WO2016189266A1

WO2016189266A1 - A sterilized sachet and a method of manufacturing same

Info

Publication number: WO2016189266A1
Application number: PCT/GB2016/000105
Authority: WO
Inventors: Guy Braverman; Gabriel Bradley
Original assignee: Gama Healthcare Ltd
Priority date: 2015-05-28
Filing date: 2016-05-25
Publication date: 2016-12-01
Also published as: GB201720071D0; GB201509161D0; GB2555309A; GB2555309B

Abstract

A sterilized sachet (1) comprises a sealed impervious pouch (2) containing a biocide (4). The pouch (2) but not the biocide (4) has been sterilized by irradiation prior to having been filled with the biocide (4) and sealed. Preferably, the biocide (4) comprises chlorhexidine gluconate. Irradiation of the pouch (2) prior to filling ensures that a sterile sachet is produced that does not contain any degradation products with undesirable carcinogenic properties that are often the result of the irradiation of biocides such as those containing chlorhexidine gluconate. A method of manufacturing the sachet is also disclosed comprising the steps of providing one or more sheets of an impervious laminate; forming a pouch (2) from the laminate; sterilizing the pouch (2) by irradiation; and filling the sterilized pouch (2) with the biocide (4) prior to sealing the edges of the pouch (2) to produce the sachet (1). Preferably, a piece of dry absorbent material (7) is located within the pouch (2) and sterilized by irradiation with the pouch (2) prior to filling of the pouch (2) with the biocide (4). The material (7) absorbs the biocide (4) and forms a swab or wipe for use when the sachet (1) is opened.

Description

A STERILIZED SACHET AND

A METHOD OF MANUFACTURING SAME

The present invention relates to a sterilized sachet and to a method of manufacturing same for use in disinfection, primarily of the skin of a human or animal prior to a medical procedure.

The need for disinfection of the skin prior to small surgical site interventions, procedures such as cannulation, or in routine community health operations such as blood donor sessions has been well recognised for many years. Early products were simple alcohol swabs or small sachet wipes in which the alcohol was usually present at concentrations between 60-90% v/v. More recently, it became recognised that skin disinfection and improved performance in procedure outcome could be obtained by adding cationic biocides to the aqueous alcohol solution. The most successful of these additions is that of 2-4% w/v chlorhexidine as a gluconate or an acetate salt because the cationic nature of the chlorhexidine gives it the property of binding to the skin and of imparting a persistent residual antimicrobial activity providing protection several hours beyond an initial application. Also, chlorhexidine gluconate is an effective broad-spectrum topical antiseptic as it is effective against both gram-positive and gram-negative bacteria.

As 70% v/v alcohol and the 70% v/v alcohol plus chlorhexidine products are known to be excellent skin degerming compositions, hitherto it has not been thought necessary to sterilise items incorporating such formulations, for example swabs, individual sachet wipes and the like, even though these products are routinely used at sites where the skin barrier is broken or is about to be broken. However, concern has been expressed that alcohol does not have a total spectrum of activity and it is possible for bacterial spores to survive for long periods in alcohol-based formulations. The addition of chlorhexidine to such formulations does not alter this situation. Recently, a number of cases of infection from small surgical sites (SSIs), including catheterisation, cannulation and injection have occurred. There have also been cases of serious infection and even death from non- sterile skin degerming products. Accordingly, sterile products have been introduced into this area of use as has increased regulation. The most commonly used method of sterilizing sealed packs and sachets containing impregnated wipes is by irradiation using gamma rays or particle beam sterilisation processes. However, a particular problem has been found with those products that contain chlorhexidine as this form of sterilisation has been shown to create unacceptable levels of degradation products, notably p-chloraniline, that have undesirable carcinogenic properties. This renders such products unusable and outside the parameters imposed by national regulatory bodies. Sterilisation by heat also generates similar levels of these degradation products. Autoclaving under heat and pressure has been claimed to produce sterile products within safe limits for degradation products but this is debatable and autoclaving can only be used for rigid containers such as glass vials, which can resist the pressures involved. Autoclaving cannot be used for flexible sachets, which either expand and burst or deform under the applied heat and pressure.

