Method for measuring the irradiation dose at product level

Abstract

A method of measuring radiation dose during irradiation includes deploying a first sensor in a first package having a first biological container and deploying a second sensor in a second package having a second biological container. The method also includes placing the first package and the second package in a container and irradiating the container including the first package and the second package. During or after irradiation, a first radiation dose associated with the first biological container is measured with the first sensor and a second radiation dose associated with the second biological container is measured with the second sensor.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to and benefits from U.S. Provisional Patent Application Serial No. 63 / 128,389, filed December 21, 2020, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to the sterilization of products, and more specifically, to methods for measuring irradiation dose at the product level. Background Technology

[0004] Traditionally, the preparation, storage, mixing, freezing, transportation, formulation, and filling of biopharmaceutical solutions have utilized multiple-use containers that are sterilized before use. In recent years, however, the use of single-use packaging or biocontainers has shifted in these processes. These single-use biocontainers include, but are not limited to, plastic bags, tubing, tubes, hoses, hubs, connectors, or vessels.

[0005] The use of single-use biocontainers eliminates the need for laboratories or manufacturing facilities to perform cleaning validation processes, including tracking, sterilization, inspection, and storage of multi-use containers, before reuse. Therefore, by switching to single-use biocontainers, laboratories and manufacturing facilities can free up additional resources to focus on production or development. For example, single-use biocontainers can save time or reduce costs compared to the cleaning validation processes required for multi-use containers. Furthermore, switching to single-use biocontainers reduces the risk of contamination compared to multi-use containers. Single-use biocontainers have been adopted because biopharmaceutical manufacturers face increasing pressure to save costs while maintaining high-quality products.

[0006] These single-use biocontainers are sterilized by the manufacturer before being distributed for use. Sterilization can be achieved through ionizing radiation, such as gamma rays, electron beams, or X-rays that penetrate parts, plastic or metal parts, to kill microorganisms on or inside the parts.

[0007] To sterilize single-use bioreactors before use, the single-use bioreactor, along with several other single-use bioreactors, is placed on a pallet or in a large container (e.g., a tote bag, carrier, or conveyor belt) and moved around to fix the radiation source. The single-use bioreactors may be placed inside packaging or cartons before being placed on the pallet or large container. To verify whether a single-use bioreactor has been exposed to radiation, indicator labels (e.g., paper labels) that change color upon exposure to irradiation can be affixed to the packaging or carton containing one or more single-use bioreactors. These indicator labels are sufficient to indicate that the packaging or carton has been exposed to radiation, but cannot measure the radiation dose absorbed by the product inside the packaging or carton.

[0008] Radiation dose can be measured using a radiation dosimeter. A radiation dosimeter is a device in which a quantifiable change occurs in a certain characteristic when the organism is irradiated; this change can be correlated with the absorbed dose in a given material. Some large containers or trays used for the sterilization of single-use biocontainers may include one or two radiation dosimeters located at the periphery of the large container or tray. It is well known that there are significant changes in radiation dose across the container and therefore within the biocontainer. Summary of the Invention

[0009] The increasing adoption of single-use biocontainers in critical applications, such as product storage, highlights the impact of polymer material interactions between the biocontainer and the product within it. These interactions have become a concern regarding product stability within the biocontainer. While the occurrence of these interactions is evident, the root cause of the problem remains difficult to pinpoint.

[0010] As detailed in this article, in addition to sterilization, irradiation of plastic parts can trigger chemical reactions and complex modifications within the plastic material, as well as modifications to plastic additives. These chemical reactions or modifications can damage the plastic itself. Not all modifications occur at the same dose or to the same degree. Any change in the dose received by the biocontainer will affect one or more different critical quality properties of the plastic and will impact products stored in or transported via the biocontainer, including but not limited to active pharmaceutical ingredients (APIs) (e.g., proteins of interest), active pharmaceutical ingredients (BDS), or intermediates.

