Human immunoglobulins are preparations of the immunoglobulins, principally immunoglobulin G (IgG) subclasses, that are present in human blood. They are derived from the plasma of donated blood and from plasma obtained by plasmapheresis.
HUMAN IMMUNOGLOBULINS
Human immunoglobulins are preparations of the immunoglobulins,
principally immunoglobulin G (IgG) subclasses, that are present in human blood.
They are derived from the plasma of donated
blood and from plasma
obtained by
plasmapheresis. Normal immunoglobulin, that is immunoglobulin that has relatively low titres of antibodies representative of those present
in the population at large, is prepared from pools of plasma obtained from not fewer than 1000 individuals. Specific immunoglobulins, that
is immunoglobulins with
a high titre
of a
particular antibody, are usually prepared from
smaller pools of plasma obtained
from individuals who have suffered recent infections or who have undergone recent immunization and who thus have a high titre of a particular antibody. Each contribution of plasma to a pool is
tested for the presence of hepatitis B surface antigen (HBsAg), for antibodies to HIV 1 and 2 and for antibodies to hepatitis C virus in order to identify,
and to exclude from a pool, any plasma capable of transmitting infection from donor to recipient. Donors
who have been resident for 6 months or more in areas endemic
for transmissible spongiform
bovine encephalopathy (BSE), which currently includes
the UK, are also excluded. The solventdetergent process,
one of the
methods used to inactivate
enveloped viruses,
uses treatment with a combination of tributyl phosphate and octoxinol 10; these reagents are subsequently removed by oil extraction or by solid phase
extraction (British Pharmacopoeia, 2010).
The immunoglobulins are
obtained from the plasma pools by fractionation methods that are based
on ethanol precipitation
in the cold with rigorous control of protein concentration, pH and ionic
strength (Cohn et al.,
1946). The variation of Kistler & Nitschmann (1962) is widely used. Some of the fractionation steps
may contribute to the
safety of immunoglobulins by inactivating or removing contaminating viruses
that have not been detected
by tests on the blood donations. The immunoglobulins may be presented either
as a freeze-dried or a liquid preparation at a concentration that is at least 10 times that
in the initial pooled plasma.
Glycine may be added as a stabilizer. Multidose
preparations contain an antimicrobial
preservative but
single-dose preparations do not (British Pharmacopoeia, 2010).
The quality
control of immunoglobulins includes potency tests and conventional tests for safety
and sterility. The potency tests consist
of toxin or virus neutralization tests that parallel those
used for the potency assay
of immune sera, except that for in-process control of some immunoglobulins wider use is made of in vitro assays. In addition to the safety and sterility tests,
total protein is determined by nitrogen estimations, the protein
composition by sodium dodecyl sulphate
(SDS)–polyacrylamide gel electrophoresis and molecular size by high performance
liquid chromatography. The presence of immunoglobulins derived from species
other than humans is
excluded by precipitin tests. Table 24.4
lists six human immunoglobulins and their requisite potencies and indicates the methods by which the potencies are determined.
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