European Commission Decision Research Articles

Renewal of an active substance found in an insecticide: How to articulate risk assessment and risk management?

In Pesticide Action Network Europe v Commission (Case T-536/22), Pesticide Action Network Europe (PAN Europe) contested the renewal by the European Commission of the active substance cypermethrin. This substance is used or is marketed as an insecticide in large-scale commercial agricultural applications as well as in consumer products for domestic purposes (ant and cockroach killer). PAN Europe sought the annulment of the European Commission's decision of 23 June 2022 by which the latter rejected the request for internal review made by PAN Europe in accordance with Regulation (EC) No. 1367/2006 on the application of the provisions of the Aarhus Convention on Access to Information, Public Participation in Decision-making and Access to Justice in Environmental Matters. The applicant argued, in essence, that where a risk is established with sufficient certainty by the European Food Safety Authority (EFSA), the Commission could not disregard the conclusions of the scientific assessment by relying on its powers as risk manager. In stressing the discretion enjoyed by the Commission, the General Court dismissed the action of PAN Europe. This casenote suggests that the General Court applied the precautionary principle too formally.

A Review on a Drug Registration Process in United Kingdom

This review outlines the regulatory modifications in several pharmaceutical industries that have been impacted by Brexit and develops new standards-based recommendations from the Medicines and Healthcare Products Regulatory Agency (MHRA). To get insight into the regulatory changes that occurred in the pharmaceutical industry during the dissolution of Europe and Britain, retrospective and contemporaneous reviews were used. As the transition period concluded, the MHRA issued a library of new guidelines on January 1, 2021. The several pharmaceutical industries covered by this guidance include clinical trials, medical equipment, imports and exports of Pharmaceuticals and Cosmetics. The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for approving medicinal products in the UK. The agency offers various routes for marketing authorisation, including national, international, and decentralised procedures. The national routes include a 150-day assessment, rolling review, European Commission (EC) Decision Reliance Procedure, decentralised and mutual recognition reliance procedure, and unfettered access procedure for marketing authorisations approved in Northern Ireland. International routes include Project Orbis and Access Consortium. Applicants must submit their applications through the MHRA submissions portal in electronic Common Technical Document (eCTD) format. The agency verifies the technical validity of submissions using the Lorenz Docubridge validation tool. The MHRA offers fast-track marketing authorisation for products with strong public health benefits or those addressing supply shortages. Applications that do not meet guidelines will be rejected, and applicants must resubmit after correcting errors. Understanding MHRA guidelines and requirements facilitates market entry for medicinal products in the UK. Conclusion: Any medicinal agent to be marked in the United Kingdom has to follow the guidelines and regulations given by the MHRA a regulatory authority which approve drug products. The objective of the review article is to highlights information regarding the requirements. Different types routes in registration of medicinal products in a market in the United Kingdom knowing the requirements of the MHRA guidelines, it is too easy for a product to get into the UK market.

VERIFICATION OF THE SCREENING METHOD FOR THE DETERMINATION OF STREPTOMYCINS RESIDUES IN HONEY SAMPLES

The main field of activity of the National Reference Laboratory of Veterinary Drug Residues Control is the expert evaluation of honey safety based on the parameter of antimicrobial drug residues in honey bathes exported from Ukraine to European and American countries. The content of streptomycin and its derivative dihydrostreptomycin is one of the safety parameters for honey, which is investigated by enzyme-linked immunosorbent assay (ELISA). Since 2002, we have developed and proposed the clear scheme to control export honey batches on the content of residual amounts of these aminoglycoside antibiotics by means of Ridascreen® Streptomycin R3104 test kit from R-Biopharm (Germany).
 The test kit has been validated at 2.0 and 5.0 µg/kg taking into account the minimum required performance limit (MRPL) or the set reference point for action (RPA) according to European Commission Decision 2002/657/EC and 2021/808/EC. The fitness-for-purpose of the methods was confirmed based on the establishing of main validation parameters for screening methods (technical threshold and cut-off factor) using control (blank) honey samples and spiked with streptomycin standard solutions at the level of ½ MRPL by means of “added – found” approach. The preparation of samples is based on the preliminary purification by the method of solid-phase extraction using C18 columns, which facilitates the purification the sample extract from the influence of matrix components as well as the additional concentration of the analyte.
 The article also presents the results of the verification and validation of the Streptomycin NA01904H test kit from Kwinbon Biotechnology (China). The results of the assay of control (blank) honey samples and spiked with streptomycin standard solutions at the level of 2.0 and 5.0 μg/kg are given. Since the advantage of the approved method is the simplicity and rapidity of its performance, so we suggest using it in the laboratory practice of manufacturing and exporting companies.

