WO2018215704A1 - Single-use isolator with laminar flow and double filtration - Google Patents

Single-use isolator with laminar flow and double filtration Download PDF

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Publication number
WO2018215704A1
WO2018215704A1 PCT/FR2018/000138 FR2018000138W WO2018215704A1 WO 2018215704 A1 WO2018215704 A1 WO 2018215704A1 FR 2018000138 W FR2018000138 W FR 2018000138W WO 2018215704 A1 WO2018215704 A1 WO 2018215704A1
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WO
WIPO (PCT)
Prior art keywords
isolator
insulator
batches
containers
envelope
Prior art date
Application number
PCT/FR2018/000138
Other languages
French (fr)
Other versions
WO2018215704A8 (en
Inventor
Jean Pascal ZAMBAUX
Bernard POUCHUCQ
Original Assignee
Disposable-Lab
Solo Containment Limited
Priority date (The priority date 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 date listed.)
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Application filed by Disposable-Lab, Solo Containment Limited filed Critical Disposable-Lab
Priority to EP18737332.9A priority Critical patent/EP3630424A1/en
Priority to GB1919306.9A priority patent/GB2577835B/en
Priority to CA3100754A priority patent/CA3100754C/en
Publication of WO2018215704A1 publication Critical patent/WO2018215704A1/en
Publication of WO2018215704A8 publication Critical patent/WO2018215704A8/en

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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

