Annales pharmaceutiques francaises最新文献

{"title":"Le dispositif des préparations pharmaceutiques dans la gestion des ruptures de stocks de médicaments à l’Agence nationale de sécurité du médicament et des produits de santé","authors":"Martine Bouley , Brigitte Rogeau , Roseline Mazet , Yvan Grange , Françoise Duperray , Guillaume Renaud , Valérie Salomon","doi":"10.1016/j.pharma.2025.04.005","DOIUrl":"10.1016/j.pharma.2025.04.005","url":null,"abstract":"<div><h3>Objectifs</h3><div>Parmi les actions mises en œuvre par l’Agence nationale de sécurité du médicament et des produits de santé pour gérer les pénuries de médicaments, le recours aux préparations pharmaceutiques peut être une solution, en relais, quand leur faisabilité est possible, avant la remise à disposition des stocks de spécialités pharmaceutiques. L’objectif de ce travail est de présenter la méthodologie originale mise en œuvre au sein de l’Agence française pour garantir la qualité et la sécurité de ces préparations pharmaceutiques.</div></div><div><h3>Méthodes</h3><div>Les différentes étapes de ce dispositif sont présentées et peuvent varier selon le contexte et la gravité de la pénurie afin de garantir une qualité homogène des préparations sur l’ensemble du territoire français.</div></div><div><h3>Résultats</h3><div>Nous rapportons le cas concret du dispositif de préparations pharmaceutiques d’amoxicilline mis en place, sous l’égide de l’Agence, lors de la pénurie d’amoxicilline pédiatrique, durant les hivers 2022 et 2023. Plus de 709 450 personnes ont été ainsi traitées.</div></div><div><h3>Conclusion</h3><div>L’encadrement scientifique et la coordination nationale des différents acteurs par l’Agence permettent de répondre efficacement à la demande, et ainsi limiter l’impact négatif des ruptures pour les patients. Cette organisation permet également d’uniformiser les pratiques et de sécuriser l’activité de préparation. Les préparations magistrales et hospitalières peuvent être mobilisées de façon quasi immédiate. Dans des cas plus critiques, le dispositif de préparations hospitalières spéciales, pérennisé juridiquement, avec une sous-traitance auprès de façonniers industriels peut être déclenché.</div></div><div><h3>Objectives</h3><div>Among the actions implemented by the French National Agency for Medicines and Health Products Safety to manage drug shortages, the use of pharmaceutical preparations can be a solution, as a relay, when feasible, before the medicines are made available again. The aim of this work is to present the original methodology employed by the Agency to guarantee the quality and safety of these pharmaceutical preparations.</div></div><div><h3>Methods</h3><div>The various steps of this process are presented and may vary depending on the context and the severity of the shortage, in order to ensure quality and safety of pharmaceutical preparations throughout France.</div></div><div><h3>Results</h3><div>We report on the concrete case of the amoxicillin pharmaceutical preparation set up, during the paediatric amoxicillin shortage over the winters of 2022 and 2023. Over 709,450 people were treated with pharmaceutical preparations of amoxicillin.</div></div><div><h3>Conclusion</h3><div>The Agency's scientific supervision and the national coordination of the various stakeholders have made it possible to respond effectively to demand, thereby limiting the negative impact of drug shortage for patients. This organisatio","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 981-991"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sommaire / Contents","authors":"","doi":"10.1016/S0003-4509(25)00126-9","DOIUrl":"10.1016/S0003-4509(25)00126-9","url":null,"abstract":"","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages v-vi"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method for the quantification of related substances of vasopressin injection: A characterization and comparative analysis of vasopressin formulation samples against vasostrict (RLD) in various diluents","authors":"Sivaji Maganti , Suryakala Duvvuri , Prudhvi Raju Pericharla , Ravi Kumar Bellam , Ameer Khan Shaik","doi":"10.1016/j.pharma.2025.03.007","DOIUrl":"10.1016/j.pharma.2025.03.007","url":null,"abstract":"<div><div>In the present study, we developed and validated a sensitive, accurate, robust and simple RP-HPLC method for quantification of related substances of vasopressin (VPS) injection. The development phase prioritized the optimization of wavelength, mobile phase composition and column selection to enhance separation and sensitivity for the analytical evaluation of VPS injection. By considering peak symmetry, resolution and retention time, chromatographic conditions of VPS injection were established. The YMC PACK ODS AM (100<!