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Heim H.-K.,Federal Institute for Drugs and Medical Devices
Biologicals | Year: 2011

In the EU, a regulatory framework has been established which defines general conditions for marketing authorisation approval of similar biological medicinal products (SBMPs). In addition, the framework provides product-class specific recommendations for non-clinical evaluation of specific SBMPs containing as active substance recombinant somatropin, granulocyte-colony stimulating factor (G-CSF), erythropoietin, interferon alpha, insulin or low molecular weight heparins.During the last years, a number of SBMPs have been succesfully licensed in the EU. This article summarizes the non-clinical evaluations performed for these medicinal products and provides a comparison with the current requests for non-clinical evaluation as laid down in the respective EU regulatory guidelines. © 2011.

Eckstein N.,Federal Institute for Drugs and Medical Devices
Journal of Experimental and Clinical Cancer Research | Year: 2011

Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade. © 2011 Eckstein; licensee BioMed Central Ltd.

Wiesner J.,Federal Institute for Drugs and Medical Devices
Journal of Ethnopharmacology | Year: 2014

Each application for authorisation of a medicinal product must be accompanied by the particulars and documents referred to in Directive 2001/83/EC on the Community code relating to medicinal products for human use. Details on the documentation needed for traditional herbal medicinal products (THMP) are given in article 16c of the above mentioned Directive. It is pointed out that a bibliographic review of safety data together with an expert report and additional data, if necessary, are required. The Committee on Herbal Medicinal Products (HMPC) provides in its "Guideline on the use of the CTD format in the preparation of a registration application for traditional herbal medicinal products" (EMA/HMPC/71049/2007 Rev. 1) guidance on how to present the information and the dossier needed for an application. There, in agreement with the Directive 2001/83/EC, a bibliographical review of safety data is required within the "Non-clinical Overview". However, it is assumable that for such products, with a long tradition of usage bibliographical information relating to non-clinical safety are available, even if incomplete or not in accordance with today's state of the art. In the "Guideline on non-clinical documentation for herbal medicinal products in applications for marketing authorisation (bibliographical and mixed applications) and in applications for simplified registration" (EMEA/HMPC/32116/2005) it is reflected how to deal with such an incomplete set of data for traditional herbal medicinal products and crucial information are highlighted. This article will focus on the explanation of the requirements needed for the non-clinical safety evaluation of THMPs and some detailed explanations of the performance and interpretation of the mutagenicity studies. © 2014 Elsevier Ireland Ltd. All rights reserved.

Siekmeier R.,Federal Institute for Drugs and Medical Devices | Wetzel D.,Federal Institute for Drugs and Medical Devices BfArM
Advances in Experimental Medicine and Biology | Year: 2013

The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD) regulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of incidents and field corrective actions, the manufacturers have to inform the responsible Competent Authorities (CA). In Germany, the Federal Institute for Drugs and Medical Devices (BfArM) is the responsible CA for most IVD. In this study all notifications regarding IVD for therapeutic drug monitoring (TDM) between begin 1999 until end of 2010 were analysed. A total of 2,851 notifications were received, of which 65 were related to IVD for TDM included in this study (54 tests vs. 11 analysers). Reports were received from manufacturers (58), CAs (5 cases) and users (2 cases). Most frequently IVD used for TDM of toxicologically relevant substances, antibiotics, antiepileptics and immunosuppressives were affected. Investigations of the manufacturers were able to identify the underlying root causes of product failures in 50 cases (76.9%), 40 (74.1%) of which were tests and 10 (90.9%) analysers. In 11 cases (16.9%, all tests), the root cause remained unclear and in 4 cases (6.2%, 3 tests, 1 analyser) a product failure was excluded. Product failures in tests were most commonly material defects (12 cases), interferences (7 cases) and manufacturing errors (7 cases), whereas in the analyser group software errors (5 cases) were most common. Corrective actions were performed in 56 cases (86.2%); 46 (85.2%) in tests, and 10 (90.9%) in analysers. In the group of tests these were predominantly (multiple entries) customer information (46 cases, mandatory in case of a recall), recall (29 cases), modifications in production or quality management (29 cases) and modifications of the instructions for use (9 cases). However, in the analyser group corrective actions were typically customer information (10 cases), recall (5 cases) and software-update (4 cases). The obtained data demonstrate that there are differences in the type of product failures between analysers and tests, which are followed by different corrective actions depending on the root causes of product failure accordingly. The results and the experience since 1999 suggest that the system for post marketing surveillance of IVD is an established tool to enhance product safety even though further optimisation is possible. © Springer Science+Business Media Dordrecht 2013.

Siener R.,University of Bonn | Bangen U.,University of Bonn | Sidhu H.,Oxthera Inc. | Honow R.,Federal Institute for Drugs and Medical Devices | And 2 more authors.
Kidney International | Year: 2013

About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium oxalate stone formers, 26 tested negative for O. formigenes and were compared with the 11 patients who tested positive. Patients provided 24-h urine samples on both a self-selected and a standardized diet. Urinary oxalate excretion did not differ significantly on the self-selected diet, but was significantly lower in O. formigenes-positive than in O. formigenes-negative patients under controlled, standardized conditions. Intestinal oxalate absorption, measured using 13 C 2 oxalate, was similar in the patients with or without O. formigenes. Plasma oxalate concentrations were significantly higher in noncolonized (5.79 μmol/l) than in colonized stone formers (1.70 μmol/l). Colonization with O. formigenes was significantly inversely associated with the number of stone episodes. Our findings suggest that O. formigenes lowers the intestinal concentration of oxalate available for absorption at constant rates, resulting in decreased urinary oxalate excretion. Thus, dietary factors have an important role in urinary oxalate excretion. The data indicate that O. formigenes colonization may reduce the risk of stone recurrence. © 2013 International Society of Nephrology.

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