Definitions

  • the present invention relates to a disposable insulator for the manufacture of batches of sensitive products, including drugs, in a sterile atmosphere with a laminar flow and a dual filtration, input and output.
  • the invention also covers the production line using at least one insulator according to the present invention.
  • the invention also relates to a ready-to-use isolator integrating the products to be treated.
  • the present invention is described for pharmaceuticals but applies to generally sensitive products.
  • insulators that allow the manufacture and packaging of batches of pharmaceuticals in smaller numbers, which offer the same guarantees of asepsis that the lines of large capacity, which allow identical handling work for transfers as for the conditioning and which are disposable, which avoids the sanitarization treatment that would be required for re-use.
  • These insulators are also supplied dismantled with a modular structure, so that the transport and the storage are also inexpensive, not very constraining.
  • Links with airlocks make it possible to connect several insulators in order to constitute a chain.
  • the requirements are generally at least two rooms, one in class B and the other in class A.
  • GMP Good Manufacturing Practices
  • the conditions at rest can be respected but in activity, it remains much more difficult.
  • This device comprises at least one duct positioned on an inner face of at least one wall of the insulator, in particular the upper face.
  • This at least one pipe has holes of given diameter and distribution, so as to limit turbulence. In the same way, to respect all the constraints, it is also necessary to avoid any return through the outlet, during a failure of the pressurized air supply and / or by exerting a movement likely to create a suction through the outlet.
  • Another desirable condition is to be able to work in full fresh air and to discharge air directly to the atmosphere. It is the object of the present invention to provide an insulator that is adapted to respond to these problems.
  • the invention also proposes a production line integrating at least one insulator according to the present invention.
  • FIG. 1 a perspective view of two insulators according to the present invention
  • FIG. 3 a view of a packaging line incorporating in particular two insulators according to the present invention
  • each insulator comprising a framework 10 forming a holding structure, a containment envelope 12 of transparent material and completely sealed, suspended from said frame .
  • the envelope is substantially in the shape of the frame so substantially cubic and smaller dimensions to be suspended.
  • This envelope is provided with at least one pair of gloves G handling, welded to said casing 12, also completely waterproof.
  • the framework is advantageously a set of bars 10-1 with 10-2 connecting nuts so as to form cubes.
  • These bars 10-1 are advantageously metallic, made of stainless steel, so as to give them sufficient mechanical strength and the possibility of sterilization if necessary, by heat or by spraying sterilizing solutions, without degradation.
  • These frames are reusable with new envelopes. These frames must only respect the degree of sterilization of the room in which the installation is located. These frames rest on a worktable T so as to place the underside of the cube on said table T and to benefit from a rigid and flat work surface.
  • the envelopes 12 are generally attached to the framework 10 and more particularly to the bars by means of lugs 12-1 integral with the edges of said envelope, the fasteners of the lugs on themselves being pressure fasteners around the tubes.
  • an air inlet 14S on the upper face of the casing and an air outlet 141 for each insulator on the underside of the casing each comprise an upper module 16S and a lower module 161. These modules are sealingly attached to the envelopes but removable.
  • Each module 16 comprises upper 18S and lower ventilation means 181 and upper 20S and lower filtration means 201.
  • the upper ventilation means 18S inject air into the upper part, that is to say inject peripheral ambient air to the insulator in the confinement of the envelope enclosure of said insulator. There is no recycling.
  • the ambient air is itself already treated, generally in class D or ISO 8, that is to say 3,500,000 particles ⁇ 0.5 ⁇ ⁇ maximum, so as not to saturate the filtration means.
  • the lower ventilation means 18f extract air adapted class A or B from the envelope of the insulator in the lower part, outwards.
  • the introduction in the upper part and the extraction in the lower part generate an air flow in a substantially vertical direction in the confinement enclosure constituted by the envelope, the circulation being substantially laminar.
  • the filtration means are advantageously constituted by a filter of the type marketed under the name HEPA (High Efficiency Particulate Air) H 14, laminar flow or any equivalent filter.
  • HEPA High Efficiency Particulate Air
  • the filter surface covers the majority of the upper and lower faces so as to generate a laminar flow over the entire section of the envelope.
  • Each insulator comprises at the output a control valve 22 of the internal pressure of the envelope 12.
  • the insulator according to the invention emits a laminar air flow from the top to the bottom, which is filtered at the inlet and at the outlet during normal operation or filtered at the outlet which has become input during an accidental re-aspiration, for example linked to a defect of the installation, thus preserving the products confined in the envelope 12.
  • the filter is pre-mounted on the envelope by sealed flanges bound to the envelope.
  • the ventilation means are attached to the flanges to blow or extract the air through the corresponding filter.
  • the ventilation means are fixed on the framework by nuts. Just change the envelope to put the device back into operation.
  • a conditioning and filling chain 24 comprising two insulators 24-1 and 24-2 for conditioning, classes A and B, a preparation isolator 24- 3 and an insulator for introducing raw materials. 24-4.
  • Airlock can connect two insulators juxtaposed on demand, this connection is voluntary and controlled by the operator.
  • the insulator of introduction of raw materials 24-4 comprises the containers of products to be packaged, possibly to be mixed beforehand, in the form of fluids and / or pastes and / or powders, the final containers, the weight control means and / or volume, necessary for dosages.
  • These products are usually packaged and gamma ray bombarded to sterilize the contents. These products are placed in the feed insulator 24-4 to undergo sterilization with nitrogen or hydrogen peroxide. They are then transferred to the insulator 24-3 where they are unpacked to remove the packaging, this also under nitrogen or hydrogen peroxide to maintain the external sterilization of the products.
  • Containers and other packaging tools are introduced into the 24-2 Class B isolator.
  • the packages remain in the 24-3 isolator.
  • the insulator 24-2 has filters identical to those of the insulator 24-1 but the pressure P2 prevailing in this insulator 24-2 is lower than the pressure prevailing in the insulator 24-1.
  • the containers and other tools are therefore treated in this first isolator in order to remove the particles and put them in condition to access the final class A conditioning insulator in which the particle ratio as indicated in the preamble, is very limit.
  • the operator can unclog the containers and ensure the dosing and filling of containers of reduced volumes, make the preparations and any mixing operations beforehand if necessary, this in class A atmosphere, therefore without the possibility of introducing particles into the reduced volume packages simultaneously with the product or mixture of products.
  • the content of containers of reduced volume is therefore sterile.
  • FIG. 4 represents a possibility of industrially producing a single insulator with the products and packaging tools with containers of reduced volume directly in the enclosure, the various steps having been previously carried out industrially.
  • the isolator is then a pre-sterilized Class A isolator directly because there is no need for additional sterilization.
  • the insulator can also be sterilized on site with Nitrogen or Hydrogen Peroxide. Insulators are also often re-sterilized before destruction especially when the repackaging has targeted sensitive products BSL2 (Biosafety Level 2) or BSL3 (Biosafety Level 3) involving microbes.
  • BSL2 Biosafety Level 2
  • BSL3 Biosafety Level 3