--> <!-->×<!--> <!-->4.6) mm, 3<!--> <!-->μm was employed in the study. Mobile phase A was prepared with 0.113<!--> <!-->M NaH<sub>2</sub>PO<sub>4</sub>.H<sub>2</sub>O (pH 3.0) while mobile phase B was a 50:50 (v/v) ratio of acetonitrile and water, pumped through a flow rate of 1.0<!--> <!-->mL/min. VPS injection was exposed to thermal, photolytic, acid, base and peroxide degradation conditions and these were analysed by the current method. The method was validated following the guidelines set by the International Council for Harmonization guideline (ICH). The linearity studies demonstrating that a correlation coefficient value is more than 0.999 for VPS and its related substances. The detection and quantification limits for all related substances were found to be 0.01% and 0.05%, respectively. All the impurities exhibited consistent recoveries ranging from 85 to 105%. The unknown impurities were eluting at <em>RRT 1.23</em> and <em>RRT 1.25</em> in the RS methodology (HPLC-UV) of VPS injection are identified and assessed the impurity levels. Furthermore, aggregate profiles and secondary structure analysis studies were carried out using FTIR and LC-HRMS, comparing the VPS formulation samples with the reference listed drug (RLD) (Vasostrict) samples across various diluents.</div></div><div><div>Dans la présente étude, nous avons développé et validé une méthode RP-HPLC sensible, précise, robuste et simple pour la quantification des substances apparentées à l’injection de vasopressine (VPS). La phase de développement a donné la priorité à l’optimisation de la longueur d’onde, de la composition de la phase mobile et de la sélection de la colonne pour améliorer la séparation et la sensibilité pour l’évaluation analytique de l’injection de VPS. En prenant en compte la symétrie des pics, la résolution et le temps de rétention, les conditions chromatographiques de l’injection de VPS ont été établies. Le YMC PACK ODS AM (100<!--> <!-->×<!--> <!-->4,6)<!--> <!-->mm, 3<!--> <!-->μm a été utilisé dans l’étude. La phase mobile A a été préparée avec 0,113<!--> <!-->M NaH2PO4.H2O (pH 3,0) tandis que la phase mobile B était un rapport 50:50 (v/v) d’acétonitrile et d’eau, pompé à un débit de 1,0<!--> <!-->ml/min. L’injection de VPS a été exposée à des conditions de dégradation thermique, photolytique, acide, basique et peroxyde et celles-ci ont été analysées par la méthode actuelle. La méthode a été validée conformément aux directives éta","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 890-906"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory frameworks and filing discrepancies in generic drug approvals: A cross-regional study with analysis of FDA ANDA deficiencies","authors":"Jyoti Pawar, Namita Hegde, Sanjay Sharma","doi":"10.1016/j.pharma.2025.03.001","DOIUrl":"10.1016/j.pharma.2025.03.001","url":null,"abstract":"<div><h3>Objectives</h3><div>This research aims to analyse the regulatory frameworks for generic drug applications in the U.S., EU, India, Japan, and China comparing their filing requirements to identify gaps and areas for harmonization. Additionally, it focuses on examining common deficiencies in ANDA from FDA submissions in 2014–2023 to address issues, facilitating more efficient approvals and minimizing delays.</div></div><div><h3>Material and methods</h3><div>The research involved analysing regulatory documents available on official websites, including the FDA, EMA, CDSCO, PMDA, and NMPA to achieve first objective. For second objective, a recurring common deficiency across key review disciplines such as bioequivalence, labelling and chemistry was identified through a detailed analysis of deficiency letters available on the FDA website. A targeted analysis was conducted on ANDA submissions filed between 2014 and 2024.</div></div><div><h3>Results</h3><div>A total of 172 deficiencies were identified, with bioequivalence (35%), chemistry (34%), and labelling (31%). Method validation had the most deficiencies, especially non-compliance with FDA guidelines. In the labelling discipline, the most common deficiency was non-compliance with reference listed drug (RLD) labelling. Comparisons with EMA and WHOPQTm revealed similarities in common deficiencies.