A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis.

Oral Janus kinase inhibitors (JAKi) have been approved for the treatment of several chronic inflammatory conditions, including rheumatoid arthritis (RA) and atopic dermatitis (AD). Prompted by new evidence, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recently reassessed the benefit-risk balance of oral JAKi. The PRAC recommended that oral JAKi should be used only if no suitable alternatives are available in patients ≥65 years of age, or who have a history of atherosclerotic cardiovascular (CV) disease, other CV risk factors (e.g. history of long-term smoking) or have malignancy risk factors, and used with caution in patients at risk of pulmonary embolism or deep vein thrombosis. The European Commission's final decision was issued in March 2023. Our goal was to highlight the PRAC recommendations, especially in the context of oral JAKi use in AD. Authors summarized the PRAC recommendations, the new clinical evidence on oral JAKi safety and key differences between patients with RA and AD. Risk of developing adverse events of special interest (e.g. cardiovascular events, malignancy) is higher in patients with RA than in patients with AD, because of the higher prevalence of the underlying risk factors. The benefit-risk profile of JAKi approved for AD remains favourable, including use as first-line systemic therapy for patients with AD <65 years of age and without CV or malignancy risk factors.

EN PRENSA. High Performance Liquid Chromatography coupled Diode Array Detector (HPLC-DAD) method development and validation for the quantification of triclosan in toothpaste. EN PRENSA

Triclosan (TCS) is used in many health care products as a broad-spectrum antimicrobial and disinfectant agent; however, it is currently considered an emerging pollutant. The present study aimed to develop an analytical HPLC method coupled to a Diode Array Detector for the TCS determination in toothpaste. Method development involved the optimization of separation and sample preparation. For chromatographic separation optimization, different RP columns and aqueous mobile phases were addressed. The optimized chromatographic separation was achieved in around 3 minutes using a Symmetry C18 column at 30 °C, 0.6 mL/min flow-rate, and 225 nm wavelength detection. For toothpaste sample preparation optimization a response surface methodology using a Box-Behnken fractional factorial design was chosen. The sample treatment consisted of leaching 0.2 g sample by sonication for 7 minutes using 2 mL of MeOH. According to the International Conference on Harmonization (ICH, 1996/2005) and European Commission Decision 200/657/EC guidelines, the developed method was validated. The developed analytical method was found fast, economic, linear, sensitive, precise, and robust and allowed to quantify TCS in different healthcare products.

Comprehensive stability study of benzimidazole drug residues in standard solution, muscle and milk

The performance criteria of analytical methods and the necessity for stability analysis to provide the accuracy of the results of the analyzed samples are explained in European Commission Decision 2021/808/EC and the guidance document SANTE/2021/11312. Detection of time-dependent changes in drug concentrations during storage or transport and re-analysis of samples are crucial to obtain high-quality results and reliable data. In this way, it allows toxicologists to interpret the analytical results accurately in drug analyses. The aim of this study was comprehensively to investigate the stability of benzimidazoles (levamisole hydrochloride, albendazole, albendazole-sulfone, albendazole-2-amino sulfone, albendazole sulfoxide, oxfendazole, 5-hydroxythiabendazole, triclabendazole, ketotriclabendazole, thiabendazole, flubendazole, fenbendazole sulfone) in working solutions, muscle and milk samples. For this purpose, long-term stability was evaluated over 6 months and under four different storage conditions (4 °C, −20 °C, 20 °C light and 20 °C dark) in the matrix. The influences of three freeze-thaw cycles, autosampler stability, and 60 min storage at 40 °C were investigated for short-term stability. Simultaneously, the stability of the working solutions were established over 6 months and under five different conditions (4 °C, −20 °C, −80 °C, 20 °C light, and 20 °C dark). It was found that working solutions can be stored at −80 °C or −20 °C, and it is appropriate to prepare the standard working solution freshly once a month. Storage of milk at 4 °C is suitable for some analytes (ABZ-SO, FBZ-SO2, FLUBZ, ABZ, ABZ-NH2-SO2) whereas for the muscle almost all substances were stable only at −20 °C. Some freeze-thaw and short-term stability changes were detected.