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

ISOLATEUR A USAGE UNIQUE, A FLUX LAMINAIRE ET FILTRATION DOUBLE  ISOLATOR FOR SINGLE USE, LAMINAR FLOW AND DOUBLE FILTRATION
La présente invention concerne un isolateur à usage unique pour la fabrication de lots de produits sensibles, notamment des médicaments, en ambiance stérile avec un flux laminaire et une filtration double, en entrée et sortie. The present invention relates to a disposable insulator for the manufacture of batches of sensitive products, including drugs, in a sterile atmosphere with a laminar flow and a dual filtration, input and output.
L'invention couvre aussi la chaîne de fabrication utilisant au moins un isolateur selon la présente invention.  The invention also covers the production line using at least one insulator according to the present invention.
L'invention vise également un isolateur prêt à l'emploi, intégrant les produits à traiter.  The invention also relates to a ready-to-use isolator integrating the products to be treated.
On sait que de nombreuses sociétés et organismes sanitaires ont à préparer, à conditionner des lots de produits sensibles, notamment pharmaceutiques, en ambiance stérile dite classe A. We know that many companies and health organizations have to prepare, packaging batches of sensitive products, including pharmaceuticals, class A sterile environment.
La présente invention est décrite pour des produits pharmaceutiques mais s'applique à des produits sensibles de façon générale.  The present invention is described for pharmaceuticals but applies to generally sensitive products.
En effet, il existe des produits dont la durée de conservation pris isolément est importante mais dont la durée de conservation après mélange devient très limitée si bien qu'il faut pouvoir produire de petits lots de contenants de volume réduit, au dernier moment, afin de permettre une utilisation au cours de ladite période de conservation.  Indeed, there are products whose shelf life taken alone is important but whose shelf life after mixing becomes very limited so that it is necessary to be able to produce small batches of containers of reduced volume, at the last moment, in order to allow use during the said retention period.
Des lots de fabrication en petites quantités peuvent être élaborés dans des unités de conditionnement général à grande capacité mais la plupart du temps, les conditions économiques ne sont pas compatibles. Small batches of production can be made in large capacity packs, but most of the time the economic conditions are not compatible.
En effet, le changement de fabrication de produits sensibles sur une chaîne industrielle de l'industrie pharmaceutique nécessite des étapes de sanitarisation complexes et très coûteuses.  Indeed, the change of manufacturing of sensitive products on an industrial chain of the pharmaceutical industry requires complex and very expensive sanitarization steps.
Il existe donc des isolateurs qui permettent la fabrication et le conditionnement de lots de produits pharmaceutiques en nombre plus restreint, qui offrent les mêmes garanties d'asepsie que les lignes de grandes capacité, qui permettent un travail identique de manipulation pour les transferts comme pour le conditionnement et qui sont à usage unique, ce qui évite le traitement de sanitarisation qui serait nécessaire pour un réemploi. Ces isolateurs sont également livrés démontés avec une structure modulaire, si bien que le transport et le stockage sont également peu coûteux, peu contraignants. There are therefore insulators that allow the manufacture and packaging of batches of pharmaceuticals in smaller numbers, which offer the same guarantees of asepsis that the lines of large capacity, which allow identical handling work for transfers as for the conditioning and which are disposable, which avoids the sanitarization treatment that would be required for re-use. These insulators are also supplied dismantled with a modular structure, so that the transport and the storage are also inexpensive, not very constraining.
Des liaisons avec des sas permettent de relier plusieurs isolateurs afin de constituer une chaîne.  Links with airlocks make it possible to connect several insulators in order to constitute a chain.
Les besoins sont généralement d'au moins deux chambres, l'une en classe B et l'autre finale en classe A.  The requirements are generally at least two rooms, one in class B and the other in class A.
Les Bonnes Pratiques de Fabrication (BPF) s'appliquent aux établissements pharmaceutiques en Union Européenne par exemple. Les normes ont tendance à être homogénéisées.  Good Manufacturing Practices (GMP) apply to pharmaceutical establishments in the European Union for example. Norms tend to be homogenized.
Ces bonnes pratiques ont fait l'objet d'une normalisation et les critères sont récapitulés dans le tableau ci-dessous. These good practices have been standardized and the criteria are summarized in the table below.
Figure imgf000004_0001
Figure imgf000004_0001
