WO2017103661A1

WO2017103661A1 - Quality control assay to monitor the completeness of pathogen or targeted cell inactivation treatments in biological, foodstuff, drinks and cosmetics products

Info

Publication number: WO2017103661A1
Application number: PCT/IB2015/059781
Authority: WO
Inventors: Mélanie ABONNENC; Philippe Tacchini; David CRETTAZ; Giona SONEGO; Michel Prudent; Niels Lion
Original assignee: Edel-For-Life SA; Service Regional Vaudois De Transfusion Sanguine
Current assignee: Edel-For-Life SA; Service Regional Vaudois De Transfusion Sanguine
Priority date: 2015-12-18
Filing date: 2015-12-18
Publication date: 2017-06-22
Anticipated expiration: 2018-06-18
Also published as: CH713411B1

Abstract

This invention refers to new methods for measuring the completeness of pathogen and targeted cell inactivation treatments such as photo-, photochemical, chemical or irradiation-based treatments in biological, foodstuff, drinks and cosmetic products, and in particular, new methods for measuring the completeness of pathogen and targeted cell inactivation techniques in blood and blood derived products for a use as quality control assay. New methods include, but are not limited to comparing the measured antioxidant power with the threshold antioxidant value that has to be defined for this specific sample and below which the product is considered as correctly treated or comparing the antioxidant power before and after treatment because their established difference accounts for an effective treatment.

Description

QUALITY CONTROL ASSAY TO MONITOR THE COMPLETENESS OF PATHOGEN OR TARGETED CELL INACTIVATION TREATMENTS IN BIOLOGICAL, FOODSTUFF, DRINKS AND COSMETICS PRODUCTS

Field of invention

The present invention relates to new methods for measuring the completeness of pathogen or targeted cell inactivation treatments such as photo-, photochemical, chemical or irradiation-based treatments in biological, foodstuff, drinks and cosmetic products, and in particular, new methods for measuring the completeness of pathogen and targeted cell inactivation techniques in blood and blood-derived products for use as quality control assay.

Background of the Invention

Pathogen or targeted cell inactivation treatments are used in various fields including health, food, drinks and cosmetic industries to secure products against the presence of pathogens, virus, bacterial contamination or unwanted contaminants. Such treatments include, but are not limited to the exposition to different wavelengths or isotopic radiation alone or in combination with one or several photo-sensitive chemical(s) or the addition of one or several chemicals responsible for the generation of free radicals or excited state molecules.

In the food, drinks and cosmetic industries, gamma irradiation is often used to control pathogens, which can be destroyed, slowed down in their growth or made unable to reproduce, depending on the dose (1 ). When pallets of products are being exposed to a source of radiation, embedded dosimeters are used to determine what dose was achieved (2), but, despite strict regulatory framework including the labelling of the irradiated products (3), the result of the treatment is not evaluated.

Pathogen or targeted cell inactivation technologies are widely implemented in blood banks to reduce the risk of bacterial contamination and to face the emergence of new pathogens in blood components. Several types of blood-derived products can be treated for pathogen and targeted cell inactivation such as platelet concentrates, plasma units, erythrocyte concentrates or whole blood units.

Pathogen or targeted cell inactivation technologies to treat platelet concentrates rely on photochemical treatments or irradiation-based treatments. Photochemical treatments use a photoactive compound in combination with an ultraviolet exposure. For example, the Intercept Blood System (Cerus, Concord, USA) uses a psoralen derivative with an ultraviolet A exposure to inactivate pathogens in both platelet concentrates and plasma units. The psoralen intercalates into double strand DNA or RNA and is cross-linked upon UVA exposure therefore blocking the replication of pathogenic DNA or RNA. As platelets are devoid of genomic DNA they are not functionally affected by this treatment. However, it has been shown that mitochondrial DNA, RNA or microRNA might be altered, apparently without any defavourable consequences. Another example is the Mirasol technology (Terumo BCT, Lakehood, USA) which relies on the addition of riboflavin in combination with an ultraviolet A and B exposure. This treatment generates oxidative damages to the pathogenic DNA. A third technology, known as Theraflex (Macopharma, France), uses ultraviolet C alone to treat the platelet concentrates. The first two technologies have proven their efficacy in reducing pathogens and are used in several blood banks worldwide while the later is still under clinical phase evaluation.

