Certification of a New Batch of the Industry Reference Standard for the Control of Specific Activity and Thermal Stability of Live Plague Vaccine

In accordance with the State Pharmacopoeia (SPh) requirements for live plague vaccine, a reference standard has to be used when testing the specific activity and thermal stability of plague vaccine commercial batches in order to assess the consistency and acceptability of the test results. Since there is no international reference standard for plague vaccine, the certification of a new batch of the industry reference standard (IRS) of live plague vaccine in terms of the above-mentioned quality parameters is an urgent challenge. Therefore, a certification programme for the industry reference standard was developed that establishes the design and scope of testing required to obtain statistically significant results. A candidate IRS was represented by a commercial batch of the product meeting the specification requirements for live plague vaccine. The certification parameters were: «Specific activity: microbial cell concentration», «Specific activity: live microbial cell percentage» and «Thermal stability». The article presents the results of the certification of a new batch of the live plague vaccine IRS, detailed evaluation of the candidate IRS in terms of: «Average weight and uniformity of weight», «Loss on drying», and statistical interpretation of the test results. It also summarises the results of the product testing in terms of «Specific activity: immunogenicity». The results of application of the previous batch of the live plague vaccine IRS (OSO 42-28-392-2013) and the results of monitoring the stability of its certification parameters demonstrated that the IRS shelf life could be extended by 6 months relative to the established period (from 2 to 2.5 years). All the certified and additional characteristics are reflected in the official documents for the scientific/technological product — live plague vaccine IRS, OSO 42-28-392-2017: passport, labelling and patient information leaflet

Аттестация новой серии отраслевого стандартного образца содержания полисахарида в вакцине Шигеллвак

The article summarises materials on the certification of the industry reference standard of Schigella sonnei polysaccharide dysentery vaccine (commercial name — Schigellvac). The industry reference standard is used to assess the consistency of the vaccine «Specific activity» testing by passive hemagglutination inhibition assay. A certification programme for the industry reference standard was developed. Samples of the candidate vaccine were tested in terms of the following quality characteristics: «Appearance», «Identification», «Extractable Volume». The test results confirmed that the samples comply with the current requirements of the manufacturer’s product specification file for Schigellvac vaccine. It was determined that the certification parameter — the polysaccharide dilution ratio which results in inhibition of passive hemagglutination in a homologous system — has to fall in the range from 1:128 to 1:512. The following set of standard documents accompanying a scientific/technological product was approved for the industry reference standard No. 42-28-386-2017: passport, patient information leaflet, mockup labels for primary and secondary packaging.В статье представлены материалы по аттестации отраслевого стандартного образца (ОСО) вакцины дизентерийной против шигелл Зонне полисахаридной, торговое наименование «Шигеллвак», предназначенного для оценки стабильности проведения испытаний данного лекарственного препарата по показателю «Специфическая активность», определяемому в реакции торможения пассивной гемагглютинации. Разработана программа аттестации ОСО. Образцы вакцины — кандидата в ОСО были испытаны по показателям: «Описание», «Подлинность», «Извлекаемый объем». Результаты испытаний подтвердили их соответствие требованиям действующей фармакопейной статьи предприятия на вакцину Шигеллвак. Определена аттестуемая характеристика: разведение полисахарида, при котором наблюдается торможение реакции пассивной гемагглютинации в гомологичной системе, должно находиться в диапазоне от 1:128 до 1:512. Утвержден пакет нормативных документов на научно-техническую продукцию ОСО 42-28- 386-2017: паспорт, инструкция по применению, макеты этикеток первичной и вторичной упаковок

Аттестация новой серии отраслевого стандартного образца для контроля специфической активности и термостабильности вакцины чумной живой

