KR20000015840A - Parametric control in pulsed light sterilization of packages and their contents - Google Patents

Abstract

PURPOSE: A flashlamp system is provided to generate a light pulse for sterilizing the microorganisms being in a target object and to inactivate the microorganisms in the target object by illuminating the generated light pulse to the target object. CONSTITUTION: An approach for sterilizing microorganisms at a target object employs a flashlamp system including means for generating pulses of light, and for deactivating microorganisms within the target object by illuminating the target object with the pulses of light having been generated; a photo-sensitive detector positioned so as to receive a portion of each of the pulses of light as a measure of an amount of light illuminating the target object, for generating an output signal in response thereto; and a control system, coupled to the flashlamp system and the photo-sensitive detector, for determining, in response to the output signal, whether the pulses of light are sufficient to effect a prescribed level of deactivation of microorganisms in the target object. In accordance with this approach sterilizing microorganisms involves steps of generating a pulse of light; deactivating microorganisms at the target object by directing the pulse of light having been generated at the target object; receiving a portion of the pulse of light as a measure of an amount of the pulse of light illuminating the target object; generating an output signal in response to the receiving of the portion of the pulse of light; and determining, in response to the generating of the output signal, whether the pulse of light is sufficient to effect a prescribed level of deactivation of microorganisms in the target object.

Description

Parametric Control in Pulsed Light Sterilization of Packaging and Contents

Polyvinyl chloride (PVC) is a small intestine (SVP), large intestine (LVP), often referred to as a mini-bag; Standard widely used plastic packaging material used in the manufacture of flexible containers (bags and pouches) for the supply of various undergarments and liquid preparations. These containers are often used to provide hydration and / or medications, oral medications, vitamins, food, and the like in a patient. Until now, PVC has been heat-resistant, so that the container is finally sterilized using high temperature treatment, i.e., the microorganisms are filled and then the container is sterilized using high temperature treatment (e.g., autoclaving), It has been found to have the advantage of inactivating microorganisms in the vessel, including suspended microorganisms.

In many cases, the overlap is safe even when the flexible container is safe during autoclaving (i.e., high temperature treatment) and gives increased MVB properties when compared to the water vapor barrier (MVB) properties of PVC alone. Contributes to increasing the shelf life of the contained intestinal fluid. In many cases, especially for SVP packages (or bags), multiple SVP packages are placed in one overlap package. Disadvantageously, once the overlap package is opened, the shelf life of the individual SVP packages contained therein is limited to approximately 30 days, due to the poor MVB properties of PVC. Therefore, if a practitioner opens an overlap containing SVP and then does not use all SVPs in a timely manner, the SVP package should be discarded approximately 30 days after the overlap is opened. The overlap also bears significant additional packaging costs and results in environmental waste.

Materials other than PVC, such as olefins (eg polyethylene or polypropylene); The use of nylon, or composite materials, laminated or co-extruded structures (including both monolayer and multilayer structures) and the like provides a number of important advantages for SVP and / or LVP packaging. One advantage is to reduce or eliminate the use of PVC due to environmental concerns. Another advantage of materials such as polyethylene is that they have better MVB properties than PVC. For example, in some cases, longer shelf lives (eg, 24 to 18 months achievable using PVC and overlap) can be achieved without inconvenience and additional overlap costs.

Another advantage of PVC substitution with materials such as polyethylene is that products such as pure deionized water (USP for injection) are effectively packaged in PVC because by-products originating in PVC packaging materials that contaminate pure deionized water are leached into pure deionized water. On the other hand, materials such as polyethylene can be formulated to contain no byproducts that leach into pure deionized water.

Intestinal pre-filled packaging is also beneficial in this way.

Empty extra enteral and enteral containers, where the pharmacist or nutritionist typically adds liquids by hand after delivery of the container, are also widely used. To date such empty containers, typically made of PVC, are often last sterilized using autoclaving. Unfortunately, this empty container also suffers from the problems described above.

Thus, the advantage lies in using olefin, nylon and composite material containers.

However, the last known sterilization methods so far known, such as autoclaving, are inadequate for using polyethylene containers or thin polypropylene containers, which are incapable of withstanding temperatures (eg, 100-200 ° C.) or pressure of autoclaving. Because. (Polypropylene containers can withstand some degree of industrial autoclaving, but they require greater thickness and higher cost than high temperature and pressure treatments to withstand autoclaving.) Therefore, they can damage the container or its contents. There is a need for an approach to inactivate microorganisms in a container without requiring the use of heat.

Other processes, for example, in US Pat. No. 4,282,863, entitled “METHODS OF PREPARING AND USING INTRAVENOUS NUTRIENT COMPOSITIONS,” published August 11, 1981, use a gamma ray for final sterilization. Unfortunately, the use of gamma rays causes another problem. For example, gamma rays can cause weakened container integrity, leakage, increased gas permeability, and other problems due to a tendency to deform the polymerized structure of the olefin container (ie, gamma rays destroy the integrity of the product container). . Gamma rays can also destroy packaging and / or contents, leading to other inverse changes in the packaging or contents, such as darkening, discoloration or color change. In addition, gamma rays can produce highly reactive species, such as hydroxyl radicals, originally produced by gamma irradiation of water, which can severely modify the chemical structure of the treated product. Accordingly, there is a need for an improved sterilization process that can utilize polyolefins or the like without using gamma rays or other such reaction processes for sterilization.

Heat treatment, ie other problems with autoclaving, and the gamma-ray treatment techniques used so far include "batch" processes. Specifically, in heat or gamma ray processing, product containers are processed in groups or batches that require additional product processing, which is uncertainly required when using on-line continuous processes. In addition, careful observation and product handling are desired to ensure that each batch is isolated and processed and tested separately.

In addition, it is not possible to monitor all the parameters necessary to ensure proper inactivation of microorganisms in all product packages of a given batch using the last sterilization techniques used so far (ie, parametric control is almost impossible). (For example, it is difficult to monitor the temperature in the autoclave at as many points as necessary than to ensure that each part of every package in the batch receives sufficient heat and saturated vapor pressure for proper inactivation of the microorganisms.) Since this parametric control using sterilization techniques is generally not possible, the last sterilization after 14 days, for example 14 days to see if contaminants are present in the selected (or all) containers from each batch, then the containers are observed. Should be. This unfortunately further cumbersome product and product container processing and delays the use of the processed packaging and product. Approaches that can be performed in a continuous manner, requiring no "batch" handling and "batch" testing, for example some packaging processes; And by means of appropriate parameter adjustment of the process parameters necessary to ensure adequate sterilization levels, an approach that requires no treatment following observation is very advantageous.

It is generally accepted that, for example, when processed in an autoclave, the last sterile article for application to drugs or foods must have a viability of at least ^{10-6 in} bacterial contaminants. That is, the probability of surviving microorganisms present in sterile articles should be less than one million. This sterilization level is referred to as a sterilization guaranteed level of ^10-6 .

Another sterilization method of the intestinal and intestinal container consists of pre-sterilizing the container using, for example, autoclaving, gamma irradiation, chemical treatment, and then filling the container in a sterile environment. A sterilization guaranteed level of ^10-6 is required for the maximum limit of intestinal and intestinal applications and is difficult to prove using sterile filling methods known to date. (Current aseptic processes are useful at sterile confidence levels of approximately 10 ⁻³ or more by using sufficient media to demonstrate the absence of growth potential.) Therefore, the US Food and Drug Administration, for example, mentions a preference for the final sterilization process. Although this has been done, it is recognized that this process damages many products and product packaging.