Pathogen inactivation concerns other blood-derived products such as plasma units that can be treated with the Intercept Blood System as described above or also with methylene blue (Macopharma, France). Methylene blue is a phenothiazine compound activated by visible light and known to generate reactive oxygen species responsible for its pathogen inactivating properties. Pathogen inactivation in whole blood is also raising interests notably for its application in resource-limited countries. At the present time, two technologies are under evaluation. The first one is the photochemical treatment Mirasol as described above (Terumo BCT) and the second one is a chemical inactivation developed by Cerus.

In specific cases, erythrocyte concentrates or platelet units can be irradiated to prevent the occurrence of transfusion associated graft-versus host disease. The aim is to inactivate lymphocytes while preserving the functionality of blood cells of interest. For this purpose, erythrocyte concentrates can be submitted to gamma irradiation at a dose comprised between 25 Gray and 50 Gray. In the past, platelet concentrates were treated with UVB irradiation but it is less frequent because photochemical-based treatments used for pathogen inactivation also inactivate the residual lymphocytes present in the platelet concentrates.

Another application of photochemical treatments in hematology is the extracorporeal photopheresis that involves the ex-vivo exposure of peripheral blood mononuclear cells, including pathogenic or autoreactive T lymphocytes, to a photoreactive compound and ultraviolet A exposure, followed by reinfusion of the peripheral blood mononuclear cells to the patient. Extracorporeal photopheresis has been applied to the treatment of cuteneous T-cell lymphoma, alloimune disorders of cell-mediated immunity and autoimmune disease (4).

The Council of Europe recommended Quality Control tests to be introduced for assessing the efficacy of pathogen inactivation in blood components (5, 6). Presently, a label applied to the illumination container after treatment, provides visual evidence that the unit received partial or complete treatment in the illuminator, and should not be re-illuminated. Optionally, the illuminator may be connected to the blood bank data management system to block the release of non illuminated or doubly illuminated products. An UVA indicator label changing from light blue to dark blue according to the UVA exposure has been tested by Isola et al. (4). This label provides a visual quality assurance assay to monitor the INTERCEPT treatment but is not currently used in blood centres. These checkpoints are necessary during the processing of blood components to avoid confusion but it is not a control of the product itself. During the preclinical and clinical phase of INTERCEPT system evaluation, the efficacy of the system has been evaluated by measuring the photodegradation of amotosalen by high performance liquid chromatography or based on the assumption that adduct formation proportionate with exerted UVA dose (7, 8, 9).

Bruchmuller et al. developed a polymerase chain reaction (PCR) inhibition assay documenting the INTERCEPT inactivation process of platelet concentrates (10, 1 1 , 12) Statistically, an amotosalen-DNA adduct is formed approximately every 268 bp in mitochondrial DNA (imtDNA) (13). Large amplicons are therefore more susceptible to contain amotosalen adducts than small amplicons serving as an internal control. Bakkour et al. worked on the same concept using real-time PCR for quality control of pathogen reduction with riboflavin and UVB light (Mirasol, Terumo BCT, Lakewood, CO, USA) (14). Even though the PCR inhibition assay has the advantage of documenting the alteration of nucleic acids, i.e. the target of pathogen inactivation treatments, the imtDNA extraction and PCR are time consuming and require an instrumentation that is not always available in blood centres. Therefore there is a need for a fast and straightforward quality control assay. The assay should also ensure that the product received both the photoactive compounds and appropriate dose of UV light.

