Agence nationale de securite du medicament et des produits de sante ANSM

La Garenne-Colombes, France

Agence nationale de securite du medicament et des produits de sante ANSM

La Garenne-Colombes, France

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PubMed | CHU de Poitiers and Agence Nationale de Securite du Medicament et des produits de sante ANSM
Type: Journal Article | Journal: Therapie | Year: 2015

Depression is a complex disorder with heterogeneous clinical anomalies whose neurobiological understanding still remains unclear. Medications have been implicated as potential causes of depression but for many of them, data are controversial. The present study aims to investigate association bet ween drugs and reports of depression. We used the case/non case method in the French pharmacovigilance database (FPVD) to identify drugs associated with depression. Cases were reports of depression in the FPVD between January 2007 and December 2011. Non cases were all other reports during the same period. Data were expressed as reporting odds ratio (ROR) with their 95% confidence interval. Of the 114,692 reports recorded in the FPVD during the studied period, we identified 474 cases of depression. For the majority of the patients, they were considered as non serious (56%) and evolution was favorable (64%). Significant RORs were found for antiepileptics (topiramate, levetiracetam), anti-infective and especially anti-retroviral drugs (efavirenz, emtricitabine, tenofovir, etravirine, raltegravir), interferons and other agents including isotretinoin, methylphenidate, sodium oxybate, varenicline, montelukast, flunarizine, adalimumab, anastrozole. Taking into account the limits of the methodology, the present study described associations with mainly expected drugs belonging to various therapeutic classes but it also found a signal with some anti-retrovirals. On the contrary, we did not find some assumed associations like cardiovascular medications, antimalarial. For most of the drugs, one or more mechanisms were found to explain these depressogenic effects on the basis of animal and human literature. Even if such associations need to be confirmed by further prospective studies, cautions are necessary for many drugs to early detect depressive symptoms.


Gimeno P.,Agence nationale de securite du medicament et des produits de sante ANSM | Maggio A.-F.,Agence nationale de securite du medicament et des produits de sante ANSM | Bousquet C.,Agence nationale de securite du medicament et des produits de sante ANSM | Quoirez A.,Agence nationale de securite du medicament et des produits de sante ANSM | And 2 more authors.
Journal of Chromatography A | Year: 2012

Esters of phthalic acid, more commonly named phthalates, may be present in cosmetic products as ingredients or contaminants. Their presence as contaminant can be due to the manufacturing process, to raw materials used or to the migration of phthalates from packaging when plastic (polyvinyl chloride - PVC) is used. 8 phthalates (DBP, DEHP, BBP, DMEP, DnPP, DiPP, DPP, and DiBP), classified H360 or H361, are forbidden in cosmetics according to the European regulation on cosmetics 1223/2009. A GC/MS method was developed for the assay of 12 phthalates in cosmetics, including the 8 phthalates regulated. Analyses are carried out on a GC/MS system with electron impact ionization mode (EI). The separation of phthalates is obtained on a cross-linked 5%-phenyl/95%-dimethylpolysiloxane capillary column 30m×0.25mm (i.d.)×0.25mm film thickness using a temperature gradient. Phthalate quantification is performed by external calibration using an internal standard. Validation elements obtained on standard solutions, highlight a satisfactory system conformity (resolution>1.5), a common quantification limit at 0.25ng injected, an acceptable linearity between 0.5μgmL -1 and 5.0μgmL -1 as well as a precision and an accuracy in agreement with in-house specifications. Cosmetic samples ready for analytical injection are analyzed after a dilution in ethanol whereas more complex cosmetic matrices, like milks and creams, are assayed after a liquid/liquid extraction using ter-butyl methyl ether (TBME). Depending on the type of cosmetics analyzed, the common limits of quantification for the 12 phthalates were set at 0.5 or 2.5μgg -1. All samples were assayed using the analytical approach described in the ISO 12787 international standard " Cosmetics-Analytical methods-Validation criteria for analytical results using chromatographic techniques" This analytical protocol is particularly adapted when it is not possible to make reconstituted sample matrices. © 2012 Elsevier B.V.


Andre M.,Agence Nationale de Securite du Medicament et des Produits de Sante ANSM | Reghin S.,Agence Nationale de Securite du Medicament et des Produits de Sante ANSM | Boussard E.,Agence Nationale de Securite du Medicament et des Produits de Sante ANSM | Lempereur L.,Agence Nationale de Securite du Medicament et des Produits de Sante ANSM | Maisonneuve S.,Agence Nationale de Securite du Medicament et des Produits de Sante ANSM
Biologicals | Year: 2016

Residual host cellular DNA (rcDNA) is one of the principal risk associated with continuous cell lines derived medicines such as viral vaccines. To assess rcDNA degradation, we suggest two quantitative real-time PCR assays designed to separately quantify target sequences shorter and longer than the 200 bp risk limit, the relative abundance of both targets reflecting the extent of rcDNA fragmentation. The conserved multicopy ribosomal 18S RNA gene was targeted to detect host cell templates from most mammalian cell substrates commonly used in the manufacture of human viral vaccines. The detection range of the method was assessed on purified DNA templates from different animal origins. The standard calibrator origin and structural conformation were shown crucial to achieve accurate quantification. Artificial mixtures of PCR products shorter and longer than 200 bp were used as a model to check the ability of the assay to estimate the fragment size distribution. The method was successfully applied to a panel of Vero cell derived vaccines and could be used as a universal method for determination of both content and size distribution of rcDNA in vaccines. © 2016 International Alliance for Biological Standardization.


