PROLASTIN-C Powder for solution for injection Ref.[27444] Active ingredients: Alfa1 antitrypsin

PROLASTIN-C is a sterile, white to beige-colored concentrate of Alpha₁-PI in lyophilized powder form for reconstitution for intravenous infusion. Each vial contains approximately 1,000 mg of functionally active Alpha₁-PI as determined by capacity to neutralize porcine pancreatic elastase. The specific activity of PROLASTIN-C is ≥0.7 mg functional Alpha₁-PI per mg of total protein. PROLASTIN-C has a purity of ≥90% Alpha₁-PI (Alpha₁-PI protein/total protein). When reconstituted with 20 mL of Sterile Water for Injection, USP, PROLASTIN-C has a pH of 6.6-7.4, a sodium content of 100-210 mM, a chloride content of 60-180 mM and a sodium phosphate content of 13-25 mM. PROLASTIN-C contains no preservative.

PROLASTIN-C is produced from pooled human plasma through modifications of the PROLASTIN process using purification by polyethylene glycol (PEG) precipitation, anion exchange chromatography, and cation exchange chromatography. All Source Plasma used in the manufacture of PROLASTIN-C is non-reactive (negative) by FDA-licensed serological test methods for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (HCV) and human immunodeficiency virus types 1 and 2 and negative by FDA-licensed Nucleic Acid Technologies (NAT) for HCV and human immunodeficiency virus type 1 (HIV-1). In addition, all Source Plasma is negative for hepatitis B virus (HBV) by either an FDA-licensed or investigational NAT assay. The goal of the investigational HBV NAT test is to detect low levels of viral nucleic acid; however, the significance of a negative result for the investigational HBV NAT test has not been established. By in-process NAT, all Source Plasma is negative for hepatitis A virus (HAV). As a final plasma safety step, all plasma manufacturing pools are tested by serological test methods and NAT.

To evaluate further the virus safety profile of PROLASTIN-C, in vitro studies have been conducted to validate the capacity of the manufacturing process to reduce the infectious titer of a wide range of viruses with diverse physicochemical properties. These studies evaluated the inactivation/removal of clinically relevant viruses, including human immunodeficiency virus type 1 (HIV-1) and hepatitis A virus (HAV), as well as the following model viruses: bovine viral diarrhea virus (BVDV), a surrogate for hepatitis C virus; pseudorabies virus (PRV), a surrogate for large enveloped DNA viruses (e.g., herpes viruses); vesicular stomatitis virus (VSV), a model for enveloped viruses; reovirus type 3 (Reo3), a non-specific model for non-enveloped viruses; and porcine parvovirus (PPV), a model for human parvovirus B19.

The PROLASTIN-C manufacturing process has several steps (Cold Ethanol Fractionation, PEG Precipitation, and Depth Filtration) that are important for purifying Alpha₁-PI as well as removing potential virus contaminants. Two additional steps, Solvent/Detergent Treatment and 15 nm Virus Removal Nanofiltration, are included in the process as dedicated pathogen reduction steps. The Solvent/Detergent Treatment step effectively inactivates enveloped viruses (such as HIV-1, VSV, HBV, and HCV). The 15 nm Virus Removal Nanofiltration step has been implemented to reduce the risk of transmission of enveloped and non-enveloped viruses as small as 18 nm. The table below presents the virus reduction capacity of each process step and the accumulated virus reduction for the process as determined in viral validation studies in which virus was deliberately added to a process model in order to study virus reduction. In addition, the Solvent/Detergent Treatment step inactivates ≥5.4 log₁₀ of West Nile virus, a clinically relevant enveloped virus.

Table 4. Virus Reduction (Log₁₀) for the PROLASTIN-C Manufacturing Process:

^* Not determined. VSV inactivation and/or removal was only determined for the Solvent/Detergent Treatment and 15 nm Virus Removal Nanofiltration steps.
^† Not applicable. This step is only effective against enveloped viruses.

Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the variant Creutzfeldt-Jakob disease (vCJD) and Creutzfeldt-Jakob disease (CJD) agents. Studies of the PROLASTIN-C manufacturing process demonstrate that a minimum of 6 log₁₀ reduction of TSE infectivity is achieved. These studies provide reasonable assurance that low levels of vCJD/CJD agent infectivity, if present in the starting material, would be removed.