JSC “Pharmstandard” has registered a domestic Plasma-Derived Coagulation Factor VIII for the treatment of Haemophilia A under trademark “Eightoplasm” . The product was developed as part of the state strategy for increasing the population's life expectancy and quality of life and improving medicine availability. Its manufacturing was launched at the end of 2022 at the facilities of JSC “Pharmstandard-UfaVITA” plant in the city of Ufa. Currently, the enterprise has reached full production capacity and is arranging to supply the product to the Russian market.

This is the first facility in the country to operate the large-scale, full-cycle manufacturing of Human Plasma-Derived Coagulation Factor VIII, starting with the initial raw material: cryoprecipitate. Its suppliers are major certified European companies managing donors from Europe and the USA: Sanquin (Netherlands) and Kedrion (Italy). Each lot delivered to the Russian Federation has a customs cargo declaration and undergoes all the necessary stages of inspection and tracking.

Within the manufacturing of the finished medicinal product, advanced chromatographic purification methods are applied, which make it possible to obtain Blood Coagulation Factor VIII of high purity, as well as state-of-the-art methods of viral inactivation, which completely eliminate the risk of transmitting viral infections through the product.

The efficacy and safety of Eightoplasm have been proven within the international multi-center clinical studies conducted in compliance with the requirements of the European Medicines Agency (EMA). The study results demonstrate that it is possible to use the product both for preventing spontaneous and post-traumatic bleeding and for reducing blood loss during surgical interventions of varying degrees of complexity in patients with severe haemophilia A. Specifically, 10 surgical interventions were performed over the course of the studies, including 9 planned inpatient interventions and 1 emergency outpatient intervention. In all 10 patients, intra-operative blood loss was less than or equal to the mean estimated blood loss for the type of procedure in a patient with normal haemostasis and of the same sex, age, and height. The product administration did not lead to any allergic reactions, thrombotic and thromboembolic complications, or formation of inhibitory antibodies to factor VIII. It is important to note that the study results are not  inferior to foreign counterparts[1][2][3], including ones in surgical interventions[4] [5].

At the same time, the registered maximum selling price for the product is 8% lower compared to the blood coagulation factor VIII products by foreign manufacturers that are currently in circulation in Russia, which will allow optimizing government costs for  therapy.

Eightoplasm, the domestic Plasma-Derived Coagulation Factor VIII, meets current requirements for efficacy and safety, is manufactured in compliance with the Good Manufacturing Practice (GMP) guidelines, and is affordable. That will make it possible to meet the needs of the national healthcare system for high-quality medical therapy to treat haemophilia A, to procure patients with life-saving therapy and to improve their quality of life.

Eightoplasm background: 

The product Eightoplasm (Coagulation Factor VIII) is manufactured in the form of a lyophilizate for the preparation of a solution for intravenous administration, in vials in two dosages, 500 and 1000 IU, complete with a solvent (water for injection) and an administration kit (10 ml disposable syringe with or without a needle, filter cannulae – 2 pcs., a butterfly needle with extension, an adhesive plaster, alcohol wipes – 2 pcs.), which facilitates administration of the product.

The product contains a natural stabilizer, the von Willebrand factor, which, along with the lyophilized dosage form, contributes to the product stability throughout its shelf life.

Eightoplasm can be used both for preventing spontaneous and post-traumatic bleeding and for reducing blood loss during surgical interventions of varying degrees of complexity in patients with severe haemophilia A.  10 surgical interventions were performed, including 9 planned inpatient interventions and 1 emergency outpatient intervention. In terms of severity, there were 2 major interventions (right thoracotomy, fistula removal, resection of the 5th, 6th, and 7th ribs, pleural cavity sanation, thoracostomy formation, and removal of neoplasm in the infrahyoid region) and 8 minor dental interventions. In all 10 patients (100%) who underwent surgical procedures, intra-operative blood loss was less than or equal to the mean estimated blood loss for the type of procedure in a patient with normal haemostasis and of the same sex, age, and height.

The product administration did not lead to any allergic reactions, thrombotic and thromboembolic complications, or formation of inhibitory antibodies to factor VIII. No antibodies to parvovirus B-19 were detected in patients with baseline negative antibody testing after 6 months of therapy with the product.

The adverse events recorded during the studies were mild to moderate in severity. None of them were unexpected or necessitated stopping or changing the product therapy regimen. No serious adverse events were reported in the studies.

Upon assessing the efficacy and safety of multiple Eightoplasm doses (over the course of at least 50 exposure days of administration) in previously treated severe haemophilia A patients aged 12 and up, a conclusion was made about the product efficacy and favorable safety profile for prophylactic use and on-demand treatment in this age cohort.

Manufacturing background:

Within the manufacturing of the finished medicinal product, 4 different purification methods are applied, including chromatographic purification. Certain purification steps are taken several times to yield a pure product.

The manufacturing process is designed to give a sharper focus on the viral safety of the medicinal product. For this purpose, the raw materials are tested for the absence of viruses at various manufacturing stages:

- The raw material manufacturer performs quality control of the initial plasma for fractionation, the plasma pool, and the resulting cryoprecipitate.

- Each batch of cryoprecipitate is tested upon arrival at the facility in Ufa, despite the data provided by the raw material manufacturer.

Intermediates are also tested during the manufacturing process to ensure that they are virus-free. At the final manufacturing stage, the finished medicinal product is tested for viral safety as well.

Though there are numerous stages of monitoring the absence of viruses, JSC “Pharmstandard-UfaVITA” has 2 main (critical) stages in place, aimed exclusively at viral inactivation and allowing the removal of potential viruses:

- the solvent/detergent treatment inactivates enveloped viruses by disrupting their lipid envelope;

- the thermal inactivation treatment degrades viruses under thermal influence. At the same time, the process ensures that temperature has no effect on the target protein, factor VIII.

These quality control stages, as well as other manufacturing processes and laboratory and processing equipment, engineering infrastructure implemented at JSC “Pharmstandard-UfaVITA” are fully qualified and validated.