PubMed | Agence Nationale de Securite du Medicament et des Produits de Sante ANSM
Type: Journal Article | Journal: Biologicals : journal of the International Association of Biological Standardization | Year: 2016

Residual host cellular DNA (rcDNA) is one of the principal risk associated with continuous cell lines derived medicines such as viral vaccines. To assess rcDNA degradation, we suggest two quantitative real-time PCR assays designed to separately quantify target sequences shorter and longer than the 200bp risk limit, the relative abundance of both targets reflecting the extent of rcDNA fragmentation. The conserved multicopy ribosomal 18S RNA gene was targeted to detect host cell templates from most mammalian cell substrates commonly used in the manufacture of human viral vaccines. The detection range of the method was assessed on purified DNA templates from different animal origins. The standard calibrator origin and structural conformation were shown crucial to achieve accurate quantification. Artificial mixtures of PCR products shorter and longer than 200bp were used as a model to check the ability of the assay to estimate the fragment size distribution. The method was successfully applied to a panel of Vero cell derived vaccines and could be used as a universal method for determination of both content and size distribution of rcDNA in vaccines.


PubMed | Agence Nationale de Securite du Medicament et des Produits de Sante ANSM
Type: Journal Article | Journal: Journal of chromatographic science | Year: 2016

Corticosteroids, hydroquinone and its ethers are regulated in cosmetics by the Regulation 1223/2009. As corticosteroids are forbidden to be used in cosmetics and cannot be present as contaminants or impurities, an identification of one of these illicit compounds deliberately introduced in these types of cosmetics is enough for market survey control. In order to quickly identify skin-whitening agents present in illegal cosmetics, this article proposes an HPLC-UV method for the identification and screening of hydroquinone, 3 ethers of hydroquinone and 39 corticosteroids that may be found in skin-whitening products. Two elution gradients were developed to separate all compounds. The main solvent gradient (A) allows the separation of 39 compounds among the 43 compounds considered in 50 min. Limits of detection on skin-whitening cosmetics are given. For compounds not separated, a complementary gradient elution (B) using the same solvents is proposed. Between 2004 and 2009, a market survey on skin-whitening cosmetic was performed on 150 samples and highlights that more than half of the products tested do not comply with the Cosmetic Regulation 1223/2009 (amending the Council Directive 76/768/EEC).


PubMed | Agence nationale de securite du medicament et des produits de sante ANSM
Type: Journal Article | Journal: Journal of separation science | Year: 2015

A gas chromatography with mass spectrometry method has already been developed and published for the identification and quantification of 14 phthalates and five nonphthalate plasticizers in polyvinylchloride medical devices. In order to assay, in addition to plasticizers, bisphenols A and B possibly present in polyvinylchloride samples, this previous method was extended to the assay of these additional potential endocrine disruptors. Furthermore, as bisphenol A could also be present in polycarbonate samples, the method used for the polyvinylchloride sample was tested and validated for the assay of bisphenols A and B in polycarbonate medical devices. The separation of all compounds, including bisphenols A and B, is obtained on a cross-linked 5%-phenyl/95%-dimethylpolysiloxane capillary column using a temperature gradient. For both plastics, samples are dissolved in tetrahydrofuran followed by a precipitation of the plastic by addition of ethanol. Results obtained point out residual bisphenol A amounts for polycarbonate samples ranging from 0.6 to 0.8% and for polyvinylchloride samples less or equal to 5 ppm. No bisphenol B was detected in the samples tested. For bisphenols A and B, mean recoveries obtained on spiked polyvinylchloride or polycarbonate sample preparations ranged from 87 to 108% in accordance with in-house specification (80-110%).