Thus, what is needed is to easily achieve a valid sterilization guarantee level of at least ^10-6 , for example, but to reduce product and product container damage that can occur using current last sterilization techniques such as autoclaving or gamma-ray treatment, It is a microorganism inactivation method in a container.

The present invention advantageously addresses the above and other needs.

Summary of the Invention

The present invention advantageously provides a high-strength in a broad spectrum that is filled and / or directly packed into an empty package to permeate the package to inactivate microorganisms suspended in its inner surface and / or product contained within or in the container. More specifically, intestinal and / or intestinal solutions and packaging or containers or contact lens fluids and packaging and / or eye drops and packaging, which inactivate microorganisms using short-term sustained, non-intrusive, multicolored pulses, and such By providing an approach for inactivating microorganisms in the product of the packaging, the above and other needs are addressed.

In one embodiment, the invention can be characterized as a device for sterilizing microorganisms in a container. Such a device comprises a polyolefin and transmits light in a spectrum containing a wavelength selected from 120 nm to 2600 nm, for example a wavelength between 180 nm and 1500 nm or a wavelength between 180 nm and 300 nm, for example. Use a container. The container is connected to a port through which product in the container can be recovered. The port can be, for example, a plastic tube or stopper with a perforated area for injection of the contents or a stopper that is unscrewed or otherwise removed prior to injection. Such ports are well known in the art. Scintillation systems generate high-intensity, short-term, persistent, non-coherent, multicolored light pulses in a broad spectrum, and light pulses generated by the scintillation light illuminate the vessel to inactivate microorganisms in the vessel.

In a variation of this embodiment, the port illuminates the contact surface area attached to the vessel and the microorganisms in the port and contact surface area are inactivated by high-intensity, short-term, persistent, non-coherent, multicolored pulses in a broad spectrum.

In another embodiment, the present invention provides a method for inactivating microorganisms in a vessel using a vessel that transmits at least about 1% light at a wavelength of 260 nm and the vessel transmits light in a spectrum having a wavelength selected from 120 nm to 2600 nm. Can be characterized as a device (see example above). This aspect also provides a port coupled with the container to allow product in the container to be recovered, and a flashlight system that generates a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum and illuminates the container to inactivate microorganisms in the container. Use

In a further aspect, the invention can be characterized as a device for inactivating microorganisms in a container. The apparatus of this aspect comprises in this embodiment a container for transmitting light in a spectrum including a wavelength selected from 120 nm to 2600 nm (see example above); And a port associated with the container such that product in the container is recovered; And a scintillation system that generates a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum and illuminates the container and port to inactivate microorganisms in the container and port.

In a further aspect, the invention provides a container comprising at least one port for product recovery in a container, the container transmitting light in a spectrum having a wavelength selected from 120 nm to 2600 nm (see example above); It can be characterized by a device that inactivates microorganisms in a vessel using a flashlight system that generates a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum and illuminates the light pulse generated in the vessel. The flashlight of this embodiment advantageously inactivates enough microorganisms to achieve a sterile guaranteed level of at least ^10-6 .

In another aspect, the invention can be characterized as a device for sterilizing microorganisms in a container. The container of this aspect includes a blister formed therein, and a backing material that, together with the blister, forms a cavity containing the contact lens and the preservative fluid. The preservative fluid transmits at most 1% of light having a wavelength of 260 nm. The scintillation system illuminates the generated light pulses in the vessel to generate a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum that inactivates the microorganisms in the vessel.

In a further aspect, the invention can be characterized as a device for sterilizing microorganisms present in a target. Such apparatus includes a flashlight system comprising means for generating a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum and illuminating the target with the generated light pulse to inactivate the microorganisms in the target; A photosensitive detector positioned to receive a portion of each light pulse as a measure of the amount of light illuminating the target to produce an output signal for the reaction; And in response to the output signal, a control system coupled to the scintillation system and photosensitive detector to determine whether the light pulse is sufficient to inactivate the microorganisms in the target to a prescribed level.

In a further aspect, the present invention produces a high-intensity, short-term sustained polychromatic pulse in a broad spectrum; Directing the generated light pulse to the target to inactivate the microorganisms on the target; Accept a portion of the light pulse as a measure of both the light pulses illuminating the target; Generating an output signal in response to a partial acceptance of the light pulse; In response to the output signal generation, it may be characterized by a method of sterilizing the microorganisms in the target, including determining whether the light pulse is sufficient to inactivate the microorganisms in the target to a prescribed level.

The present invention relates to parametric control in inactivation of microorganisms, more particularly in inactivation of microorganisms using pulsed light. More particularly, the present invention relates to parametric control in inactivating microorganisms present on packages or contents using high-intensity, short-term, persistent, non-coherent, multicolored light pulses in a broad spectrum. Even more particularly, the present invention monitors critical pulsed light parameters that inactivate microorganisms present on the package or contents using high-intensity, short-term, non-intrusive, multicolored light pulses in a broad spectrum to confirm completed sterilization. And control.

These and other aspects, features and advantages of the present invention will become more apparent from the following detailed description, set forth in conjunction with the accompanying drawings.

1 is a schematic representation of an apparatus for the formation, filling, sealing and sterilization of an intestinal or intestinal packaging.

2 is a side view of a typical over-the-counter package suitable for use in sterilizing the chamber (or tunnel) of the device of FIG. 1.

2A is a perspective view of another exemplary over-the-counter package suitable for use in sterilizing the chamber (or tunnel) of the device of FIG. 1.

3 is a top view of a contact lens package having a “semi-spherical” blister and suitable for use to sterilize the chamber (or tunnel) of the device of FIG. 1.

4 is a side view of the contact lens package of FIG. 3 suitable for use in sterilizing the chamber (or tunnel) of the FIG. 1 device.

5 is a top view of a contact lens package having a “rectangular” blister and suitable for use to sterilize the chamber (or tunnel) of the device of FIG. 1.

6 is a side view of the contact lens package of FIG. 5 suitable for use to sterilize the chamber (or tunnel) of the FIG. 1 device.

FIG. 7 is a distal end view of one variation of the intestinal packaging of FIG. 2 and the sterilization chamber of the FIG. 1 device.

FIG. 8 is a distal end view of another variant of the intestinal packaging of FIG. 2 and the sterilization chamber (or tunnel) of the FIG. 1 device.

FIG. 9 is a perspective view of a sterilization chamber, such as the sterilization chamber of FIG. 7, wherein a photodetector is used to measure the properties of the treated light, such as fluence / light, to maintain parametric control over the sterilization of packages and contents within this sterilization chamber. do.

10 is a perspective view of a transport device for moving the over-the-counter package, further modifications of the sterilization chamber (or tunnel) of the device of FIG. 1, and the over-the-counter package through the sterilization chamber.

11 is a perspective view of several blow-fill-sealing containers on several cards, further modifications of the sterilization chamber (or tunnel) of the device of FIG. 1, and a conveying device for moving the card through the sterilization chamber.

12 is a perspective view of a delivery device for moving the intestinal packaging through various intestinal packaging, further addition of the sterilization chamber of the device of FIG.

Corresponding reference numerals indicate corresponding components throughout the several aspects of the drawings.

The following description of the best mode currently under consideration for the practice of the invention is not to be taken in a limiting sense, but merely for the purpose of describing the general principles of the invention. The scope of the invention should be determined on the basis of the claims.

