Committed to Plasma Safety
Shire is committed to high standards of quality in plasma collection and processing and the manufacture of life-saving therapeutics from plasma.1 Shire takes steps to support safety from collection to delivery by employing seven safety steps before production (See Figure 1). Our processes have been certified by the Plasma Protein Therapeutics Association (PPTA) Quality Standards of Excellence, Assurance and Leadership (QSEAL) Voluntary Standard since 2001.2-3
Plasma donation from qualified donors is held up to 60 days in inventory before entering fractionation. Potential donors must donate a second time within 6 months, and if screening tests of the first donation are negative, their plasma may be used. If the donor does not return for a second donation, their plasma may not be used.5
*Formulations made from human plasma may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt-Jakob disease agent.
†PCR=polymerase chain reaction; HIV=human immunodeficiency virus; HBV=hepatitis B virus; HCV=hepatitis C virus; HAV=hepatitis A virus.
‡Virus inactivation/removal steps include solvent/detergent (S/D) treatment, 35 nm nanofiltration, and a low pH incubation at elevated temperature (30°C to 32°C).
Products made from human plasma may contain infectious agents, such as viruses, that can cause disease.4 FLEXBUMIN® 25% is made from pooled human plasma. It may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease.4
Although the risk of viral transmission with albumin treatment cannot be completely eliminated, steps taken during the collection of source plasma and processing minimize the risk. First, source plasma donations are only accepted from repeat donors who do not demonstrate high risk behavior.1 Albumin is manufactured from human blood by the modified Cohn-Oncley cold ethanol fractionation process, which includes a series of cold-ethanol precipitation, centrifugation and/or filtration steps followed by pasteurization of the final product. This process accomplishes both purification of albumin and removal/inactivation of viruses.4
Specific steps in the processing of FLEXBUMIN 25% help support the viral safety of this therapeutic product. In vitro studies demonstrate that the manufacturing process for FLEXBUMIN 25% provides for significant viral removal/inactivation.4
Summary of Viral Reduction Factor for Each Virus and Processing Step
|PROCESS (STEP)||VIRAL REDUCTION FACTOR (LOG10)|
|LIPID ENVELOPED||NON-LIPID ENVELOPED|
|Processing of Fraction I+II+III/II+III Supernatant to Fraction Ivcuno 70° Filtrate*||>4.9||>4.8||>5.7||>5.5||>4.5||3.0|
|Mean Cumulative Reduction Factor, Log10||>12.7||>11.3||>5.7||>12.9||>7.7||4.6|
n.d. = not determined
* Other Albumin fractionation process steps (processing of cryo-poor plasma to Fraction I+II+III/II+III supernatant and processing of Fraction V suspension to Cuno 90LP filtrate) showed virus reduction capacity in in-vitro viral clearance studies. These process steps also contribute to the overall viral clearance effectiveness of the manufacturing process. However, since the mechanism of virus removal is similar to that of this particular process step, the viral inactivation data from other steps were not used in the calculation of the Mean Cumulative Reduction Factor.
** Recent scientific data suggest that the actual human parvovirus B19 (B19V) is far more effectively inactivated by pasteurization than indicated by model virus data.
1. Data on file (BioLife Press Kit) Baxter Healthcare Corporation. 2. Quality Standards of Excellence, Assurance and Leadership (QSEAL) Program Certification Program. Plasma Protein Therapeutic Association. Version 1.6. January 2010. 3. Plasma Protein Therapeutic Association website (http://www.pptaglobal.org/safety-quality/standards/qseal), 2013. 4. FLEXBUMIN 25% [Albumin (Human)], USP, 25% Solution [package insert]. Westlake Village, CA: Baxter Healthcare Corporation. 5. Marketing Research Bureau. The plasma proteins market in the United States 2011. Published June 2012. 6. Data on file. Pathogen Safety Monograph. Baxter Healthcare Corporation. 2009.