is arranged in a lower portion 23 of the interspace 1 , and in particular on a bottom
[0031] 24 of the interspace 11 , and is directed towards an upper portion
[0032] 25 of the interspace 11 to generate a j et 22a of nebuli zed decontaminating substance directed towards the delivery opening 16 . As can be seen from figures 1 and 2 , the lower portion 23 communicates with the lower portion 12 of the work chamber 2 through the return opening 13 and the upper portion 25 communicates with the upper portion 15 of the work chamber 2 through the delivery opening 16 . In this way, the distance between the height of the nebuli zer noz zle 22 and the height of the delivery opening 16 combined with the dispersion rate of the kinetic energy of the j et 22a allows finer particles with lower speed of the nebuli zed decontaminating substance to be introduced into the work chamber 2 : the reduced speed of the particles reduces the probability of condensation of the nebuli zed decontaminating substance . The nebuli zer noz zle 22 is a mist type nozzle . The decontaminating substance supply system 21 comprises a pump 26 for supplying the decontaminating substance in liquid form to the nebuli zer noz zle 22 and a compressor 27 operating in parallel with the pump 26 to supply a compressed air flow to the nebuli zer noz zle 2 .
[0033] The isolator 1 comprises an air extraction system 28 to ventilate the work chamber 2 , comprising a suction assembly 29 communicating with the upper portion 25 of the interspace 11 to extract air from the work chamber 2 through the return opening 13 when the hatch 17 is closed and the laminar air flow generation system 5 is switched on ( figure 2 ) .
[0034] The suction assembly 29 comprises an aspirator 30 and an outlet duct 31 connected to an outlet of the aspirator 30 to expel the air into the environment .
[0035] The suction assembly 29 comprises an air treatment device 32 adapted to el iminate , for example by catalysis , the decontaminating substance from the air extracted from the work chamber 2 . Preferably, the air treatment device 32 is arranged between an inlet of the aspirator 30 and the upper portion 25 of the interspace 11 . Preferably, the nebuli zed decontaminating substance is nebuli zed hydrogen peroxide and the air treatment device is a hydrogen peroxide absorber device .
[0036] The suction assembly 29 comprises a filter 33 , for example a HEPA filter to eliminate the particulate from the air to be expelled . Preferably, the filter 33 is arranged between an outlet of the air treatment device 32 and the inlet of the aspirator 30 .
[0037] The suction assembly 29 comprises an electrovalve 34 to allow or block the expulsion of air . Preferably, the electrovalve 34 is arranged at an inlet of the air treatment device 32 .
[0038] In further detai l , the air extraction system 28 comprises an extraction chamber 35 , which communicates with the upper portion 25 of the interspace 11 , through an expulsion opening 36 , and with the suction assembly 29 , in particular with the electrovalve 33 , and an opening / closing device 37 , which is applied to the expulsion opening 36 and is movable between an open position of the expulsion opening 36 ( figure 2 ) and a closing position of the expulsion opening 36 ( figure 1 ) . The opening / closing device 37 comprises a respective actuator (not illustrated) .
[0039] The decontaminating substance supply system 21 is adapted to supply the nebuli zed decontaminating substance when the opening / closing device 37 is in the closed position ( figure 1 ) . The suction assembly 29 is adapted to extract air from the work chamber 2 when the opening / closing device 37 is in the open position ( figure 2 ) .
[0040] In the example o f figures 1 and 2 , the opening / closing device 37 comprises a butterfly valve hinged to the inside of the extraction chamber 35 to rotate , for example , around a substantially hori zontal axis . According to an alternative embodiment not illustrated, the opening / closing device 37 comprises a partition movable inside the extraction chamber 35 , and in particular with one side of the partition hinged to rotate , for example , around a substantially hori zontal axis .
[0041] The isolator 1 further comprises a bypass conduit 38 , which connects the lower portion 23 of the interspace 11 to the extraction chamber 35 to prevent the work chamber 2 from overpressuri zing during nebuli zation of the decontaminating substance . The bypass conduit 38 comprises an electrovalve 39 .
[0042] According to an embodiment not i llustrated, the bypass conduit 38 is connected to the bottom 24 of the interspace 11 .
[0043] The isolator 1 comprises a control unit 40 , for example a PLC, adapted to control the laminar air flow generation system 5 , the actuator of the hatch 17 , the pump of the inflatable gasket 18 , the decontaminating substance supply system 21 , the suction assembly 29 and the air extraction system 28 , and the electrovalve 39 . In particular, the laminar air flow generation system 5 is controlled by acting on the fan 7 and on the electrovalve 10 . The decontaminating substance supply system 21 is controlled by acting simultaneously on the pump 26 and on the compressor 27 . The air extraction system 28 is controlled by acting on the suction assembly 29 , then on the aspirator 30 and on the electrovalve 34 , and on the opening / closing device 37 .
