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Pathogen safety and characterisation of a highly purified human alpha1-proteinase inhibitor preparation
Scott Kee1, David Weber1, Birgit Popp2
1CSL Behring LLC, Box 511, Kankakee, IL, USA.
Insights
Respreeza/Zemaira, a purified alpha1-proteinase inhibitor (A1PI) therapy, demonstrates high purity and stability for emphysema treatment. Its manufacturing process effectively reduces viruses and prions, ensuring a safe therapeutic product.
Area of Science:
- Biochemistry
- Pharmacology
- Biotechnology
Background:
- Alpha1-proteinase inhibitor (A1PI) deficiency is a genetic disorder linked to emphysema development.
- Respreeza/Zemaira is a human plasma-derived therapeutic preparation of A1PI.
- Ensuring product purity, stability, and pathogen reduction is critical for A1PI therapies.
Purpose of the Study:
- To evaluate the purity and stability of Respreeza/Zemaira.
- To assess the efficacy of virus and prion reduction steps in the manufacturing process.
- To confirm the safety profile of the therapeutic preparation.
Main Methods:
- Purity and stability assessed using established analytical techniques.
- Virus and prion clearance capacity evaluated using validated scale-down models with spiked pathogens.
- Manufacturing steps including pasteurization, viral filtration, and cold ethanol fractionation were tested.
Main Results:
- Respreeza/Zemaira exhibited 99% A1PI purity and 96% monomer content.
- The product remained stable for 3 years at 25°C with a specific activity of 0.895 mg active A1PI/mg protein.
- Pasteurization inactivated enveloped and non-enveloped viruses; viral filtration effectively removed all tested viruses, including parvoviruses; cold ethanol fractionation reduced prions.
Conclusions:
- The manufacturing process yields a pure and stable Respreeza/Zemaira product.
- Effective virus and prion reduction steps contribute to a high safety margin.
- Respreeza/Zemaira is a safe and reliable therapeutic option for A1PI deficiency.
Abstract:
Alpha1-proteinase inhibitor (A1PI) deficiency is a genetic condition predisposing to emphysema. Respreeza/Zemaira, a therapeutic preparation of A1PI, is prepared from human plasma. This article describes the purity and stability of Respreeza/Zemaira and the capacity of virus and prion reduction steps incorporated into its manufacturing process. Purity and stability of Respreeza/Zemaira were analysed using established methods. To test pathogen clearance capacity, high levels of test viruses/prions were spiked into aliquots of production intermediates and clearance studies were performed for selected manufacturing steps, under production and robustness conditions, using validated scale-down models. Respreeza/Zemaira had a purity of 99% A1PI and consisted of 96% monomers. It remained stable after storage for 3 years at 25 °C. Specific activity was 0.895 mg active A1PI/mg protein. Pasteurisation inactivated enveloped viruses and the non-enveloped hepatitis A virus. 20 N/20 N virus filtration was highly effective and robust at removing all tested viruses, including parvoviruses, to below the limit of detection. Cold ethanol fractionation provided substantial reduction of prions. The manufacturing process of Respreeza/Zemaira ensures the production of a stable and pure product. Taking into consideration the donor selection process, the testing of donations, and the highly effective virus and prion reduction, Respreeza/Zemaira has a high safety margin.