GB2577835A - Single-use isolator with laminar flow and double filtration - Google Patents
Single-use isolator with laminar flow and double filtration Download PDFInfo
- Publication number
- GB2577835A GB2577835A GB1919306.9A GB201919306A GB2577835A GB 2577835 A GB2577835 A GB 2577835A GB 201919306 A GB201919306 A GB 201919306A GB 2577835 A GB2577835 A GB 2577835A
- Authority
- GB
- United Kingdom
- Prior art keywords
- isolator
- envelope
- outlet
- batches
- products
- 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.)
- Granted
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B25—HAND TOOLS; PORTABLE POWER-DRIVEN TOOLS; MANIPULATORS
- B25J—MANIPULATORS; CHAMBERS PROVIDED WITH MANIPULATION DEVICES
- B25J21/00—Chambers provided with manipulation devices
- B25J21/02—Glove-boxes, i.e. chambers in which manipulations are performed by the human hands in gloves built into the chamber walls; Gloves therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L1/00—Enclosures; Chambers
- B01L1/02—Air-pressure chambers; Air-locks therefor
- B01L1/025—Environmental chambers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L1/00—Enclosures; Chambers
- B01L1/04—Dust-free rooms or enclosures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B15/00—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area
- B08B15/02—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area using chambers or hoods covering the area
- B08B15/023—Fume cabinets or cupboards, e.g. for laboratories
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F24—HEATING; RANGES; VENTILATING
- F24F—AIR-CONDITIONING; AIR-HUMIDIFICATION; VENTILATION; USE OF AIR CURRENTS FOR SCREENING
- F24F3/00—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems
- F24F3/12—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems characterised by the treatment of the air otherwise than by heating and cooling
- F24F3/16—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems characterised by the treatment of the air otherwise than by heating and cooling by purification, e.g. by filtering; by sterilisation; by ozonisation
- F24F3/163—Clean air work stations, i.e. selected areas within a space which filtered air is passed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B15/00—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area
- B08B15/02—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area using chambers or hoods covering the area
- B08B15/026—Boxes for removal of dirt, e.g. for cleaning brakes, glove- boxes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B08—CLEANING
- B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
- B08B2215/00—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area
- B08B2215/003—Preventing escape of dirt or fumes from the area where they are produced; Collecting or removing dirt or fumes from that area with the assistance of blowing nozzles
Abstract
The invention relates to a single-use isolator for manufacturing batches of sensitive products, particularly medicines, in a sterile environment, comprising a framework (10) and an enclosure (12) suspended from said framework (10), an upper air inlet (14S) on the upper side of the enclosure (12) and an air outlet (141) on the lower side of the enclosure (12), characterised in that said air inlet and outlet (14S, 141) are provided with an upper module (16S) and a lower module (161) respectively comprising upper ventilation means (18S) and lower ventilation means (181) as well as upper filtration means (20S) and lower filtration means (201).
Description
DOUBLE-FILTRATION LAMINAR-FLOW SINGLE-USE ISOLATOR
The present invention concerns a single-use isolator for the manufacture of batches of sensitive products, notably drugs, in sterile surroundings with a laminar flow and double filtration, at the inlet and outlet.
The invention also covers a production line utilising at least one isolator according to the present invention.
The invention is also directed to an isolator ready for use, incorporating the products to be processed.
It is known that numerous companies and health organisations have to prepare, to package batches of sensitive products, notably pharmaceutical products, in sterile surroundings termed of class A. The present invention is described for pharmaceutical products but applies to sensitive products in general.
In actual fact, there exist products whose own shelf life is long but whose shelf life after mixing becomes very limited so that it is necessary to be able to produce small batches of containers of small volume, just in time, in order to enable use during said shelf life.
Production batches in small quantities can be produced in general packaging units of high capacity but most of the time the economic conditions are not compatible.
In actual fact, changing the sensitive products produced on an industrial production line in the pharmaceutical industry necessitates complex and very costly sanitisation steps.
There therefore exist isolators that enable the manufacture and packaging of batches of pharmaceutical products in smaller numbers, that offer the same guarantees of asepsis as lines of high capacity, that enable identical handling tasks for transfers and for packaging and that are for single use, which avoids the sanitisation treatment that would be necessary for re-use.
These isolators are also shipped dismantled with a modular structure, and so transport and storage are also relatively inexpensive and relatively free of constraints.
Connections using airlocks enable a plurality of isolators to be connected to constitute a line. The requirements are generally for at least two chambers, one of class B and the other, final chamber, of class A. Good manufacturing practices (GMP) apply to pharmaceutical establishments in the European Union for example. The standards tend to be homogenised.
These good practices are the subject of standardisation and the criteria are summarised in the table below.