[0011] Furthermore, large containers can include multiple types (one or more) of biocontainers formed from different materials deployed within the container. Because existing containers may include only one or two radiation dose sensors, it can be difficult to determine the dose absorbed by a specific disposable biocontainer within the container. Therefore, separate radiation dose sensors can be associated with each biocontainer or each type of biocontainer within the container, allowing for accurate measurement of the absorbed radiation by each biocontainer or each type of biocontainer within the container. Measuring the radiation dose of each biocontainer and / or each type of biocontainer within the container allows for more accurate measurement of the effects of radiation on the biocontainers. The radiation dose of each biocontainer can be used to predict the effects of sterilization on products stored or transported via biocontainers. The effects of sterilization can be used to predict the degradation of products transported via or stored in biocontainers.

[0012] In embodiments of this disclosure, a method for sterilizing a biocontainer includes irradiating a first biocontainer and measuring a first radiation dose received by the first biocontainer. The method further includes calculating a first aging time for the first biocontainer after irradiation based on the first radiation dose received by the first biocontainer, and preventing the use of the first biocontainer until the first aging time has elapsed.

[0013] In embodiments of this disclosure, a method for measuring radiation dose during irradiation includes deploying a first sensor in a first package having a first biological container and deploying a second sensor in a second package having a second biological container. The method further includes placing the first and second packages in a container and irradiating the container comprising the first and second packages. During or after irradiation, a first radiation dose associated with the first biological container is measured using the first sensor and a second radiation dose associated with the second biological container is measured using the second sensor.

[0014] In another embodiment of this disclosure, a method for sterilizing a biological container includes irradiating a first biological container, measuring a first radiation dose received by the first biological container, calculating a first aging time of the first biological container after irradiation based on the first radiation dose received by the first biological container, and preventing the use of the first biological container before the first aging time has elapsed.

[0015] In one embodiment, the method includes irradiating a second biological container simultaneously with a first biological container, measuring a second radiation dose received by the second biological container, calculating a second aging time for the second biological container after irradiation based on the second radiation dose received by the second biological container, and preventing the use of the second biological container until the second aging time has elapsed. The second aging time may differ from the first aging time. Calculating the second aging time may include a second radiation dose greater than the first radiation dose and the second aging time being calculated as less than the first aging time.

[0016] In some embodiments, the calculation of the first aging time is based on a first radiation dose and the material forming the first biocontainer. Measuring the first radiation dose received by the first biocontainer may include measuring the first radiation dose using a first sensor, the first sensor comprising a membrane formed of a material similar to the material forming the first biocontainer. Measuring the first radiation dose using the first sensor may include measuring the properties of the membrane.

[0017] In some embodiments, the method includes determining the shelf life of a product stored within a first biocontainer. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the first biocontainer based on measurements taken by a first sensor after an aging period and before the first biocontainer is filled with the product. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the first biocontainer and the product based on measurements taken by the first sensor after the first biocontainer is filled with the product. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the product before the first biocontainer is filled with the product.

[0018] In another embodiment of this disclosure, a method for sterilizing biological containers includes simultaneously irradiating multiple biological containers, measuring different radiation doses of each biological container using multiple sensors, calculating different aging times of each biological container after irradiation based on the different radiation doses received by the respective biological containers, preventing the use of a first biological container based on a first aging time of a first biological container among the multiple biological containers, and preventing the use of a second biological container based on a second aging time of a second biological container among the multiple biological containers. The second aging time is different from the first aging time. Each of the multiple sensors is associated with a biological container among the multiple biological containers.

[0019] In one embodiment, calculating the second aging time involves a second radiation dose greater than the first radiation dose and the second aging time being calculated to be less than the first aging time. The first aging time can be calculated based on the first radiation dose and the material forming the first biological container.

[0020] In some embodiments, measuring a first radiation dose received by a first biocontainer includes measuring the first radiation dose using a first sensor among the plurality of sensors, the first sensor comprising a first membrane formed of a material similar to the material forming the first biocontainer. Measuring the first radiation dose using the first sensor may include measuring the properties of the membrane. Measuring a second radiation dose received by a second biocontainer may include measuring the second radiation dose using a second sensor among the plurality of sensors, the second sensor comprising a second membrane formed of a material similar to the material forming the second biocontainer. The second membrane may be different from the first membrane.