Les conditions au repos peuvent être respectées mais en activité, cela reste beaucoup plus difficile. The conditions at rest can be respected but in activity, it remains much more difficult.
Il est une condition impérative, c'est le caractère laminaire du flux émis de façon à limiter les perturbations.  It is an imperative condition, it is the laminar nature of the flow emitted so as to limit the disturbances.
C'est ainsi que l'on connaît par la demande de brevet français au nom de la société Disposabie Lab N° 1670675 du 10/11/2016 qui décrit un dispositif de diffusion d'un fluide gazeux dans un isolateur pour la manipulation de produits sensibles tels que des médicaments.  Thus, it is known from the French patent application on behalf of the company Disposabie Lab No. 1670675 of 10/11/2016 which describes a device for diffusing a gaseous fluid in an insulator for handling products. sensitive ones such as drugs.
Ce dispositif comporte au moins un conduit positionné sur une face intérieure d'au moins une paroi de l'isolateur, de façon particulière la face supérieure. Ce au moins un conduit possède des trous de diamètre et de répartition donnés, de façon à limiter les turbulences. De même, pour respecter toutes les contraintes il faut aussi éviter tout retour par la sortie, lors d'une panne d'alimentation en air sous pression et/ou en exerçant un mouvement susceptible de créer une aspiration par la sortie. This device comprises at least one duct positioned on an inner face of at least one wall of the insulator, in particular the upper face. This at least one pipe has holes of given diameter and distribution, so as to limit turbulence. In the same way, to respect all the constraints, it is also necessary to avoid any return through the outlet, during a failure of the pressurized air supply and / or by exerting a movement likely to create a suction through the outlet.
Une autre condition souhaitable est de pouvoir travailler en air neuf intégral et de rejeter un air directement à l'atmosphère. C'est le but de la présente invention de proposer un isolateur qui soit adapté pour répondre à ces problématiques.  Another desirable condition is to be able to work in full fresh air and to discharge air directly to the atmosphere. It is the object of the present invention to provide an insulator that is adapted to respond to these problems.
L'invention propose également une chaîne de fabrication intégrant au moins un isolateur selon la présente invention.  The invention also proposes a production line integrating at least one insulator according to the present invention.
L'invention est maintenant décrite en détail, suivant un mode de réalisation particulier, non limitatif, en regard des dessins annexés, dessins sur lesquels les différentes figures représentent :  The invention is now described in detail, according to a particular embodiment, not limiting, with reference to the accompanying drawings, drawings in which the different figures represent:
- Figure 1 : une vue en perspective de deux isolateurs selon la présente invention, FIG. 1: a perspective view of two insulators according to the present invention,
- Figure 2 : une vue en coupe verticale d'un des isolateurs de ia figure 1, 2: a vertical sectional view of one of the insulators of FIG.
- Figure 3 : une vue d'une chaîne de conditionnement intégrant notamment deux isolateurs selon la présente invention  FIG. 3: a view of a packaging line incorporating in particular two insulators according to the present invention
- Figure 4 : isolateurs selon l'invention prêts à servir.  - Figure 4: insulators according to the invention ready to serve.
Sur les figures 1 et 2, on a représenté deux isolateurs jumelés, sensiblement cubiques dans le mode de réalisation retenu, chaque isolateur comprenant une ossature 10 formant structure de maintien, une enveloppe 12 de confinement en matériau transparent et totalement étanche, suspendue à ladite ossature. L'enveloppe est sensiblement à la forme de l'ossature donc sensiblement cubique et de dimensions inférieures pour y être suspendue. Cette enveloppe est munie d'au moins une paire de gants G de manipulation, soudés sur ladite enveloppe 12, de façon totalement étanche également.  In FIGS. 1 and 2, there are shown two twin insulators, substantially cubic in the embodiment chosen, each insulator comprising a framework 10 forming a holding structure, a containment envelope 12 of transparent material and completely sealed, suspended from said frame . The envelope is substantially in the shape of the frame so substantially cubic and smaller dimensions to be suspended. This envelope is provided with at least one pair of gloves G handling, welded to said casing 12, also completely waterproof.
