Current Issue : July - September Volume : 2012 Issue Number : 3 Articles : 5 Articles
Prior to the introduction of regulated process validation activities it was generally assumed that the production process for protein drugs per se is under control and appropriate for their generation, if the final product fulfils the criteria raised for the bioanalytical quality end control for therapeuticals. However nowadays, the production process is being considered in a much deeper and considerably more differentiated fashion. The use of in-process and on-/at-line controls and supervisions on a regular basis encompassing all critical parameters about the individual sub-processes and the emerging intermediary and side products is generally thought to significantly contribute to the demonstration that the production process is under control at the time point of the measurements and with high probability also thereafter. The deep understanding of the interrelationship between process and product can not completely eliminate but will considerably reduce the risk for the emergence of product variants, impurities and contaminants during critical sub-processes that may escape detection during final quality control for technical and/or economical reasons. The test systems required for elucidation of the multiple process-product interactions have to be chosen, validated and calibrated according to commonly accepted and approved criteria. In the near future novel platform technologies, such as protein chips and biosensors that are based on novel capturing/immobilising probes, e.g. glycosylphosphatidylinositol-anchored proteins, and detection probes, e.g. nanoparticles, will greatly contribute to the rapid and reliable measurement of many samples for multiple parameters in cell-free and cell-based assay configurations in parallel rather than consecutive fashion....
Background: The identification of proteins by mass spectrometry is a standard method in biopharmaceutical quality control\r\nand biochemical research. Prior to identification by mass spectrometry, proteins are usually pre-separated by\r\nelectrophoresis. However, current protein staining and de-staining protocols are tedious and time consuming, and\r\ntherefore prolong the sample preparation time for mass spectrometry.\r\nMethodology and Principal Findings: We developed a 1-minute covalent pre-gel staining protocol for proteins, which does\r\nnot require de-staining before the mass spectrometry analysis. We investigated the electrophoretic properties of derivatized\r\nproteins and peptides and studied their behavior in mass spectrometry. Further, we elucidated the preferred reaction of\r\nproteins with Uniblue A and demonstrate the integration of the peptide derivatization into typical informatics tools.\r\nConclusions and Significance: The Uniblue A staining method drastically speeds up the sample preparation for the mass\r\nspectrometry based identification of proteins. The application of this chemo-proteomic strategy will be advantageous for\r\nroutine quality control of proteins and for time-critical tasks in protein analysis....
Monoclonal antibodies (mAbs) can be potent and highly specific therapeutics, diagnostics and research reagents.\r\nNonetheless, mAb discovery using current in vivo or in vitro approaches can be costly and time-consuming, with no\r\nguarantee of success. We have established a platform for rapid discovery and optimization of mAbs ex vivo. This DTLacO\r\nplatform derives from a chicken B cell line that has been engineered to enable rapid selection and seamless maturation of\r\nhigh affinity mAbs. We have validated the DTLacO platform by generation of high affinity and specific mAbs to five cell\r\nsurface targets, the receptor tyrosine kinases VEGFR2 and TIE2, the glycoprotein TROP2, the small TNF receptor family\r\nmember FN14, and the G protein-coupled receptor FZD10. mAb discovery is rapid and humanization is straightforward,\r\nestablishing the utility of the DTLacO platform for identification of mAbs for therapeutic and other applications....
Biosimilars (or follow-on biologics) are a new class of medicine which enters\r\nthe market subsequent to a previously approved version. They have demonstrated\r\nsimilarity to innovator biologic products in terms of quality, safety, and efficacy. The EMA\r\nhas taken the lead in the regulatory approval framework for biosimilar products, and WHO\r\nhas published guidelines on the evaluation of biosimilars in order to facilitate the global\r\nharmonization. Based on EMA and WHO guidelines, many other countries such as\r\nCanada, Japan and Korea have also issued their own guidance for evaluating follow-on\r\nbiologics. The US FDA was authorized to approve follow-on biologics by the BPCI Act\r\npassed by the US Congress on March 23, 2010, and has just issued a draft guidance in\r\nearly 2012. The basic concepts and main principles of approving biosimilars are similar\r\namong various nations, notwithstanding some differences in regard to the scope, the choice\r\nof reference product, and the data requirement. This article reviews the regulatory approval\r\npathway of biosimilar products in different regions....
Background: It is now a decade since the World Trade Organization (WTO) adopted the ââ?¬Ë?ââ?¬Ë?Declaration on the TRIPS\r\nAgreement and Public Healthââ?¬â?¢Ã¢â?¬â?¢ at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead\r\nnations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented\r\ninnovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many\r\nCLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The\r\nsubsequent decade has seen little systematic assessment of the Doha Declarationââ?¬â?¢s impact.\r\nMethods and Findings: We assembled a database of all episodes in which a CL was publically entertained or announced by\r\na WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases,\r\nyielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government\r\nparticipation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome,\r\nnational income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and\r\n2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL\r\nepisodes involved communicable disease, and none occurred in least-developed or low-income countries.\r\nConclusions: Given skepticism about the Doha Declarationââ?¬â?¢s likely impact, we note the relatively high occurrence of CLs, yet\r\nCL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs\r\ncompared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude\r\nthat there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global\r\nhealth governance actions....
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