[0021] In some embodiments, the method includes determining the shelf life of a product stored within a first biocontainer. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the first biocontainer based on measurements taken by a first sensor among a plurality of sensors after a first aging time and before the first biocontainer is filled with the product. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the first biocontainer and the product based on measurements taken by the first sensor after the first biocontainer is filled with the product. Determining the shelf life of the product stored within the first biocontainer may include determining the mass of the product before the first biocontainer is filled with the product.

[0022] In another embodiment of this disclosure, a method for measuring radiation dose includes deploying a first sensor in a first package having a first biological container, deploying a second sensor in a second package having a second biological container, placing the first and second packages in a container, irradiating the container including the first and second packages, and measuring a first radiation dose associated with the first biological container using the first sensor and a second radiation dose associated with the second biological container using the second sensor.

[0023] In an embodiment, measuring the first radiation dose and the second radiation dose includes the first radiation dose being different from the second radiation dose. Deploying the first sensor in the first package may include deploying the first sensor in the first package having a first biological container and a third biological container, such that the first sensor is associated with the first biological container and the third biological container.

[0024] In some embodiments, placing the first package and the second package in the container includes placing the first package and the second package on a tray.

[0025] In some embodiments, irradiating containers comprising a first package and a second package involves exposing the containers to a first radiation cycle and a second radiation cycle. Measuring the first radiation dose may occur between the first and second radiation cycles.

[0026] In another embodiment of this disclosure, the method of measuring radiation dose includes placing a plurality of packages in a container, each of the plurality of packages including a sensor associated with a biological container deployed within the package, irradiating the container comprising the plurality of packages, and measuring the radiation dose of each package using the sensor associated with the biological container deployed within the respective package.

[0027] In an embodiment, placing the plurality of packages in a container includes placing the plurality of packages on a tray. Placing the plurality of packages, including sensors associated with the biological container, in the container includes at least one of the plurality of packages including a first sensor associated with a first biological container and a second sensor associated with a second biological container.

[0028] In some embodiments, placing the plurality of packages, including sensors associated with the biocontainer, within a container includes at least one of the packages, which includes sensors associated with a first biocontainer and a second biocontainer deployed within the at least one package. Irradiation may include exposing the container to a first radiation cycle and a second radiation cycle. Measurement of radiation dose may occur between the first and second radiation cycles.

[0029] Furthermore, to the extent that they are consistent, any embodiment or aspect described herein may be used in conjunction with any or all other embodiments or aspects described herein. Attached Figure Description

[0030] Various aspects of this disclosure are described below with reference to the accompanying drawings, which are incorporated in and form part of this specification, wherein:

[0031] Figure 1 This is a schematic diagram of the top of a sterilization device used for biological containers;

[0032] Figure 2 yes Figure 1 A side view of the sterilization device;

[0033] Figure 3 This is a graph illustrating the XPS spectra of the EVA film under different absorbed radiation doses;

[0034] Figure 4 The diagram shows carboxylic acid with H3O. + A graph of pH;

[0035] Figure 5 It is a graph showing empirical data on the increase in oxidation of products in plastic bags exposed to different doses of radiation;

[0036] Figure 6This is a graph showing empirical data on the increase in oxidation of products in plastic bags at storage intervals after sterilization;

[0037] Figure 7 This is a flowchart of a method for determining the radiation dose of a biological container according to embodiments of the present disclosure; and

[0038] Figure 8 This is a flowchart of a method for determining the shelf life of a product within a biological container according to embodiments of the present disclosure. Detailed Implementation

[0039] This disclosure will now be described more fully below with reference to exemplary embodiments thereof and to the accompanying drawings, in which similar reference numerals indicate the same or corresponding elements in each of several views. These exemplary embodiments are described so that this disclosure will be thorough and complete, and will fully convey the scope of this disclosure to those skilled in the art. Features from one embodiment or aspect may be combined with features from any other embodiment or aspect in any suitable combination. For example, any individual or collective feature of a method aspect or embodiment may be applied to an apparatus, product, or component aspect or embodiment, and vice versa. This disclosure may be practiced in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided to enable this disclosure to meet applicable legal requirements. As used in the specification and appended claims, the singular forms “a,” “an,” “the,” etc., include plural objects unless the context clearly specifies otherwise. Furthermore, while quantitative measurements, values, geometric relationships, etc., may be referenced herein, any one or more (if not all) may be absolute or approximate unless otherwise stated, to account for acceptable variations that may occur, such as those due to manufacturing or engineering tolerances.