In accordance with the State Pharmacopoeia (SPh) requirements for live plague vaccine, a reference standard has to be used when testing the specific activity and thermal stability of plague vaccine commercial batches in order to assess the consistency and acceptability of the test results. Since there is no international reference standard for plague vaccine, the certification of a new batch of the industry reference standard (IRS) of live plague vaccine in terms of the above-mentioned quality parameters is an urgent challenge. Therefore, a certification programme for the industry reference standard was developed that establishes the design and scope of testing required to obtain statistically significant results. A candidate IRS was represented by a commercial batch of the product meeting the specification requirements for live plague vaccine. The certification parameters were: «Specific activity: microbial cell concentration», «Specific activity: live microbial cell percentage» and «Thermal stability». The article presents the results of the certification of a new batch of the live plague vaccine IRS, detailed evaluation of the candidate IRS in terms of: «Average weight and uniformity of weight», «Loss on drying», and statistical interpretation of the test results. It also summarises the results of the product testing in terms of «Specific activity: immunogenicity». The results of application of the previous batch of the live plague vaccine IRS (OSO 42-28-392-2013) and the results of monitoring the stability of its certification parameters demonstrated that the IRS shelf life could be extended by 6 months relative to the established period (from 2 to 2.5 years). All the certified and additional characteristics are reflected in the official documents for the scientific/technological product — live plague vaccine IRS, OSO 42-28-392-2017: passport, labelling and patient information leaflet.В соответствии с требованиями Государственной фармакопеи Российской Федерации (XIII издание, том III) на вакцину чумную живую при проведении испытания специфической активности и термостабильности производственных серий вакцины необходимо использование стандартного образца для оценки стабильности и приемлемости полученных результатов. Так как Международный стандартный образец вакцины чумной отсутствует, то аттестация новой серии отраслевого стандартного образца (ОСО) вакцины чумной живой для контроля специфической активности и термостабильности производственных серий вакцины необходима и актуальна. Для этого разработали программу аттестации, установив в ней схему и объем проводимых исследований для получения статистически значимых результатов. В качестве кандидата в ОСО использовали производственную серию препарата, удовлетворяющую требованиям нормативной документации на вакцину чумную живую. Аттестуемыми характеристиками являются: «Специфическая активность: концентрация микробных клеток», «Специфическая активность: процент живых микробных клеток» и «Термостабильность». В статье представлены результаты аттестации и статистически обработанные результаты испытаний по показателям: «Средняя масса и однородность по массе», «Потеря в массе при высушивании» новой серии ОСО вакцины чумной живой. Приведены результаты исследования по показателю «Специфическая активность: иммуногенность». Итоги применения предыдущей серии ОСО вакцины чумной живой (ОСО 42-28-392-2013) и мониторинга стабильности ее аттестованных характеристик показали возможность увеличения срока годности ОСО на 6 месяцев по отношению к установленному (с 2 до 2,5 лет). Все аттестованные и дополнительные характеристики утверждены в документах на научно-техническую продукцию ОСО 42-28-392-2017 вакцины чумной живой: паспорт, макеты этикеток упаковок и инструкция по применению

Аттестация и продление срока годности новой серии отраслевого стандартного образца специфической активности и иммуногенности вакцины туляремийной живой

The article presents the results obtained in the study of a new batch of a candidate branch reference standard for live tularemic vaccine (vaccine BRS). The candidate vaccine BRS was represented by a commercial batch of a product that met all applicable requirements of the manufacturer’s monograph (MM) for live tularemic vaccine’s quality attributes. The candidate vaccine BRS was certified for specific activity including a range of parameters, such as: microbial cells concentration, percentage of living microbial cells, dissociation degree (percent of SR (white) immunogenic colonies from the total number of colonies grown), as well as immunogenicity. Results of analysis that addressed the use of this batch of vaccine BRS and its quality attributes made it possible to extend the shelf-life of the product for 6 months.В статье представлены результаты по изучению новой серии кандидата в отраслевой стандартный образец вакцины туляремийной живой (ОСО вакцины). В качестве кандидата в ОСО вакцины, использовали коммерческую серию препарата, удовлетворяющую требованиям фармакопейной статьи предприятия (ФСП) по всем показателям качества, предъявляемым к вакцине туляремийной живой. Кандидат в ОСО вакцины аттестован по показателю специфическая активность, включающей в себя комплекс показателей: концентрация микробных клеток, процент живых микробных клеток, степень диссоциации (процент SR (белых) иммуногенных колоний от общего количества выросших), а также иммуногенность. На основании анализа результатов применения и оценки показателей качества данной серии ОСО вакцины продлен срок годности ОСО на 6 мес