L'ossature est avantageusement un ensemble de barres 10-1 avec des noix 10-2 de connexion de façon à former des cubes. Ces barres 10-1 sont, de façon avantageuse, métalliques, en acier inoxydable, de façon à leur conférer la résistance mécanique suffisante et une possibilité de stérilisation si nécessaire, par ia chaleur ou par projection de solutions stérilisantes, sans dégradation. Ces ossatures sont réutilisables avec des enveloppes neuves. Ces ossatures ne doivent respecter que le degré de stérilisation du local dans lequel est disposée l'installation. Ces ossatures reposent sur une table de travail T de façon à placer la face inférieure du cube sur ladite table T et à bénéficier d'une surface de travail rigide et plane. . Les enveloppes 12 sont généralement rapportées sur l'ossature 10 et plus particulièrement sur les barres au moyen de pattes 12-1 solidaires des arêtes de ladite enveloppe, les fixations des pattes sur elles-mêmes étant des fixations à pressions, autour des tubes. The framework is advantageously a set of bars 10-1 with 10-2 connecting nuts so as to form cubes. These bars 10-1 are advantageously metallic, made of stainless steel, so as to give them sufficient mechanical strength and the possibility of sterilization if necessary, by heat or by spraying sterilizing solutions, without degradation. These frames are reusable with new envelopes. These frames must only respect the degree of sterilization of the room in which the installation is located. These frames rest on a worktable T so as to place the underside of the cube on said table T and to benefit from a rigid and flat work surface. . The envelopes 12 are generally attached to the framework 10 and more particularly to the bars by means of lugs 12-1 integral with the edges of said envelope, the fasteners of the lugs on themselves being pressure fasteners around the tubes.
Selon la présente invention, il est prévu une entrée d'air 14S sur la face supérieure de l'enveloppe et une sortie d'air 141 pour chaque isolateur sur la face inférieure de l'enveloppe. L'entrée et la sortie d'air comporte chacune un module supérieur 16S et un module inférieur 161. Ces modules sont solidaires de façon étanche des enveloppes mais démontables. According to the present invention, there is provided an air inlet 14S on the upper face of the casing and an air outlet 141 for each insulator on the underside of the casing. The inlet and the air outlet each comprise an upper module 16S and a lower module 161. These modules are sealingly attached to the envelopes but removable.
En effet, les modules sont solidarisés aux barres de l'ossature Indeed, the modules are joined to the bars of the frame
Chaque module 16 comprend des moyens de ventilation supérieurs 18S et inférieurs 181 ainsi que des moyens de filtration supérieurs 20S et inférieurs 201.  Each module 16 comprises upper 18S and lower ventilation means 181 and upper 20S and lower filtration means 201.
Les moyens de ventilation supérieurs 18S injectent de l'air en partie supérieure, c'est-à-dire injectent de l'air ambiant périphérique à l'isolateur dans l'enceinte confinée de l'enveloppe dudit isolateur. On constate l'absence de recyclage. L'air ambiant est lui-même déjà traité, généralement en classe D ou ISO 8, c'est-à-dire 3 500000 particules < 0,5 μ ι au maximum, de façon à ne pas saturer les moyens de filtration.  The upper ventilation means 18S inject air into the upper part, that is to say inject peripheral ambient air to the insulator in the confinement of the envelope enclosure of said insulator. There is no recycling. The ambient air is itself already treated, generally in class D or ISO 8, that is to say 3,500,000 particles <0.5 μ ι maximum, so as not to saturate the filtration means.
Les moyens de ventilation inférieurs 18f extraient l'air en classe adaptée A ou B de l'enveloppe de l'isolateur en partie inférieure, vers l'extérieur. L'introduction en partie supérieure et l'extraction en partie inférieure génèrent un flux d'air suivant une direction sensiblement verticale dans l'enceinte de confinement constituée par l'enveloppe, la circulation étant sensiblement laminaire.  The lower ventilation means 18f extract air adapted class A or B from the envelope of the insulator in the lower part, outwards. The introduction in the upper part and the extraction in the lower part generate an air flow in a substantially vertical direction in the confinement enclosure constituted by the envelope, the circulation being substantially laminar.
En effet, le flux n'étant pas perturbé par une entrée et/ou une sortie focalisée en un point, les turbulences d'entrée et de sortie sont supprimées.  Indeed, the flow is not disturbed by an input and / or an output focused at a point, the input and output turbulence are suppressed.
Les moyens de filtration sont avantageusement constitués d'un filtre du type commercialisé sous la dénomination HEPA {High Efficiency Particulate Air) H 14, à flux laminaire ou tout filtre équivalent.  The filtration means are advantageously constituted by a filter of the type marketed under the name HEPA (High Efficiency Particulate Air) H 14, laminar flow or any equivalent filter.
De façon adaptée, la surface du filtre couvre la majorité de la face supérieure et inférieure de façon à générer un flux laminaire sur toute la section de l'enveloppe.  Suitably, the filter surface covers the majority of the upper and lower faces so as to generate a laminar flow over the entire section of the envelope.