[0040] Now for reference Figure 1 and Figure 2 The illustration shows an apparatus for sterilizing biological containers and is generally referred to as apparatus 1000. Apparatus 1000 includes an outer wall 1010 and a radiation source 1020. The outer wall 1010 encloses the chamber 1012 and shields the environment outside apparatus 1000 from radiation provided by the radiation source 1020.

[0041] To sterilize a biocontainer, a biocontainer 1200 may be loaded into one or more containers 1100. Container 1100 is positioned within a chamber 1012, and one or more radiation sensors 1110 are deployed within container 1100. A radiation source 1020 is then placed in an irradiation configuration or activated to emit gamma rays, electron beams, X-rays, or other forms of sterilizing radiation. Radiation passes through container 1100 and biocontainer 1200 to sterilize the materials forming biocontainer 1200. Radiation sensors 1110 measure the radiation dose at various locations within container 1100. It is known that the radiation within container 1100 can vary considerably depending on the location of biocontainer 1200 and other biocontainers 1200 within container 1100. Furthermore, the materials forming one biocontainer 1200 may differ from those forming another. This variation in materials can also affect the radiation dose deposition absorbed by different biocontainers 1200. It has been shown that the radiation dose absorbed during sterilization affects the performance of biocontainer 1200. In some embodiments, the biological container 1200 may be placed on a conveyor belt through which the radiation source 1020 passes.

[0042] refer to Figure 3 The effects of gamma irradiation on multilayer films (such as those used to form disposable biocontainers) have been investigated using various techniques, including but not limited to FTIR spectroscopy and X-ray photoelectron spectroscopy. These studies have shown that, as a result of irradiation, the materials forming the multilayer films undergo chemical modification, exhibiting polymer oxidation and the generation of oxidants both within and on the polymer surface. This generation of oxidants leads to the formation of free radicals, which in turn cause polymer modification. These free radicals can induce protein aggregation and protein oxidation within the product of the disposable biocontainer. Figure 3 As shown, oxidation depends on the dose of radiation absorbed by the polymer.

[0043] Radiation dose can affect products stored in single-use biocontainers after irradiation. These effects can include a decrease in protein concentration, changes in the concentration of buffer components due to absorption, migration of free radicals from the biocontainer to the product, or pH shifts within the product. All of these effects can lead to protein aggregation, chemical modification, or the introduction of unwanted leaching compounds into the product. Figure 4 As shown, the carboxylic acid concentration within a disposable biological container is represented in response to different radiation doses.

[0044] refer to Figure 5It has been shown that the amount of amino acid oxidation in biocontainer 1200 after sterilization is affected by the radiation dose received during sterilization. As shown in the figure, the amount of amino acid oxidation decreases with increasing radiation dose when a particular biocontainer receives an increased radiation dose. For example, when a particular biocontainer 1200a receives 25 kJ of radiation (kGy), amino acid oxidation increases by 500% to 750%; when it receives 50 kGy, amino acid oxidation increases by 120% to 275%; and when it receives 100 kGy, amino acid oxidation increases by less than 100%. This is confirmed by another biocontainer 1200b, which increases by 350% when exposed to 25 kGy, by 100% when exposed to 50 kGy, and by 50% when exposed to 100 kGy. This is contrary to the accepted view that higher radiation doses cause greater damage to the material and therefore increase amino acid oxidation. Specifically, the conventional thinking is that higher radiation doses result in more damage, such as oxidation and the generation of free radicals; however, this is different from... Figure 5 Conversely, as shown in the diagram, the lower the radiation dose, the more amino acid oxidation occurs in the disposable biocontainer.

