rus
Exacte Labs LLC (Moscow) since 2011 performs research in the field of pharmacy, specializing in preclinical and clinical studies of medicines in accordance with the standards of good laboratory and clinical practice. The methods used include high-performance liquid chromatography in combination with tandem mass spectrometry (HPLC-MS / MS), immunoferment analysis, dissolution kinetics test. Special attention is paid to quality, which is controlled at all stages of research.
DOI: 10.22184/2227-572X.2018.39.2.90.92
DOI: 10.22184/2227-572X.2018.39.2.90.92
Теги: hplc-ms / ms immunoferment analysis medicines вэжх-мс/мс иммуноферментный анализ лекарственные средства
Exacte Labs was established in 2011 on the basis of the Research Institute for Chemical Diversity (ChemRAR high-tech center). "In 2010, Russian legislation changed with regard to the requirements for reporting data for the registration of medicines", co-founder and CEO of Exacte Labs, Vasily Kazey, said. "In accordance with the new legislation, foreign pharmaceutical companies are obliged to conduct clinical research in Russia, within the framework of which quite specific tasks related to determining the concentration of drugs in the blood plasma are being solved. As a result, there was a demand for certain types of laboratory studies that were not previously conducted in our country ". Exacte Labs' specialists mastered the new HPLC-MS/MS methods, in particular, they began to perform a pharmaceutical analysis, including the evaluation of the quantitative content of the active substance in dosage forms, the identification of impurities and the determination of other data that are required for drug registration.
In 2013 the laboratory became an independent organization and moved to Technopark Slava. New areas of activity began to develop: clinical diagnostic tests and veterinary diagnostics. At present, about 25 people work in the laboratory engaged in pharmaceutical research and clinical diagnostics, and 10 people work in the department of veterinary diagnostics. Annually Exacte Labs performs about 30 clinical studies, examines about two dozen medicinal products for the kinetics of dissolution and the quantitative content of active substances, and also processes up to 10 thousand samples obtained for the diagnosis of diseases. Among the customers are private individuals and the largest foreign and Russian pharmaceutical companies, for example Zentiva, which is a member of the Sanofi group and is one of the fastest growing generics manufacturers (third in Europe).
QUALITY MANAGEMENT
The very name of the laboratory, derived from the Latin "exacte" (accuracy), speaks of the company's priority. "The specificity of our work lies in the fact that the conducted research is strictly regulated by the current legislation both in Russia and abroad", V.Kazey notes. "For example, the criteria for the accuracy and reproducibility of analytical methods are regulated, therefore, before we begin the analysis, we spend two to three weeks for the development and validation of the method. At the same time, the requirements set by the Ministry of Health are gradually harmonized with European norms, which facilitates tasks for foreign pharmaceutical companies. In turn, we should reach the level of the leading European and American laboratories from the point of view of the quality management system, the validation of computer systems and other aspects".
The staffing table of the laboratory includes the position of director for quality, the corporate policy in this area was adopted and formalized. The laboratory is certified in accordance with the standard ISO 9001: 2015 and regularly passes qualification audits of customers, as well as audit of the studies.
"Every our laboratory assistant or chemical analyst thoroughly knows the operational procedures", V.Kazey continues. "Before starting to work, we make a plan for the development of the method, a validation plan that the customer signs. The stages of the life of the sample are documented from the moment it enters the laboratory and before disposal, after which the materials are transferred to the archive and stored for 20 years. With the help of these documents, the studies carried out can be reproduced literally by the day".
ANALYTICAL EQUIPMENT
Four mass spectrometers were installed in the laboratory: two AB Sciex and two Shimadzu.
According to V.Kazey, AB Sciex tools were chosen based on previous positive experience with the equipment of this brand, and also taking into account that many foreign laboratories of similar profile use them. They have established themselves as reliable, easy-to-maintain and efficient tools. Thus, AB Sciex QTRAP 5500 is a unique tandem device capable of functioning as a triple quadrupole mass spectrometer for quantitative analysis or as a mass spectrometer with a highly sensitive linear ion trap for qualitative analysis. AB Sciex Triple Quad 4500 is a triple quadrupole mass spectrometer characterized by increased sensitivity, which makes it particularly effective in the analysis of small molecules.
