Research

Research objective―analysis of scientific approaches and development of Guidelines for evaluation of (different groups of) medicinal products.

Research results.

The research teams:

- drafted the guidelines for evaluation of (different groups of) medicinal products;

- developed a test procedure for the bacterial endotoxin determination, based on the complete implant dissolution in dimethyl sulfoxide;

- developed a test procedure for the white hellebore alkaloids identification in medicinal products by high-performance thin-layer chromatography;

- developed uniform test procedures for the identification and quantification of anthracene derivatives in Aloe arborescens medicines;

- developed a test procedure for the determination of amiodarone and its metabolite in human plasma and serum (patent No. 2749566 of 15 June 2021 “Procedure for the determination of amiodarone and its main metabolite desethylamiodarone in human serum”);

- developed a procedure for the separation of main organoarsenic compounds obtained from medicinal plant extracts, by HPLC using an arsenic-selective column;

- formulated the main methodological approaches that improve the quality and safety of pollen herbal preparations used in the production of pollen allergens;

- received two software registration certificates for: “Software for carrying out post-authorisation studies of antiepileptic agents” (No. 2021664963 of 16 September 2021); “Software for carrying out post-authorisation studies of antiarrhythmic agents” (No. 2021664964 of 16 September 2021);

- submitted three patent applications for inventions;

- prepared two lectures for the industry: “Evaluation of the pharmacokinetics of medicinal products in special populations”, “Preclinical safety evaluation during development of medicines for children”.

The research materials were used in 40 papers published in scientific journals with an RSCI impact factor >0.3, and 11 papers published in journals included in the Web of Science/Scopus international citation databases.

Scientific analysis of modern approaches to medicine evaluation, and development of evidence-based principles for conducting clinical trials of medicines used to treat: heart diseases (coronary syndrome, etc.), diabetes, viral hepatitis C, alcoholism.

Scientific analysis of the compendial requirements of the Russian Pharmacopoeia, USP, Ph.Eur., and approaches described in the EMA/FDA guidelines to the assessment of organic impurities in antibiotic active substances and finished products.

Anticipated results:

Elaboration of draft guidelines for the Russian and EAEU pharmaceutical industry:  

- on preclinical and clinical development of medicines for the treatment of heart diseases (coronary syndrome, etc.);

- on preclinical and clinical development of medicines for the treatment of diabetes;

- on clinical development of medicines for the treatment of alcoholism;

- on preclinical and clinical development of medicines for the treatment of viral hepatitis.

Publication of research results in scientific journals included in Web of Science Core Collection and/or Scopus.

Presentation of research results at leading international scientific conferences and workshops in the Russian Federation and abroad.

Research objective―improvement of the methodological approaches to the evaluation of biological products’ quality, efficacy, and safety, and streamlining of the respective test methods.  

Research results.

The research teams:

- drafted the following guidelines: “Quality control of therapeutic and prophylactic bacteriophage products―in terms of Identification and Potency”, “Immunnogenicity assessment of biotechnology-derived products in the EAEU countries”, “Efficacy and safety evaluation of human plasma-derived and recombinant factor IX products in the EAEU countries”, “Francisella tularensis 15 NIIEG vaccine strain: handling and distribution”;

- developed an assay procedure for the determination of aluminum hydroxide gel by electrothermal atomic absorption spectroscopy;

- developed and validated a test procedure for assessing the allergenic activity of allergen products;

- streamlined the test procedures for the determination of prekallikrein activator in human immunoglobulin and human albumin products;

- carried out quality control of therapeutic and prophylactic bacteriophage products in terms of Potency;

- improved the test procedure for assessing the potency of Rho(D) human immunoglobulin products.

The research materials were used in 19 papers published in scientific journals with an impact factor >0.3 and 2 patent applications.

Improvement of the methodological approaches to the evaluation of biological products’ quality, efficacy, and safety, and streamlining of the respective test methods. 

Analysis of phenotypic stability of collection strains, including spectrum of biochemical activity and antigenic characteristics, collection strains.

Anticipated results:

- Elaboration of the draft guideline “Procedure for the management of pathogenic microorganism collections”.

- Elaboration of the draft guideline “Evaluation of efficacy and safety of human plasma-derived and recombinant factor VIII products in the EAEU countries ".

- Publication of research results in scientific journals included in Web of Science Core Collection and/or Scopus.

- Submission of patent applications.

Presentation of research results at leading international scientific conferences and workshops in the Russian Federation and abroad.

Research objective―analysis of the feasibility of using the current instrumental spectroscopic methods for the assessment of as many medicine quality characteristics as possible, and for the verification of the corresponding limit values given in the Russian Pharmacopoeia.

Research results.