[0045] in addition, Figure 5 It is also shown that the materials forming the biocontainer can affect the dose on the biocontainer. For example, the first biocontainer 1200a is affected to a greater extent than the second biocontainer 1200b, while the third biocontainer 1200c is affected less than the second biocontainer 1200b. Therefore, the effect of the dose can depend on the amount of the dose and the type of material receiving the dose.

[0046] One explanation for the increased amino acid oxidation is that the increased oxidation could be a result of free radicals generated by the irradiation of the biocontainer. Specifically, radiation sterilization of the biocontainer causes complex modifications within the material, leading to alterations in additives or damage to the polymer itself. For example, irradiation of the biocontainer can trigger chemical reactions within the plastic material, resulting in an increase or decrease in the polymer's molecular weight. These modifications can lead to the formation of free radicals on the material's surface and core. Although antioxidants are present in the membrane, free radicals are still generated because they are rapidly scavenged by the antioxidants present in the material. Electron spin resonance (ESR) indicates the presence of free radicals in the biocontainer material after irradiation. The competition between antioxidants and free radical scavenging, along with the oxidation of hydrocarbon chains, leads to the presence of oxygen-containing organic molecules. This competition can depend on the gamma irradiation dose rate. It is hypothesized that the direct availability of oxygen and antioxidants also influences this competition.

[0047] Now for reference Figure 6The passage of time from the start of irradiation can reduce the amount of protein oxidation in disposable biocontainer materials. This reduction in protein oxidation can be a result of the dissipation of free radicals generated during irradiation. For example... Figure 6 As shown, for biocontainer 1200, the relative increase in protein oxidation after 4 weeks can range from 125% to 225%, decreasing to 90% to 165% after 15 weeks, decreasing to 80% to 150% after 17 weeks, and decreasing to 50% after 45 weeks. Therefore, the amount of time after irradiation can be important for reducing the oxidation of proteins ultimately stored in the biocontainer. This amount of time can be characterized as aging time.

[0048] Given the foregoing, it is clear that multiple factors can influence the potential impact of single-use biocontainers on products stored within or flowing through them. This potential impact can be characterized by protein oxidation within the biocontainer. Based on the studies summarized above, the material of the biocontainer, the radiation dose, and the aging time of the biocontainer after irradiation can be used to predict protein oxidation within the biocontainer. Therefore, if the material of the biocontainer and the radiation dose are known, an appropriate aging time or aging period can be calculated to reduce or eliminate the effects of irradiation on the biocontainer.

[0049] As detailed above, one factor used to determine the effects of irradiation on biocontainers is the dose of radiation received by each biocontainer. Therefore, a method is needed to accurately determine the dose of radiation received by each disposable biocontainer. Dosage sensors that accurately measure the dose to a specific biocontainer can allow for improved predictions of the biocontainer's performance after sterilization.

[0050] Type I or Type II dosimeters are known to be used to measure the radiation dose absorbed by disposable biocontainers during irradiation. For Type I dosimeters, the response must be adjusted for the effects of relevant influencing factors (temperature, dose rate, etc.) by applying independent corrections. Type I dosimeters can use Fricke solutions, which employ spectrophotometric evaluation, such as alanine dosimeters using electron paramagnetic resonance (EPR) analysis, dichromate solutions using spectrophotometric evaluation, cerium-cerium solutions using spectrophotometry or potentiometry, or ethanol-chlorobenzene solutions using titration analysis, to determine the absorbed radiation dose during irradiation. Independent correction factors are not practical for Type II dosimeters due to the influence of radiation dose-related factors (including temperature and dose rate). Therefore, Type II dosimeters include process calorimeters, cellulose triacetate, lithium fluoride-containing polymer matrices (fluorescent), Perspex systems, and radiochromic films and liquids. Furthermore, the calibration process for Type I and Type II requires waiting several hours after using UV-VIS, FTIR, or spectrometer radiation sensors, thus making it impossible to detect dose changes in real time.

