The quality assurance process employed by BPL ensures that Gammaplex is produced to consistently high levels of quality and safety.
- Manufactured from a Food and Drug Administration (FDA) accredited plasma source
- Manufactured by BPL to Good Manufacturing Practice (GMP) standards
- Produced using a manufacturing process based on cold ethanol fractionation followed by ion exchange chromatography
- Manufactured using specific solvent/detergent, virus filtration and low pH incubation virus inactivation procedures
Rigorous plasma screening process
BPL draws its plasma from collection centers based in the U.S. These centers are licensed by the U.S. FDA and are members of the highly respected Plasma Protein Therapeutics Association (PPTA). The quality assurance processes employed by BPL to maximize the quality and safety of Gammaplex is shown in the figure below.
Virus reduction/elimination: The 3-step process
The manufacturing process for Gammaplex is based on cold ethanol fractionation with additional ion exchange chromatography purification steps. The cold ethanol fractionation process has been validated for virus clearance and shows removal of enveloped and non-enveloped viruses. In addition, a series of dedicated virus clearance steps have been introduced for viruses of concern, such as HBV, HCV and HIV.¹
A number of methods are available for improving the viral safety of plasma derivatives, several of which are relevant to Gammaplex. In particular, BPL has incorporated and validated several specific and well-proven virus inactivation steps using solvent/detergent treatment, virus filtration and low pH/elevated temperature incubation in the manufacture of Gammaplex. Full validation and robustness testing has been completed for each step.
The procedure was designed to inactivate enveloped viruses such as HBV, HCV and HIV, which are the viruses of principal concern in plasma products. The solvent/detergent procedure will also inactivate more recently described enveloped viruses, such as Hepatitis C virus and West Nile virus. The non-ionic detergent and the solvent components have the capacity to dissolve viral lipid envelopes and are particularly effective in combination. However, they do not inactivate non-enveloped viruses. The solvent/detergent procedure has been in widespread use in the plasma products industry for over 20 years and has become a well-established and proven method of enveloped virus inactivation.2
20 nm virus filtration
The second specific virus reduction step in the Gammaplex process is virus filtration. This involves passing the immune globulin solution through a filter with a pore size of just 20 nm; the immune globulin molecules can pass through the filter, but any virus of approximately 20 nm or larger is trapped. Virus filtration has many advantages as a removal procedure:
- It is a validated process
- Removal is based on size and it is therefore effective against enveloped and non‑enveloped viruses
- It is a relatively gentle method and allows high levels of protein recovery
Terminal low pH/elevated temperature incubation
An additional feature of the Gammaplex production process is the inactivation of viruses during the terminal low pH incubation.3 The filled product in its final closed container is incubated at 30°C (86°F) for 2 weeks. Under these conditions the low pH formulation and temperature contribute to effective inactivation of lipid-enveloped viruses and some non-enveloped viruses.
Gammaplex has High Purity
1. Chidwick K, Matejtschuk P, Gascoigne E, et l, Clinical experience with a new solvent detergent-treated intravenous immunoglobulin free of hypotensive effects. Vox Sang 1999; 77:204-209
2. Horowitz B, Prince AM, Hamman J, et al. Viral safety of solvent/detergent-treated blood products. Blood Coagul Fibrinolysis 1994;5 (Suppl 3):S21-S28.
3. Gammaplex FDA CMC review. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/ Bl oodBl oodProducts /ApprovedProducts / LicensedProductsBLAs/Fractionated PlasmaProducts/ UCM186256.pdf [Accessed June 2010].
4. IDF – Characteristics of Immune Globulin Products Used to Treat Primary Immunodeficiency Diseases Licensed for Use in the United States, Table updated March 2013
5. Gammaplex Prescribing Information, 2014 VSUS5PI