The Invention

A goal of the present invention is to fulfil the need mentioned above in relation with the prior art. The invention meets this goal by providing a method for determining the completeness of pathogen or targeted cell inactivation treatments in foodstuff or drink products, cosmetic products, chemical or biological products, said products being products that show a measurable antioxidant power prior to treatment, the method comprising: a) providing a sample of one of said products, the one of said products having been subjected to a photo-, photochemical, chemical or irradiation-based pathogen or targeted cell inactivation treatment; b) measuring the antioxidant power of said sample; c) comparing the value of the antioxidant power obtained in step (b) to a value of the antioxidant power obtained by measuring another sample of said product, said another sample not having been subjected to said pathogen inactivation treatment and/or comparing the value of the antioxidant power obtained in step (b) to a predetermined antioxidant power threshold value, below which said product is considered as successfully treated.

The measurement of the antioxidant power, in agreement with the chemical definition of an antioxidant, corresponds to the ability of the measured sample to donate one or several electrons, so that they can be used for neutralizing free radicals species. Some synonyms of "antioxidant power" known to the person skilled in the art are "total antioxidant capacity", "antioxidant level" or "antioxidant activity" or "reducing capacity". Antioxidant power is defined by the ability to prevent oxidation according to the definition of oxidation-reduction reactions, involving the simultaneous oxidation and reduction of 2 reactive compounds, one being oxidized, the other being reduced. Such measurements include but are not limited to the use of electrochemical based methods (15) including the technology developed by Edel-for-life and using Edel devices and methodology (16, 17), spectro-photochemical based methods, including but not limited to the ORAC (18), DPPH (19), TRAP, TEAC and FRAP (20) and antioxidants trapping (22) methods, liquid chromatography (23), mass spectrometry (24) measurements and/or any other methods designed and available for measuring antioxidant power.

According to a preferred implementation of the invention, the method is for use with blood or blood-derived products. The use of a comparison of the antioxidant power of a blood product in a treated and in a non-treated condition, or the use of a comparison of the antioxidant power of a treated blood or blood-derived product to a predetermined threshold value, as a quality control assay brings a new and innovative solution for performing such assay. Brief Description of the Drawings

Figure 1 illustrates the quality control assay as measured by the antioxidant power of a product treated with a pathogen or targeted cell inactivation treatment.

Figure 2 illustrates the determination of the threshold antioxidant power that distinguishes the treated from the untreated samples as measured by A) the ROC curve. In this particular example, the product is a double dose apheresis platelet concentrate treated with a photochemical treatment (Intercept Blood System, Cerus) (B) The threshold EDEL value is the crossing point between the sensitivity and specificity curves. C) The largest positive likelihood and D) smallest negative likelihood ratios are associated with the optimal threshold value.

Figure 3 illustrates A) the significant decrease (P value < 0.0001 ) of the antioxidant power in double dose apheresis platelet concentrates treated with a photochemical treatment (Intercept Blood System, Cerus). A threshold of 74.5 EDEL has been predefined for this specific blood-derived product. Below this value the double dose apheresis platelet concentrate is considered as correctly treated. B) The distribution histogram shows two distinct populations for the untreated and treated double dose apheresis platelet concentrates.

Figure 4 illustrates the significant decrease (P value < 0.0001 ) of the antioxidant power in plasma units treated with a photochemical treatment (Intercept Blood System, Cerus). A threshold of 130 EDEL has been pre-defined for this specific blood-derived product. Below this value the plasma unit is considered as correctly treated.

Figure 5 illustrates the significant decrease of the antioxidant power of a cosmetic cream treated with ultraviolet exposure (280 nm, d = 5 cm) for 15, 20 and 30 minutes. Detailed description of the Invention

The present invention relates to new methods for measuring the completeness of pathogen or targeted cell inactivation treatments such as photo-, photochemical, chemical or irradiation-based treatments in biological, foodstuff, drinks and cosmetic products. In particular, the present invention provides new methods for measuring the completeness of pathogen or targeted cell inactivation techniques in blood and blood-derived products. The method may be used as a quality control assay to verify the complete treatment of blood or blood derived products. The quality control assay can be either compulsory to liberate a product or a random test to assess the stability and efficiency of a production process.

