One of the promising areas in the development of innovative products for the treatment of cancer is the use of oncolytic (native or genetically modified) viruses (OLVs) for selective targeting of tumour cells and their destruction, especially as part of combination therapy. At present, there are three OLV-based products approved for medical use (two in China and one in the USА and EU). The aim of the study was to analyse data on specific aspects of OLV-based products’ development, preclinical and clinical research, and authorisation process in China. The authors analysed data freely available on the manufacturers’ websites, in public reports and documents of the Chinese regulatory authorities, in international clinical trial registries, and scientific publications. The products Gendicine^® (SiBiono GeneTech Co., Ltd.) and Oncorine^® (Shanghai Sunway Biotech Co., Ltd.) were originally developed and approved in China for clinical use as part of combination therapy. The analysis demonstrated long product development periods (Gendicine had been studied for 14 years before the start of the authorisation procedures), complex preclinical trial designs, and potential use of the products for several medical conditions with different tumour localisation. The identified specific aspects of OVL-based products’ development and authorisation in China could be taken into account in the regulatory practice of the Russian Federation.

The aim of the study was to review literature data on cell models for experimental assessment of drug nephrotoxicity in vitro. Because of nephrotoxicity, 2% of new investigational medicinal products are discarded at the stage of preclinical in vivo studies in laboratory animals, and 19%—after phase 3 clinical trials. Prediction of toxicity in cell models could make drug development more cost-effective and help to reduce/avoid animal testing. At present, there are no official international guidelines for assessment of nephrotoxicity in vitro, but there is a lot of research underway. The main toxicity target in kidneys is renal proximal tubule epithelial cells, therefore the main research is focused on the development of renal proximal tubule epithelial cell lines with stable functional characteristics. Another important aspect in nephrotoxicity modeling is the choice of relevant test methods and end points which would reflect potential toxicity mechanisms. The paper reviews existing human renal proximal tubule epithelial cell lines and current test methods for assessing cytotoxicity. Promising areas for future development of cell models for nephrotoxicity assessment— are optimisation and standardisation of in vitro systems that would help to make preclinical predictions of drug nephrotoxicity in vivo.  

Until now, there have been no effective treatments for some ophthalmic diseases that have high social significance. Development of therapeutic approaches to such diseases may be complicated due to challenges in diagnosis and selection of clinical trial endpoints. The aim of the study was to analyse current approaches to selection of endpoints in clinical trials of ophthalmic drugs. Clinical efficacy studies of new medicinal products use surrogate endpoints in addition to clinical endpoints. However, currently used surrogate endpoints are not always relevant and do not fully reflect changes in the status of patients with chronic or progressive diseases. The study analysed published approaches to the selection of endpoints in clinical studies of ophthalmic drugs intended for the treatment of glaucoma, uveitis, dry eye syndrome, and age-related macular degeneration. It was demonstrated that the choice of surrogate endpoints in a clinical trial should take into account specific aspects of a particular disease. The assessment of dynamic patterns of changes in visual functions generally requires a complex approach for a comprehensive characterisation of the eye condition in a particular disease. The paper analyses the possibility of using potential surrogate endpoints in studies of the most common eye diseases, and highlights that none of them has been recommended for use in clinical trials or routine clinical practice.

Vitamin A is present in multivitamin products mainly in the form of retinol esters: retinyl acetate, retinyl palmitate, and beta carotene—retinol precursor (dimer) found in plants, which is capable of converting into retinol in liver cells. Retinol is determined in medicinal products primarily by high performance liquid chromatography (HPLC), with preliminary purification and vitamin isolation by liquid-liquid extraction. However, scientific literature also describes other methods of sample preparation and analysis of such compounds. An important issue is differentiation of vitamin A from other fat-soluble vitamins often included as components in multivitamin products. The aim of the study was to analyse and summarise data on current methods used for determination of vitamin A and its derivatives in medicinal products. The authors analysed the range of vitamin A products authorised in the Russian Federation, and the test methods described in their product specification files. The study demonstrated that the test method most often used for determination of retinol esters was HPLC with isocratic elution mode using octadecylsilyl packing in the reverse-phase mode, and, less frequently, aminopropylsilyl packing in the normal phase mode. Determination of beta carotene in medicinal products is most often performed using spectrophotometry. 

