Non-A, Non-B Hepatitis From Intravenous Immunoglobulin

Welch, AnneG.; Cuthbertson, B.; McIntosh, R. V.; Foster, Peter R.

doi:10.1016/s0140-6736(83)91250-3

Cited by 22 publications

(7 citation statements)

References 6 publications

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“…In 1985, Leen et al [30] reported that an IGIV produced by the Scottish National Blood Transfusion Service by the pH 4/mild pepsin method [31,32] showed no evidence of transmission of NANB. Accordingly, it was felt appropriate to perform a retrospective review of patients treated with IGIV.…”

Section: Introductionmentioning

confidence: 99%

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey

Rousell¹,

Good²,

Pirofsky³

et al. 1988

Vox Sanguinis

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Evidence for transmission of non-A non-B hepatitis (NANB) was sought in 41 patients with primary immune deficiency who were receiving human intravenous immune globulin (IGIV) over periods ranging from 6 to 15 months at a monthly dosage of 400 mg/kg body weight. One lot of a reduced and alkylated IGIV and three lots of a nonmodified preparation stabilized at pH 4.2 were used. No evidence of NANB was found, although transient elevations in serum glutamic pyruvic transaminase (alanine aminotransferase) were found in 6 of the patients. The possible causes of the elevated levels in these 6 patients are discussed.

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Section: Introductionmentioning

confidence: 99%

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey

Rousell¹,

Good²,

Pirofsky³

et al. 1988

Vox Sanguinis

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“…The Scottish intravenous IgG product is treated in this way, following ultrafiltration to remove residual ethanol. It has been speculated [15] that pH 4/pepsin treatment may provide a significant degree of viral inactivation. Data is presented in this report which indicates that pH 4/pepsin treatment is, indeed, capable of inactivating certain virus species, and may, therefore, make a significant contribution to the viral safety of immunoglobulin products treated in this way.…”

Section: Introductionmentioning

confidence: 99%

Potential Contribution of Mild Pepsin Treatment at pH4 to the Viral Safety of Human Immunoglobulin Products

Reid¹,

Cuthbertson²,

Jones³

et al. 1988

Vox Sanguinis

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Different manufacturers use several different processes for the production of intravenous immunoglobulin. Several manufacturers include a production step where the immunoglobulin is treated with low levels of pepsin at pH 4. A series of experiments were undertaken to assess whether or not pH 4/pepsin treatment could inactivate a range of test viruses. Acid-labile viruses such as vaccinia, herpes simplex, mumps and Semliki Forest virus were found to be susceptible to pH 4/pepsin treatment whereas poliovirus type 2, an acid-stable virus, was completely resistant to this treatment. In immunoglobulin preparations, viral contaminants are likely to be present as antibody/ virus complexes and such complexing was found to help protect the test viruses from inactivation by pH 4/pepsin treatment. Despite this protection, at least 99% of the test inoculum of two susceptible viruses (vaccinia and herpes simplex) was found to be inactivated after treatment and the subsequent dissociation of virus/antibody complexes. It is concluded that pH 4/pepsin treatment may contribute to the safety of intravenous IgG by inactivating potential viral contaminants.

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“…The World Health Organization (WHO) advises the use of pasteurization (60°C 10h in liquid) as one of the most appropriate methods of viral inactivation for plasma fractionated products [l]. The use of sorbitol and other polyols for virus inactivation of IgG solution for intravenous production has been reported [2][3][4]. Ideally, the heat treatment of liquid IgG allows safe virus inactivation and has several technical advantages compared with other processes.…”

Section: Introduction Materials and Methodsmentioning

confidence: 99%

Thermal Stability of Human Immunoglobulins with Sorbitol: A Critical Evaluation

1995

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The effect of the additive sorbitol on the thermal stabilization of human IgG was investigated by differential scanning calorimetry and size exclusion chromatography. In the presence of 33% sorbitol, the temperature at which denaturation of IgG began (Ti) was increased from 52 to 65 degrees C. Similarly, the temperature of the maximum heat capacity (Tmax) was increased from 69 to 76 degrees C. Sorbitol also decreased dimer aggregation and the extent of oligomerization during heating compared with IgG dissolved in phosphate buffer. Sorbitol at 33% prevented massive protein denaturation but a 10-15% of oligomerization of high molecular weight aggregates with turbidity could not be avoided when heating for 10 h at 60 degrees C. The use of sorbitol 33% to avoid heat denaturation of human IgG during viral inactivation did not prevent protein aggregation or the appearance of turbidity. Consequently, further processing will be required to achieve a product suitable for pharmaceutical use.

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Non-A, Non-B Hepatitis From Intravenous Immunoglobulin

Cited by 22 publications

References 6 publications

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey

Potential Contribution of Mild Pepsin Treatment at pH4 to the Viral Safety of Human Immunoglobulin Products

Thermal Stability of Human Immunoglobulins with Sorbitol: A Critical Evaluation

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