According to a preferred implementation, the present invention provides a method for determining the completeness of pathogen or targeted cell inactivation treatments such as photo-, photochemical, chemical or irradiation-based treatments in blood and blood-derived products, the method comprising the sequential steps of: a) providing a blood or blood-derived product that has been treated with a photo- photochemical, and/or in combination with the addition of one or several photo-sensitive compound(s), chemical or irradiation-based treatment; b) obtaining a sample of said treated blood or blood-derived product; c) measuring the antioxidant power of said sample from said treated blood or blood-derived product; d) comparing the measured antioxidant power between the treated and not- treated sample and/or with the threshold antioxidant value that has to be defined for each blood or blood-derived product and below which the product is considered as correctly treated.

In one embodiment, the threshold antioxidant power between untreated and treated samples is determined for each type of blood product in each blood center before using the assay in routine. Indeed, the antioxidant power is dependent on the characteristics of the blood product and notably of its content of plasma that can be influenced by the preparation techniques of the blood products differing from one blood center to another.

In one embodiment, the antioxidant power is measured only in the treated blood or blood products and compared to the threshold antioxidant value. There is no need to analyze the blood or blood product before and after treatment.

In one preferred embodiment, the antioxidant power is measured with the EDEL technology. Measuring with the EDEL technology basically consists in an electrochemical analysis by pseudo-titration (17, 18). The sample to be analyzed is loaded onto an electrochemical sensor, exposed to an increasing potential of oxidation, while the resulting current of oxidation is measured and pseudo-titrated against an ideal antioxidant. The obtained result is expressed in EDELs, an arbitrary unit, corresponding to the equivalent antioxidant activity of a solution of 1 micromolar of vitamin C. In more details, the EDEL method comprises the sequential steps of:

- Sampling of the blood or blood product before and after the photo-, photochemical or irradiation-based treatments of the blood or blood product.

- A few microliters of the blood or blood product are dispensed into the EDEL microchip for measuring the antioxidant power. The antioxidant power is expressed in EDEL value, where one EDEL is equivalent to one micromolar of vitamin C.

- A threshold EDEL value is define for each blood and blood product below which the blood or blood product is considered as correctly treated.

- Once the threshold value is determined for a type of product, e.g. blood or type of blood product, the antioxidant power is measured only in the treated products.

Examples

The following examples serve to illustrate certain preferred embodiments and aspects of the present invention and are not construed as limiting the scope thereof. Figure 1 illustrates the workflow for the quality control assay assessing the completeness of oxidative treatments as measured by the antioxidant power in biological, chemical, foodstuff, drinks and cosmetic products. In this particular example, the antioxidant power is measured by electrochemical pseudo-titration with the EDEL technology (EDEL For Life, Lausanne, Switzerland). A few microliters of the treated product are deposited into the EDELstrip for the measurement of the antioxidant power that is expressed in EDEL value (one EDEL is equivalent to one micromolar of vitamin C). The treatment is considered as uncomplete when the measured EDEL value remains above the threshold value and complete when the EDEL value is below the threshold value. The quality control assay takes only a few minutes from the sampling of the product to the results. The threshold EDEL value has to be determined once for each type of product before applying the quality control assay in routine use.

Blood-derived products such as platelet concentrates and plasma units can be treated for pathogen inactivation with photochemical treatments (Figures 2, 3 and 4). In the present example, the Intercept Blood System (Cerus, Concord, USA) has been used for pathogen inactivation and consists in the sequential steps:

- Adding a photoactive compound, the amotosalen-HCI, into the platelet concentrate or plasma container;

- Treating the platelet concentrate or plasma container with an ultraviolet-A exposure at a dose of 3.9 J/cm²;

- Removal of the residual photoactive compound using a compound adsorbing device;

- Storage of the platelet concentrate or plasma unit in standard blood bank conditions before delivery.