PubMed | French Institute of Health and Medical Research and Agence nationale de securite du medicament et des produits de Sante ANSM
Type: Journal Article | Journal: Annales d'endocrinologie | Year: 2016

After the diagnosis of transsexualism, hormone therapy is an established stage of gender identity disorder treatment for inducing secondary sex characteristic development of the target gender while reducing that of the birth sex. The aim of this study was to review existing data about the risk of hormone therapy in transsexual people.A PubMed search was done to identify relevant data about adverse drug reactions (ADRs) and mortality associated to hormones exposure. Furthermore, case reports of hormonal therapy-induced ADRs were identified in the French Pharmacovigilance DataBase (FPDB).Review of currently available data showed an increase of thromboembolic effects and hyperprolactinemia with oestrogens. Both oestrogens and testosterone derivatives could induce hepatic effects. Currently, there is no significant association between hormone exposure and cancer or mortality in transsexual people. Five ADRs were found in FPDB, and two of them were related to misuse (voluntary overdose and prescription error).Potential for under-reporting and under-identification in the FPDB of hormonal therapy-induced ADRs in transsexual people should be underlined. Technical improvement of the FPDB could facilitate further identification of reports concerning the risk associated with hormonal therapy in transsexual subjects.


PubMed | Agence nationale de securite du medicament et des produits de sante ANSM
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2015

This manuscript presents an HPLC/UV method for the determination of hydrogen peroxide present or released in teeth bleaching products and hair products. The method is based on an oxidation of triphenylphosphine into triphenylphosphine oxide by hydrogen peroxide. Triphenylphosphine oxide formed is quantified by HPLC/UV. Validation data were obtained using the ISO 12787 standard approach, particularly adapted when it is not possible to make reconstituted sample matrices. For comparative purpose, hydrogen peroxide was also determined using ceric sulfate titrimetry for both types of products. For hair products, a cross validation of both ceric titrimetric method and HPLC/UV method using the cosmetic 82/434/EEC directive (official iodometric titration method) was performed. Results obtained for 6 commercialized teeth whitening products and 5 hair products point out similar hydrogen peroxide contain using either the HPLC/UV method or ceric sulfate titrimetric method. For hair products, results were similar to the hydrogen peroxide content using the cosmetic 82/434/EEC directive method and for the HPLC/UV method, mean recoveries obtained on spiked samples, using the ISO 12787 standard, ranges from 100% to 110% with a RSD<3.0%. To assess the analytical method proposed, the HPLC method was used to control 35 teeth bleaching products during a market survey and highlight for 5 products, hydrogen peroxide contents higher than the regulated limit.


PubMed | Agence Nationale de Securite du Medicament et des Produits de Sante ANSM
Type: | Journal: Pharmeuropa bio & scientific notes | Year: 2016

The current hepatitis A vaccine (HAV), inactivated, non-adsorbed, European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) is used for the in vitro potency assay of HAV as prescribed by the Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. This reference preparation was calibrated in 2008 through an international collaborative study and was assigned a potency of 12 IU/mL. During use of this BRP it appeared to be inapplicable in certain cases due to a low nominal antigen content. Consequently, the European Directorate for the Quality of Medicines and HealthCare (EDQM) established replacement batches for this BRP, calibrated against the 1(st) WHO International Standard (IS) for HAV (inactivated), using the standard in vitro ELISA (enzyme-linked immunosorbent assay) method validated previously. The results of the study showed that the candidate BRPs were suitable for the intended purpose, and following completion of the study, they were adopted in November 2014 by the Ph. Eur. Commission as HAV (inactivated, non-adsorbed) BRP batches 2 and 3, with an assigned potency of 1350 IU/mL, for in vitro antigen content determination by ELISA. As the amount of material in each vial largely exceeds the amount required for the performance of a single assay, the BRPs are to be aliquoted by users as single-use aliquots and refrozen below -50 C prior to their use as reference preparations.


PubMed | Agence Nationale de Securite du Medicament et des Produits de Sante ANSM
Type: | Journal: Pharmeuropa bio & scientific notes | Year: 2016

The current batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Reagents (BRRs) used for the in vitro potency assay of hepatitis A vaccines (HAV) by ELISA (enzymelinked immunosorbent assay) was established in 2012 for use in conjunction with Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. It is composed of a coating reagent and a set of detection antibodies. As stocks of the latter are running low, the European Directorate for the Quality of Medicines & HealthCare (EDQM) organised a collaborative study to qualify replacement batches. The candidate BRR antibodies (primary monoclonal antibody and labelled secondary antibody) were prepared under appropriate conditions from starting materials similar to those used for the current batches. The new batches of antibodies were tested alongside previous batches of BRRs to ensure continuity, and the results confirmed that they were suitable for use in the potency assay of hepatitis A vaccines by ELISA using the standard method referenced in Ph. Eur. general chapter 2.7.14 at the same final concentrations as the previous batches, i.e. 1:500 for the primary monoclonal antibody and 1:400 for the secondary conjugated antibody. The outcome of the study allowed their establishment by the Ph. Eur. Commission in March 2015 as anti-hepatitis A virus primary detection antibody BRR batch 3 and conjugated secondary detection antibody BRR batch 3 respectively. They are available from the EDQM as hepatitis A vaccine ELISA detection antibodies set BRR batch 3.

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