Conditions Class A Class B Particular conditions when Maximum number of particles 3 500 3 500 inactive (d < 0.5 pm) per m3 Maximum number of particles 0 0 (d 5 pm) per m3 Particular conditions when Maximum number of particles 3 500 350 000 active (d < 0.5 pm) per m3 Maximum number of particles 0 2 000 (d 5 pm) per m3 The conditions when inactive can be complied with but this is much more difficult when active.
There is one imperative condition, namely the laminar nature of the flow emitted so as to limit disturbances.
Thus there is known from French patent application No. 1670675 of 10/11/2016 in the name of the company Disposable Lab a device for diffusion of a gaseous fluid into an isolator for the manipulation of sensitive products such as drugs.
That device includes at least one conduit positioned on an interior face of at least one wall of the isolator, in particular the upper face. This at least one conduit includes holes of given diameter with a given distribution, so as to limit turbulence.
Likewise, to comply with all constraints it is also necessary to prevent any backflow via the outlet in the event of a failure of the compressed air supply and/or on exerting a movement liable to create suction via the outlet.
Another desirable condition is to be able to work in entirely new air and to reject air directly to the atmosphere. The object of the present invention is to provide an isolator that is adapted to address these problematics.
The invention also proposes a production line incorporating at least one isolator according to the present invention.
The invention is described in detail next, in accordance with one particular non-limiting embodiment, with reference to the appended drawings, in which the various figures represent: - Figure 1: a perspective view of two isolators according to the present invention, -Figure 2: a view in vertical section of one of the isolators from figure 1, - Figure 3: a view of a packaging line notably incorporating in particular two isolators according to the present invention, - Figure 4: isolators according to the invention ready for use.
In figures 1 and 2 there have been represented two twinned isolators, which are of substantially cubic shape in the embodiment chosen, each isolator comprising a framework 10 forming a retaining structure, a transparent and totally fluid-tight material confinement envelope 12, suspended from said frame. The envelope is substantially the same shape as the frame and therefore of substantially cubic shape with smaller dimensions in order to be suspended therefrom. This envelope is provided with at least one pair of manipulation gloves G welded to said envelope 12, also in a totally fluid-tight manner.
The frame is advantageously a set of rods 10-1 with connecting nuts 10-2 to form cubes. These rods 10-1 are advantageously made of metal, of stainless steel, so as to confer on them sufficient mechanical strength and the possibility of sterilisation if necessary, by heat or by spraying sterilising solutions, without damage. These frames are reusable with new envelopes.
These frames have to comply only with the degree of sterilisation of the premises in which the installation is placed. These frames rest on a work table T in such a manner as to place the lower face of the cube on said table T and to benefit from a rigid and plane working surface. The envelopes 12 are generally mounted on the frame 10 and more particularly on the rods by means of lugs 12-1 attached to the edges of said envelope, the fixing of the lugs to themselves being press-fixings around the tubes.
According to the present invention, an air inlet 145 is provided on the upper face of the envelope and an air outlet 141 for each isolator on the lower face of the envelope. Each air inlet and outlet includes an upper module 165 and a lower module 161. These modules are fastened to the envelopes in a fluid-tight manner but demountable.
In actual fact, the modules are fastened to the bars of the frame.
Each module 16 comprises upper ventilation means 185 and lower ventilation means 181 as well as upper filter means 205 and lower filter means 201.
The upper ventilation means 185 inject air in the upper part, that is to say inject air from around the periphery of the isolator into the confined enclosure of the envelope of said isolator. Note the absence of recycling. The surrounding air has itself already been treated, generally to class D or ISO 8, that is to say 3 500 000 particles < 0.5 ktm maximum, so as not to saturate the filter means.
The lower ventilation means 181 extract the air in adapted class A or B from the envelope of the isolator in the lower part, to the outside. Introduction in the upper part and extraction in the lower part generate a flow of air in a substantially vertical direction in the confinement enclosure constituted by the envelope, the flow being substantially laminar.
In actual fact, the flow not being disturbed by an inlet and/or an outlet focused at a point, inlet and outlet turbulence are eliminated.
The filter means advantageously consist of a filter of the type marketed under the tradename NEPA (High Efficiency Particulate Air) H 14, with laminar flow, or any equivalent filter.
The surface of the filter appropriately covers most of the upper face and the lower face so as to generate a laminar flow over the entire section of the envelope.
Moreover, if air were to be aspirated from the outlet toward the air inlet or merely into the envelope, either in the event of a breakdown or accidentally, that air aspirated inappropriately via the outlet would be filtered in the same manner because the filters are identical with the same inlet/outlet or outlet/inlet filtration performance.
The internal volume of air confined by the envelope is always treated and any products contained but not yet packaged would be preserved in terms of their integrity and their aseptic properties.
Each isolator includes at the outlet a valve 22 for controlling the internal pressure in the envelope 12.