Platelet concentrates can be collected by apheresis in which the blood of the donor is passed through an apparatus that separates out via centrifugation one particular constituent, here the platelets, and returns the other constituents to the donor. Depending on the donor characteristics in terms of platelet concentration, several types of blood-derived products can be obtained, i.e. single dose, double or triple dose apheresis platelet concentrates. In the present example, double dose apheresis platelet concentrates collected in 39% plasma and 61 % additive solution and exhibiting an averaged platelet dose of 5.2- 10¹¹ platelets are analysed.

Figure 2 illustrates the determination of the threshold antioxidant power that distinguishes untreated from treated samples. The threshold antioxidant power for double dose apheresis platelet concentrates treated with the Intercept Blood System (Cerus) has been determined using a ROC curve (Figure 2A). This threshold was determined from 27 untreated and 42 treated samples. The area of the ROC curve was 0.9802 with a P value < 0.0001 showing a very good sensitivity and specificity of the assay. The threshold value is the crossing point between the sensitivity and specificity curves (Figure 2B) and was 74.5 EDEL for this particular product. The

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largest positive likelihood

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ratios are associated with the optimal threshold.

The validity of the present invention is further demonstrated by the following results obtained with double dose apheresis platelet concentrates treated with the Intercept Blood System (Cerus) (Figure 3). Treated platelet concentrates showed a significantly lower EDEL value (53 ± 17 EDEL) compared to their untreated counterparts (97 ± 15 EDEL , p < 0.0001 ). A threshold EDEL value of 74.5 has been defined for this product (Figure 2). Below this threshold value we can consider that the photochemical treatment was completely achieved. In this particular example, we calculated a false positive rate of 1 % and a false negative rate of 4%. This is due to the inter-donor variability in terms of antioxidant power in plasma. As example, the mean antioxidant power of untreated double dose apheresis platelet concentrate is of 97 EDEL with a minimal value of 71 EDEL and a maximal value of 131 EDEL.

The present invention can also be applied to alternate blood-derived products, including, as example but not limited to plasma units treated with the Intercept Blood System (Cerus) (Figure 4). Plasma units (n = 6 and n = 12 for untreated and treated plasma units, respectively) were analysed to measure their antioxidant power with the EDEL technology. The antioxidant power in untreated plasma was 175 ± 13 EDEL. Following the Intercept treatment the EDEL value drastically falls from 175 ± 13 EDEL to 90 ± 7 EDEL (p < 0.0001 ). No false positive, neither false negative were detected in this case.

Ultraviolet exposure is also a common procedure for killing potential contaminants in a variety of products, including foodstuff, drinks and cosmetics. Figure 5 shows that 15 minutes of ultraviolet exposure (280 nm, d = 5 cm) reduces the antioxidant power of a cosmetic formulation by half and that 30 minutes brings it to about 0. The same results is obtained with a variety of samples, including foodstuff and drinks, thereby demonstrating the use of the present invention for discriminating photo-oxidative treated products from untreated ones.

The present invention, including but not limited to the use of the EDEL antioxidant power based assay can be used to confirm the completeness of pathogen or targeted cell inactivation treatments in biological, chemical, foodstuff, drinks and cosmetics products according to the present disclosure. In particular, the use of the EDEL antioxidant power based assay can be used to confirm the completeness of pathogen or targeted cell inactivation treatments in blood and blood-derived products.

References

1. anon,, Gamma Irradiators for Radiation Processing, IAEA, Vienna, 2005

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nswers.pdf

3. GENERAL STANDARD FOR THE LABELLING OF PREPACKAGED FOODS, CODEX STAN 1-1985

4. Transfusion medicine and hemostasis, CD. Hilly er, B.H. Shaz, J.C. Zimring, T.C Abshire, Elsevier ISBN 978-0-12-374432

5. Council of Europe EDftQoMH, European Committee on Blood Transfusion. Guide to the reparation, use and quality assurance of blood components, 18th edition (CD-P-TS), p.102.2015; Bakkour S, Chafets DM, Wen L, et al.

