HPE Human albumin handbook | Page 9

TABLE 2

Example of virus safety data for human albumin manufactured using the Cohn-Oncley process

Ethanol precipitation ≥5.1 ≥5.3 ≥6.6 4.1 3.5

Pasteurisation ≥6.7 ≥8.8 ≥7.5 > 6.8 > 4.0

Overall reduction factor ≥11.7 ≥14.1 ≥14.1 ≥10.9 ≥7.5

1 Bovine viral diarrhoea virus ; 2 Herpes virus ( enveloped , double-stranded DNA virus – a non-specific model virus ); 3 Parvovirus B19V or canine parvovirus .

culture infectivity assays that both lipid-enveloped viruses ( for example , HIV , HCV model viruses and West Nile virus ) and non-enveloped viruses ( for example , HAV and B19V ) were effectively inactivated . ^{5 , 6}

Specific steps during the manufacture of albumin are therefore effective in removing / inactivating a wide range of relevant and model viruses exhibiting diverse physicochemical properties very effectively ( Table 2 ).

Tolerability and safety of albumin products Albumin has an excellent long-term safety record . When assessing the risks and benefits of human albumin preparations , judgements should be based upon experience with modern generation products .

Modern production techniques ensure that concentrations of impurities such as aluminium and PKA are minimised ; some of the adverse reactions observed in the past may be attributable to impurities that are eliminated or minimised in modern preparations . This calls into question the relevance of side effects reported in clinical studies that were performed more than 30 years ago .

Tolerability and pharmacovigilance Modern human albumin products are generally well tolerated , especially considering that they are often administered in large volumes . This is illustrated by the low incidence of spontaneously reported adverse events , and although reporting may underestimate the true incidence of adverse events , this finding nonetheless provides a good indication of the favourable tolerability profile of modern albumin products .

Two large pharmacovigilance studies have examined the incidence of spontaneously reported adverse events associated with administration of albumin . The first study by von Hoegen and Waller examined serious adverse events reported by nine major suppliers of therapeutic albumin worldwide . ⁷ Nearly 100,000,000 doses of albumin , corresponding to nearly 4,000,000kg , were distributed by suppliers during the study period . A total of 123 serious adverse events ( SAEs ) were reported , corresponding to an incidence of 1.29 SAEs per 1,000,000 doses .

Notably , no deaths were judged to be probably attributable to the administration of albumin . Five deaths per 100,000,000 doses were possibly related to the administration of albumin . The majority ( 75 %) of deaths were considered to be unrelated to albumin , and the study concluded that both non-fatal and fatal adverse reactions in albumin recipients are very rare .

The second pharmacovigilance study was performed by Vincent et al ⁸ during a period of heightened interest in the safety of albumin following the publication of controversial safety data . Approximately 16,000,000 doses of albumin were distributed by 10 major suppliers worldwide during the study period . A total of 211 serious adverse events were reported , corresponding to an incidence of 5.28 SAEs per 1,000,000 doses .

In agreement with results from the first pharmacovigilance study , no deaths were judged to be probably attributable to the administration of albumin . Although the incidence of SAEs was higher than in the first study , only half of the number of non-fatal SAEs was judged to be probably related to albumin in the second study , as compared to the first . Results of this analysis confirmed those from the first pharmacovigilance study : spontaneously reported SAEs are rare and human albumin has an excellent tolerability profile .

Conclusions The production of human albumin is a continually improving process , with biopharmaceutical companies striving to produce preparations with increased purity that continue to exceed the strict guidelines specified by regulatory bodies worldwide .

Albumin has an excellent long-term safety record , is well tolerated and has an excellent virus safety record . Many randomised controlled trials have demonstrated a favourable efficacy and safety profile for human albumin , and further studies are underway to define the efficacy , safety and tolerability of human albumin across a wide variety of clinical settings .

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