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All plasma-derived medicinal products carry a theoretical risk of pathogen transmission because infective agents can not be completely excluded during manufacturing. Strategies developed over the last 20 years have helped to minimize this risk, and the standard of safety for plasma-derived products is currently very high.
Factors that help to contribute to human plasma product safety include: strict donor selection criteria; serological viral marker testing and polymerase chain reaction (PCR) testing of plasma donations; and virus removal and/or inactivation processes during production of the highly purified factor concentrates used in the final product.
The viruses most likely to occur in human plasma and to carry a major risk to the recipient are hepatitis B virus (HBV), hepatitis C virus (HCV), HIV-1 and HIV-2. Additionally, hepatitis A virus (HAV) and human parvovirus B19 (B19V) are also potential contaminants. Viruses such as herpes simplex 1 (HSV-1), cytomegalovirus (CMV) and Epstein-Barr virus (EBV), although relevant for blood transfusion, rarely occur in plasma.
Non-viral pathogens with a hypothetical risk of blood-borne transmission include the transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease (CJD). Currently, there is no evidence that CJD is transmitted via plasma-derived medicinal products or blood transfusion.1,2 New variant CJD (nvCJD), which may be caused by the agent responsible for bovine spongiform encephalopathy BSE in cattle, differs in its clinical profile and disease progression from other forms of the disease. Cases of nvCJD have largely been confined to the UK, and transmission by plasma-derived products is considered very unlikely.1
There are many strategies that can be used to achieve virus inactivation, but only those that preserve the activity of the final product can be incorporated into the manufacturing procedure.
Pasteurization, introduced by CSL Behring as a virus inactivation step in factor VIII preparation, is now used with almost all plasma protein concentrates at CSL Behring. Other heat inactivation treatments include dry heat and steam treatment, but pasteurization is considered more effective than dry heat treatment for enveloped and certain nonenveloped viruses.
Procedures that physically remove the pathogens from plasma concentrate include chromatography, precipitation, adsorption and nanofiltration.3. These methods are particularly relevant for the removal of agents causing spongiform encephalopathies which remain otherwise unaffected by heat and radiation treatment.
Virus validation studies have been carried out to establish how effectively the production process for plasma concentrates in Beriplast® P Combi-Set inactivates and/or removes viruses.4
Factors that help to contribute to human plasma product safety include: strict donor selection criteria; serological viral marker testing and polymerase chain reaction (PCR) testing of plasma donations; and virus removal and/or inactivation processes during production of the highly purified factor concentrates used in the final product.
The viruses most likely to occur in human plasma and to carry a major risk to the recipient are hepatitis B virus (HBV), hepatitis C virus (HCV), HIV-1 and HIV-2. Additionally, hepatitis A virus (HAV) and human parvovirus B19 (B19V) are also potential contaminants. Viruses such as herpes simplex 1 (HSV-1), cytomegalovirus (CMV) and Epstein-Barr virus (EBV), although relevant for blood transfusion, rarely occur in plasma.
Non-viral pathogens with a hypothetical risk of blood-borne transmission include the transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease (CJD). Currently, there is no evidence that CJD is transmitted via plasma-derived medicinal products or blood transfusion.1,2 New variant CJD (nvCJD), which may be caused by the agent responsible for bovine spongiform encephalopathy BSE in cattle, differs in its clinical profile and disease progression from other forms of the disease. Cases of nvCJD have largely been confined to the UK, and transmission by plasma-derived products is considered very unlikely.1
There are many strategies that can be used to achieve virus inactivation, but only those that preserve the activity of the final product can be incorporated into the manufacturing procedure.
Pasteurization, introduced by CSL Behring as a virus inactivation step in factor VIII preparation, is now used with almost all plasma protein concentrates at CSL Behring. Other heat inactivation treatments include dry heat and steam treatment, but pasteurization is considered more effective than dry heat treatment for enveloped and certain nonenveloped viruses.
Procedures that physically remove the pathogens from plasma concentrate include chromatography, precipitation, adsorption and nanofiltration.3. These methods are particularly relevant for the removal of agents causing spongiform encephalopathies which remain otherwise unaffected by heat and radiation treatment.
Virus validation studies have been carried out to establish how effectively the production process for plasma concentrates in Beriplast® P Combi-Set inactivates and/or removes viruses.4
References
1. Committee for Proprietary Medicinal Products (CPMP). Position statement on new variant CJD and plasma-derived medicinal products. CPMP/201/98. © EMEA 1998.
2. Wilson K, Code C, Ricketts MN. Risk of acquiring Creutzfeldt-Jacob disease from blood transfusions: systematic review of case-control studies. BMJ 2000;321:17-19.
3. Johannsen R, Bonik K. Integrated safety system for plasma-derived pharmaceuticals. Biomed Prog 1997;10:37-44.
4. Joch C, Witzke G, Grõner A, Phillips M. Clinical safety of fibrin sealants. IXth World Congress of Cardio-Thoracic Suregons, Lisbon, Portugal, 14-17 November 1999.