Secondary Validation of a Liquid Scintillation Counter-method for Residues of Tetracyclines, Beta-lactams, and Sulfonamides in Seafood/Aquaculture Products

This study was carried out to validate the liquid scintillation counter method (Charm II) for the detection of tetracyclines, beta-lactams, and sulfonamides (Sulfa drugs) in a range of Aquaculture Products. This method of validation followed primary validation performed in Belgium and was therefore transferred to Nigeria but further validation was required, and this was performed according to the European Commission Decision 2002/657/EC. Method performance was based on the detection capability (CCβ), specificity (cross-reactivity), robustness, repeatability, and reproducibility for the detection of antimicrobial residues. Seafood and aquaculture samples used for the validation process included tilapia (Oreochromis niloctus), catfish (Siluriformes), African threadfin (Galeoides decadactylus), common carp (Cyprinus carpio), and shrimps (penaeidae). These were spiked with varying concentrations of tetracyclines, beta-lactams, and sulfonamides standards to determine the validation parameters. Results of the validation showed tetracyclines had detection capabilities of 50 µg/kg, while beta-lactams and sulphonamides had detection capabilities of 25 µg/kg. The relative standard deviation for both repeatability and reproducibility studies ranged between 1.36% and 10.50%. Results of this study are suitable and comparable to the initial validation reports from the primary validation ofCharm II tests forthedetection ofantimicrobial residues inarange ofaquaculture fish conducted in Belgium. The results also prove the specificity, ruggedness, and reliability of the radio receptor assay tests for detection of the various antimicrobials in aquaculture products. This could be used in seafood/aquaculture products monitoring in Nigeria.

VETERINARY LEGISLATION AND GENERAL REQUIREMENTS TARGETING INSECTS AS FOOD

The European Commission's decision to approve the use of insects and their parts for human consumption caused a wave of public discussion and media interest in our country. However, the veterinary perspective on the matter seems to have remained in the shadow of the predominantly discussed ethical and moral considerations on the subject and the opinions of specialists from other fields such as technologists, nutritionists, and control authorities. This led us to consider the issue of the usage of insects as food ingredients for human consumption from the veterinarian's perspective. As a starting point, we use the knowledge about insects, normatively regulated as part of the education process during the study of veterinary medicine and acquired by veterinarians nowadays. In the course of reasoning, we compare that knowledge with the questions, which have arisen in front of the veterinary guild in connection to the input of insects into the composition of foods, and as ingredients of human nutrition, which the European bodies have officially accepted and permitted. We explored normative documents and literary sources, which could answer the question: "Does the veterinary medical profession have a place in this type of husbandry and food production in the future?".

THE VALIDATION OF THE METHOD FOR QUINOLONES RESIDUES DETERMINATION IN SAMPLES OF MILK, EGG POWDER, TISSUES, BLOOD PLASMA OF ANIMALS USING THE METHOD OF ENZYME-LINKED IMMUNOSORBENT ASSAY