The use of sealed glass ampoules containing a skin degerming composition that is released when the ampoule is broken by a specialized mechanism at the time of application is impractical in many healthcare situations. It will be appreciated that in a modern healthcare setting, such as the National Health Service in the United Kingdom, there is a requirement for tens of millions of these skin preparation products every year. The use of a sealed glass ampoule that requires a specialized mechanism to break it may provide an article of choice to a healthcare practitioner but the cost differential between it and a conventional unsterilized sachet containing a wipe or swab is considerable and often unaffordable, despite the regulatory and litigious pressures which healthcare providers are under. There is therefore a need for an inexpensive sterile alternative. The object of the present invention is substantially to fulfil said need.

According to a first aspect of the present invention there is provided a sterilized sachet comprising a sealed impervious pouch containing a biocide, the pouch but not the biocide having been sterilized by irradiation prior to having been filled with the biocide and sealed.

According to a second aspect of the present invention there is provided a method of manufacturing a sterilized sachet comprising the steps of

providing one or more sheets of an impervious laminate;

forming a pouch from said laminate;

sterilizing the pouch by irradiation;

filling the sterilized pouch with a biocide and sealing the edges of the pouch to produce the sachet.

Preferably, the method comprises the additional steps of

enclosing the pouch within a sealed wrap prior to sterilization;

sterilizing the wrapped pouch;

locating the wrapped pouch within a sterile environment and removing the wrap prior to filling; and

filling the pouch and sealing the edges of the pouch to produce the sachet prior to removal of same from the sterile environment.

Preferably, the biocide comprises chlorhexidine gluconate. However, it will be appreciated that other biocides that are deleteriously affected by irradiation may be used. Advantageously, the biocide comprises a solution containing chlorhexidine gluconate at up to 6% w/v concentration and an alcohol at a concentration between 40% v/v and 90% v/v of the solution. Preferably also, the alcohol comprises isopropyl alcohol, n-propanol or ethanol at a concentration between 65% v/v and 85% v/v of the solution.

Preferably also, the sachet comprises a sterilized, absorbent material that is impregnated with the biocide. The absorbent material is preferably located within the pouch prior to the pouch being enclosed by the sealed wrap whereby it is irradiated at the same time as the pouch.

Preferably also, pouch is made from a weldable, flexible laminate in order that the edges of the sachet are sealed by welds. Advantageously, the laminate comprises layers including at least one impervious layer and at least one weldable plastics layer on one side. For example, the laminate may comprise a polyester or polythene layer along with aluminium foil and, optionally, paper layers where the aluminium foil layer is the impervious layer.

Preferably also, the laminate is capable of withstanding gamma ray irradiation at up to 40kGy inclusive. The various aspects of the present invention will now be described by way of example with reference to the accompanying drawings, in which:-

Fig. 1 is a schematic representation of a sterilized sachet in accordance with the present invention;

Fig. 2 is a cross-section of the sachet shown in Fig. 1 along the line II- II and to an enlarged scale;