Разработка и изучение отраслевого стандартного образца активности вакцины против краснухи

Presents information on 1st series of branch standard sample to characterization the quality of the candidate of branch standard sample tested for performance evaluation: specific activity of authenticity, a description of sterility, presence of mycoplasma, loss on drying, pH, filling accuracy, the residual oxygen content in the vials. Attested feature of the new series of the standard sample is a specific activity, because the purpose of the of branch reference standard activity live Rubella vaccine is the suitability of the results of determining the specific activity of the Rubella virus in vaccines. Indicator specific activity of the candidate in the of branch reference standard was assessed by interlaboratory studies compared to current 1st standard sample of the enterprise and 1st International Reference Reagent For Rubella (Live) NIBSC-91/688. Certified value of the index is set «Specific activity of branch reference standard activity for rubella (4,63±0,50) lgCCE50/0,5 ml. Shelf-life stated by using test accelerated the degradation is not less than at minus 20°C.Представлены материалы по аттестации первой серии отраслевого стандартного образца (ОСО) активности вакцины против краснухи. Для характеристики качества кандидата в ОСО проведены испытания по оценке показателей: специфическая активность, подлинность, описание, стерильность, присутствие микоплазм, потеря в массе при высушивании, рН, точность наполнения, остаточное содержание кислорода в ампулах. Аттестуемой характеристикой стандартного образца является специфическая активность. Назначение ОСО активности вакцины против краснухи - это оценка приемлемости результатов определения активности вируса краснухи в вакцинах. Показатель «Специфическая активность» кандидата в ОСО оценивали по результатам межлабораторных исследований в сравнении со стандартным образцом предприятия и международным стандартом: 1st International Reference Reagent For Rubella (Live) NIBSC-91/688. Установлено аттестованное значение показателя «Специфическая активность» ОСО активности вакцины против краснухи: (4,63±0,50)lg ТЦД50/0,5 мл. Срок годности, установленный с помощью теста ускоренного старения, при условии хранения при минус 20°С, - не менее 5 лет. Результаты мониторинга стабильности ОСО подтверждают его стабильность за период наблюдения

International practice of allergen products standardization

The article demonstrates that safe and efficacious use of allergen products for detection and treatment of allergic diseases relies on standardization and quality control methods. The article summarises various approaches to allergen products standardization that are used in the United States, the European Union and the Russian Federation. Development of requirements for allergen products of natural origin must take account of the heterogeneity of raw materials used in their production, since native allergen extracts are complex protein-polysaccharide mixtures consisting of allergenic (primary and secondary) and non-allergenic components. Standardization of methods used for evaluation of allergen products potency is performed using reference standards. To date, there exist several approaches to allergens standardization. The United States introduced a system of national reference standards whose biological activity is determined by one technique (IntraDermal Dilution for 50 mm sum of Erythema determines bioequivalent Allergy Units - ID50EAL). In Europe each manufacturer establishes their own in-house reference standards (IHRS) and assigns them with units of activity. Products manufactured in the Russian Federation are standardized in protein nitrogen units (PNU)

Certification of a New Batch of the Industry Reference Standard of Polysaccharide Content in Schigellvac Vaccine