The article presents the results of validation of screening method for the determination of quinolone antibiotics residues (enrofloxacin, ciprofloxacin, marbofloxacin, danofloxacin) in tissue samples, egg powder, milk and blood plasma using RIDASCREEN®Chinolone/Quinolones test kits from R-Biopharm (Germany). According to the information provided by the manufacturer of the kit, the quantitative determination of quinolones content of can be carried out in the following matrices: shrimp, fish, eggs, meat. In accordance with European Commission Decision 2002/657/EC, the methods proposed by the manufacturer were validated taking into account the maximum permissible levels (MRLs), and the results of the development of sample preparation techniques for the assay of liver, milk and blood plasma for various representatives of antibiotics of quinolone group and the corresponding validation results were presented.&#x0D; The suitability of the technique was confirmed on the basis of establishing of main validation parameters for screening methods (technical threshold and cut-off factor) using control (blank) samples (muscle and parenchymal tissues of poultry and animals, cow’s milk, blood plasma of broiler chickens and egg powder) and spiked with quinolones standard solutions at the level of ½ MRL according to the "added-found" criterion. The main advantages of the developed method are the simplicity of performance, rapidity and economic efficiency.&#x0D; The reliability of the results obtained by the developed method was verified using confirmatory UPLC-MS/MS method. The results of comparative study of control (blank) samples of chicken muscle tissues, egg powder and cow’s milk and spiked with enrofloxacin standard solution at the level of 2.5 and 5.0 μg/kg are presented.&#x0D; The proposed methods for liver, milk and blood plasma sample preparation can be used to study withdrawal periods and bioequivalence of veterinary drugs based on quinolone antibiotics.

A simplified method for the indirect evaluation of the “embodied pollution” of natural stones (marble) working chain to be applied for achieving the Ecolabel brand of the product

The constant push toward higher energy and environmental quality buildings makes the acquisition of excellence marks for products and materials, of which the building envelope is constituted, increasingly urgent. The recent European (EU) Commission Decision 2021/476 is applicable to marble used in construction. It sets out criteria that companies producing marble have to accomplish to obtain the EU Ecolabel brand. Unfortunately, some criteria such as, for example, those that refer to the application of the Environmental Management System, ISO 14001 and EMAS certifications, or those that concern the ISO 14067 as well as the Product Environment Footprint procedure, are difficult to apply for companies in the marble extraction and processing sector. These companies, in fact, are usually family-run and find it difficult to adhere to such complex schemes. This difficulty obviously limits the number of companies and products that can aspire to an environmental excellence label.

Simultaneous Determination of Pyrrolizidine and Tropane Alkaloids in Honey by Liquid Chromatography-mass Spectrometry.

IntroductionPyrrolizidine alkaloids (PAs) and tropane alkaloids (TAs) are natural contaminants of honey and respectively hepatoxic and neurotoxic compounds. Because honey is a popular constituent of the human diet, it is relevant to warrant the safety of the product. For that reason, a method for simultaneous determination of PAs and TAs in honey based on liquid chromatography– mass spectrometry was developed.Material and MethodsThe analytical protocol used sulphuric acid extraction and solid-phase extraction purification. The developed procedure was subjected to validation in terms of linearity, selectivity, repeatability, reproducibility, limits of quantification and determination, matrix effect and uncertainty. A total of 29 honey samples were analysed for the determination of PAs and TAs.ResultsAll the evaluated validation parameters fulfilled the requirements of European Commission Decision 2002/657/EC. At least one of the monitored alkaloids was determined in 52% of the samples. Among the most abundant alkaloids were echimidine, intermedine and lycopsamine. The total PA concentrations ranged from 2.2 to 147.0 μg kg−1. Contrastingly, none of the monitored TAs was detected in the analysed samples. An assessment of the dietary exposure to PAs from the consumption of the contaminated honeys showed that three of them would pose a risk to consumers, especially if they were children.ConclusionA sensitive method suitable for simultaneous determination of PAs and TAs in honey was developed and validated. The analysis of 29 honey samples for PAs and TAs revealed that honey destined for retail could pose a risk to consumers.

Article 102 TFEU, Equal Treatment and Discrimination after Google Shopping

In Google Shopping, the General Court took a giant leap forward. Remarkably, it held that the general principle of equal treatment, as a general principle of EU law, applies in the context of Article 102 TFEU for dominant undertakings.1 Based on this finding, it reframed the European Commission decision as an abusive discrimination case, with self-preferencing amounting to an independent form of abuse under Article 102 TFEU. According to the General Court, the legal test requires exclusionary effects, which must be considered in light of the individual circumstances of each case.2 Contrary to views in the literature,3 the Bronner4 criteria, particularly indispensability, are not part of this legal test.5 This paper, first, introduces the past practice of abusive discrimination law and its roadmap towards Google Shopping. It concludes that the prior EU abusive discrimination law practice lacked a clear and consistent approach. In...