Figs. 3 to 6 are schematic views showing a sequence of steps in a method of manufacture in accordance with the second aspect of the present invention of a plurality of sterilized sachets as shown in Figs. 1 and 2. An example of a sterilized sachet l in accordance with the present invention is shown in Fig. l. It comprises a pouch 2 made from a piece of material that has been folded and sealed around its edges 3 or made from two pieces of material sealed together around all of their edges 3 in order to envelope a biocide 4 thereby forming the sachet 1. As is described below, during manufacture the pouch 2 is sterilized by irradiation prior to it being filled with the biocide 4 and sealed to form the sachet 1. The inside of the sachet 1 is thereby sterilized so that the biocide 4 is itself stored in a sterile environment prior to use. Also, the pouch 2 is made of an impervious material in order that its interior and contents remain sterile, contaminants being prevented from penetrating into the interior of the sachet 1 after manufacture and prior to use. This is achieved by making the pouch 2 from a laminate that has at least one layer which is an impervious material, for example a suitable plastics layer or more preferably a layer of aluminium foil. Preferably also, the laminate is a flexible, weldable laminate in order that the edges 3 of the pouch 2 are sealed by welds as opposed to by a separately applied adhesive, such as a hot melt adhesive, to form the sachet 1. This enables the sachet 1 to be manufactured, as described below, using a specially adapted but otherwise conventional fill, form and seal sachet machine. Hence, the laminate used in the manufacture of a pouch 2 for a sachet 1 in accordance with the present invention preferably comprises at least one outer layer 5 that is a weldable plastics layer, for example made of polyester or polythene, and an aluminium foil layer 6. Other layers may also be included, for example a paper layer may be applied over the aluminium foil layer 6 that can be pre-printed with appropriate information relating to the sachet 1, its contents and use. It will be appreciated that during manufacture of the pouch 2 the weldable plastics layer 5 is to the inside of the pouch 2. Also, although the pouch 2 may be manufactured with welds along all of its edges 3, as shown in Fig.i, it is also possible for the pouch 2 to be manufactured by folding a length of an appropriate laminate and welding down two opposing edges. In practice, in some conventional fill, form and seal sachet machine lengths of the laminate are pulled from a reel, folded in half lengthwise and then chopped into appropriately sized widths dependent on the size of sachet required. The two opposing edges of the chopped lengths are sealed to form the pouch 2 which is then filled and sealed along its remaining edge to form the sachet. In the present invention, this operation is interrupted after formation of the pouch 2 to enable the sachet 1 to be sterilized prior to filling as is described below.

The biocide 4 used in the sachet 1 may take any appropriate form, for example liquid, cream or gel, but it should be pumpable so that it can be handled by the fill, form and seal sachet machine as described below. It should be prepared to a pharmacopoeia specification compliant with the final product classification and appropriate steps taken to minimise any bioburden. Preferably, the biocide comprises chlorhexidine gluconate, for example in an aqueous solution, an aqueous alcoholic solution or a purely alcoholic solution. Preferably, the biocide 4 comprises a solution containing chlorhexidine gluconate at at least a 2% w/v concentration. In particular, the biocide 4 comprises an aqueous alcoholic solution containing chlorhexidine gluconate at up to 6% w/v concentration and an alcohol at a concentration between 40% v/v and 90% v/v of the solution. Advantageously the alcohol comprises isopropyl alcohol, n-propanol or ethanol at a concentration between 65% v/v and 85% v/v of the solution.

Whilst the sachet 1 may contain only the biocide 4, preferably it also comprises a sterilized, absorbent material 7 that is impregnated with the biocide 4.The absorbent material 7 thereby forms a swab or wipe that can be used to apply the biocide to the skin of a patient or animal to be treated. As it is important that the interior of the sachet 1 is sterile, the absorbent material 7 is also sterilized, preferably by irradiation, while it is dry. As the biocide 4 is not irradiated, a piece of the dry material 7 or a swab comprising absorbent material such as a swab stick is located within the pouch 2 and irradiated along with the pouch 2 prior to filling of the pouch 2 with the biocide 4. The material 7 must therefore also be capable of withstanding gamma ray irradiation and is preferably capable of withstanding same up to 40kGy inclusive. On filling of the pouch 2, the material 7 absorbs the biocide 4 to form the swab or wipe for use when the sachet 1 is opened.

The material 7 may comprise, for example, a woven, knitted, sponge or nonwoven swab, wipe, towelette, or swab stick that is made from any or a variety of polymers in fibre or sponge form. Examples of such polymers are polypropylene, polyethylene, polyester, viscose, cotton, paper bamboo, polyurethane, polyamide, polyacrylate and other synthetic or natural fibres. One particularly appropriate absorbent material 7 comprises a spunlace nonwoven material made from polyethylene terephthalate (PET) fibres. Preferably, this material has a weight between 90 and 110 g/m², advantageously 100 g/m² and a thickness between 0.85 and 1.15 mm, advantageously 1.0 mm. In addition, its liquid absorptive capacity is preferably between 600% and 1200%, advantageously 900% using the NonWovens Standard Procedure 10.1 (NWST 10.1).