6. Development of a mitochondrial DNA real-time polymerase chain reaction assay for quality control of pathogen reduction with riboflavin and ultraviolet light. Vox Sang. 2014.

7. Monitoring photochemical pathogen inactivation treatment using amotosalen and ultraviolet-A light: evaluation of an indicator label. Isola H, Brandner D, Cazenave JP, et al. Vox Sang. 2010;99(4):402.

8. Pathogen Inactivation of Platelet and Plasma Blood Components for Transfusion Using the INTERCEPT Blood System. Irsch J, Lin L. Transfus Med Hemother. 2011;38(1):19-31.

9. Effect of the psoralen-based photochemical pathogen inactivation on mitochondrial DNA in platelets. Platelets. ; Bruchmuller I, Losel R, Bugert P, et al. 2005;16(8):441-5;

10. Targeting DNA and RNA in Pathogens: Mode of Action of Amotosalen HCI. Transfusion Medicine and Hemotherapy. Wollowitz S 2004:11-6.

11. Effect of the psoralen-based photochemical pathogen inactivation on mitochondrial DNA in platelets. Platelets. Bruchmuller I, Losel R, Bugert P, et al. 2005;16(8). -441-5. . Polymerase chain reaction inhibition assay documenting the amotosalen- based photochemical pathogen inactivation process of platelet concentrates. Transfusion. Bruchmuller I, Janetzko K, Bugert P, et al. 2005;45(9):1464-72. . Effect of the psoralen-based photochemical pathogen inactivation on mitochondrial DNA in platelet. Bruchmuller I, Losel R, Bugert P, et al Platelets. 2005;16(8):441. . Development of a mitochondrial DNA real-time polymerase chain reaction assay for quality control of pathogen reduction with riboflavin and ultraviolet light. Bakkour S, Chafets DM, Wen L, et al. Vox Sang. 2014. Potentiometric study of antioxidant activity: development and prospects. Crit Rev Anal Chem. Ivanova A V1, Gerasimova EL, Brainina KhZ.2015;45(4):311- 22. Electrochemical Pseudo-Titration of Water-Soluble Antioxidants. Philippe Tacchini, Andreas Lesch, Alice Neequaye, Gregoire Lagger, Jifeng Liu, Fernando Cort.s-Salazar, Hubert H Girault, Electroanalysis, vol. 25(4), p. 922- 930, 2013. WO 2006094529 A 1 Role of alkoxyl radicals on the fluorescein-based ORAC (Oxygen Radical Absorbance Capacity) assay. Dorta E, Atala E, Aspee A, Speisky H, Lissi E, Lopez- Alarcon C. Free Radio Biol Med. 2014 Oct;75 Suppl 1:S38. Use and Abuse of the DPPH(') Radical. Foti MC. J Agric Food Chem. 2015 Oct 14;63(40):8765-76. Assessing and comparing the total antioxidant capacity of commercial beverages: application to beers, wines, waters and soft drinks using TRAP, TEAC and FRAP methods. Queiros RB1, Tafulo PA, Sales MG, Comb Chem High Throughput Screen. 2013 Jan;16(1 ):22-31. A Continuous Visible Light Spectrophotometric Approach To Accurately Determine the Reactivity of Radical-Trapping Antioxidants. Haidasz EA, Van Kessel AT, Pratt DA. J Org Chem. 2015 Nov 13. Determination of polyphenolic compounds in Cirsium palustre (L.) extracts by high performance liquid chromatography with chemiluminescence detection. Nalewajko-Sieliwoniuk E, Malejko J, Mozolewska M, Wotyniec E, Nazaruk J. Talanta. 2015 Feb;133:38-44. talanta.2014 Identification and semi-quantitative determination of anti-oxidants in lubricants employing thin-layer chromatography-spray mass spectrometry. Kreisberger G, Himmelsbach M, Buchberger W, Klampfl CW. J Chromatogr A. 2015 Feb 27;1383:169-74.