A MULTICLASS METHOD FOR THE ANALYSIS OF ANTIBIOTIC RESIDUES IN MILK POWDER AND WHEY POWDER BY UPLC-MS/MS

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) multi-class method was developed and validated for the determination of 27 antibiotic residues from five classes (macrolides, sulfonamids, quinolones, lincosamids, diaminopyrimidines) in milk powder and whey powder which are commonly used as raw material of many products in the food industry. A simple, inexpensive and fast sample preparation based on the extraction of samples with methanol is the main advantage of the validated method. The validation of the method was performed following the requirements outlined in the European Commission Decision 2002/657/EC, which is required procedure for the methods used in analysis of official audits samples in Europe and Turkey. Matrix effect and uncertainties related with sample preparation and instrumental analysis were minimised by using matrix-matched calibration. The method is capable of detecting residues at very low concentrations.

Analysis of β-agonists in Different Biological Matrices By Liquid Chromatography-tandem Mass Spectrometry.

IntroductionWide use is made of β-agonists in therapy due to their smooth muscle–relaxant properties. They also have a side effect of increasing muscle mass. Besides improving oxygen utilisation as bronchodilators, β-agonists increase protein synthesis and promote fat burning. The growth- and performance-enhancing effects are often exploited in illegal use. The guiding objective of this study was to develop a procedure for the determination of β-agonists by a single method in different types of matrices.Material and MethodsFive grams of homogenised samples were subjected to enzymatic hydrolysis with β-glucuronidase in ammonium acetate, pH 5.2. Purification was performed by solid phase extraction. Analytes were eluted with 10% acetic acid in methanol. The eluted β-agonists were analysed by high-performance liquid chromatography–tandem mass spectrometry.ResultsValidation results met the requirement of the confirmation criteria according to European Commission Decision 2002/657/EC in terms of apparent recoveries (93.2–112.0%), repeatability (3.1–7.1%) and intra-laboratory reproducibility (4.1–8.2%).ConclusionThe method can be successfully applied in the detection and determination of clenbuterol, salbutamol, mabuterol, mapenterol, terbutaline, brombuterol, zilpaterol, isoxsuprine and ractopamine in feed, drinking water, urine, muscle, lung and liver matrices.

The Commission's Burden of Proof in Respect of Fiscal State Aid Following the ECJ Decision in the Spanish Sports Clubs Case

The ECJ, in European Commission v. Fútbol Club Barcelona (Case C-362/19 P), ruled that the special tax regime for certain Spanish sports clubs constitutes State aid, annulling the previous decision of the General Court of the European Union and endorsing the European Commission's decision. In this case, the burden of proof that falls on the Commission in State aid procedures in tax matters was particularly contentious. This article provides commentary on the decision.

DOXYCYCLINE DETERMINATION IN ANIMAL TISSUES AND BLOOD PLASMA SAMPLES USING SCREENING AND CONFIRMATORY METHODS

The article presents the results of validation of sample preparation method for muscle and parenchymal tissues of animals for further determination of doxycycline residual amounts by enzyme-linked immunosorbent assay using Oxytetracycline ELISA test kits from EuroProxima (Netherlands), initially developed for the analysis of other target matrices, viz. honey and shrimp. The results of modification of shrimp sample preparation method for the analysis of muscle and parenchymal tissue samples are showed. In accordance with the European Commission Decision 2002/657/EC, the proposed method was validated taking into account the maximum residue levels (MRLs) of doxycycline in tissues of productive animals: 100 μg/kg for muscle tissue and 300 μg/kg for liver. The suitability of the technique was confirmed on the basis of the established main validation parameters for screening methods (technical threshold and cut-off factor) using control (pure) and spiked with standard doxycycline solution at the level of ½MRL samples of muscle and parenchymal tissues of broiler chickens by means of “added – found” criterion. It was discovered that this approach to sample preparation makes it possible to determine doxycycline residues in poultry tissues at the level of 5-10 μg/kg with the absolute recovery about 54 %. The main advantages of the developed technique are simplicity of performance, rapidity and cost-effectiveness.&#x0D; The reliability of the results obtained by the screening method was verified using confirmatory UPLC-MS/MS method, viz. a comparative study of blank and spiked samples of muscle and parenchymal tissues of broiler chickens. The method of sample preparation of the studied specimens, the conditions of analysis carrying out, and the main validation parameters of the confirmatory method are also presented. Based on the obtained results, it was concluded that the developed screening method of enzyme-linked immunosorbent assay is suitable for the determination of doxycycline residual amounts in muscle and parenchymal tissues samples, and it is possible to use it for routine laboratory tests, as well as for the establishment of withdrawal periods of veterinary drugs based on doxycycline from the tissues of productive animals. Also using the same test kit, the sample preparation method for blood plasma samples for doxycycline content assay (at the levels of μg/ml) was suggested to study the bioequivalence of veterinary drugs containing doxycycline as an active pharmaceutical ingredient, which was as well confirmed by UPLC-MS/MS.