</div></div><div><h3>Conclusion</h3><div>This descriptive study highlights regulatory frameworks for generics share significant differences in practical requirements. A harmonized approach could enhance efficiency and standardized submissions. Bioequivalence issues were the most prevalent, with chemistry-related deficiencies, while labelling issues were the least common seen in ANDA applications. This offer concerns to manufacturers for dossier compilation, aiming to accelerate generic drug registration.</div></div><div><h3>Objectifs</h3><div>Cette recherche vise à analyser les cadres réglementaires pour les demandes de médicaments génériques aux États-Unis, dans l’UE, en Inde, au Japon et en Chine en comparant leurs exigences de dépôt afin d’identifier les lacunes et les domaines d’harmonisation. De plus, il se concentre sur l’examen des lacunes courantes de l’ANDA dans les soumissions à la FDA de 2014 à 2023 afin de résoudre les problèmes, de faciliter des approbations plus efficaces et de minimiser les retards.</div></div><div><h3>Matériels et méthodes</h3><div>La recherche a consisté à analyser les documents réglementaires disponibles sur les sites web officiels, y compris la FDA, l’EMA, le CDSCO, la PMDA et la NMPA pour atteindre le premier objectif. Pour le deuxième objectif, une lacune commune récurrente dans les principales disciplines d’examen telles que la bioéquivalence, l’étiquetage et la chimie a été identifiée grâce à une analyse détaillée des lettres de déficience disponibles sur le site web de la FDA. Une analyse ciblée a été menée sur les soumissions ANDA déposées entre 2014 et 2024.</","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 876-889"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photodynamic anti-cancer therapy and arachidonic acid metabolism: State of the art in 2024","authors":"Hicham Wahnou ,&nbsp;Youness Limami ,&nbsp;Raphaël Emmanuel Duval ,&nbsp;Bassel Ismail ,&nbsp;David Yannick Léger ,&nbsp;Vincent Sol ,&nbsp;Bertrand Liagre","doi":"10.1016/j.pharma.2025.02.010","DOIUrl":"10.1016/j.pharma.2025.02.010","url":null,"abstract":"<div><div><span><span><span>Photodynamic therapy (PDT) has emerged as a promising and evolving modality in cancer treatment leveraging light-sensitive compounds known as photosensitizers to selectively induce cell death in malignant tissues through the generation of </span>reactive oxygen species (ROS). This review delves into the intricate mechanisms of PDT highlighting the pivotal role of photosensitizers and the resultant oxidative stress that damages cancer cells. It explores the versatile applications of PDT across various cancer types alongside the advantages and limitations inherent to this therapy. Recent technological advancements including improved photosensitizers and novel light delivery systems are also discussed. Additionally the review examines the critical role of arachidonic acid (AA) metabolism in cancer progression detailing the </span>cyclooxygenase<span>, lipoxygenase and </span></span>cytochrome P450 pathways and their contributions to tumor biology. By elucidating the interplay between PDT and AA metabolism the review underscores the potential of targeting AA metabolic pathways to enhance PDT efficacy. Finally it provides clinical and translational perspectives highlighting ongoing research and future directions aimed at optimizing PDT for improved cancer treatment outcomes.</div></div><div><div><span>La thérapie photodynamique (PDT) a émergé comme une modalité prometteuse et en évolution dans le traitement du cancer exploitant des composés photosensibles appelés photosensibilisateurs pour induire sélectivement la mort cellulaire dans les tissus malins par la génération d’espèces réactives de l’oxygène (ERO). Cette revue explore les mécanismes complexes de la PDT en mettant en évidence le rôle crucial des photosensibilisateurs et le stress oxydatif résultant qui endommage les cellules cancéreuses. Elle examine les applications variées de la PDT dans différents types de cancers ainsi que les avantages et les limitations inhérents à cette thérapie. Les avancées technologiques récentes y compris des photosensibilisateurs améliorés et de nouveaux systèmes de délivrance de la lumière sont également discutées. De plus, la revue analyse le rôle critique du métabolisme de l’acide arachidonique (AA) dans la progression du cancer détaillant les voies cyclooxygenase, lipoxygenase et </span>cytochrome P450 et leurs contributions à la biologie tumorale. En élucidant l’interaction entre la PDT et le métabolisme de l’AA, la revue souligne le potentiel de cibler les voies métaboliques de l’AA pour améliorer l’efficacité de la PDT. Enfin, elle fournit des perspectives cliniques et translationnelles en mettant en lumière les recherches en cours et les futures directions visant à optimiser la PDT pour de meilleurs résultats dans le traitement du cancer.