[0051] The dosimeter allows for real-time measurement of absorbed radiation during sterilization and its effects on the materials of a specific biocontainer. The dosimeter can also allow for prediction of reductions in the concentration of proteins or other formulation buffering components due to absorption or free radical migration from the biocontainer into the product, potentially causing pH shifts within the product due to protein aggregation, chemical modification, or the introduction of leachable compounds into the materials forming the biocontainer. The dosimeter and method disclosed herein allow for reading radiation doses at the level of each biocontainer within the container, which contrasts with previous sensors detailed above (e.g., sensor 1110). Figure 1 The container level is the opposite. As used herein, the term "packaging" describes the transport packaging of one or more biological containers. Packaging can be a cardboard box or plastic tote bag that serves as a transport unit for one or more biological containers. Packaging can also be referred to as a carton.

[0052] Furthermore, the radiation dose sensor detailed herein is applicable to a wide range of radiation doses, such as from 10 Gy to 150 kGy, and a wide range of radiation energies and wavelengths, such as from 100 keV to 10 MeV. Additionally, the radiation dose sensor detailed herein can take environmental factors into account and must operate under all irradiation conditions, including but not limited to temperature, dose rate, percentage of dose absorbed per hour, gray per hour, and type of radiation.

[0053] Now for reference Figure 7 According to this public reference Figure 1 and Figure 2 The sterilization apparatus 1000 discloses a method 500 for measuring irradiation dose and modification or damage to biocontainer materials. Regarding method 500, the dosimeter or sensor 1210 may be a sensor deployed in or on the packaging 1300 along with the biocontainer, or it may be a sensor deployed in the packaging 1300 along with one or more biocontainers.

[0054] To begin measuring the radiation dose of one or more biocontainers 1200 during their irradiation, a sensor 1210 is deployed on or within a package 1300 together with the biocontainers 1200 (step 510). A single package 1300 may include multiple biocontainers 1200 (each biocontainer 1200 including a separate sensor 1210) or may include a single sensor 1210 associated with multiple biocontainers 1200 within the package 1300. It should be recognized that each package 1300 is relatively small, enabling the single sensor 1210 deployed therein to accurately measure the radiation dose of each biocontainer 1200. With the sensor 1210 deployed in the package 1300 such that each biocontainer 1200 is associated with a corresponding sensor 1210 deployed therewith within the package 1300, the package 1300 is placed in an irradiated container 1100 (step 520). Container 1100 may include multiple packages 1300, each package 1300 having a similar or different biological container. Each of the multiple packages 1300 in container 1100 may have one or more sensors 1210 deployed therein.

[0055] By placing the package 1300 containing sensor 1210 inside container 1100, container 1100 is exposed to radiation from a radiation source (such as radiation source 1020) (step 540). During the delivery of radiation, sensor 1210 can provide a measurement of the radiation dose to a controller outside container 1100 (step 542). Sensor 1210 can provide the measurement to the controller in real time, such that the measurement of sensor 1210 can be used to control the duration of exposure to radiation source 1020. The transmission of the signal from sensor 1210 to the controller outside container 1100 can be direct to the controller outside container 1100 or to an intermediate antenna, repeater, or controller of container 1100, which then transmits the signal from sensor 1210 to the controller outside container 1100. The intermediate antenna, repeater, or controller of container 1100 can communicate with multiple sensors (e.g., sensor 1210) inside container 1100 and send a single combined signal to the controller outside container 1100, including data from multiple sensors. When all sensors (e.g., sensor 1210) within container 1100 are at or above the desired radiation dose, or when one or more sensors within container 1100 reach the maximum radiation dose, a controller outside container 1100 may terminate radiation delivery (step 546). Radiation delivery terminates when the desired dose or the maximum dose is reached (step 548). In some embodiments, real-time measurements of sensor 1210 may be obtained continuously or at predetermined intervals during radiation delivery. In some embodiments, real-time measurements of sensor 1210 are obtained between cycles of radiation delivery. Obtaining real-time measurements between cycles of radiation delivery improves measurement accuracy due to reduced interference from active gamma irradiation.