1 first shows a diagram of an apparatus 10 for the formation, filling, sealing and sterilization of an over or intestinal packaging 12. The roll 14 (or other supply) of packaging material is fed, for example, by a roller 15 to a forming, filling and sealing device 16 known in the art. Alternatively, the packaging material may be in the form of resin beads, typically in the case of a blow / fill / sealing device. Forming, filling and sealing device 16 includes forming / filling / sealing devices, which are well known in the art; Blowing / filling / sealing devices; Injection blow molding apparatus; Extrusion and coextrusion blow molding apparatus; Film / sheet extrusion and coextrusion apparatus; Thermoforming apparatus; Or an injection molding apparatus. Various sealing devices and techniques can be used, including thermal encapsulation, high frequency (RF) formation, hot plate welding, induction welding, and / or spin welding, all of which are well known in the art.

As can also be seen, treatment zones, or sterile tunnels 18 (sterilization chambers 18) are present, through which, for example, formed, filled and sealed over- or intestinal packaging through the conveyor belt 20 are sterilized. do. The conveyor belt 20 may utilize one or more shelves on which the over- or intestinal packaging is placed during transportation, or one or more hooks or a number of other well-known transportation devices on which the over- or intra- packaging is suspended during transportation. In this way, the intestinal or intestinal packaging is not shielded from light when passing through the sterilization chamber 18.

The forming, filling and sealing device 16 mentioned above may be of the type well known in the art, and preferably at high speeds, one or more cavitations may be used to produce a container (or package).

One example of a suitable blow / fill / seal device available for this aspect is sold under model number 603 by Automatic Liquid Packaging, Inc., Illinois, USA. Another device is marketed under model number 624 from Automatic Liquid Packaging, Inc., Woodstock, Illinois.

Suitable forming / filling / sealing devices use extruded films to form pouches or bags. One example of a forming / filling / sealing device available in this aspect is available from Inpaco, Allentown, Pennsylvania, as a System Model Mark II.

The aforementioned blow / fill / seal device and the form / fill / seal device allow for attachment of accessories (see FIGS. 2 and 2A) during packaging or container formation.

As can be seen, the sterilization chamber 18 consists of one or more reflectors 22, and one or more flashlights (not shown), all of which are part number 01812- from PurePulse Technologies, Inc., San Diego, California, USA. Available as 525. Such flashlights and accompanying pulse-generating hardware (not shown) can generate high-intensity, short-term, non-coherent polychromatic pulses in a broad spectrum. Suitable flashlights and accompanying pulse generating hardware are described in US Pat. No. 4,871,559 to METHODS FOR PRESERVATION OF FOODSTUFFS, issued by Dunn et al .; 4,910,942 to METHODS FOR ASEPTIC PACKAGING OF MEDICAL DEVICES; And METHODS FOR PRESERVATION OF FOODSTUFFS (Patents 559, 942 and 235, respectively), which are incorporated herein by reference in their entirety. As will be appreciated by the skilled person, many known and developed variations of flashlight and pulse generation hardware are suitable for use in the embodiments described herein.

One or more reflectors 22 direct light from the flashlight into the complete out-of-field or in-field packaging 12. Preferably, the reflector 22 is made of aluminum, for example, and optimally reflects light across the complete broad spectrum generated by the flash. Advantageously, the reflector is generally designed using known design techniques to induce a uniform or non-uniform energy distribution of light shining across the intestinal or intestinal packaging. In this way, for example, larger amounts of light energy (ie, concentrations) may be used, for example, thicker extra- or intra-intestinal packaging, such as in the vicinity of additional ports and / or injection ports; And / or direct to the product site contained in the middle of the intestinal or intestinal packaging where a larger dose of product in need of treatment may be present.

In accordance with this embodiment, the light pulse passes through the intestinal or intestinal package 12 to reach the contents of the package, sterilizing or inactivating microorganisms present in the package 12 and suspended in the product contained in the package 12. Let's do it.

In this way, an effective method is provided for sterilizing the product contents, as well as in the intestinal or intestinal packaging, without requiring a high temperature process involving autoclaving. In addition, other product containers and products contained therein can be processed using the approach of this aspect. For example, the contact lens package and the contact lenses contained therein can be processed using the above-approach. As a result, materials such as olefins, nylons, and composite materials can be advantageously used for product packaging instead of conventional materials such as polyvinyl chloride (PVC). Since the olefins, nylons, and composite materials can have better moisture vapor barrier properties than PVC, and cannot contain components that are easily absorbed into the products contained therein, the apparatus and accompanying methods are considerably superior to the methods available to date. Provide formation, filling, sealing and sterilization methods. In addition, this embodiment achieves a sterilization guaranteed level of at least 10 ⁻⁶ and does not require the use of gamma rays or other highly disruptive processes.

2 illustrates a typical small scale over-the-air container 12 or large scale over-the-air container 12 arrangement (generally referred to herein as bag assembly 12). The bag assembly 12 is in a preferred embodiment made of polyolefin, such as polyethylene, and uses a flexible pouch 30 connected to the accessory 32. The accessory 32 generally includes two short tubes 36, 38 (or ports) through which a supply tube (not shown), or implementer (often) from a flexible pouch 30 (or an over-the-bag) When a pharmacist or nurse manufactures an adjunct, a connection may be made to deliver the liquid to the flexible pouch, such as the flexible pouch 30.

The port 36 used for making the adduct is typically referred to as the additional port 36 and another port 38 used for fluid delivery is typically referred to as the supply port 38. In the case of the device referred to as "spiking" at the feed port 36, ie perforated intravenous set (not shown), the contents of the flexible pouch 30 may be gravitational or use of a pump or regulator ( (Not shown) to the patient.

Intestinal containers (not shown), preferably made of polyolefins such as polyethylene, use similar accessories, while enteric sets (spike sets) and flexible tubing used with enteric containers are typically used, for example, for liquid supply. It is used to supply liquid to the patient by various methods such as through the gastric tube.

The flexible pouch 30 is preferably composed of a material that transmits light in the spectrum of, for example, 180 nm to 1500 nm. Many materials, such as polyethylene, polypropylene, EVOH, nylon and many other plastic materials, easily transmit this spectrum in single or multiple layers and can be used according to variations of this embodiment.

The connection of the accessory 32 to the flexible pouch 30 and the filling of the flexible pouch 30 are preferably packaging machines to minimize the injection of contaminants such as microorganisms, in aseptic environments such as HEPA-filtration chambers. Can be performed. (These HEPA-filtration chambers are well known in the art.) The accessory 32 is a flexible pouch (30) by thermal encapsulation, high frequency (RF) welding or "plastic welding" techniques generally known in the art. ) Can be connected. Another example of an over-the-counter package suitable for use in the aspect of FIG. 1 is shown in FIG. 2A.

FIG. 3 shows a top view of a contact lens package 50 having a “semi-spherical” blister 52 and suitable for use in a sterile chamber (or tunnel). The contact lens package 50 has a polyolefin panel 54 (eg, polyethylene or polypropylene panel) in which blisters 52 are formed. The blisters 52 protrude from the upper side 56 of the polyolefin panel 56 (FIG. 4), and the lead stock (FIG. 4), which may include a foil backing 58, is the base side of the polyolefin panel 54 (FIG. 4). 60). Between the lid stock 58 and the interior of the blister 52 is formed a cavity 62 filled with an antiseptic fluid such as saline, and a contact lens 67 such as a soft contact lens.

