Intravenous immunoglobulins: can the blood pressure response in laboratory animals be considered a predictive criterion for good clinical tolerance?

Having noted that the only physico-chemical and biological test recommended cannot ensure good tolerance of i.v. IgG in man, we studied a physiological test consisting of evaluating blood pressure during infusion in conscious dogs (10 mg/kg/min) or after i.v. injection in rats (250 mg/kg in 12 sec.). The data were obtained on more than 100 dogs and 500 rats. For preparations known to be well tolerated in man or inducing a few clinical intolerances, the correlation with hypotension in rats and dogs seems good. Therefore, we think this test has its place in the battery of i.v. IgG qualification tests carried out before passage to man. Institut Mérieux has developed a new intact i.v. IgG equilibrated in sub-classes, without PKA, low in IgA and not hypotensive in these two species.

Antibodies to meningococcus polysaccharides in nonspecific gamma-globulins from different regions of the world.

Seventy-one batches of nonspecific gamma-globulin obtained from France, USSR and Mongolia were studied for presence of specific antibody to group A and C meningococcus polysaccharide. Specific activity was tested by two methods: radioimmunoassay (Lyon) and reaction of passive haemagglutination inhibition (Moscow). Antibodies were detected in all the gamma-globulin batches tested, in some of them at high titres. The summary results indicated that approximately equal levels of specific A antibodies were present in preparations obtained from the different regions of the world. Antibodies to group C polysaccharide showed considerable variation in level from selection country to country; the highest level of C antibodies was in gamma-globulin from France. The authors feel entitled by the results to recommend testing of nonspecific gamma-globulin, selection of batches with a high level of specific antimeningococcus antibodies, and their judicious use.

Report of a working group for the European Pharmacopoeia. Collaborative assay on human albumin of different origin.

A collaborative assay was conducted by 9 laboratories on 31 samples of human albumin which were in clinical use. It was the object of the study to establish test systems which would differentiate between albumins of venous or placental origin. The properties examined for this purpose were: appearance, total protein, haem, polymers, alkaline phosphatase and blood group substances. Additional tests such as for beta-thromboglobulin and citrate were included; pyrogenicity, however, was excluded because this was under study for all plasma proteins at that time. Results obtained were in satisfactory agreement both between laboratories and between samples. They, therefore, enabled the verification of a number of correlations in the test systems. The evaluation did not allow, however, the differentiation of the samples in relation to their origin. The results were, therefore, regarded as a tool to define the upper limits of acceptance for human albumins corresponding to the quality prescribed by the European Pharmacopoeia.

Clinical tolerance and catabolism of plasmin-treated gamma-globulin for intravenous application.

Plasmin-treated gamma-globulin of placental origin was tested in clinical and laboratory studies and found to be suitable for intravenous use both for prophylactic and therapeutic purposes. Plasmin treatment of gamma-globulin (IgG) results in proteolytic cleavage of 60-70% of the molecules into Fab and Fc fragments whereas 30-40% of the molecules are plasmin resistant. The antibody spectrum of plasmin-treated gamma-globulin is similar to that of standard gamma-globulin. Catabolic properties of the plasmin-resistant portion of this preparation and of standard gamma-globulin are identical. Plasmin-treated gamma-globulin has no anticomplementary activity and its intravenous administration is well tolerated even by highly sensitive immunodeficient patients.