Shimadzu mass-spectrometers attracted the attention of laboratory because they are among the registered medical products, therefore the obtained data can be used for clinical diagnostics. Shimadzu LCMS-8050 is a triple quadrupole mass spectrometer with ultra-fast scanning of the mass range for simultaneous qualitative and quantitative analysis and ultrafast switching of ionization polarity.
ATTENTION TO DETAILS
In carrying out high-precision research, even minor at first glance components may have a big impact on the final result. The laboratory staff once again became convinced of this, when the failure of the water treatment device led to a loss of time and money, slowed down the implementation of projects. After that incident, a two-stage system was introduced in the laboratory, in which the water first passes through coarse and fine filters, and the final purification is performed by a Sartorius device. As V.Kazey noted, the new two-stage system allowed, on the one hand, to maintain high standards of water treatment to ensure the accuracy of research, on the other hand, to reduce labor costs and costs for consumables.
Another factor, the influence of which should not be underestimated, is the quality of the dosing devices. V.Kazey: "Pipettes are not just tools for transferring liquids between test tubes, but also are measuring instruments, since it is necessary to handle strictly defined volumes of substances, therefore, like any measuring instrument in our laboratory, they are subject to quarterly calibration and annual verification. If during calibration it turns out that the pipette does not meet the requirements, then it is necessary to start the procedure for checking the projects in which it was used and could distort the results of the research, which involves additional time and means expenditures. Thanks to the choice of Sartorius pipettes, we have minimized the number of such cases". At present, there are about 200 mechanical and electronic dosing devices in the laboratory in regular circulation. An additional advantage of Sartorius pipettes for Exacte Labs is the possibility of their use in diagnostic projects.
Consumables for dosing devices – pipette tips – also affect the accuracy and reproducibility of measurements. "We tried a lot of different tips for single- and multichannel pipettes, manual and automatic systems", says V.Kazey. "The quality of plastic from different suppliers can be very different, and in some cases, there is a wide scatter of the parameters of the tips from batch to batch, which leads to unsatisfactory results when using tips from different batches at the same time. As a result, we decided not to save on pipette tips, and we buy Sartorius tips that are stable high quality".
DEVELOPMENT PLANS
The management of the laboratory does not stop in development. V.Kazey: "We are constantly improving the quality management system, in particular, we have passed the GLP (Good Laboratory Practice) audit this year and expect to receive the corresponding certificate. We also begin preparation for certification according to ISO / IEC 17025 with subsequent accreditation as a testing laboratory, so that it is possible to carry out the control of medicines". In addition to the above, Exacte Labs plans to develop a clinical and diagnostic business and to master new diagnostic methods. ■
In 2013 the laboratory became an independent organization and moved to Technopark Slava. New areas of activity began to develop: clinical diagnostic tests and veterinary diagnostics. At present, about 25 people work in the laboratory engaged in pharmaceutical research and clinical diagnostics, and 10 people work in the department of veterinary diagnostics. Annually Exacte Labs performs about 30 clinical studies, examines about two dozen medicinal products for the kinetics of dissolution and the quantitative content of active substances, and also processes up to 10 thousand samples obtained for the diagnosis of diseases. Among the customers are private individuals and the largest foreign and Russian pharmaceutical companies, for example Zentiva, which is a member of the Sanofi group and is one of the fastest growing generics manufacturers (third in Europe).
QUALITY MANAGEMENT
The very name of the laboratory, derived from the Latin "exacte" (accuracy), speaks of the company's priority. "The specificity of our work lies in the fact that the conducted research is strictly regulated by the current legislation both in Russia and abroad", V.Kazey notes. "For example, the criteria for the accuracy and reproducibility of analytical methods are regulated, therefore, before we begin the analysis, we spend two to three weeks for the development and validation of the method. At the same time, the requirements set by the Ministry of Health are gradually harmonized with European norms, which facilitates tasks for foreign pharmaceutical companies. In turn, we should reach the level of the leading European and American laboratories from the point of view of the quality management system, the validation of computer systems and other aspects".