The research team:

- prepared and implemented the recommendations: “Development and validation of test procedures for the determination of heavy metals and arsenic in herbal substances and herbal medicinal products, by inductively coupled plasma spectroscopic techniques”;

- prepared the lecture: “Development and validation of test procedures for the determination of elemental toxicants in herbal substances and herbal medicinal products”;

- developed structurally interpreted NMR spectra and the identification procedures for 62 active substances, which were included in the “Library of NMR spectra of active substances”, for the certification of candidate pharmacopoeial reference standards;

- received patent No. 2773851 for the invention “Method for Impurity A determination in gabapentin dosage forms”.

The research materials were used in 5 papers published in scientific journals with an RSCI impact factor >0.3, including 4 papers published in journals included in the Web of Science/Scopus international citation databases.

The researchers made 3 reports about the research results at international scientific conferences and workshops.

Development of NMR-based quality control procedures which would not require the use of reference standards.

Obtaining of structurally interpreted NMR spectra (¹Н, ¹³С, ¹⁹F, ³¹P) of compounds from the List of Essential Medicines and their inclusion in the “Library of NMR spectra of active substances”.

Obtaining experimental data on the content of elemental toxicants in various types of herbal medicinal products, by inductively coupled plasma spectroscopic techniques, and proposing limits for elemental toxicants in herbal medicinal products, depending on the degree of herbal substance processing.  

Experimental evaluation of available methods of selective determination of various forms of arsenic in herbal medicinal products, and proposing ways to improve them.

Anticipated results:

- Development of an NMR-based quality control procedure for medicines, which would not require the use of reference standards.

- Improvement of the procedure for the selective determination of organic and inorganic arsenic compounds in herbal medicinal products.

- Development of recommendations for the limits for elemental toxicants in herbal medicinal products, depending on the degree of herbal substance processing.

- Publication of research results in scientific journals included in Web of Science Core Collection and/or Scopus.

- Presentation of research results at leading international scientific conferences and workshops in the Russian Federation and abroad. 

- Preparation of an application for intellectual property registration.

Research objective: - provide scientific substantiation of clinical and pharmacological risks in efficacy and safety assessment of the most common groups of antimicrobials;

- assess the information needs of healthcare and regulatory agency professionals on antibiotic adverse reactions.

Research results.

The research team:

- identified clinical and pharmacological risks of adverse reactions and drug interactions, and lack of efficacy of the most common groups of antimicrobials in the treatment of community-acquired lower respiratory tract infections;

- updated the information on adverse reactions and drug interactions of β-lactam antibiotics―according to the VigiBase data for 2018‒2020;

- prepared two lectures:

“The importance of antimicrobial studies in ensuring the efficacy and safety of pharmacotherapy’,

“Pharmacokinetics of antibiotics in pregnancy”;

          - received a software registration certificate for “Risk-based antimicrobial therapy information system” (No. 2021681259 of 20 December 2021).

The research materials were used in 5 papers published in scientific journals with an RSCI impact factor >0.3, including 2 papers published in journals included in the Web of Science/Scopus international citation databases.

The research results were reported at an international scientific congress.

Determination of clinical and pharmacological risk predictors of adverse reactions to antibiotics.

Comparison of known markers of toxic effects of antimicrobials.

Determination of the predictive role and value of nephrotoxicity markers (CystatinC, KIM-1, NGAL) for predicting adverse reactions to antimicrobials.

Anticipated results:

- Elaboration of the guidelines:

1) Recommendations for the determination of clinical and pharmacological risk predictors of adverse reactions to antibiotics;

2) Recommendations for the use of nephrotoxicity markers (CystatinC, KIM-1, NGAL) in antimicrobial treatment of community-acquired lower respiratory tract infections.

- Publication of research results in scientific journals included in Web of Science Core Collection and/or Scopus.

- Presentation of research results at leading international scientific conferences and workshops in the Russian Federation and abroad. 

- Preparation of an application for intellectual property registration.

Research objective―study of transport genes expression and functional characteristics in RPTEC cells.

Research results.

The research team:

- determined PCR test conditions for the RPTEC cell line;

- substantiated the choice of GAPDH as the most suitable reference gene for the RPTEC cell line;

- identified candidate biomarkers for early diagnosis of acute kidney injury;

- received a software registration certificate for “Nephrotoxicity biomarkers” (registration No. 2021680197 of 08 December 2021);

- prepared a lecture for the industry: “Current concepts of nephrotoxicity biomarkers and their role in the diagnosis of acute drug-induced kidney injury”, which covers the classification of acute kidney injuries, types of biomarkers, their role in in vitro studies, and clinical use;

Comparison of cell lines and substantiation of the choice of the cell line to be used in experimental models in medicine nephrotoxicity studies.

Selection and experimental testing of a test procedure for assessing the functional activity of renal drug transporters.

Anticipated results:

- Preparation of lectures for the industry.

- Publication of research results in scientific journals included in Web of Science Core Collection and/or Scopus.

- Presentation of research results at leading international scientific conferences and workshops in the Russian Federation and abroad.