Effective inactivation of a wide range of viruses by pasteurization

Abstract

BACKGROUND Careful selection and testing of plasma reduces the risk of blood‐borne viruses in the starting material for plasma‐derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood‐borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. STUDY DESIGN AND METHODS The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product‐specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. RESULTS The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. CONCLUSION Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood‐borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product.

Novel method for reduction of virus load in blood plasma by sonication

“…Other methodologies such as temperature changes as previously tested may prove generally efficient in virus inactivation, however, unsuitable for use on plasma products [16,17]. Previous authors have tested similar methodologies, including pasteurization with regard to its effectiveness on virus inactivation and similar to our research proven the necessity of additional protective measures [18]. Others have tested the effectiveness of light waves on virus inactivation, but so far not yet with regard to human plasma products [19].…”

Helping doctors hasten COVID-19 treatment: Towards a rescue framework for the transfusion of best convalescent plasma to the most critical patients based on biological requirements via ml and novel MCDM methods

“…SARS-CoV-2 is a large virus (approximately 120 nm in diameter). Its relatively large size and lipid envelope make it highly susceptible to viral inactivation and removal capacity steps during manufacturing processes, such as solvent-detergent processing [8] , low-pH incubation, caprylate incubation, pasteurisation [9] , dryheat treatment [10] , nanofiltration and fractionation [11] . Plasma or immunoglobulins collected from patients who recovered from a viral infection, such as COVID -19, have been used as a last resort to improve the survival rate of patients with the novel coronavirus whose conditions have continued to deteriorate despite treatment with pulsed methylprednisolone [12] .…”

Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper

“…While the method has been widely accepted in manufacturing of HSA in industry, the emergence of new viruses, e.g., Zika virus and Chikungunya virus, stipulates constant revalidation of the process [13][14][15][16][17]. Pasteurization of HSA (60 • C, 10 h) was shown to reduce the infectivity of most known human viruses including human parvovirus B19, hepatitis A virus, human immunodeficiency virus and West Nile virus [18][19][20][21], but it may be ineffective against animal parvoviruses, e.g., canine parvovirus (CPV) and minute virus of mice (MVM) [21]. The presence of N-acetyl-tryptophan or caprylate in HSA has little effect on inactivation kinetics during pasteurization, unlike other blood-derived products which may be stabilized by different excipients such as sucrose and CaCl 2 .…”

“…The presence of N-acetyl-tryptophan or caprylate in HSA has little effect on inactivation kinetics during pasteurization, unlike other blood-derived products which may be stabilized by different excipients such as sucrose and CaCl 2 . [21]. However, the presence of high quantities of HSA stabilizers (e.g., typical stabilizer: Albumin molar ratio > 5:1) negatively affects the binding and transport properties of HSA, especially with respect to lipophilic molecules [22,23].…”