The staffing table of the laboratory includes the position of director for quality, the corporate policy in this area was adopted and formalized. The laboratory is certified in accordance with the standard ISO 9001: 2015 and regularly passes qualification audits of customers, as well as audit of the studies.
"Every our laboratory assistant or chemical analyst thoroughly knows the operational procedures", V.Kazey continues. "Before starting to work, we make a plan for the development of the method, a validation plan that the customer signs. The stages of the life of the sample are documented from the moment it enters the laboratory and before disposal, after which the materials are transferred to the archive and stored for 20 years. With the help of these documents, the studies carried out can be reproduced literally by the day".
ANALYTICAL EQUIPMENT
Four mass spectrometers were installed in the laboratory: two AB Sciex and two Shimadzu.
According to V.Kazey, AB Sciex tools were chosen based on previous positive experience with the equipment of this brand, and also taking into account that many foreign laboratories of similar profile use them. They have established themselves as reliable, easy-to-maintain and efficient tools. Thus, AB Sciex QTRAP 5500 is a unique tandem device capable of functioning as a triple quadrupole mass spectrometer for quantitative analysis or as a mass spectrometer with a highly sensitive linear ion trap for qualitative analysis. AB Sciex Triple Quad 4500 is a triple quadrupole mass spectrometer characterized by increased sensitivity, which makes it particularly effective in the analysis of small molecules.
Shimadzu mass-spectrometers attracted the attention of laboratory because they are among the registered medical products, therefore the obtained data can be used for clinical diagnostics. Shimadzu LCMS-8050 is a triple quadrupole mass spectrometer with ultra-fast scanning of the mass range for simultaneous qualitative and quantitative analysis and ultrafast switching of ionization polarity.
ATTENTION TO DETAILS
In carrying out high-precision research, even minor at first glance components may have a big impact on the final result. The laboratory staff once again became convinced of this, when the failure of the water treatment device led to a loss of time and money, slowed down the implementation of projects. After that incident, a two-stage system was introduced in the laboratory, in which the water first passes through coarse and fine filters, and the final purification is performed by a Sartorius device. As V.Kazey noted, the new two-stage system allowed, on the one hand, to maintain high standards of water treatment to ensure the accuracy of research, on the other hand, to reduce labor costs and costs for consumables.
Another factor, the influence of which should not be underestimated, is the quality of the dosing devices. V.Kazey: "Pipettes are not just tools for transferring liquids between test tubes, but also are measuring instruments, since it is necessary to handle strictly defined volumes of substances, therefore, like any measuring instrument in our laboratory, they are subject to quarterly calibration and annual verification. If during calibration it turns out that the pipette does not meet the requirements, then it is necessary to start the procedure for checking the projects in which it was used and could distort the results of the research, which involves additional time and means expenditures. Thanks to the choice of Sartorius pipettes, we have minimized the number of such cases". At present, there are about 200 mechanical and electronic dosing devices in the laboratory in regular circulation. An additional advantage of Sartorius pipettes for Exacte Labs is the possibility of their use in diagnostic projects.
Consumables for dosing devices – pipette tips – also affect the accuracy and reproducibility of measurements. "We tried a lot of different tips for single- and multichannel pipettes, manual and automatic systems", says V.Kazey. "The quality of plastic from different suppliers can be very different, and in some cases, there is a wide scatter of the parameters of the tips from batch to batch, which leads to unsatisfactory results when using tips from different batches at the same time. As a result, we decided not to save on pipette tips, and we buy Sartorius tips that are stable high quality".
DEVELOPMENT PLANS
The management of the laboratory does not stop in development. V.Kazey: "We are constantly improving the quality management system, in particular, we have passed the GLP (Good Laboratory Practice) audit this year and expect to receive the corresponding certificate. We also begin preparation for certification according to ISO / IEC 17025 with subsequent accreditation as a testing laboratory, so that it is possible to carry out the control of medicines". In addition to the above, Exacte Labs plans to develop a clinical and diagnostic business and to master new diagnostic methods. ■
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