In actual fact, adjusting the opening/closing of this control valve 22 decelerates the outlet flow so that the internal pressure increases or accelerates the outlet flow so that the internal pressure decreases.
The isolator according to the invention emits a downward laminate flow of air that is filtered at the inlet and at the outlet in normal operation or filtered at the outlet that has become an inlet in the event of accidental re-aspiration linked for example to a fault in the installation, thus preserving the products confined in the envelope 12.
The filter is pre-mounted on the envelope by fluid-tight flanges joined to the envelope. The ventilation means are mounted on the flanges to blow or to extract air through the corresponding filter.
The ventilation means are advantageously fixed to the frame by nuts. It suffices to change the envelope for the device to be operational again.
According to the present invention, there is provided a packaging and filling line 24 comprising two packaging isolators 24-1 and 24-2, of classes A and B, a preparation isolator 24-3 and a raw materials introduction isolator 24-4. Airlocks enable two juxtaposed isolators to be connected at will, this connection being intentional and controlled by the operator.
The raw materials introduction isolator 24-4 contains containers of products to be packaged, and where applicable to be mixed beforehand, in the form of fluids and/or pastes and/or powders, the final containers, the means for checking weight and/or volume, necessary for metering.
These products are generally contained in packaging and bombarded with gamma rays to sterilise the contents. These products are placed in the raw materials introduction isolator 24-4 to be sterilised therein using nitrogen or hydrogen peroxide.
They are then transferred into the isolator 24-3 where they are unpacked to remove the packaging, also in a nitrogen or hydrogen peroxide atmosphere to preserve the external sterilisation of the products.
The containers and other packaging tools are introduced into the class B isolator 24-2. The packaging remains in the isolator 24-3.
The isolator 24-2 includes filters identical to those of the isolator 24-1 but the pressure P2 in this isolator 24-2 is lower than the pressure in the isolator 24-1.
The containers and other tools are therefore treated in this first isolator in order to clear them of particles and to condition them for access to the final class A packaging isolator in which the number of particles is very low as indicated in the preamble.
The pressure P1 in the isolator 24-1 being higher, the atmosphere of the isolator 24-2 with its number of particles remains confined in the enclosure of this isolator 24-2 and the containers and the other packaging tools enter the isolator 24-1 cleared of their particles and are subjected to a laminar flow of air free of particles.
During transfer, the flow of air circulates from the isolator 24-1 to the isolator 24-2.
In the isolator 24-1, the operator can open the containers and carry out metering and filling of the containers of small volume, and effect all mixing and preparation operations beforehand if necessary, in a class A atmosphere and therefore with no possibility of introducing particles into the packaging of small volume simultaneously with the product or mixture of products. These containers of small volume, filled and closed, are then ready to be evacuated to the outside of the class A isolator 24-1 via the appropriate airlock, in known manner.
The content of the containers of small volume is therefore sterile.
Figure 4 represents a possibility of industrial production of a single isolator with the products and packaging tools with the containers of small volume directly in the enclosure, the various steps having been carried out beforehand in an industrial manner. The isolator is then directly a pre-sterilised class A isolator, because there is no need for additional sterilisation.
The isolator can also be sterilised in situ using nitrogen or hydrogen peroxide.
The isolators are also often re-sterilised before they are destroyed, especially when the repackaging involves sensitive products of Biosafety Level 2 (BSL2) or Biosafety Level 3 (BSL3) containing microbes.
Claims (6)
- CLAIMS1. Single-use isolator for the production of batches of sensitive products, notably drugs, in sterile surroundings, comprising a frame (10) and an envelope (12) suspended from said frame (10), an upper air inlet (14S) on the upper face of the envelope (12) and an air outlet (141) on the lower face of the envelope (12), characterised in that said air inlet and outlet (14S, 141) are respectively equipped with an upper module (16S) and a lower module (161) including upper ventilation means (18S) and lower ventilation means (181) as well as upper filter means (205) and lower filter means (201).
- 2. Single-use isolator according to claim 1 for the production of batches of sensitive products, characterised in that the upper and lower filter means (20S, 201) each comprise a laminar-flow 1-114 type FIEPA filter.
- 3. Single-use isolator according to claim 2 for the production of batches of sensitive products, characterised in that the filter is mounted in a frame fastened to the envelope.
- 4. Single-use isolator according to any one of the preceding claims for the production of batches of sensitive products, characterised in that it includes, at the outlet, a valve (22) for controlling the internal pressure of the envelope (12).
- 5. Packaging and filling line (24) comprising two class A and 8 isolators (24-1, 24-2) according to any one of the preceding claims, a preparation isolator (24-3) and a raw materials introduction isolator (24-4), interconnected by airlocks enabling two of said airlocks that are juxtaposed to be connected at will.