The high-intensity, short-duration, non-coherent polychromatic pulse 66 (FIG. 4) is actually direct on the top 56 of the polyolefin panel 54 and the sides of the blisters. The high-intensity, short-term, non-coherent polychromatic pulse 66 (FIG. 4) has the following intensity, duration, and wavelength: intensity of 0.01 J / cm 2 to 50 J / cm 2, for example 0.05 J / cm 2 to 5 J / cm 2, for example 2 J / cm 2; A duration of 0.001 to 100 minutes, for example 0.3 minutes; And a wavelength selected from 120 nm to 2600 nm, for example 180 nm to 1500 nm, or for example 180 nm to 300 nm. The high-intensity, short-term, non-coherent multicolored light pulse 66 (FIG. 4) penetrates the blisters 52, which transmit a significant amount of light with a selected range of wavelengths, and contain the antiseptic fluids and contact lenses contained therein. 64). As a result, the microorganisms present inside the blister 52 and suspended on or in the antiseptic solution and the contact lens 64 are inactivated.

Advantageously, the contact lens 64 is sealed inside the polyolefin package 50 and then illuminated the package 50 with a high-intensity, short-term, non-coherent multicolored light pulse, such as within the blister, antiseptic fluid, or contact lens. Contamination of 64 is prevented and subsequently treated (ie irradiated). Also advantageously, the high-intensity, short-term, non-coherent polychromatic pulses do not demote the polyolefin panel 54, lead stock 58, or contact lens 64 contained therein.

Thus, the last sterilization method is used for sealed contact lens packaging without degrading the nature of the treated package or the contact lens contained therein, unlike the autoclaving and gamma ray treatment methods so far known.

4 shows a side view of the contact lens package 50 of FIG. 3 suitable for use in the sterilization chamber (or tunnel) of the FIG. 1 device. The top and bottom portion of the contact lens package 50 of FIG. 3 is more clearly shown, and arrows represent high-intensity, short-term, non-coherent multicolored light pulses 66 directly directed to the blister 52. . Similar shapes have reference numerals similar to those of FIG. 3.

FIG. 5 shows a top view of a contact lens package 70 having a “rectangular” blister 72 and suitable for use in the sterilization chamber (or tunnel) of the FIG. 1 device. The contact lens wrap 70 of FIG. 5 is quite similar to the contact wrap 50 of FIG. 5 except that the blister 72 is generally rectangular in shape. However, the sterilization method described above with reference to FIG. 3 can be used for the contact lens of FIG. 5 with similar effects. Shapes shown in FIG. 5 that are similar to the shape of FIG. 3 have similar reference numerals.

FIG. 6 shows a side view of the contact lens package 70 of FIG. 5 suitable for use in the sterilization chamber (or tunnel) of the FIG. 1 device. The contact lens package of FIG. 5 more clearly shows the top 56 and the base 60 of the package 70, with arrows pointing to high-intensity, short-term, non-coherent multicolored pulses 66 directly in the blisters. ). Similar shapes have reference numerals similar to those of FIGS. 3 and 5.

FIG. 7 shows the distal end of the sterilization chamber 18 of FIG. 1. In the variant shown, a single reflector 22 is positioned around the flashlight 40 and on top of the over-the-counter container 12, for example when passed through a sterilization chamber on a conveyor belt (not shown). The enteral container 12 can be easily replaced with an enteric container or a contact lens container, depending on the application.

In accordance with the present invention, high-intensity, short-duration multicolored light pulses in a broad spectrum are passed directly through the sterilization chamber 18 to the flexible pouch 30 and the accessory 32. Typically, the intensity of the pulse is from 0.01 J / cm 2 to 50 J / cm 2, for example from 0.05 J / cm 2 to 5 J / cm 2, for example 2 J / cm 2. Advantageously, inactivation of the microorganisms suspended within the fluid contained in the flexible pouch 30 by light pulses, microbial inactivation of the contact surface 42 between the accessory 32 and the flexible pouch 30, and the accessory ( A high degree of microbial inactivation is achieved within the flexible pouch 30, including microbial inactivation above or within 32.

In some cases, accessory 32 may not be sufficiently permeable to permit complete sterilization of accessory 32 using high-intensity, short-term, continuous multicolor light pulses in a broad spectrum. However, if sufficient permeable material is selected as the accessory 32 and the appropriate shape and thickness of the accessory is selected, the accessory 32 can be sufficiently sterilized using a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum. have. The choice of accessory design suitable for sterilization with high-intensity, short-term sustained multicolor pulses in a broad spectrum is within the skill of the skilled person.

According to this aspect and the fact that the accessory cannot be fully sterilized using a high-intensity, short-term, continuous multicolor light pulse in a broad spectrum, the internal portion of the accessory 32 is heat or gamma-rays before it is connected to the flexible pouch. Can be pre-sterilized. In FIG. 2A, the contact area 42 around the accessory 32, best shown so that the accessory 32 connects to the flexible pouch 30, may be provided before and / or the flexible pouch 30 is filled with fluid. After filling, it can be treated with high-intensity, short-term, continuous multicolored light pulses in a broad spectrum to inactivate the microorganisms in the contact area, in or around it. Such light pulses preferably have a range of intensities in the aforementioned range, i.e. 0.01 J / cm 2 to 50 J / cm 2, for example 0.05 J / cm 2 to 5 J / cm 2, or 2 J / cm 2 (flexible pouch ( 30 and measured at the contact surface of the accessory 30).

The pulsed light process described above inactivates a wide range of microorganisms, including bacterial and fungal spores, using high-intensity, short-term sustained multicolored light, ie, “white” light pulses, in a broad spectrum. During each flash, the intensity of the light is about 20,000 times the solar intensity of the earth's surface, ie 0.01-J / cm 2 to 50 J / cm 2, for example when measured in microorganisms in which "high-intensity" light is inactivated. , 0.05 J / cm 2 to 5 J / cm 2 or 2 J / cm 2. Each light pulse, or flash, has a duration of only one second of time (eg, a "short duration" of 0.001 to 100 minutes, eg, 0.3 minutes).

Flash is typically applied at a rate of about 1 to 20 flashes per second, and for most applications, some, 1 to 3 flashes, applied at 1 second of moisture, inactivate or kill microorganisms at very high levels. The duration of the light pulse is typically 200 to 300 ms.

The process of this aspect utilizes a technique referred to herein as a pulse energy process. The electrical energy is stored in a high energy density electrical storage battery, which is released in a high energy, short duration pulse, to achieve high peak power levels. These high-peak, power levels of electrical energy can be used to generate high-intensity, short-term, continuous multicolor light pulses in a broad spectrum. (Pulse energy processes are described in patents 559, 942 and 235, which are incorporated herein by reference.) These high intensity light pulses are observed when the same energy is applied at low intensity in continuous or continuous wavelength (CW) applications. It does not give rise to the only sterilizing effect. Although the peak power of each pulse is preferably very high, due to the short duration duration, the total energy of each pulse is relatively low, and the average power requirement ("wall plug power") is reasonable. Therefore, this process is not only effective, but also economical in terms of energy consumption.

