Materials for the development and certification of a standard sample for anti-D antibody contents in human immunoglobulin drugs are presented. Preparation of the negative component of the standard sample from blood plasma of Rh-positive group IV(AB) donors without anti-D antibodies; the positive component, from blood plasma of Rh-negative group IV(AB) donors is justified. The immunoglobulin should be concentrated to produce a solution with protein contents in the range 48 – 51 mg/mL and anti-D antibody titer 1:8. Flow cytofluorimetry is shown to allow standardization of the preparation of the standard sample positive component.

Regulation of processes to ensure specific safety of human immunoglobulin drugs is designed to ensure the availability of eff ective and safe drugs on the Russian pharmaceutical market. Expertise within the framework of registration ensures the formation of conditions for the issuance of drugs corresponding to the level of safety. Compliance with the requirements for expert evaluation of the stages of pharmaceutical development, technological process, taking into account the control of critical stages of production, the finished form of the drug in terms of specific safety, allows to predict the degree of their negative impact on the hemostatic system, complement and kallikrein-kinin.

The evaluation of anticomplementary activity, being an obligatory component of the quality control ofhuman immunoglobulin preparations, requires the use of a number of reagents of biological origin that are difficult to standardise. In order to standardise the quality control method used for determination of antiсomplementary activity it is advisable to use a reference standard which demonstrates whether obtained results comply with the acceptance criteria, and helps to assess the stability of analytical performance. The aim of the study was to assess the stability of analytical performance of the test procedure used for determination of antiсomplementary activity of human immunoglobulin preparations using human immunoglobulin reference standards of various grades. Materials and methods: anticomplementary activity was determined by the complement fixation test in accordance with the general monograph of the State Pharmacopoeia of the Russian Federation (14th ed.) OFS.1.8.2.0007.15 using different batches of guinea pig complement and sheep red blood cells. The test procedure was standardised using the OSO 42-28-430-2018 human immunoglobulin reference standard and the human immunoglobulin BRP, batch 1 (cat. No. Y0001504). The obtained results of anticomplementary activity of the reference standards were used to construct Shewhart control charts, using the certified values as control limits. Results: the analysis of the constructed Shewhart charts helped to assess trends, and estimate the influence of different batches of guinea pig complement and sheep red blood cells on the stability of analytical performance of the test procedure used for determination of antiсomplementary activity of human immunoglobulin preparations. Conclusions: the use of the OSO 42-28-430-2018 reference standard in combination with Shewhart control charts for the quality control of human immunoglobulin preparations in terms of Anticomplementary activity makes it possible to control the testing process, and assess any of its changes associated with the replacement of the batch of the reagent. At the same time, the reference standard of the European Pharmacopoeia, which has a wide range of permissible values, can only be used to confirm the acceptance of the results. Further studies to determine the mean value of the anticomplementary activity of control samples, as well as the standard deviation, may increase the possibilities of using this reference standard for assessment of analytical performance stability.

The article summarises materials on the certification of a candidate branch standard sample (BSS) of anti-alpha-staphylolysin content - OSO 42-28-342-2017 FSBI «SCEEMP» of the Ministry of Health of Russia, batch No. 34, production date April 1, 2017, expiry date April 1, 2018. According to the Certification programme the reaction of neutralization of staphylococcal toxin hemolytic properties was carried out to establish the range of the certified property of the candidate BSS against the WHO international standard (21±2 IU/ml). The BSS of anti-alpha-staphylolysin content can be used for quantitative determination of antibodies to staphylococcal exotoxin (alpha-staphylolysin) in the reaction of neutralization of staphylococcal toxin (alpha-toxin) hemolytic properties by specific antibodies present in human blood plasma and in a number of biologicals (normal and specific human immunoglobulins, purified and adsorbed staphylococcal toxins, and diagnostic staphylococcal toxin).

The article summarises materials on the certification of a candidate branch standard sample (BSS) of anti-alpha-staphylolysin content - OSO 42-28-342-2017 FSBI «SCEEMP» of the Ministry of Health of Russia, batch No. 34, production date April 1, 2017, expiry date April 1, 2018. According to the Certification programme the reaction of neutralization of staphylococcal toxin hemolytic properties was carried out to establish the range of the certified property of the candidate BSS against the WHO international standard (21±2 IU/ml). The BSS of anti-alpha-staphylolysin content can be used for quantitative determination of antibodies to staphylococcal exotoxin (alpha-staphylolysin) in the reaction of neutralization of staphylococcal toxin (alpha-toxin) hemolytic properties by specific antibodies present in human blood plasma and in a number of biologicals (normal and specific human immunoglobulins, purified and adsorbed staphylococcal toxins, and diagnostic staphylococcal toxin).

The article gives an account of the stability study performed for two batches of human immunoglobulin reference standard (RS) used for determination of anticomplementary activity (industry reference standard, IRS 42-28-430). The first batch of human immunoglobulin reference standard used for determination of anticomplementary activity showed sustainable results during 30 months of storage at (5±3) °C which makes it possible to extend the RS shelf life from 18 months (corresponding to the initial monitoring period) to 30 months from the date of determining the certified parameter, given the acceptable range of more than 50 % for the positive control and less than 50 % for the negative control. Based on the results obtained, the re-certification was performed for the second RS batch after 18 months of storage. The main certified parameter (anticomplementary activity) of the negative control was within the range of 41.6±7.2 %, and of the positive control 75.7±6.8 % for the confidence level of 0.95. Therefore, the shelf life of the second batch of the human immunoglobulin reference standard used for determination of anticomplementary activity (IRS 42-28-430) was extended until February 2018, which makes 30 months.