- 6. Single-use isolator according to any one of claims 1 to 4 for packaging and filling containers of small volume, comprising containers of products to be conditioned, and where applicable to be mixed beforehand, in the form of fluids and/or pastes and/or powders, the containers of small volume, the means for checking weight and/or volume, necessary for metering, everything having been sterilised beforehand.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1770535A FR3066712B1 (en) | 2017-05-24 | 2017-05-24 | ISOLATOR FOR SINGLE USE, LAMINAR FLOW AND DOUBLE FILTRATION |
| PCT/FR2018/000138 WO2018215704A1 (en) | 2017-05-24 | 2018-05-24 | Single-use isolator with laminar flow and double filtration |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB201919306D0 GB201919306D0 (en) | 2020-02-05 |
| GB2577835A true GB2577835A (en) | 2020-04-08 |
| GB2577835B GB2577835B (en) | 2022-02-16 |
Family
ID=59297164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB1919306.9A Active GB2577835B (en) | 2017-05-24 | 2018-05-24 | Double-filtration laminar-flow single-use isolator |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP3630424A1 (en) |
| CA (1) | CA3100754C (en) |
| FR (1) | FR3066712B1 (en) |
| GB (1) | GB2577835B (en) |
| WO (1) | WO2018215704A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2566552B (en) * | 2017-09-19 | 2023-07-19 | Solo Containment Ltd | Flexible enclosure |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0342599A (en) * | 1989-07-10 | 1991-02-22 | Shikoku Electric Power Co Inc | Radioactive oil-laden waste liquid treatment device |
| US20080139865A1 (en) * | 2006-07-14 | 2008-06-12 | Xcellerex, Inc. | Environmental containment systems |
| US20100044372A1 (en) * | 2007-10-30 | 2010-02-25 | Her Majesty The Queen in Right of Canada as Represented by the Minister of Public Safety | Portable and collapsible chem./bio. isolators |
| JP2010046226A (en) * | 2008-08-20 | 2010-03-04 | Sanyo Electric Co Ltd | Isolator |
| GB2502972A (en) * | 2012-06-11 | 2013-12-18 | Bioquell Uk Ltd | Aseptic processing workstation with two independently regulated fans |
| CN105684920A (en) * | 2016-03-23 | 2016-06-22 | 山东新华医疗器械股份有限公司 | Breed conservation isolator for genetic engineering mice |
| EP3037110A1 (en) * | 2014-12-25 | 2016-06-29 | Shibuya Corporation | Aseptic manipulation system and object-introducing method for aseptic manipulation system |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0632639Y2 (en) * | 1989-09-01 | 1994-08-24 | ミドリ安全株式会社 | Disposable glove box |
-
2017
- 2017-05-24 FR FR1770535A patent/FR3066712B1/en active Active
-
2018
- 2018-05-24 CA CA3100754A patent/CA3100754C/en active Active
- 2018-05-24 GB GB1919306.9A patent/GB2577835B/en active Active
- 2018-05-24 EP EP18737332.9A patent/EP3630424A1/en active Pending
- 2018-05-24 WO PCT/FR2018/000138 patent/WO2018215704A1/en unknown
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0342599A (en) * | 1989-07-10 | 1991-02-22 | Shikoku Electric Power Co Inc | Radioactive oil-laden waste liquid treatment device |
| US20080139865A1 (en) * | 2006-07-14 | 2008-06-12 | Xcellerex, Inc. | Environmental containment systems |
| US20100044372A1 (en) * | 2007-10-30 | 2010-02-25 | Her Majesty The Queen in Right of Canada as Represented by the Minister of Public Safety | Portable and collapsible chem./bio. isolators |
| JP2010046226A (en) * | 2008-08-20 | 2010-03-04 | Sanyo Electric Co Ltd | Isolator |
| GB2502972A (en) * | 2012-06-11 | 2013-12-18 | Bioquell Uk Ltd | Aseptic processing workstation with two independently regulated fans |
| EP3037110A1 (en) * | 2014-12-25 | 2016-06-29 | Shibuya Corporation | Aseptic manipulation system and object-introducing method for aseptic manipulation system |
| CN105684920A (en) * | 2016-03-23 | 2016-06-22 | 山东新华医疗器械股份有限公司 | Breed conservation isolator for genetic engineering mice |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2566552B (en) * | 2017-09-19 | 2023-07-19 | Solo Containment Ltd | Flexible enclosure |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018215704A8 (en) | 2019-05-16 |
| EP3630424A1 (en) | 2020-04-08 |
| CA3100754A1 (en) | 2018-11-29 |
| FR3066712B1 (en) | 2019-07-26 |
| GB2577835B (en) | 2022-02-16 |
| FR3066712A1 (en) | 2018-11-30 |
| WO2018215704A1 (en) | 2018-11-29 |
| GB201919306D0 (en) | 2020-02-05 |
| CA3100754C (en) | 2023-07-04 |
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