Light pulses are generated by electrically ionizing a xenon gas that emits a wide "white" light band. A flashlight system suitable for use in the present invention is readily available from Pure Pulse Technologies, San Diego, California, under model number PBS-1 or PBS-2, which model is, for example, PurePulse, San Diego, California. A flashlight is used as is available from Technologies, Inc. as part number 01812-525. The emitted light pulse has a wavelength ranging from far ultraviolet (200-300 nm), near ultraviolet (300-380 nm), and visible light (380-780 nm) to infrared (780-1100 nm). Approximately 25% of the energy distribution is ultraviolet light, 45% of the energy distribution is visible light, and 30% of the light energy distribution is infrared light. Because only one to how many light flashes, i.e. 1-3 light flashes, are required for bacterial inactivation and can be delivered in a fairly short period of time, the process can be done very quickly and can be highly utilized throughout the application.

Light is a range of wavelengths known as conventional non-ionizing wavelengths and does not transmit opaque materials, but can pass through a number of packaging materials and be used for the treatment of the above-mentioned intestinal and intestinal packaging products. The primary effects of treatment, and the main anti-bacterial mechanism, are believed to be related to the nature of abundant broad-spectrum ultraviolet light, and very high-intensity, short-term sustained pulses.

FIG. 8 illustrates the distal end of the over-package of FIG. 2, which is another variation of the sterilization chamber 18 (or tunnel) of the FIG. 1 device. In the variant shown, a pair of reflectors 22 are positioned around one or more flashlights 40 and the over-the-counter container 12 such that the over-the-air container, for example, sterilizes the sterilization chamber 18 on a conveyor belt (not shown). If passing, form a tunnel. The illustrated variant passes through the overload container 12 after being emitted from the flashlight 40, or the light passing through or the light reflected from the upper reflector 22 is directed toward the outboard container 12 by the lower reflector 22. Except for the reflection, it works in a similar way to that of the variant of FIG. Advantageously, such a variant maximizes the amount of light that affects the over-the-counter container 12 to inactivate the microorganisms contained therein by maximizing the amount of light that passes through the over-the-counter container 12.

Example 1

A flexible pouch of polyethylene is prepared and contains 55 ml of brine or dextrose. Flexible pouches are inoculated and mixed with 1 ml of Clostridium sporogene spore suspension (6.7 log per ml) or Bacillus pumilius spore suspension (8.0 log per ml). Inoculation control samples are collected from each bag with a sterile syringe to quantify the number of viable inoculated spores that can be recovered from each bag prior to treatment.

The flexible pouch is then placed in the center of the two reflectors (as described in FIG. 8), forming a reflective steel (or tunnel) and exposed to eight pulses of high-intensity, short-duration multicolored light in a broad spectrum. After treatment, 1 ml of solution was removed from each bag and removed from tryptic bean agar (for solutions transferred from soluble pouches inoculated with Clostridium sporazine) or standard method agar (flexible pouches inoculated with Bacillus pumilus). Plate directly). The remainder of each flexible pouch is analyzed for sterility by filtration. The experiment is repeated three times for each inoculum / solution combination (12 total tests: 3 saline / clostridium; 3 dextrose / clostridium; 3 saline / bacillus; and 3 dextrose / bacillus).

Clostridium sporozin spores were recovered from the brine-filled flexible pouches and treated at a log concentration of 5 log per ml (or 6.7 log spores per flexible pouch) and 4.7 log per ml (or 6.4 log spores per flexible pouch). Recover from dextrose bag prior to treatment at concentration. Bacillus pumilus spores are recovered at a concentration of 6.5 log per ml in saline-filled flexible pouches (or 8.2 log of spores per flexible pouch) prior to treatment and 6.2 log (or spores per flexible pouch 7.9 log) in a dextrose solution sample. Recover at a concentration of. After treatment, no visible organisms are recovered from the sample, indicating that the treatment can sterilize the contents of the intestinal pouch for each inoculum / solution combination tested. Thus, Example 1 achieves a sterilization assurance level of at least ^10-6 .

Example 2

Blown / Fill / Sealed Polyethylene containers are filled with water for injection in various volumes (0.5, 5, 15 and 120 ml). Bacillus pumilus spores (ATCC 27142), Bacillus subtillus strain Niger bar. Contains niger var. Globigii spores (ATCC 9372), Bacillus Stearothermophilus (commercially available from AMSCO) and Aspergillus niger (ATCC 16404; conidia bag, mycelia and hair Try).

Six logs of each organism are inoculated by injection into a small gauge needle. Twelve replicate samples are inoculated for each combination of organism, container volume, and treatment modality. Two of the 12 samples are provided as inoculation controls and small inoculation ruptures are sealed with medical grade silicone sealant. Ten samples are treated with high-intensity, short-term sustained multicolor pulses in a broad spectrum before applying medical grade silicone sealant to prevent shadowing of the sample volume by the sealant.

Test two forms of treatment. The vessel is processed using a single lamp and reflector (as shown in FIG. 7) and each vessel from above is lit with 1.0 flash of 1.0 J / cm ² / flash. In a second treatment modality, the vessel is treated in a reflective cavity (as shown in FIG. 4) comprising a single lamp with ten flashes of single fluence. These 0.5, 5 and 15 ml volumes are tested directly using 20, 20 and 60 ml spill plates respectively. 120 ml volume samples are tested by filtration. In a single lamp and reflector (SLR) treatment modality, 36 out of 40 A. niger samples are sterile, and 40 B. subtilis globigi spores and B. stearothermophilus inoculation samples are aseptic, ie, viable microorganisms. It does not contain All of the samples treated using the river treatment modality were sterile, ie, none of the 160 individual samples tested for viable organisms were recovered. These results indicate that treatment with high-intensity, short-term, sustained multicolor pulses in a broad spectrum can sterilize water for injection in polyethylene containers inoculated at 6 log levels with four resistant strain microorganisms. Thus, Example 2 also achieves a sterilization assurance level of at least ^10-6 .

Based on the above and a number of other embodiments, high-intensity, short-term, persistent, non-coherent, multicolored light pulses in a broad spectrum can be used to sterilize or dissolve microorganisms in pharmaceuticals, food and medical products and devices, and food and medical packaging. It has been found to be effective in activation. See, for example, the '559,' 942 and '235 patents and US Pat. No. 4,464,336; And 5,489,442 (hereinafter referred to herein as the '336 and' 442 patents, respectively), all of which are fully described and incorporated herein by reference. High-intensity, short-duration multicolored pulses in the broad spectrum The product, packaging, and conditions in which high-intensity, short-duration multicolored pulses in the broad spectrum can be arranged to access all important surfaces and / or volumes of the target. It can be used to create an effective and efficient sterilization method for other targets. (Important surfaces and volumes are those surfaces and volumes for which microbial inactivation is required.) By properly arranging treatment methods and apparatuses, the skilled person can ensure that light pulses reach critical surfaces and / or volumes to be treated. have.

In addition, unlike the last known sterilization methods such as autoclaving, key sterilization parameters can be monitored and controlled in accordance with embodiments described herein. Such monitoring and control of other key sterilization parameters in the embodiments described herein ensures a high degree of quality and stability, i.e., high inactivation, to the target prior to release and use by the end user of the target.

Sterilization parameters important to achieve sterilization include (a) the spectral content of each flash, (b) the energy of each flash (or fluence per flash into J / cm ² / flash), and (c) the delivered flash. It is a number.