</div></div>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 785-795"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and herbal approach to diabetes mellitus type 2 management: A comparative analysis of conventional therapy and alternative remedy","authors":"Zahra Shareef ,&nbsp;Afsana Murtaza ,&nbsp;Ghousia Fatima ,&nbsp;Amjad Islam Aqib ,&nbsp;Zahid Manzoor ,&nbsp;Muhammad Sibghat Ullah Malik ,&nbsp;Hafiz Iftikhar Hussain","doi":"10.1016/j.pharma.2025.03.002","DOIUrl":"10.1016/j.pharma.2025.03.002","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;span&gt;Diabetes mellitus is a heterogeneous metabolic disorder that affects the metabolism of protein, fats, and carbohydrates due to the destruction of beta-cells resulting disruptions in insulin action/insulin secretion. According to International Diabetes Federation (IDF) prevalence of 90% people with diabetes has type 2 diabetes is driven by socio-economic, demographic, environmental, and genetic factors. DM type 2 sparks myriad of debilitating disease needs management to cure it. Management needs multifactorial authentication including diet, lifestyle and pharmacotherapy. Literature reveals, metformin is the first line of medication used to cure diabetes Mellitus type 2, also associated with contraindications and adverse effects which spark the interest in alternative herbal remedies. This review will compare pharmacological therapy (metformin) with alternative herbal remedies (&lt;/span&gt;&lt;em&gt;Moringa oleifera&lt;/em&gt;) in the management of diabetes mellitus type 2 including in mechanism, dosing relationship consequential effect. According to various guidelines and recommendations, &lt;em&gt;Moringa oleifera&lt;/em&gt; is herbal remedy to exhibit anti-diabetic properties by enhancing insulin sensitivity and glucose regulation, reducing oxidation stress and inhibiting free radicals. Significant outcomes suggest that moringa leaf extract is a valuable adjoining therapy with safety high profiling with fewer or no side effects as compared to metformin. There is a need for alternative approaches to diabetes management due to side effects of pharmacological therapies. This review paper will also demonstrate the potential of alternative remedy (&lt;em&gt;Moringa oleifera&lt;/em&gt;) in the management of DM type 2 and to what extent its dosing is related to efficacy and safety as compared to the pharmacological approach (Metformin).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;div&gt;Le diabète sucré est un trouble métabolique hétérogène qui affecte le métabolisme des protéines, des graisses et des glucides en raison de la destruction des cellules bêta, entraînant des perturbations de l’action/sécrétion d’insuline. Selon la Fédération internationale du diabète (FID), la prévalence de 90 % des personnes diabétiques atteintes de diabète de type 2 est déterminée par des facteurs socioéconomiques, démographiques, environnementaux et génétiques. Le diabète de type 2 déclenche une myriade de maladies débilitantes qui doivent être prises en charge pour être guéries. La prise en charge nécessite une authentification multifactorielle incluant l’alimentation, le mode de vie et la pharmacothérapie. La littérature révèle que la metformine est la première ligne de médicaments utilisée pour guérir le diabète sucré de type 2, également associée à des contre-indications et à des effets indésirables qui suscitent l’intérêt pour les remèdes alternatifs à base de plantes. Cette revue comparera la thérapie pharmacologique (metformine) avec des remèdes alternatifs à base de plantes (&lt;em&gt;Moringa oleifera&lt;/em&gt;) dans la prise ","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 796-809"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacovigilance européenne des médicaments de thérapie innovante","authors":"Nadine Petitpain ,&nbsp;Viktoryia Prontskus ,&nbsp;Mélanie Gauthier ,&nbsp;Lena Loutterbach ,&nbsp;Cécile Pochon ,&nbsp;Jean Hugues Dalle ,&nbsp;Danièle Bensoussan","doi":"10.1016/j.pharma.2025.02.011","DOIUrl":"10.1016/j.pharma.2025.02.011","url":null,"abstract":"<div><div>Les médicaments de thérapie innovante (MTI) prennent une place progressivement croissante en thérapeutique et représentent, parfois, le seul espoir d’amélioration, voire de guérison, de certaines pathologies. Leur origine biologique, leur composition, leur mode d’action et leur fréquente complexité