Claims

CLAI MS

1 . A method for determining the completeness of pathogen or targeted cell inactivation treatments in foodstuff or drink products, cosmetic products, chemical or biological products, said products being products that show a measurable antioxidant power prior to treatment, the method comprising: a) providing sample of a product that has been subjected to a photo-, photochemical, chemical or irradiation-based pathogen or targeted cell inactivation treatment; b) measuring the antioxidant power of said sample; c) comparing the value of the antioxidant power obtained in step (b) to a value of the antioxidant power obtained by measuring another sample of said product, said another sample not having been subjected to said pathogen inactivation treatment and/or comparing the value of the antioxidant power obtained in step (b) to a predetermined antioxidant power threshold value, below which said product is considered as successfully treated.

2. The method of claim 1 , wherein the predetermined antioxidant power threshold value is determined prior to step (c) using measurements of the antioxidant power of treated and untreated samples of said product.

3. The method of claim 1 or 2, wherein said product consists in a foodstuff selected from the group consisting of fresh produce and prepared, cooked and/or processed food.

4. The method of claim 1 or 2, wherein said product is a drink selected from the group consisting of fresh and/or processed fruit and vegetable juices, sodas and juice derived drinks, milk and milk derived drinks, fermented drinks, including but not limited to fermented milk and yogurts, wine and beers, comestible oils, including but not limited to olive oil, and vinegar.

5. The method of claim 1 or 2, wherein said product is a cosmetic product selected from the group consisting of formulations used for the treatment of the skin, the nails, the lips, the hair and the eyes.

6. The method of claim 1 or 2, wherein said product is a biological product selected from the group consisting of blood and blood derived products.

7. The method of claim 6, wherein the blood derived product is selected from the group consisting in platelet concentrate, plasma and erythrocyte concentrate.

8. The method of any one of claims 1 to 7, wherein the pathogen or targeted cell inactivation treatment is a photo-treatment selected form the group consisting in treatments by exposure to any light, including but not limited to exposure to ultraviolet light.

9. The method of any one of claims 1 to 7, wherein the pathogen or targeted cell inactivation treatment is chemical treatment selected from the group consisting in treatments involving the addition of one or several active molecules.

10. The method of any one of claims 1 to 7, wherein the pathogen or targeted cell inactivation treatment is a photochemical treatment selected from the group consisting in treatments involving the addition of one or several photoactive molecule(s), in combination with exposure to any light.

1 1 . The method of any one of claims 1 to 7, wherein the pathogen or targeted cell inactivation treatment is selected from the group consisting in irradiation- based treatments, including but not limited to gamma irradiation based treatments.

12. The method of any one of claims 1 to 1 1 , wherein the antioxidant power of the sample is measured by electrochemistry, by spectrophotometry or by liquid chromatography and/or mass spectrometry or any other methods designed and/or available for measuring such activity.

13. The method of any one of claims 1 to 12, wherein the antioxidant power is measured by electrochemical pseudo-titration with the EDEL technology.

14. The method of any one of claims 1 to 13, wherein the predetermined antioxidant power threshold value for the product is determined prior to step (c) by measuring the antioxidant power of the product in a statistically relevant number of samples, both before and after the oxidative treatment.

15. The method of any one of claims 1 to 14, wherein the value of the antioxidant power obtained in step (b) is compared to the value of the antioxidant power of the same product not having been treated for pathogen or targeted cell inactivation, so as to compute an antioxidant power fall (= antioxidant power of the untreated product - antioxidant power of the treated product), and as to compare the antioxidant power fall with a pre-defined value (expected fall).