The importance of the spectral content of each flash is explained by the results disclosed in the '559 patent, which is incorporated herein by reference, and indicated that the ultraviolet content of the pulsed light is very important for the strong antibacterial effect of the pulsed light treatment. This is illustrated in the results of the examples where the ultraviolet content of the flash of wavelengths up to about 320 nm was removed by light filtration through 1 / 4-inch thick Pyrex glass filters. Although these results demonstrate that high levels of bacterial inactivation can be obtained when wavelengths below about 320 nm are removed from the treatment flash, further higher fluences and numbers of flashes result in such reduced ultraviolet content. It appears to have to be used for the production of inactivation effects under conditions.

The importance of flash energy (as distinguished from the total energy delivered for some number of flashes) is exemplified in the results of bacterial and / or fungal spore survival tests in which different pulsed light throughputs are generated that produce sterile levels of inactivation. .

Example 3

The sterilization capacity of several different pulsing and treatments for Bacillus pumilus spores inoculated into packaging materials is illustrated in Table 1 below. Bacillus pumilus (ATCC 27142) spores are sprayed with 10 ⁷ spores per 1.75 cm ² on the inner surface of the multilayer milk carton polyethylene / fiberboard / aluminum / polyethylene package. Control and treated samples are analyzed for viable organisms by sealing a sterile glass cylinder (3 cm diameter) onto the inoculated site using a sterile paraffin wax / petrolatum mixture (50/50). Treated packaging and attached cylinders are placed in sterile petri dishes and culture medium is added to fill the cylinders and wet the inoculation surface of the packing material. Samples are incubated for at least 7 days at 35 ° and analyzed for microbial growth. In one set of samples, a treatment regimen consisting of eight pulses of light to an incident fluence of 0.5 J / cm ² / flash (total 4 J / cm ² treatment fluences) was applied to six sterile assays out of 19 trials. Viable organisms are obtained (ie, about one third of the samples are not sterilized by this treatment). However, the same inoculated sample had an incident fluence of 0.8 J / cm ² (total treatment of a total of 3.2 J / cm ² / flash, ie 0.8 J / cm ² or less, 0.5 J / cm ² / flash Viable organisms were obtained only in one of ten trials upon treatment with four pulses of light of treatment fluence); No viable organisms were obtained in each of the 10 trials when treated with 4 flashes of 1 J / cm ² / flash (total 4 J / cm ² treated fluence) (0 survival). Thus, tests performed using higher per-flash fluences at the following total treatment fluences result in significantly improved inactivation for tests performed at higher total treatment fluences but with lower flues per flash. do.

Total Treatment Fluence (J / cm ² ) Fluence per flash (J / cm ² / F) 2.4 2.5 2.56 3.2 4 6 0.3 13/25 * 0.5 11/25 6/19 1/20 0.64 7/25 0.8 1/10 One 1/10 3 2/30 * Number of samples positive for growth / total number of samples tested

(It should be noted that the sterilization test detailed in Example 3 has inherent background failure due to sample contamination after treatment. This background false positive rate is the required post-treatment sample manipulation—eg handling, media, to complete the analysis. Filling, etc. The results of a control test using sterile, non-inoculated samples treated with high levels of pulsed light and then analyzed suggest that the false positive rate is about 1 or less in 10 samples. The limit of accuracy is about 90%, and the experimental sample set results with one (or less) growth positive sample per 10 total test assays result in a treatment that produces the maximum detectable level of sterilization accuracy for the test method used. Is interpreted as.)

Example 4

The importance of fluence per flash is that the antimicrobial effect of pulsed light treatment is inoculated by spraying onto the surface of white plastic packaging material (aspergillus bag, mycelium fragment recovered by the original wash of mature culture). And pockets). Log survival results are recorded for the range of treatments used as a single flash (0.34, 0.53, 0.75, 1 and 1.3 J / cm ² per flash) or after the total number of flashes (and thus various total treatment fluences). . When performing a 0.34 J / cm ² flash treatment, the resulting inactivation results in a treatment in the range after about 7 flashes and 40 flashes (40 flashes exceeding 13 J / cm ² equal to the total accumulation treatment fluence). It is relatively constant through about 2 log survival. However, the treatment consisting of a single flash with 1.3 J / cm ² / flash does not appear to result in recovered viable organisms for each of the three identically inoculated samples tested. Thus, a treatment consisting of a lower fluence per flash but a significantly higher total treatment fluence appears to be much inferior to a treatment consisting of a single blast of higher fluence per flash.

Fluence per flash (J / cm ² / flash) Total Treatment Fluence (J / cm ² ) 0.3 0.53 0.75 One 1.3 One 3.48 2.23 1.18 0.48 NS 2 3.38 2.31 NS 4 1.95 0.60 0.15 NS 6 0.74 7 0.50 0.53 8 2.22 1.47 NS 12 1.96 NS 16 1.68 1.23 20 1.67 24 2.07 32 1.92 40 1.73 NS = no survivors detected

Thus, the fluence per flash used for pulsed light treatment (as opposed to total fluence) appears to have a significant impact on the overall inactivation efficacy achieved in bacterial or fungal spores.

The total number of flashes delivered is also important. At least one flash must be delivered. In addition, if the product is processed in a flow state, for example in the continuous filling machine for example in the continuous filling machine as illustrated in the '559 patent, or for the treatment of running water, a slight overlap of treatment pulses It is necessary (because of the quantified and quantified nature of the light pulses and the continuity of the treated medium) to deliver some minimum average number per unit volume and to ensure that the desired deactivation efficiency is achieved.

Thus, as illustrated above, fluence per flash (or flash peak power) is important for achieving inactivation at sterile levels during pulsed light sterilization. In many applications, the materials, methods and forms of the processing arrangement can be arranged to optimize and enhance the efficiency of the pulsed light process and its ancillary killing effects.

An example has been reported in which pulsed light treatment to sterilize the inner surface of the reflective multilayer packaging material is optimized by material selection (US Pat. No. 5,451,367: hereafter referred to as the '367 patent). The unique and important aspect of this patent is not directly exposed in the absence of reflective advantages, thus providing pulsed light exposure of microorganisms (and other particles) on the pavement surface by providing a mechanism for reflecting light on top or bottom surfaces that are less in contact with pulsed light. Is the ability of the reflective inner layer of the multi-layer packaging material to promote.

A fairly beneficial method that is not apparent from this initial report (ie, the '367 patent) and not until recently to the inventors thereof is the efficiency of the pulsed light processing method by an increase in fluence per flash (or flash peak power) and It relates to the ability of the described arrangements, materials, methods and forms to enhance efficacy. In certain applications described in the '367 patent, that is, the sterilization of the inner surface of the reflective multilayer packaging material, the devices, materials, methods and forms described above, provides increased exposure to the shaded surface of microorganisms and particles, and also concomitant with flashlight power. It is possible to produce an increase in fluence per flash without increasing phosphorus. This is due to the light reflectivity limiting the steel inherent in some forms that are incidental to the devices, materials, methods and forms described above. The microbial benefits of this enhancement in effective per sugar flashes are described in the discussion presented earlier.

According to a further embodiment, a reflective steel (as shown in FIG. 8), which is constructed of a broadband reflective material and designed to contain a pulsed light source and a transmissive product in a transmissive packaging material, is effective for fluence per flash, thus pulsed light. It can be used to increase the microbial inactivation effect of the treatment. As a result of this arrangement, pulsed light that is not directly incident on the package is reflected and essentially "recycled" in the reflecting cavity to eventually interact with the product. Similarly, pulsed light passing through the pavement and product is reflected and "recycled" in the reflecting cavity to re-interact with the product. “Recycling” of pulsed light causes fluence per flash more effective than that observed in the absence of reflective steel.