[0056] After the radiation delivery is complete, sensor 1210 can provide the radiation dose received during irradiation to determine the total radiation absorbed by the associated biocontainer 1200 during irradiation (step 550). The radiation dose can be used to determine whether the material of the associated biocontainer 1200 has been modified or whether free radicals have formed due to irradiation. Given the radiation dose and the material of the biocontainer 1200, an aging time can be calculated to minimize the risk of protein oxidation within the biocontainer 1200 (step 560). The aging time can be the amount of time it takes for the material of the associated biocontainer 1200 to stabilize after irradiation, as described above regarding... Figure 6 As detailed above, storing one or more biocontainers 1200 associated with sensor 1210 until the material of biocontainer 1200 stabilizes can reduce the degradation of products that come into contact with the material of biocontainer 1200. The aging time can be calculated or determined based on data collected from previous tests exposing similar biocontainers or materials to different doses of radiation, similar to... Figure 6As shown in the illustration. In some embodiments, calculating the aging time based on materials and radiation dose may include developing tables or formulas for each type or material of the biocontainer for protein oxidation as a function of aging time and radiation dose. When the aging time has elapsed, the packaging 1300 of the biocontainer 1200 may be transported or put into use (step 570).

[0057] refer to Figure 8 The present disclosure describes a method for determining the characteristics of a biocontainer 1200 and a method for determining the characteristics of a product stored within the biocontainer 1200.

[0058] As described above, the dose of radiation received by the biocontainer 1200 during irradiation affects the performance of the biocontainer 1200. The performance of the biocontainer 1200 can be based on the mass of the materials forming the biocontainer 1200 after irradiation and / or may be a result of the dissipation of free radicals or other particles from the biocontainer 1200. The mass of the materials forming the biocontainer 1200 and / or the dissipation of free radicals can affect the product stored within the biocontainer 1200, for example, protein oxidation in the product stored within the biocontainer 1200. Continuing to obtain measurements from the sensor 1210 after the aging time has been completed allows for the determination or estimation of the dissipation of free radicals or other particles from the biocontainer 1200 after the aging time has been completed. This dissipation of free radicals or other particles from the biocontainer 1200 can be used to determine how the product stored within the biocontainer 1200 may be affected.

[0059] The quality of the materials forming the biocontainer 1200 can be determined based on measurements taken by the sensor 1210 during and / or after the aging period. For example, measurements can be taken using the sensor 1210 and a table or formula can be associated with each type of material in the biocontainer as a function of different properties (e.g., capacitance) measured by the sensor 1210. This table can be developed for each material in the biocontainer such that a specific reading from the sensor 1210 can be correlated with the quality of the materials forming the biocontainer 1200.

[0060] After the biocontainer 1200 is filled with product, the quality of the biocontainer 1200 can be associated with its lifespan. This lifespan of the biocontainer 1200 at the time of product filling can be referred to as its "shelf life" or the amount of time the biocontainer 1200 can be used to store product in a usable state. Shelf life can be determined based on the quality of the biocontainer 1200 before or after it is filled with product. In embodiments, measurements by sensor 1210 can be taken after an aging time and before the biocontainer 1200 is filled, so that the shelf life of the biocontainer 1200 is determined once it is filled with a specific product. In some embodiments, measurements by sensor 1210 can be taken after the biocontainer 1200 is filled with product to determine its shelf life. In a particular embodiment, measurements by sensor 1210 are taken both before and after the biocontainer 1200 is filled with product to determine its shelf life. The shelf life may be determined by one or more of the following factors, including but not limited to the characteristics of the biocontainer 1200, the mass of the biocontainer 1200 as measured by the sensor 1210, the type of product, the quantity of the product, or the temperature at which the product is stored in the biocontainer 1200.

[0061] The method 600 for determining the shelf life of the bag and the product contained therein may include determining the state or quality of the biocontainer 1200 before it is filled (step 610), determining the state or quality of the product filling the biocontainer 1200 before it is filled (step 620), and determining the state or quality of the biocontainer 1200 and the product within it after it is filled with the product (step 640). The quality of the biocontainer 1200 and the product obtained separately before filling may be correlated with the quality of the biocontainer 1200 and the product obtained together after filling (step 630) to determine the shelf life of the biocontainer 1200 at the time of product filling (step 650). The quality of the biocontainer 1200 may be determined by measurement using the sensor 1210 detailed above. Furthermore, once the biocontainer 200 is filled with the product, the quality of the biocontainer 1200 and the product may be determined by measurement using the sensor 1210. For example, the characteristics of sensor 1210 (e.g., capacitance) can be used to determine the quality of biocontainer 1200 and the product contained within biocontainer 1200.