[0044] The control unit 40 is configured to control the above-listed systems and devices so as to implement a method for decontaminating, in particular disinfecting, the work chamber 2 in the presence of a sterile pharmaceutical product inside the work chamber or prior to placing a sterile pharmaceutical product in the work chamber 2 .
[0045] The method for decontaminating the work chamber 2 comprises essentially a step of inj ecting the nebuli zed decontaminating substance into the work chamber 2 ( figure 1 ) , and a step of ventilating the work chamber 2 ( figure 2 ) . Advantageously, the inj ection step i s preceded by a step of dehumidi fying the work chamber 2 .
[0046] The inj ection step is characteri zed by a recipe that can be set by the user on a man-machine interface (not illustrated) connected to the control unit 40 . The recipe comprises predetermined fixed execution times so as to reach a relative humidity target value and a concentration target value of decontaminating substance in the work chamber 2 . With reference to figure 1 , the inj ection step comprises opening the hatch 17 , closing the opening / closing device 37 , switching of f the laminar air flow generation system 5 and switching on the decontaminating substance supply system 21 to generate in the interspace 11 the j et 22a of nebuli zed decontaminating substance , so that the nebuli zed decontaminating substance is inj ected into the work chamber 2 through the delivery opening 16 , according to a flow indicated by Fl . The nebuli zed decontaminating substance circulates in the work chamber 2 , according to the flow indicated by F2 , spreading uni formly, and exits from the return opening 13 , according to the flow indicated by F3 .
[0047] The inj ection step comprises switching of f the aspirator 30 , but opening the electrovalve 34 . In fact , also the electrovalve 39 of the bypass conduit 38 is left open to prevent the work chamber 2 from over pressuri zing . In this way, the overpressure is relieved via the bypass conduit 38 in the direction indicated by F4 , through the extraction chamber 35 , and runs through the suction assembly 29 .
[0048] The inj ection step continues until the above-mentioned relative humidity and decontaminating substance concentration target values are reached inside the work chamber 2 .
[0049] With reference to figure 2 , the ventilation step comprises switching of f the decontaminating substance supply system 21 and at the same time closing the hatch 17 , inflating the inflatable gasket 18 to guarantee the seal of the hatch 17 , opening the opening / closing device 37 , and switching on the laminar air flow generation system 5 and the suction assembly 29 to extract air from the work chamber 2 through the return opening 13 . The laminar air flow F5 expels the air saturated with nebuli zed decontaminating substance from the work chamber 2 through the return opening 13 and a flow of expelled air F6 travels through the interspace 11 to be extracted by the suction assembly 29 and exit via the outlet duct 31 .
[0050] Advantageously, the electrovalve 39 is left open also during the ventilation step to remove any residues of nebuli zed decontaminating substance in the bypass conduit 38 .
[0051] Although the invention described above refers in particular to a certain use , namely decontaminating the work chamber 2 in the presence , inside the same , of a sterile pharmaceutical product load, it should not be considered limited to said example of use , since the use in which the work chamber 2 is decontaminated before sterile products are placed therein by means of a trans fer system that preserves the sterility of the products also falls within its scope .
[0052] An advantage of the pharmaceutical isolator and the decontamination method described above is that a uni form di f fusion of the nebuli zed decontaminating substance inside the work chamber 2 is obtained, since the nebuli zed decontaminating substance enters the work chamber 2 at a relatively reduced speed due to generation of the nebuli zed j et 22a which occurs in a volume ( interspace 11 ) separate from the work chamber 2 .
[0053] Furthermore , the distance between the height of the nebuli zer noz zle 22 and the height of the delivery opening 16 , through which the nebuli zed decontaminating substance enters the work chamber 2 , allows a greater quantity of fine particles of the nebuli zed decontaminating substance to be introduced into the work chamber 2 , and this minimi zes condensation of the decontaminating substance on the surfaces inside the work chamber 2 .
[0054] Another advantage guaranteed by generation of the nebuli zed j et 22a in a chamber ( interspace 11 ) separate from the work chamber 2 , is that it prevents parts of the product load in the work chamber from being moved by the pressure of the nebuli zed j et 22a . Besides , the pressure of the nebuli zed j et 22a on any surface of the work chamber 2 or of the products contained in the work chamber 2 would increase the probability of condensation of the decontaminating substance .
[0055] Lastly, the interspace 11 used to recapture the air introduced by laminar flow into the work chamber 2 during normal operation of the isolator 1 and the movable hatch 17 arranged in the interspace 11 al low the work chamber 2 to be ventilated at the end of the inj ection phase in a simple ef fective manner .