Such reflective steels, i.e., reflective steels exhibiting this "recycle" capability, can be of many shapes and designs. For example, the reflective cavity may be elliptical with the pulsed light source at one focal point of the ellipse and the product to be processed at another focal point. Reflective steel may also be shaped or typed to facilitate the return of unabsorbed light to the processed product or package or to reflect various fluence levels to various portions of the product or package being processed.

Similarly, the product or package to be treated can be of many forms, types, materials and designs. For example, the product may be a solution to be processed that is delivered through a reflective pulsed light processing chamber upon flow in a light transmissive tube or the product may be air or other gas that is processed upon flow in a reflective pipe or tube. The product may or may not be deliverable to all or part of the pulsed light processing spectrum used. Thus, variations of the aspects described herein may be directed to design surfaces, such as the surface of the product (eg, the surface of the package), the interior package and the surface of the product (eg, the surface of the product enclosed within the deliverable package) or the surface of the product volume. (Eg, a deliverable package containing a deliverable product). Thus, a broad array of products and steels has been considered by the inventors named herein.

However, the usual properties of the possible forms, designs, arrangements and arrangements of products, packaging materials, devices and processing chambers are preferably devices, methods, materials and forms in which such light is finally produced or packaged; Or reflection of light not initially absorbed within the product, package, etc. in such a way that it can be recycled within the river to increase the likelihood of light being interacted with or absorbed by microorganisms, chemicals or contaminants on the product or package material. It must be arranged to provide or allow.

The recycling success or efficiency of light that is not initially absorbed will vary with the device, material, method and form used.

For example, the steel index or Q (ratio of energy loss per cycle to energy stored in steel) is based on the pulsed light wavelength used, the steel wall reflectivity, and the steel's ability to refocus light on useful product surfaces or volumes. Will change.

Preferably, however, in all cases the steel will provide an increase in fluence per flash and an improvement in efficiency by providing recycling of light that is not initially absorbed.

For packaging and / or product and processing chamber designs where the special frequency in-spectrum pulsed light used for sterilization is to achieve all the critical volumes and surfaces, pulsed light sterilization requires the energy (or J / cm ² / fluence per flash into flashes) and the number of flashes delivered. Advantageously, these three parameters can be measured relatively easily and reliably during pulsed light processing. These three parameters according to this aspect are monitored, controlled and verified during pulsed light processing operation. Such monitoring, control and verification can be used for validation of the process, i.e. validation where sufficient inactivation is achieved. Specifically, the monitoring, control, and verification of such suitable treatments is contrary to the observation of packages or products processed during the waiting time after microbial activation, allowing validation of the treatment based only on the measurement of these three parameters.

The main advantage for the use of pulsed light is the ability to monitor, control and verify the main processing parameters and thus the sterilization effect in real time and for each package. This importance, that is, the importance of the ability to control, monitor and verify sterilization techniques, will be understood by those familiar with the use and acceptance of sterilization techniques.

Immediate on-line monitoring and measurement of each flash of the pulsed light treatment process can be performed on the product, package, material, device or other target. For deliverable products and packaging, light passing through the products and packaging can be measured for fluence per flash (or flash peak power) and for spectral content. For products and packages that are not deliverable at that wavelength, the reflection of the product or package can be measured similarly. In both cases the measurements may be performed in volumetric form, in which the volume of one or more sites, or alternatively a large area or product or area of pavement illumination, is sampled through the use of a lens or other mechanism capable of collecting light for large angles. Can be. In this way the pulsed light processing can be well monitored and controlled (via a suitable close loop feedback control system) and verified. Thus, each treatment flash can be verified to have a sample and have a minimum sufficient fluence per flash and a minimum sufficient spectral content, and the fluence and spectral content per light flash received by the product or package is also contemplated in this aspect. Therefore it is monitored. This monitoring is performed in an instant on-line manner that allows for the highest level of parameter control and verification.

In FIG. 9, the perspective view shows a process in which the photodetector is used to measure the fluence per light flash emitted from the scintillator 104 to maintain parameter control for sterilization of the package and its content in the process chamber 100. The chamber 100 is shown. Photodetector 102 works in conjunction with a suitable monitor and control circuit 106 and has a fluence per flash within a defined spectral bandwidth, ie energy per flash, total energy for some preselected processing time, preselected for time. Control the range of spectral energy and / or other detectable parameters within the bandwidth. In a similar manner, the pulse parameters involved in energizing the flashing light 104 such as current, peak current, current wavelength, voltage, voltage wavelength, and / or a range of other pulse parameters can be monitored and known as known in the art. It can be monitored and controlled by the control circuit 106. Flashlights to energize components and parameters and outputs from the monitor and control circuit 106 to monitor the generated flash parameters completely describe the operation of pulsed light generation in the processing chamber 100. Data acquisition and control cars that can be added to suitable monitor and control circuits 106, such as personal computer 108, are readily available. In combination with appropriate programmatic control by the personal computer 106, the electronic output of the monitor and control circuit 106 may be used to monitor, adjust and record the pulsed light processing. Feedback circuitry implemented within the monitor and control circuit 106 and programmatically implemented in the personal computer 108 by providing instantaneous electronic signals indicative of parameters related to system operation in the presence of output or operation outside a preselected range is well known. It can be easily arranged to adjust the system operating parameters and outputs according to the feedback / control system approach.

For example, the ultraviolet output from the strobe 104 may be coupled to the lamp voltage and current acting circuitry in the monitor and control circuit 106 via suitable feedback / control system circuitry. By monitoring the ultraviolet output, system performance can be monitored, adjusted and maintained at minimum and maximum, respectively, by coupling this information to circuit pulses through a suitable feedback control system circuit. Similarly, fault detection circuitry in monitor and control circuitry 106 can be used to call the operator and close the system or perform the system overnight and the alarm action should pulse or output a parameter below or outside the desired level. In addition, quality control recording can be performed in an on-line and immediate manner by supplying electronic signals from the operational monitoring system and the output monitoring system to the personal computer 108 or other computer or electronic storage device.

For pulsed light processing, a wide range of photodetectors and optics can be adapted in various ways to monitor, control and verify that proper pulsed light sterilization treatment has been achieved. For example, a variety of optics methods and detectors are available that can be used to "view" or retrieve each processing flash to confirm that the resulting light pulses are of desired intensity and contain the appropriate spectral distribution and content. Components of suitable monitor and control systems are available from various sources and those skilled in the art of photodetectors or optical systems can design and assemble suitable systems. For example, surface or volume absorbing calorimeter systems that can be used to monitor pulsed light fluence per flash or total light output are obtained from a number of sources (Gentec, Ophir, Molectron, Digirad, etc.). Similarly, systems for photodetection alone or in combination with suitable filters or other components are widely available (Hamatsu, Phillips, EG & G, UDT Sensors, etc.) and can be used to investigate the UV content or spectral distribution of pulsed light flashes. Pulsed light can be collected and monitored using a wide variety of methods. For example, fiber optic probes, focused or defocused lenses, integrated spheres, CCD analysis, etc., can be used to collect light from a wide or narrow angle and provide partial resolution of multi-point analysis for optical imaging systems. Can be. Parts or systems for light collection, handling, monitoring and analysis are obtained from multiple sources; Such parts or systems can be designed and assembled from many manufacturers or suppliers.

