In 2009-2010 there was an influenza pandemic that occurred despite all preventive measures. Analysis of this pandemic revealed some gaps in the regulatory requirements applied both to the development of new influenza vaccines and to the change/update of the seasonal influenza vaccine strains. Taking into account the lessons learned from this pandemic the European Medicines Agency revised the existing guidelines in 2014-2016 and proposed new recommendations on quality evaluation and conduct of non-clinical and clinical trials in the development of influenza vaccines. The revised requirements encompass not only quality evaluation issues, but also changes/update of strain composition of seasonal, pre-pandemic and pandemic influenza vaccines. The experience acquired by the Agency can help update the Russian regulatory framework in order to improve efficacy and safety of influenza vaccines.

The review looks into various aspects of assessing specific activity of biotechnological products, which is one of their key quality parameters. Approaches to the analysis of this parameter and the choice of test procedures are governed by the nature and characteristics of a medicinal product. Test procedures should be adequate and have sufficient sensitivity and specificity. Specific activity of the products in question can be assessed by biological methods both in vivo using laboratory animals, which demonstrate the most adequate response to the tested product, and in vitro using sensitive cell lines. Assessment of specific biological activity helps to characterize the product’s pharmacological action and systematically examine the mechanisms of therapeutic effects in clinical practice. Therefore, specific activity of biotechnological products should be assessed using methods appropriate for the proposed mechanism of action. Many biotechnological products, such as cytokine system products, mAbs, fusion proteins and some others call for individual methods for assessment of their specific activity. Biotechnological products are successfully used in the treatment of autoimmune, infectious, oncological, and allergic diseases.

The article summarises the results of analysis of guidelines and regulations as well as experience in validation of analytical methods and certification of reference standards (RS) of biological medicinal products. Based on the results of the analysis the authors propose an approach to estimation of test methods and reference standards uncertainty to determine biologicals quality parameters in the context of intermediate precision/reproducibility. Expanded uncertainty of the test method was estimated as 2 standard deviations of the test results in the context of intermediate precision/reproducibility for the predetermined range of the tested parameters, and the uncertainty of the reference standards - as 2 standard deviations of the test results for the reference standards in the context of intermediate precision/reproducibility. Since reference standards for most biologicals are currently tested by the same method by which they were certified, an analytical system (a reference standard and a test method) is used as a means of measurement units representation.

The article is devoted to a comparative analysis of requirements to the heterologous serum products stipulated in the world leading Pharmacopoeias: the US Pharmacopoeia, the European Pharmacopoeia, the British Pharmacopoeia, the Japanese Pharmacopoeia and the State Pharmacopoeia of the Russian Federation. It was revealed that the range of antibacterial and antiviral heterologous serum products manufactured in the USA, Europe and Japan differs from that manufactured in Russia. Prevention and treatment of some infectious diseases abroad is mainly achieved with the help of human immunoglobulins, while the prevention of other infections, such as anthrax, is only achieved by vaccination. Nevertheless, heterologous serum products are still used in clinical practice all over the world. The range of such products is the same in all countries. Some of these products are included into the WHO Essential Medicines List. The results of the analysis demonstrate that Russian antitoxic serum products are not inferior to foreign analogues in terms of safety and efficacy. A more detailed characterization of Russian products could help harmonize requirements of Russian and foreign pharmacopoeias to these products and help Russian products enter the foreign market.

The article contains data on the use of heterologous serum products in the treatment of some infectious diseases and snake bites. Despite achievements of preventive vaccination there are still cases of diphtheria and tetanus registered annually all over the world. Cases of botulism and gas gangrene are not uncommon either. There is also an important problem of snake bites treatment. Heterologous serum is mainly derived from the blood of horses immunized with bacterial anatoxins or toxins (snake venoms). They are included into the Russian List of Vital and Essential Medicines and in the WHO Essential Medicines List. Antivenoms are the only effective antidotes for the bites of venomous snakes, spiders, and scorpions. However, despite a self-evident demand in such products, there is a lack of antitoxic serum caused by the phasing out of its production in some countries, its low economic efficiency and stringent regulatory requirements for the safe production of blood products.

The article is devoted to a challenging issue of stability of seed lot systems that have been used in Russia since 1947 to produce BCG vaccines. This problem is underexplored and needs further investigation. In an earlier study the authors of the article used innovative (molecular genetic) methods to demonstrate the conformity of BCG-1 seed lots used in Russia to the international reference reagent ( BCG Vaccine of Russian BCG-I sub-strain-International Reference Reagent ) in terms of «Identification». This article lays out the results of new comparative studies of BCG-1 367 «shch» (1982) and 368 «shch» (2006). During the study special emphasis was put on such quality parameters as residual virulence (survival), specific safety (absence of virulent mycobacteria tuberculosis), sensitization effect (by induction of immune-mediated delayed hypersensitivity to tuberculin), and protective effects. The values obtained in the batches evaluation were very close and did not differ from the results obtained during certification performed just after the production of each seed lot. These results testify to the high degree of stability of the seed lots biological properties. The article also cites literary sources that address the issue in question.

Physiological immunodeficiency during pregnancy contributes to activation of chronic urogenital pathology which often causes intrauterine infections. Recombinant interferon-alpha based rectal suppositories VIFERON^® are often used in Russia for treatment of pregnant women with urogenital pathology. The treatment results in a marked decrease in the number of pregnancy complications and perinatal pathology accompanied by a decrease in peripheral blood CD56^bright natural killer cells.

Prekallikrein activator (PKA) is regarded as one of the most important factors determining the safety of blood products such as albumin and intravenous immunoglobulin. PKA impurity at a high concentration may cause undesired side effects when administered to patients of blood products. According to requirements of the State Pharmacopoeia of the Russian Federation (13th edition) human albumin preparations have to pass test for the quantitative determination of prekallikrein activator (PKA), but there is no description of the method. The purpose of this study consisted in validation of a method of the quantitative definition of PKA in the preparations Albumin (human albumin) solution for infusions 10 % and 20 % with use of the commercial kit PreKallikrein Activator Assay Kit PW301EP («Pathway Diagnostics Ltd», UK). It is established that the method is accurate, linear, high-precision and specific. The method is characterized by the simplicity of the experiment, high accuracy and reproducibility that can be used in terms of control and analytical laboratories. It is shown that in all investigated batches of the drug Albumin (human albumin) solution for infusion 10 % and 20 % PKA content was less than 1 IU/ml, which corresponds to the requirements of the State Pharmacopoeia of the Russian Federation to these drugs.