The article summarises materials on the certification of the industry reference standard of Schigella sonnei polysaccharide dysentery vaccine (commercial name — Schigellvac). The industry reference standard is used to assess the consistency of the vaccine «Specific activity» testing by passive hemagglutination inhibition assay. A certification programme for the industry reference standard was developed. Samples of the candidate vaccine were tested in terms of the following quality characteristics: «Appearance», «Identification», «Extractable Volume». The test results confirmed that the samples comply with the current requirements of the manufacturer’s product specification file for Schigellvac vaccine. It was determined that the certification parameter — the polysaccharide dilution ratio which results in inhibition of passive hemagglutination in a homologous system — has to fall in the range from 1:128 to 1:512. The following set of standard documents accompanying a scientific/technological product was approved for the industry reference standard No. 42-28-386-2017: passport, patient information leaflet, mockup labels for primary and secondary packaging

The development and certification of the industrial reference standard for identification of meningococcal polysaccharide vaccine group A

The article highlights the materials on the development and certification of the industrial reference standard (IRS) for identification of meningococcal polysaccharide vaccine group A. The scheme and methodology for IRS certification have been developed. Samples of the vaccine IRS candidate have been tested in terms of: «Description», «Dissolution time», «Transparency of reconstituted solution «, «Colourity of reconstituted solution», «Particulate matter «, «Loss on drying», «Accuracy of filling» «Phosphorus», «Sterility», «Pyrogenicity», «Abnormal toxicity», confirming their compliance with the current Pharmacopoeia monograph MP-00392-180512. The certified characteristic has been determined: IRS should slow down passive hemagglutination (PHIA) in «A» homologous system with polysaccharide concentration in the range from 0.19 to 0.39 μg per 1 ml in the absence of the inhibitory effect in «C» heterologous system with polysaccharide concentration of 50 μg per 1 ml. The shelf life of the IRS meningococcal group A polysaccharide vaccine for identification has been set against the vaccine shelf life and has been equal to 2 years. The set of regulatory documents on the scientific and technical product IRS 42-28-428-2014 IRS meningococcal group A polysaccharide vaccine for identification (certificate, draft label of primary package and patient information leaflet) has been approved

Analysis of the demand for reference standards used in quality evaluation of biologicals

Quality evaluation of biologicals entails some specific considerations and problems associated with inherent variability of biological systems. This has implications not only for biological and immunological test methods, but for physical and physico-chemical methods as well. Usage of reference standards (RSs) has an important role to play in the improvement of evaluation of biologicals’ quality. Absence of some industry RSs, which have the status of national RSs, makes it impossible to standardize corresponding products and to assess comparability of test results obtained by different manufacturers for similar (similarly named) products. The first step in the creation of the national system of RSs for medicines is the analysis of the demand for RSs used in quality evaluation of medicines, including biologicals. The analysis of the range of RSs demonstrated that existing industry RSs are not sufficient for performing quality evaluation of available biologicals. At present new industry RSs are being developed

Certification of the industry reference standard for the specific activity of «BiVac polio» - live attenuated bivalent oral polio vaccine type 1 and 3

The standardization and control of «BiVac polio» (live attenuated bivalent oral polio vaccine type 1 and 3) developed by M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides of the Russian Academy of Medical Sciences, called for establishment of an industry reference standard (IRS) to be used in determination of infectious units for each type of the poliovirus in a vaccine dose, according to the requirements of the quality standard. The article gives an account of certification performed for the first batch of a live attenuated bivalent oral polio vaccine type 1 and 3 IRS. The following parameters were tested: Clarity, Colourity, рН, Sterility, Identification, Specific activity, Thermal stability. Identification, Specific activity and Thermal stability of the candidate reference standard were assessed in comparison with the vaccine poliovirus type 1 IRS (IRS 42-28-362-2016) and vaccine poliovirus type 3 IRS (IRS 42-28-372-2015). The IRS certified parameter was found to be: 107.38±0.38 TCID50/ml for type 1 and 106.7±0.48 TCID50/ml for type 3. The IRS was assigned with the number IRS 42-28-434-2016 and a shelf life of 1.5 years. The IRS can be used in specific activity testing of «BiVac polio» commercial batches