title: Impact of manufacturing improvements on clinical safety of albumin: Australian pharmacovigilance data for 1988-2005.
abstract: OBJECTIVE
  To evaluate the impact of manufacturing improvements on the clinical safety of human albumin solutions in Australia.
  
  
  METHODS
  This retrospective study examined the incidence of spontaneously reported post-market adverse drug reactions (ADRs) in Australia associated with successive generations of albumin products manufactured by the Bioplasma Division of CSL Limited (CSL Bioplasma) over 18 years (1988-2005). Key characteristics of each product generation which could affect clinical safety, such as purity, aggregates and prekallikrein activator (PKA) levels, were also identified from CSL batch release records.
  
  
  RESULTS
  A total of 3.7 million bottles of iso-oncotic and hyperoncotic albumin products were distributed in Australia over the period. Improvements to manufacturing processes resulted in products with increased albumin purity, lower levels of impurities such as aggregates and PKA, and reduced batch-to-batch variation. The total ADR incidence (number of ADRs per 100 000 bottles distributed) associated with the products currently supplied was 1.5 and 1.7 for Albumex 4 (2VI) and Albumex 20 (2VI), respectively. This was a significant reduction compared with the earlier generation products Stable Plasma Protein Solution (14.1) and 20% Normal Serum Albumin (11.5), respectively (P<0.0001). In particular, hypotensive reactions declined substantially.
  
  
  CONCLUSIONS
  Post-market pharmacovigilance data collected for successive generations of human albumin products supplied in Australia over 18 years indicates that manufacturing improvements have significantly improved the clinical safety profile of this product.
authors.affiliation: CSL Bioplasma, Melbourne, VIC, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Che
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Wilson
authors.forename: Joseph
authors.initials: J
authors.lastname: Bertolini
authors.forename: Peter
authors.initials: P
authors.lastname: Schiff
authors.forename: Darryl W
authors.initials: DW
authors.lastname: Maher
mesh_terms: D000418:Albumins / Q000009:adverse effects / Q000737:chemistry / Q000592:standards*; D001315:Australia; D015956:Factor XIIa / Q000032:analysis; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies
chemical_list: D000418:Albumins; D015956:Factor XIIa