[0062] While several embodiments of the present disclosure have been shown in the accompanying drawings, they are not intended to be limited thereto, as the disclosure is intended to have a broad scope within the limits permitted by the art, and the specification is read as such. Any combination of the above embodiments is also contemplated and within the scope of the appended claims. Therefore, the above description should not be construed as limiting, but merely as examples of particular embodiments. Other modifications within the scope of the appended claims will be contemplated by those skilled in the art.

Claims

1. A method for measuring radiation dose, the method comprising: The first sensor is deployed in a first package having a first biological container; The second sensor is deployed in a second package containing a second biological container; Place the first and second packages in the container; Irradiation of the containers, including the first and second packages, occurs before the first and second biocontainers are filled with the product. as well as A first radiation dose associated with the first biological container is measured using a first sensor, and a second radiation dose associated with the second biological container is measured using a second sensor.

2. The method of claim 1, wherein measuring the first radiation dose and the second radiation dose includes the first radiation dose being different from the second radiation dose.

3. The method of claim 1, wherein deploying the first sensor in the first package comprises deploying the first sensor in the first package having a first biological container and a third biological container, such that the first sensor is associated with the first biological container and the third biological container.

4. The method of claim 1, wherein placing the first package and the second package in the container comprises placing the first package and the second package on a tray.

5. The method of claim 1, wherein irradiating the containers comprising the first package and the second package comprises exposing the containers to a first radiation cycle and a second radiation cycle, and wherein measuring the first radiation dose occurs between the first radiation cycle and the second radiation cycle.

6. The method of claim 1, further comprising filling a second biological container with the product after an aging time at least in part based on the second radiation dose.

7. The method of claim 6, further comprising calculating an aging time, at least in part, based on the second radiation dose, after measuring the second radiation dose and before filling the second biological container.

8. A method for measuring radiation dose, the method comprising: Multiple packages are placed in a container, each of the multiple packages including a sensor associated with a biocontainer deployed within the package; Irradiation includes the containers of the aforementioned multiple packages; as well as The radiation dose of each package is measured using sensors associated with the biocontainer deployed within the corresponding package.

9. The method of claim 8, wherein placing the plurality of packages in the container comprises placing the plurality of packages on a pallet.

10. The method of claim 8, wherein placing the plurality of packages including a sensor associated with a biological container in the container includes at least one of the plurality of packages including a first sensor associated with a first biological container and a second sensor associated with a second biological container.

11. The method of claim 8, wherein placing the plurality of packages including sensors associated with the biocontainer in the container includes at least one of the plurality of packages including sensors associated with the first and second biocontainers deployed within the at least one package.

12. The method of claim 8, wherein irradiating the containers comprising the plurality of packages comprises exposing the containers to a first radiation cycle and a second radiation cycle, and wherein measuring the radiation dose occurs between the first radiation cycle and the second radiation cycle.

13. The method of claim 8, further comprising filling the biological container with the product after an aging time at least in part based on the radiation dose.

14. The method of claim 13, further comprising calculating the aging time, at least in part, based on the radiation dose, after measuring the radiation dose and before filling the biological container.

15. A method for measuring radiation dose, the method comprising: The first sensor is deployed in a first package having a first biological container; The second sensor is deployed in a second package containing a second biological container; Place the first and second packages in the container; Irradiation includes the containers of the first and second packages; A first radiation dose associated with the first biological container is measured using a first sensor, and a second radiation dose associated with the second biological container is measured using a second sensor; and The first biological container is filled with the product after an aging time based at least in part on the first radiation dose.

16. The method of claim 15, further comprising calculating an aging time, at least in part, based on the first radiation dose, after measuring the first radiation dose and before filling the first biological container.

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