De plus, en cas de panne ou de façon accidentelle, si de l'air venait à être aspiré de la sortie vers l'entrée d'air ou juste au sein de l'enveloppe, cet air aspiré de façon inappropriée par la sortie serait filtré de la même manière puisque les filtres sont identiques et de performances de filtration identiques en entrée/sortie ou en sortie/entrée. Le volume interne de l'air confiné par l'enveloppe est toujours traité et les produits éventuellement contenus et non encore conditionnés seraient préservés dans leur intégrité et leurs qualités aseptiques. Moreover, in case of a breakdown or accidentally, if air was to be sucked from the outlet to the air inlet or just inside the envelope, this air sucked inappropriately by the exit would be filtered in the same way since the filters are identical and filter performance identical in input / output or output / input. The internal volume of the air confined by the envelope is always treated and the products possibly contained and not yet conditioned would be preserved in their integrity and their aseptic qualities.
Chaque isolateur comporte en sortie une vanne de contrôle 22 de la pression interne de l'enveloppe 12.  Each insulator comprises at the output a control valve 22 of the internal pressure of the envelope 12.
En effet, en réglant la fermeture/ouverture de cette vanne de contrôle 22, on obtient un ralentissement du flux en sortie si bien que la pression interne augmente ou une accélération du flux en sortie si bien que la pression interne diminue.  Indeed, by adjusting the closing / opening of this control valve 22, there is a slowing of the output flow so that the internal pressure increases or an acceleration of the output stream so that the internal pressure decreases.
L'isolateur selon l'invention émet un flux d'air laminaire du haut vers le bas, qui est filtré en entrée comme en sortie en fonctionnement normal ou filtré en sortie devenue entrée lors d'une ré-aspiration accidentelle par exemple liée à un défaut de l'installation, préservant ainsi les produits confinés dans l'enveloppe 12.  The insulator according to the invention emits a laminar air flow from the top to the bottom, which is filtered at the inlet and at the outlet during normal operation or filtered at the outlet which has become input during an accidental re-aspiration, for example linked to a defect of the installation, thus preserving the products confined in the envelope 12.
Le filtre est prémonté sur l'enveloppe par des brides étanches liées à l'enveloppe. Les moyens de ventilation sont rapportés sur les brides pour souffler ou extraire l'air à travers le filtre correspondant.  The filter is pre-mounted on the envelope by sealed flanges bound to the envelope. The ventilation means are attached to the flanges to blow or extract the air through the corresponding filter.
De façon avantageuse, les moyens de ventilation sont fixés sur l'ossature par des noix. Il suffit de changer l'enveloppe pour remettre le dispositif opérationnel.  Advantageously, the ventilation means are fixed on the framework by nuts. Just change the envelope to put the device back into operation.
Selon la présente invention, il est prévu une chaîne 24 de conditionnement et de remplissage comprenant deux isolateurs 24-1 et 24-2 de conditionnement, classes A et B, un isolateur 24- 3 de préparation et un isolateur d'introduction des matières premières 24-4. Des sas permettent de connecter à la demande deux isolateurs juxtaposés, cette connexion étant volontaire et maîtrisée par l'opérateur.  According to the present invention, there is provided a conditioning and filling chain 24 comprising two insulators 24-1 and 24-2 for conditioning, classes A and B, a preparation isolator 24- 3 and an insulator for introducing raw materials. 24-4. Airlock can connect two insulators juxtaposed on demand, this connection is voluntary and controlled by the operator.
L'isolateur d'introduction des matières premières 24-4 comprend les contenants de produits à conditionner, éventuellement à mélanger préalablement, sous forme de fluides et/ou pâtes et/ou poudres, les contenants finaux, les moyens de contrôle de poids et/ou de volume, nécessaires pour les dosages.  The insulator of introduction of raw materials 24-4 comprises the containers of products to be packaged, possibly to be mixed beforehand, in the form of fluids and / or pastes and / or powders, the final containers, the weight control means and / or volume, necessary for dosages.
Ces produits sont généralement contenus dans des emballages et soumis à un bombardement aux rayons Gamma pour stériliser le contenu. Ces produits sont placés dans l'isolateur d'introduction des matières premières 24-4 pour y subir une stérilisation à l'azote ou au peroxyde d'hydrogène. Ils sont ensuite transférés dans l'isolateur 24-3 où ils sont déballés pour retirer les emballages, ceci également sous atmosphère d'azote ou de peroxyde d'hydrogène pour conserver la stérilisation extérieure des produits. These products are usually packaged and gamma ray bombarded to sterilize the contents. These products are placed in the feed insulator 24-4 to undergo sterilization with nitrogen or hydrogen peroxide. They are then transferred to the insulator 24-3 where they are unpacked to remove the packaging, this also under nitrogen or hydrogen peroxide to maintain the external sterilization of the products.