LC-MS/MS Determination of 21 Non-Steroidal Anti-Inflammatory Drugs Residues in Animal Milk and Muscles.

The presented procedure combines experience from two LC-MS/MS methods previously developed by our team for NSAIDs determination in meat and milk. The novelty was a modification of sample preparation and combining LC-MS/MS method for milk and muscle. The clean-up procedure was investigated, leading to a change from SPE to dSPE with C18 bulk sorbent. Unlike most of the existing methods, chromatographic separation was achieved on a C8 chromatographic column. This method was developed and validated under European Commission Decision 2002/657/EC. Recovery for milk samples values between 86.3% to 108%, with the coefficient of variation, varied from 5.51% to 16.2%. The recovery for muscle was calculated to be between 85.0% and 109%, and the coefficient of variation was—4.73% to 16.6%. The validation results prove that the method is suitable for confirmatory purposes in milk and muscle. Of 452 samples tested in 2019 and 2020, two have been identified as non-compliant.

No Automatic Moving Up in the Leniency Queue: Case C-694/19 P Italmobiliare

Judgment of 15 April 2021, Italmobiliare SpA and Others v European Commission, C-694/19 P, ECLI: EU: C: 2021: 286 Leniency applicants cannot claim immunity or move up in the leniency reductions queue automatically and solely by reason of the fact that another undertaking, which was already granted immunity has ceased to be eligible for that benefit. In April 2021, the Court of Justice (‘the Court’) rejected an appeal against the General Court’s decision in the Italmobiliare case (Case T-523/15 Italmobiliare SpA and Others v European Commission, ECLI:EU:T:2019:499) and found that the General Court had correctly dismissed the applicants’ action for annulment against the European Commission Decision C(2015) 4336 final in case AT.39563—Retail Food Packaging. On 24 June 2015, the European Commission (‘Commission’) adopted Decision C(2015) 4336 final in case AT.39563—Retail Food Packaging. By that decision, the Commission fined eight manufacturers and...

Court of Justice

This overview highlights (i) the ECJ’s decision on the compatibility of legislation that denies certain tax advantages because the income is exempt pursuant to a tax treaty in the other Member State and (ii) the General Court’s decision not to annul a European Commission decision to formally open a State aid procedure.

The European Commission’s Approval of Google / Fitbit – A Case Note and Comment

The note summarizes and comments on the European Commission's decision to approve Google's acquisition of Fitbit, a maker of fitness trackers and smartwatches. The Commission approved the deal in December 2020, but made long-lasting behavioural remedies binding on Google. The case constitutes only the second time an acquisition by GAFAM has triggered an intervention by the Commission (in 2016, the Commission cleared Microsoft’s acquisition of LinkedIn with remedies). Yet, in a sign of just how much the views regarding acquisitions by Big Tech have changed, many observers greeted the Commission’s decision with disappointment. Market participants, privacy advocates and many scholars had been vocal in opposing the deal. They had warned of dire consequences for competition and privacy. The case raises interesting questions relating to the role of privacy in EU merger control and the effectiveness of long-lasting behavioural remedies in fast-moving digital markets.