A sachet 1 comprising such a material 7 in a wipe or swab stick form with a biocide 4 comprising a solution containing chlorhexidine gluconate at at least a 2% w/v concentration is suitable for use both immediately prior to an invasive medical treatment and also as a pre-surgery body wash and microbial decolonizer, in particular with regard to the decolonization of MRSA and other antibiotic-resistant bacteria. When used as a pre-surgery body wash, one or more sachets 1 in accordance with the invention may be used to apply the biocide 4 to patient's skin at least one day, before the surgical procedure in order to cumulatively reduce skin bacteria levels before pre-surgical preparation, which takes place immediately prior to surgery or invasive procedure. This can significantly reduce the risk of a post-surgical infection occurring. The use of several sachets 1 in this way enables the whole of the patient's body to be cleansed, different sachets 1 being used on different parts of the body to reduce the risk of cross- contamination. A method of manufacturing a sachet l in accordance with the present invention will now be described. The method uses a conventional fill, form and seal sachet machine that has been adapted as described below. First, the machine is adapted when forming the sachets l to form a pouch 2 rather than a completely sealed sachet l. For example, in machines adapted to form rectangular sachets the machines is adapted to leave one edge or part of one edge unsealed so that pouches 2 are formed instead. Second, the machine is mechanically and electronically disabled to omit any liquid filling stage.

Once adapted, the machine is supplied with lengths of the laminate to be used to manufacture the sachet l and the absorbent material 7 to be inserted into the sachets 1. The machine then operates in a conventional fashion to form the pouches 2 in each of which is inserted the absorbent material 7 in the required form. Although the machine only partially seals the laminate sheet or sheets together to form each pouch 2, the machine still applies pressure to the pouch 2 to exclude air. Preferably, the pouches 2 are retained in an inverted position by the machine with their lower edges unsealed. The pressure exerted by the machine therefore holds the material 5 in place inside each pouch 2 in addition to excluding air, thereby preventing airborne particles from settling into the pouches. The machine then operates to fill trays 8 with batches of inverted pouches 2, as shown in Fig. 3. The trays 8 are used to hold the partially filled pouches 2 during sterilization by gamma ray irradiation. As with the laminate and the absorbent material 5, the trays 8 must also be capable of withstanding gamma ray irradiation up to 4okGy inclusive. Such trays 8 may therefore be disposable plastics trays made of polyethylene terephthalate (PET). The filled trays 8 are then made ready for sterilization by irradiation.

To do this a first protective wrap 9, for example a bag of polythene film or similar polymeric film, is applied around the filled tray 8 as shown schematically in Fig 3. This first wrap 9 may be left unsealed one end as shown in Figs. 3 to 5 but in an alternative method may be sealed to enclose the filled tray 8. Thereafter, second and third wraps 10 and 11 of the same or a similar film are then applied over the top of the first wrap 9 as shown respectively in Figs. 4 and 5. Both the second and third wraps 10 and 11 are sealed, as at 12, in order to isolate the tray 8 and its contents completely from the external environment. In order to prevent unnecessary contamination of the tray 8 and its contents before irradiation, the wraps 9, 10 and 11 are preferably applied in a controlled environment such as a "cleanroom" which is designed, maintained, and controlled to prevent particle and microbiological contamination. Such a room should preferably have an appropriate air cleanliness ISO 14644-1 designation.

The wrapped trays 8 are then sterilized by gamma ray irradiation in a conventional manner using gamma rays at up to 4okGy inclusive. Thereafter, appropriate quality control checks compliant to the regulatory requirements for the finished products are carried out and the still wrapped trays 8 are transported to a controlled area, as described above, with an adjoining sterile area. These areas are ones in which the environmental conditions are designed to maintain sterility of the unwrapped tray 8 and its contents. The sterile areas preferably comprise a Class 5 sterile enclosure in accordance with the ISO 14644-1 designation and a Class 7 sterile area in accordance with the ISO 14644-1 designation. Within the Class 5 sterile enclosure is located a second sachet manufacturing machine that has been adapted to fill and seal the pouches 2 in the tray 8 to form the sachets 1, as described below. The first wrap 9 and the sealed wraps 10 and 11 are therefore successively removed in environments that are increasingly more sterile.