Les contenants et autres outils de conditionnement sont introduits dans l'isolateur 24-2 de classe B. Les emballages restent dans l'isolateur 24-3.  Containers and other packaging tools are introduced into the 24-2 Class B isolator. The packages remain in the 24-3 isolator.
L'isolateur 24-2 dispose de filtres identiques à ceux de l'isolateur 24-1 mais la pression P2 régnant dans cet isolateur 24-2 est inférieure à la pression régnant dans l'isolateur 24-1. Les contenants et autres outils sont donc traités dans ce premier isolateur afin de les débarrasser des particules et de les mettre en condition pour accéder à l'isolateur final de conditionnement de classe A dans lequel le taux de particules comme indiqué dans le préambule, est très limité.  The insulator 24-2 has filters identical to those of the insulator 24-1 but the pressure P2 prevailing in this insulator 24-2 is lower than the pressure prevailing in the insulator 24-1. The containers and other tools are therefore treated in this first isolator in order to remove the particles and put them in condition to access the final class A conditioning insulator in which the particle ratio as indicated in the preamble, is very limit.
La pression PI régnant dans l'isolateur 24-1 étant supérieure, l'atmosphère de l'isolateur 24- Since the pressure P1 prevailing in the insulator 24-1 is greater, the atmosphere of the insulator 24-
2 avec son taux de particules reste confinée dans l'enceinte de cet isolateur 24-2 et les contenants et autres outils de conditionnement entrent dans l'isolateur 24-1, débarrassés de leurs particules et sont soumis à un flux laminaire d'air sans particules. 2 with its particle content remains confined in the enclosure of this insulator 24-2 and the containers and other conditioning tools enter the insulator 24-1, free of their particles and are subjected to a laminar flow of air without particles.
Durant le transfert, la circulation du flux d'air s'effectue de l'isolateur 24-1 vers l'isolateur 24- During the transfer, the flow of air flows from isolator 24-1 to isolator 24.
2. 2.
Dans l'isolateur 24-1, l'opérateur peut déboucher les contenants et assurer le dosage et le remplissage des contenants de volumes réduits, effectuer les préparations et toutes opérations de mélange préalablement si nécessaire, ceci sous atmosphère de classe A donc sans possibilité d'introduire de particules dans les conditionnements de volume réduit simultanément au produit ou au mélange de produits.  In the insulator 24-1, the operator can unclog the containers and ensure the dosing and filling of containers of reduced volumes, make the preparations and any mixing operations beforehand if necessary, this in class A atmosphere, therefore without the possibility of introducing particles into the reduced volume packages simultaneously with the product or mixture of products.
Ces contenants de volume réduit, remplis et rebouchés, sont alors prêts pour être évacués à l'extérieur de l'isolateur 24-1 de classe A par le sas adapté, ceci de façon connue.  These containers of reduced volume, filled and refilled, are then ready to be discharged outside the insulator 24-1 class A by the adapted lock, this in a known manner.
Le contenu des contenants de volume réduit est donc stérile. The content of containers of reduced volume is therefore sterile.
La figure 4 représente une possibilité de produire industriellement un isolateur unique avec les produits et outils de conditionnement avec les contenants de volume réduit directement dans l'enceinte, les différentes étapes ayant été réalisées préalablement de façon industrielle. L'isolateur est alors un isolateur pré-stérilisé de classe A, directement, car il n'y a pas de besoin de stérilisation supplémentaire.  FIG. 4 represents a possibility of industrially producing a single insulator with the products and packaging tools with containers of reduced volume directly in the enclosure, the various steps having been previously carried out industrially. The isolator is then a pre-sterilized Class A isolator directly because there is no need for additional sterilization.
L'isolateur peut aussi être stérilisé sur place à l'Azote ou au Peroxyde d'Hydrogène. Les isolateurs sont aussi souvent re-stérilisés avant destruction surtout lorsque les reconditionnements ont visé des produits sensibles BSL2 (Biosafety Level 2) ou BSL3 (Biosafety Level 3) impliquant des microbes. The insulator can also be sterilized on site with Nitrogen or Hydrogen Peroxide. Insulators are also often re-sterilized before destruction especially when the repackaging has targeted sensitive products BSL2 (Biosafety Level 2) or BSL3 (Biosafety Level 3) involving microbes.