Claims
CLAIMS1. An isolator for sterile applications, in particular a pharmaceutical isolator, comprising a work chamber (2) , a laminar air flow generation system (5) communicating with a ceiling (9) of the work chamber (2) , an interspace (11) for the air return, which extends vertically outside the work chamber (2) and communicates with a lower portion (12) of the work chamber (2) through a return opening (13) and with an upper portion (15) of the work chamber (2) through a delivery opening (16) , a hatch (17) , which is applied to the delivery opening (16) and is movable within the interspace (11) , and a decontaminating substance supply system (21) for feeding a nebulized decontaminating substance, preferably nebulized hydrogen peroxide; said decontaminating substance supply system (21) comprising a nebulizer nozzle (22) arranged in the interspace (11) so that the nebulized decontaminating substance circulates in the work chamber (2) when the hatch (17) is open and the laminar air flow generation system (5) is switched off.
2. The isolator according to claim 1, wherein said nebulizer nozzle (22) is arranged in a lower portion (23) of the interspace (11) , in particular on a bottom (24) of the interspace (11) , and is directed towards an upper portion (25) of the interspace (11) to generate a jet of nebulized decontaminating substance directed towards the delivery opening (16) .
3. The isolator according to claim 1 or 2, wherein said delivery opening (16) is provided with an inflatable gasket (18) to achieve an airtight seal with the hatch (17) when the latter is closed.
4. The isolator according to any one of claims 1 to 3, wherein the decontaminating substance supply system (21) comprises a pump (26) for supplying the decontaminating substance in liquid form to the nebulizer nozzle (22) and a compressor (27) operatingin parallel with the pump (26) for supplying a flow of compressed air to the nebulizer nozzle (22) .
5. The isolator according to any one of claims 1 to 4, and comprising an air extraction system (28) for ventilating the work chamber (2) ; the air extraction system (28) comprising a suction assembly (29) , which comprises an aspirator (30) and communicates with an upper portion (25) of the interspace (11) to extract air from the work chamber (2) through the return opening (13) when the hatch (17) is closed and the laminar air flow generation system (5) is on.
6. The isolator according to claim 5, wherein the suction assembly (29) comprises an air treatment device (32) connected between the suction assembly (30) and the upper portion (25) of the interspace (11) and suitable for removing the decontaminating substance from the air extracted from the work chamber ( 2 ) .
7. The isolator according to claim 5 or 6, wherein the air extraction system (28) comprises an extraction chamber (35) , which communicates with the upper portion (25) of the interspace (11) through an ejection opening (36) and with the suction assembly (29) , and an opening / closing device (37) , which is movable between an open position and a closed position of the ejection opening (36) ; the suction assembly (29) being suitable for extracting air from the work chamber (2) when the opening / closing device (37) is in the open position; the nebulizer nozzle (22) being arranged in the interspace (11) in such a way that the nebulized decontaminating substance circulates in the work chamber (2) when the opening / closing device (37) is in the closed position.
8. The isolator according to any one of claims 1 to 7, comprising an air extraction system (28) for ventilating the work chamber (2) ; the air extraction system (28) comprising anextraction chamber (35) , which communicates with an upper portion (25) of the interspace (11) via an ejection opening (36) , and an opening / closing device (37) applied to the ejection opening (36) ; the isolator (1) comprising a bypass conduit (38) , which connects a lower portion (23) of the interspace (11) with the extraction chamber (35) to prevent the work chamber (2) from over pressurizing during nebulization of the decontaminating substance .
9. A method for decontaminating a work chamber (2) of an isolator for sterile applications, for example a pharmaceutical isolator (1) , comprising a laminar air flow generation system (5) communicating with a ceiling (9) of the work chamber (2) and an interspace (11) for the air return, which extends vertically outside the work chamber (2) and communicates with a lower portion (12) of the work chamber (2) through a return opening (13) and with an upper portion (15) of the work chamber (2) through a delivery opening (16) , the latter being provided with a movable hatch (17) , the method comprising:- while the laminar air flow generation system (5) is off and the hatch (17) is open, generating in the interspace (11) a jet of nebulized decontaminating substance by means of a nebulizer nozzle (22) arranged in the interspace (11) in such a way that the nebulized decontaminating substance circulates in the work chamber (2) by entering through the delivery opening (16) and exiting through the return opening (13) .
10. The method according to claim 9, comprising: stopping the generation of the jet of nebulized decontaminating substance and, at the same time, closing the hatch (17) , turning on the laminar air flow generation system (5) and extracting air from the work chamber (2) through the return opening (13) by means of an air extraction system (28) communicating with an upper portion (25) of the interspace (11) .