First, prior to entry into the Class 7 sterile area the outermost wrap 11, which is likely to have been contaminated externally during transportation to and from the gamma ray irradiating apparatus, is removed from the tray 8. The now double wrapped tray 8 is transferred to the Class 7 sterile area where the second wrap 10 is removed. The tray 8 and its contents is then placed on a feed tray, for example made of stainless steel, that is connected to an inlet of the second machine located in the Class 5 enclosure. If the first wrap 9 has been sealed, the sealed end is now opened. In either case, the tray 8 is located on the feed tray with the open end of the first wrap 9 facing into the sterile Class 5 enclosure. The wrap 9 is then slid clear of the tray 8 when the tray 8 is in the Class 5 enclosure. Hence, the wraps 9, 10 and 11 are each successively removed in environments that meet increasingly higher sterile standards from a regulatory standpoint. The pouches 2 in the unwrapped tray 8 are then fed into the inlet of the second machine, the tray 8 being no longer required can be discarded or retrieved for reuse. Each pouch 2 from the tray 6 is inverted prior to being fed into the second machine so that its unsealed edge is uppermost.

The pouches 2 that are fed into the second machine are handled carefully to ensure that they are maintained in a vertical orientation without any stress that which could distort their dry contents. Each pouch 2 is then presented to vacuum suckers 13 which hold the pouch 2 vertically and transmit the pouch 2 to a filling area. In this area, the unsealed edge of the pouch 2 is opened to form a mouth 14 by the external application of negative pressure to the pouch 2 by the suckers 13. It is important to note that this opening is not accomplished by the more normal procedure of blowing air into a pouch to open it. This negates any risk of contamination from the air supply. The use of negative pressure also removes the need for hydraulic controls for blowing equipment, thereby eliminating any possibility of oil contamination. The pumpable, preferably liquid biocide 4 is then delivered to each opened pouch 2 by a filling needle 15 with a lumen. The needle 15 is preferably comprised of stainless steel. The needle 15 is positioned precisely so that its tip aligns with an open edge of the mouth 14 of the pouch 2. This avoids splash-back from and deformation of the contents of the pouch 2 when the biocide 4 is pumped in. It also ensures a precise volumetric fill of the pouch 2 with an appropriate quantity of the biocide 4. The biocide 4 is pumped into the pouch 2 by a peristaltic pump, preferably a double-head peristaltic pump (not shown), through a micropore filter, preferably a 0.2 micron or lower micropore filter, and thence through the filling needle 15 into the pouch 2. The filter ensures sterile delivery of the biocide 4 under precise calibration. It will be appreciated that batches of the pouches 2 may be simultaneously filled by a bank of filling needles 15. Each filled pouch 2 is then sealed within the second machine to form the sachets 1 while it is still within the Class 5 sterile area. Batches of the sachets 1 are then wrapped and packed as required by regulation for the particular end use. In will be appreciated that the size of the sachet 1 and the quantity and type of the material 7 used along with the quantity of biocide 4 enclosed within the sachet 1 can be adjusted to suit the intended use of the sachet 1.

The sachets 1 in accordance with the present invention therefore have a sterile content. In particular, should the sachet 1 contain a chlorhexidine solution there will be no deleterious breakdown products present. Such a sachet 1 therefore complies with the regulatory requirements for classification as a medical device or PL registered medicinal product.

Claims

A sterilized sachet comprising a sealed, impervious pouch containing a biocide, the pouch but not the biocide having been sterilized by irradiation prior to having been filled with the biocide and sealed.

A sachet as claimed in Claim l, wherein the biocide comprises chlorhexidine gluconate.

A sachet as claimed in Claim 2, wherein the biocide comprises chlorhexidine gluconate in one of an aqueous, an aqueous alcoholic or a purely alcoholic solution.

A sachet as claimed in claimed in Claim 2 or Claim 3, wherein the biocide comprises a solution containing chlorhexidine gluconate at a concentration of at least 2% w/v.