A great variety of components in multivitamin preparations containing folic acid, and a variety of test methods and conditions of folic acid determination proposed by manufacturers, require alignment of test procedures for products with similar composition.

The aim of the study was to compare the results of experimental verification of folic acid determination procedures which use reversed phase high-performance liquid chromatography (RP HPLC) with isocratic elution mode. 

Materials and methods: The Agilent 1260 Infinity II LC system with a diode array detector (280 nm), isocratic elution mode, C8- and C18-bonded silica gel chromatographic columns, model mixtures containing folic acid, cyanocobalamin, ferrous sulfate, and potassium iodide, were used in the study.

Results: The lowest relative standard deviation of the folic acid peak area (RSD=0.09%), and the lowest asymmetry factor (A_s=1.04) for folic acid were observed for the model mixture “ferrous sulfate+folic acid+cyanocobalamin” and the following test conditions. Column: 250×4.0 mm, silica gel for chromatography, octylsilyl (C8), endcapped; mobile phase:  methanol‒phosphate buffer (12:88), pH 6.6; column temperature: 25ºС. The study demonstrated the feasibility of using these conditions for determination of pteroic acid impurity with simultaneous precipitation of interfering ferrous ions, using ethylenediaminetetraacetic acid solution, pH 9.5, as a solvent.

Conclusions: RP HPLC can be recommended as an optimal aligned test procedure for determination of folic acid in combination products. It is recommended to use a solution containing folic and pteroic acids for system suitability testing.

Critical phases (stages) of preclinical studies are those procedures or types of research activities whose accurate and correct implementation is a prerequisite for obtaining valid and reliable results. Russian and foreign standards require determination of the critical phases of each individual study by quality assurance staff based on checking the study protocol (plan).

The aim of the study was to identify critical phases typical for most preclinical studies, and assess the potential risks during inspections.

Materials and methods: the study was carried out by analysing the types and consequences of nonconformities. Numerical parameters of risks were analysed for each critical phase of the preclinical study identified by quality officers of the Joint Stock Company “Scientific and Production Association ‘HOME OF PHARMACY’”.

Results: it was discovered that incorrect implementation of a procedure constituted a potential nonconformity at all the identified critical phases, and a potential consequence was acquisition of low-quality data. A combination of incorrectly implemented procedures at two or more critical phases could pose an unacceptable risk and lead to complete loss of data or failure to process data, and, as a result, the need to repeat the study.

Conclusions: the highest risk was identified for such critical phases as preparation and administration of final doses of test samples, performance of physiological tests, collection of biological material samples, and handling of biological material samples by other relevant departments. Summarising the data obtained on the risks of all the critical phases, it can be concluded that risk action should take the form of regular inspections by the quality assurance staff and the study director. By adjusting the frequency of inspections, the risk of each critical phase can be made insignificant.

The criteria for diagnosis and classification of spondyloarthritides (SpAs) have undergone significant changes over the past 10 years. The emergence of new diagnostic methods and availability of new information on the prognosis of the disease outcome made it possible to distinguish a separate group of SpAs—axial SpA. Axial SpA is distinguished as a separate disease due to its high social significance, and special mechanisms of its development. The development of medicinal products for the treatment of axial SpA has some specific features, which requires preparation of specific recommendations for conducting clinical trials of such products. The aim of the study was to elaborate a methodological approach to clinical research and evaluation of efficacy and safety of medicinal products for systemic treatment of axial SpA. The study took into account the requirements/recommendations of the European Medicines Agency for planning clinical trials of medicinal products for the treatment of axial SpA, in order to streamline evaluation of national and foreign clinical trial results. The paper identifies the main stages of clinical trials, and proposes criteria for assessing product efficacy at each stage. It defines methods and tools for assessing clinical trial endpoints, which are necessary for evaluation of treatment effects. The paper describes specific aspects of clinical trial designs and their duration, and identifies the objectives of exploratory and confirmatory clinical trials. It also reviews treatment goals and treatment outcome evaluation. The study results could be used in elaboration of recommendations for clinical research of new medicinal products for axial SpA.