A simple method of quantifying the optical signal of a pulsed light processing flash is shown. Samples of the light flash are collected through a small diameter hole 110 or “pinhole” 110 and placed in a reflector 112 system used to focus or focus the light on the object to be treated. The pinhole 110 in the reflector 112 may direct light to one or more light sensing devices (photodetectors 102), such as photometers, photomultipliers, calorimeters, pyroelectric meters, bolometers, dipoles or dipoles, or To other photosensitive or photodetector systems. Photodetector 102 may be used to sample processing optical characteristics (eg, fluence and spectral content per flash) through various means. Light is either directly "visible" or passed through a sampling port, lens, through aperture, collimating, filtered, focused, blurred, reflected, refracted, handled, manipulated or collected before measurement.

One or more photodetectors may retrieve the processing light from the flashlight such that fluence and / or spectral distribution per flash can be monitored and controlled in the presence or absence of suitable filter (s).

The signal from photodetector 102 changes in time with suitable filter (s) that can be specific to the fluence per flash and a particular portion of the light spectrum. For example, since fluence per ultraviolet flash is generally important, photodetector 102 can measure the fluence per flash of only the ultraviolet portion of the spectrum through the use of a suitable ultraviolet bandpass filter. The output of photodetector 102 can be integrated to measure the total ultraviolet energy of the light pulses at the selected bandwidth. The integrated signal is then recorded by the computer or other means over time, the overall pulsed light processing method, to provide a permanent record of the total energy of the light pulses.

Another major factor is the calibration of the measurement system. Many approaches are considered for calibration. According to one approach, an ultraviolet calorimeter is placed in the processing chamber instead of the target. The calorimeter can measure the ultraviolet energy of light pulses and track international standards. Therefore, the measurement by the calorimeter can be compared with the measurement by the photodetector in that it corrects the photodetector to international standards. In a second approach, light passing through or reflected from the package is measured by a calorimeter.

In general, for the treatment of pulses of light, the package must be moved through the process in such a way that the complete package is processed. In transparent packaging designed for the treatment of products in the package, the method is more complicated due to the internal reflection and refraction of the light as it passes through the package. The following is an example of a packaging transparent approach.

With respect to FIG. 10, a perspective view shows a transport approach for moving the over-the-counter package 200, further modifications of the processing chamber 202 (or tunnel) and the sterile chamber through the sterilization chamber. Types used to hold the over-the-counter package 200 (IV bags), eg, the vein (IV) and the over-the-counter solution, hang on a ladder transport mechanism 204 that carries them vertically through the processing chamber 202. Is processed. A pair of flashlights 206 are disposed on each side of the package 200 as they move through the processing chamber 202. The processing chamber 206 includes a flashing light 206 and a reflector 208 for projecting light onto the over-the-counter package 200. In order to establish the distribution of light as the type of reflector 208 is required by the over-the-counter package 200, i.e., the over-package 200 and the product volume of each unit of the product in which sufficient fluence per flash performs inactivation of the microorganisms. Control to distribute the light in the over-the-counter package to guide the light. The reflector 208 also increases the Q (ratio of energy stored in the river to energy loss per cycle) of the processing chamber 202 and allows for multiple bounces of light, thereby increasing the efficiency and efficacy of the processing chamber 202. Increase. Also shown are photodetectors 210 and other detectors that provide monitoring, control and verification of processing processes.

Pulsed light sterilization of the IV bag 200 or the over-the-counter solution pays attention to the design, material and its thickness and other key parameters to ensure that the light can reach and thus sterilize all important volumes and surfaces of the product. It may cost. Special attention should be paid to the bag, which, due to special properties such as fixtures and other normal parts, or rigid requirements or other considerations, may still meet the rigid requirements and require a design or material selection that is particularly suitable for use with pulsed light. Can be.

Another method of treating the product is to place the product on a conveyor as shown in FIG. The choice of conveyor is preferably transparent and in this area the packaging is processed from top to bottom to provide full coverage.

Claims (19)

Scintillation systems for generating high-intensity, short-term, continuous multicolor light pulses in a broad spectrum and inactivating microorganisms in the target by illuminating the target with the generated light pulses; A photosensitive detector for generating an output signal in response to the light pulse, the photosensitive detector arranged to receive a portion of each light pulse as a measure of the amount of light illuminating the target; And Sterilize the microorganisms in the target, including a flashlight system and a control system coupled to the photosensitive detector to determine whether the light pulse is sufficient to perform a prescribed level of inactivation of the microorganisms in the target in response to the output signal. Letting device. 2. The method of claim 1, wherein the control system monitors another output signal that is an indicator of the pulse parameter and, in response to the other output signal, whether the pulse parameter is sufficient for light pulse generation to perform a defined level of inactivation of the microorganisms in the target. The apparatus further comprises means for further measuring. 3. The system of claim 2, wherein the control system comprises: monitor and control circuitry; And a computer comprising software. 3. The apparatus of claim 2, wherein the control system comprises means for monitoring another output signal indicative of a pulse parameter selected from the group of pulse parameters consisting of current, voltage, peak current, current waveform, peak voltage and voltage waveform. 2. The output of claim 1, wherein the photosensitive detector displays an optical parameter selected from the group of optical parameters consisting of total fluence per flash, fluence per flash, total energy over time, and energy within a preselected bandwidth over time. Device for generating a signal. 6. The system of claim 5, wherein the control system comprises: monitor and control circuitry; And a computer comprising software. 2. The apparatus of claim 1, wherein the control system comprises means for measuring whether the light pulse is at least a defined fluence per flash in response to the output signal. 2. The apparatus of claim 1, wherein the control system comprises means for measuring, in response to the output signal, whether the light pulse is at least defined per fluence within a defined frequency band. The device of claim 1, wherein the means for inactivation comprises means for achieving a sterilization assurance level of at least 10 ⁻⁶ . The apparatus of claim 1, wherein the means for inactivation comprises means for achieving a sterile coverage level of at least 10 ⁻³ . The flashlight bulb and a reflector at least partially surrounding the target, wherein the flashlight system reflects the light pulse towards the target and reflects at least a portion of the transmitted light back through the target toward the target. Containing device. 2. The apparatus of claim 1, further comprising a reflector disposed proximate to a flashing light for reflecting light pulses towards the target. 13. The apparatus of claim 12, further comprising a hole positioned in the reflector and disposed with the photosensitive device. Generate a high-intensity, short-term continuous multicolor light pulse in the broad spectrum; Inactivating the microorganisms at the target by directing the generated light pulses to the target; Receive a portion of the light pulse as a measure of the amount of light pulses illuminating the target; Generating an output signal in response to receipt of the light pulse portion; In response to generating an output signal, determining whether the light pulse is sufficient to effect a prescribed level of inactivation of the microorganism in the target. 15. The method of claim 14, wherein determining whether the light pulse is sufficient comprises measuring whether the light pulse is at least a defined fluence per flash. The method of claim 14, wherein determining whether the light pulse is sufficient comprises measuring whether the pulse contains at least a defined spectral content. The method of claim 14, wherein the inactivation comprises achieving a sterile guaranteed level of at least 10 ⁻⁶ . The method of claim 14, wherein the inactivation comprises achieving a sterile guaranteed level of at least 10 ⁻³ . 15. The method of claim 14, further comprising reflecting at least a portion of each light pulse towards the target.