A sachet as claimed in Claim 3 or Claim 4, wherein the biocide comprises a solution containing chlorhexidine gluconate at a concentration of up to 6% w/v inclusive and an alcohol at a concentration between 40% v/v and 90% v/v inclusive of the solution.

A sachet as claimed in Claim 4 or Claim 5, wherein the alcohol comprises isopropyl alcohol, n-propanol or ethanol at a concentration between 65% v/v and 85% v/v inclusive of the solution.

A sachet as claimed in any of Claims 1 to 6, wherein the pouch is made of a weldable, impervious laminate.

A sachet as claimed in Claim 7, wherein the laminate comprises layers including at least one impervious layer and at least one weldable plastics layer on one side.

9. A sachet as claimed in Claim 8, wherein the impervious layer comprises aluminium foil and the weldable layer comprises a polyester or a polythene layer. 10. A sachet as claimed in any of claims 1 to 9, wherein the pouch is capable of withstanding gamma ray irradiation at up to 4okGy inclusive.

11. A sachet as claimed in any of Claims 1 to 10, wherein the pouch contains a sterilized, absorbent material that is impregnated with the biocide.

12. A sachet as claimed in Claim 11, wherein the absorbent material was sterilized by irradiation at the same time as the pouch.

13. A sachet as claimed in Claim 11 or Claim 12, wherein the absorbent material comprises a woven, knitted, sponge or nonwoven swab, wipe, towelette, or swab stick that is made from any or a variety of polymers in fibre or sponge form.

14. A sachet as claimed in Claim 13, wherein the polymer or polymers comprise any or a combination of polypropylene, polyethylene, polyester, viscose, cotton, paper bamboo, polyurethane, polyamide and polyacrylate.

15. A sachet as claimed in Claim 13, wherein the absorbent material comprises a nonwoven material made from polyethylene terephthalate (PET) fibres with a weight between 90 and 110 g/m² and a thickness between 0.85 and 1.15 mm.

16. A method of manufacturing a sterilized sachet comprising the steps of:- providing one or more sheets of an impervious laminate; forming a pouch from said laminate;

sterilizing the pouch by irradiation; and

17. A method as claimed in Claim 16, wherein a piece of dry absorbent material is located within the pouch and sterilized by irradiation with the pouch prior to filling of the pouch with the biocide. 18. A method as claimed in Claim 16 or Claim 17, wherein the pouch is sterilized by gamma ray irradiation at up to 4okGy inclusive.

19. A method as claimed in any of Claims 16 to 18, comprising the additional steps of

enclosing the pouch within a first sealed wrap prior to sterilization;

sterilizing the wrapped pouch;

locating the wrapped pouch within a sterile environment and removing the first sealed wrap prior to filling; and

20. A method as claimed in Claim 19, comprising the additional steps of packing batches of the pouches into trays prior to enclosure by the sealed wrap.

21. A method as claimed in Claim 20, wherein the pouches are packed into the trays in an inverted position with their lower edges unsealed. 22. A method as claimed in Claim 20 or Claim 21, wherein each filled tray is initially enclosed within an unsealed wrap prior to being enclosed within said first sealed wrap prior to sterilization. A method as claimed in Claim 22, wherein each filled tray is enclosed within a second sealed wrap after being enclosed within said first sealed wrap.

A method as claimed in Claim 23, wherein after irradiation the unsealed wrap and the first and second sealed wraps are each successively removed in environments that are increasingly more sterile. 25. A method as claimed in any of Claims 16 to 24, wherein after irradiation the pouch is opened by the external application of negative pressure in order that it can be filled with the biocide.

26. A method as claimed in any of Claims 16 to 25, wherein the pouch is filled with the biocide using a filling needle with a lumen.

27. A method as claimed in Claim 26, wherein the needle is positioned so that its tip aligns with an open edge of the pouch. 28. A method as claimed in any of Claims 16 to 27, wherein the biocide is pumped into the pouch by a peristaltic pump.

29. A method as claimed in any of Claims 16 to 28, wherein the biocide is filtered through a micropore filter prior to filling of the pouch.

30. A method as claimed in Claim 29, wherein the micropore filter is a 0.2 micron or lower micropore filter.