technique sont générateurs de nouveaux risques. Par ailleurs, les essais cliniques ne portent généralement que sur un très faible nombre de patients. La pharmacovigilance des MTI doit s’adapter à ces contraintes et à ces nouveaux risques identifiés ou potentiels pour être autorisés en Europe selon une procédure centralisée. La conception et l’analyse du plan de gestion des risques sont essentielles pour permettre, en complément de la pharmacovigilance dite « de routine », de continuer l’évaluation de la sécurité du MTI en conditions réelles et d’adapter les mesures de surveillance si besoin. Cet article fait un état des lieux des MTI et des spécificités réglementaires en matière de pharmacovigilance, en détaillant le rôle des comités européens dont le <em>Committee for Advanced Therapies</em>, l’importance du plan de gestion des risques et en abordant la problématique des effets indésirables retardés. La pharmacovigilance des MTI préparés ponctuellement (MTI-PP), dans le cadre de l’exemption hospitalière, est également décrite en prenant l’exemple de MTI-PP d’immunothérapie adoptive.</div></div><div><div>Advanced therapy medicinal products (ATMPs) are playing an increasingly important role in therapeutics, and sometimes represent the only hope of improving or even curing some pathologies. Because of their biological origin, composition, mode of action, and their frequent technical complexity, ATMPs are potentially generating new risks. Moreover, clinical trial data generally concern only a very small number of patients. The pharmacovigilance of ATMPs must adapt to these constraints and to these new identified or potential risks to be authorized according to an European centralized procedure. The conception and the assessment of the Risk Management Plan are essential to complete routine pharmacovigilance with post-authorization studies and additional risk minimisation measures adapted to the identified safety concerns. This article provides an overview of existing ATMPs and their specific regulatory pharmacovigilance requirements, involving the role of the European committees. It aims to describe the essential elements of the risk management plan of ATMPS, with a focus on delayed adverse reactions. The particular case of ATMPs prepared in the context of « hospital exemption », is also addressed, with the example of ATMPs for adoptive immunotherapy.</div></div>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 825-840"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vie de l’Académie – 1er semestre 2025","authors":"","doi":"10.1016/j.pharma.2025.07.003","DOIUrl":"10.1016/j.pharma.2025.07.003","url":null,"abstract":"","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 5","pages":"Pages 1011-1018"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of advanced therapy medicinal products status in European regulations on their production cost: The case of hematopoietic stem cells","authors":"Thibault Cousin ,&nbsp;Frédéric Chantreuil ,&nbsp;Eric Barat ,&nbsp;Olivier Boyer ,&nbsp;Françoise Norol ,&nbsp;Rémi Varin ,&nbsp;Isabelle Lebon ,&nbsp;Camille Giverne","doi":"10.1016/j.pharma.2025.01.013","DOIUrl":"10.1016/j.pharma.2025.01.013","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;The therapeutic promises of somatic cell and gene therapy (Advanced Therapy Medicinal Products – ATMP) and the significant current or future costs of such therapies raise questions about the impact of European health policy on these expenses. Regulation 1394/2007 currently imposes the medicinal product status on many treatments derived from cell therapy. This study aims to determine the impact of new regulations on manufacturing costs of cell therapy treatments, used as ATMP.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In our study, using counterfactual reasoning, we analyze the consequences that a change of status would have on the hematopoietic stem cells (HSC) used for treatment of leukemia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Under the existing status of cell transplantation (CT, Directive 2004/23/EC), the annual production cost of these cell therapy products (CTP) in France is estimated at €5.6 million. If the HSC used in leukemia indication were under the medicinal product status of ATMP, the cost would rise to approximately €9.9 million, without accounting for expenses related to facilities, which are much higher for ATMP than for CT.