Claims

REVENDICATIONS
1. Isolateur à usage unique pour la fabrication de lots de produits sensibles, notamment des médicaments, en ambiance stérile, comprenant une ossature (10) et une enveloppe (12} suspendue à ladite ossature (10), une entrée d'air (14S) supérieure sur la face supérieure de l'enveloppe (12) et une sortie d'air (141) sur la face inférieure de l'enveloppe (12), caractérisé en ce que lesdites entrée et sortie d'air (14S, 141) sont équipées respectivement d'un module supérieur (16S) et d'un module inférieur (161) comportant des moyens de ventilation supérieurs (18S) et inférieurs (181) ainsi que des moyens de filtration supérieurs (20S) et inférieurs (201). 1. Single-use isolator for manufacturing batches of sensitive products, including drugs, in a sterile environment, comprising a framework (10) and an envelope (12) suspended from said framework (10), an air inlet (14S ) on the upper face of the casing (12) and an air outlet (141) on the underside of the casing (12), characterized in that said air inlet and outlet (14S, 141) are respectively equipped with an upper module (16S) and a lower module (161) having upper (18S) and lower (181) ventilation means as well as upper (20S) and lower (201) filtration means.
2. Isolateur à usage unique pour ia fabrication de lots de produits sensibles selon la revendication 1, caractérisé en ce que les moyens de filtration supérieur et inférieur (20S, 201) comprennent chacun un filtre du type HEPA H14 laminaire.  2. Single-use isolator for the manufacture of batches of sensitive products according to claim 1, characterized in that the upper and lower filtration means (20S, 201) each comprise a laminar HEPA H14 type filter.
3. Isolateur à usage unique pour la fabrication de lots de produits sensibles selon la revendication 2, caractérisé en ce que le filtre est monté dans un cadre solidarisé à l'enveloppe.  3. Single-use isolator for the manufacture of batches of sensitive products according to claim 2, characterized in that the filter is mounted in a frame secured to the casing.
4. Isolateur à usage unique pour la fabrication de lots de produits sensibles selon l'une quelconque des revendications précédentes, caractérisé en ce qu'il comporte, en sortie, une vanne de contrôle (22) de la pression interne de l'enveloppe (12).  4. Single-use isolator for the manufacture of batches of sensitive products according to any one of the preceding claims, characterized in that it comprises, at the output, a control valve (22) of the internal pressure of the envelope ( 12).
5. Chaîne de conditionnement et de remplissage (24) comprenant deux isolateurs (24-1, 24-2) de conditionnement, classes A et B, selon l'une quelconque des revendications précédentes, un isolateur (24-3) de préparation et un isolateur d'introduction des matières premières (24-4), reliés entre eux par des sas permettant de connecter, à la demande, deux desdits isolateurs juxtaposés.  A packaging and filling line (24) comprising two conditioning isolators (24-1, 24-2), classes A and B, according to any one of the preceding claims, an isolator (24-3) for preparing and an insulator of introduction of the raw materials (24-4), interconnected by airlock allowing to connect, on demand, two of said insulators juxtaposed.
6. Isolateur à usage unique pour le conditionnement et le remplissage en contenants de volume réduit selon l'une quelconque des revendications 1 à 4, comprenant les contenants de produits à conditionner, éventuellement à mélanger préalablement, sous forme de fluides et/ou pâtes et/ou poudres, les contenants de volume réduit, les moyens de contrôle de poids et/ou de volume, nécessaires pour les dosages, l'ensemble ayant été stérilisé préalablement.  6. Disposable isolator for packaging and filling in reduced volume containers according to any one of claims 1 to 4, comprising the containers of products to be packaged, optionally to be mixed beforehand, in the form of fluids and / or pastes and / or powders, containers of reduced volume, weight control means and / or volume, necessary for the assays, the assembly having been previously sterilized.
PCT/FR2018/000138 2017-05-24 2018-05-24 Single-use isolator with laminar flow and double filtration WO2018215704A1 (en)

Priority Applications (3)

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EP18737332.9A EP3630424A1 (en) 2017-05-24 2018-05-24 Single-use isolator with laminar flow and double filtration
GB1919306.9A GB2577835B (en) 2017-05-24 2018-05-24 Double-filtration laminar-flow single-use isolator
CA3100754A CA3100754C (en) 2017-05-24 2018-05-24 Single-use isolator with laminar flow and double filtration

Applications Claiming Priority (2)

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FR1770535A FR3066712B1 (en) 2017-05-24 2017-05-24 ISOLATOR FOR SINGLE USE, LAMINAR FLOW AND DOUBLE FILTRATION
FR1770535 2017-05-24

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GB2566552B (en) * 2017-09-19 2023-07-19 Solo Containment Ltd Flexible enclosure

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0342599U (en) * 1989-09-01 1991-04-22
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2772827B2 (en) * 1989-07-10 1998-07-09 四国電力株式会社 Radioactive oil-containing waste liquid treatment equipment

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0342599U (en) * 1989-09-01 1991-04-22
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

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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
GB201919306D0 (en) 2020-02-05
CA3100754C (en) 2023-07-04
GB2577835A (en) 2020-04-08

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