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Review
. 2005;19(2):79-96.
doi: 10.2165/00063030-200519020-00002.

Ensuring the biologic safety of plasma-derived therapeutic proteins: detection, inactivation, and removal of pathogens

Kang Cai  1 , Todd M Gierman, JoAnn Hotta, Christopher J Stenland, Douglas C Lee, Dominique Y Pifat, Steve R Petteway Jr
Affiliations
Review

Ensuring the biologic safety of plasma-derived therapeutic proteins: detection, inactivation, and removal of pathogens

Kang Cai et al. BioDrugs. 2005.

Abstract

Human plasma-derived proteins, such as immunoglobulins, coagulation factors, alpha1-antitrypsin, fibrin sealants, and albumin, are widely used as therapeutics for many serious and life-threatening medical conditions. The human origin of these proteins ensures excellent efficacy and compatibility but may also introduce the risk of unintentional disease transmission. Historically, only viruses, particularly hepatitis and HIV, have posed serious threats to the safety of these therapeutics. Fortunately, between 1970 and 1990, the molecular biology of each of the major viruses was elucidated. These advances led to the development and implementation of effective donor screening tests, mainly based on immunoassays and nucleic acid testing, which resulted in a significant reduction of disease transmission risk. In addition, viral inactivation and removal steps were implemented and validated by manufacturers, further reducing the risk associated with known, as well as unidentified, viruses. Since the late 1990s, a different class of transmissible agent, referred to as prions, has been identified as a new risk for disease transmission. However, prion diseases are very rare, and prion transmission through plasma-derived proteins has not been reported to date. The prion-related risk is minimized by deferring donors with certain key risk factors, and by the manufacturing processes that are capable of removing prions. Advances in science and pathogen safety-related technology, compliance with good manufacturing practices by manufacturers, and increasingly stringent regulatory oversight, has meant that plasma-derived proteins have been developed into today's highly effective therapeutics with very low risk of disease transmission.

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Figures

Table I
Table I
Pathogens transmissible or potentially transmissible by blood
Table II
Table II
WHO international standards for nucleic acid testing methods
Table III
Table III
Models used in viral validation studies
Fig. 1
Fig. 1
A Cohn-Oncley plasma fractionation scheme.
Table 4
Table 4
Reduction of enveloped and non-enveloped viruses across manufacturing processes[1,9]
Table V
Table V
Removal of prion protein scrapie form and purification process parameters
See this image and copyright information in PMC

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