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This additional burden for manufacturers must be weighed against the theoretical benefits for patients, such as reduced contamination risk. Given the very low contamination levels reported by facilities using transplant standards, the extra cost seems excessive and could hinder the development of new advanced therapies. Furthermore, it raises the need to adapt existing Good Manufacturing Practice guidelines for autologous products or those made from a single donor for a single patient, ensuring safety and cost reduction, which should encourage further development of cell therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectifs&lt;/h3&gt;&lt;div&gt;Les promesses thérapeutiques de la thérapie génique et des cellules somatiques (Médicaments de Thérapie Innovante – MTI) et les coûts actuels ou futurs significatifs de ces thérapies soulèvent des questions quant à l’impact des politiques de santé européennes sur ces dépenses. Le règlement 1394/2007 impose actuellement le statut de médicament à de nombreux traitements issus de la thérapie cellulaire. Cette étude vise à déterminer l’impact des nouvelles réglementations sur les coûts des traitements issus de la thérapie cellulaire, utilisés comme MTI.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthodes&lt;/h3&gt;&lt;div&gt;Dans notre étude, à l’aide du raisonnement contrefactuel, nous analysons les conséquences d’un changement de statut des cellules souches hématopoïétiques (CSH) utilisées pour le traitement de la leucémie.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;Sous le statut actuel de la transplantation cellulaire, le coût annuel de production des produits de thérapie cellulaire (PTC) est estimé à 5,6 millions d’euros. Si les CSH utilisées dans l’indication de la leucémie relevaient du statut de médicament sous les ATMP, le coût augmenterait à environ 9,9 millions d’e","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 4","pages":"Pages 690-697"},"PeriodicalIF":1.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of antioxidant excipients on N-nitrosamine formation and bioequivalence in metformin formulations (review article)","authors":"Güler Yağmur Akyüz","doi":"10.1016/j.pharma.2025.01.012","DOIUrl":"10.1016/j.pharma.2025.01.012","url":null,"abstract":"<div><div>The discovery of N-nitrosamine impurities in pharmaceutical products has raised serious quality concerns, particularly in metformin products, which are widely used in the treatment of type 2 diabetes mellitus. The detection of N-nitrosodimethylamine (NDMA) in metformin products has led to global recalls and increased regulatory investigations. Generic manufacturers face the challenge of balancing stringent bioequivalence requirements for Biopharmaceutical Classification System (BCS) Class III drugs, which require strict control of excipient composition while ensuring N-nitrosamine control and therapeutic equivalence. The use of antioxidants as a strategy to reduce N-nitrosamine formation requires careful consideration to maintain both bioequivalence and product safety. This article evaluates the use of antioxidants for the prevention of N-nitrosamine formation in metformin formulations, addressing the implications of this strategy on bioequivalence and its relationship with the regulatory framework.</div></div><div><div>La découverte d’impuretés de type N-nitrosamines dans des produits pharmaceutiques a soulevé de sérieuses préoccupations en matière de qualité, en particulier dans les produits à base de metformine, largement utilisés dans le traitement du diabète de type 2. La détection de N-nitrosodiméthylamine (NDMA) dans ces produits a entraîné des rappels de produits à l’échelle mondiale et un renforcement des enquêtes réglementaires. Les fabricants de génériques doivent relever le défi de concilier les exigences strictes en matière de bioéquivalence pour les médicaments de classe III du système de classification biopharmaceutique (BCS), qui imposent un contrôle rigoureux de la composition des excipients, tout en assurant le contrôle des N-nitrosamines et l’équivalence thérapeutique. L’utilisation d’antioxydants comme stratégie pour réduire la formation de N-nitrosamines doit être examinée avec soin pour préserver à la fois la bioéquivalence et la sécurité du produit. Cet article évalue l’emploi d’antioxydants pour prévenir la formation de N-nitrosamines dans les formulations de metformine, en abordant les implications de cette stratégie sur la bioéquivalence et son lien avec le cadre réglementaire.</div></div>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":"83 4","pages":"Pages 605-616"},"PeriodicalIF":1.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}