Table 1

Prior changes in manufacturing processes

ProductManufacturing changeResult
Interferon α2ABiferonics biopartners had master cell bank but could not produce identical product. Inadequate validation, stability and impurities present formation of aggregates led to immunogenicity6No approval
Interferon β1A: AvonexProduced by biogen in new mammalian cell line. The resulting product, Avonex, had reduced immunogenicity compared with that produced in original CHO cell line7Initial production stopped
Subsequent product improved
rHuEPO: Eprex1998: ortho biotech switched protein stabiliser from human serum albumin to detergent polysorbate 80, with variations in storage and handling; 2003 introduced prefilled syringe w/rubber plunger7–10Aggregate formation led to formation of anti-EPO Abs and 175 cases of pure red cell aplasia 1998–2004
p55TNF-R:Ig: lenerceptManufacturing processes yielded product with differing glycosylation patterns, resulting in differences in pharmacokinetics and efficacy9–11Development discontinued
Muromonab aritox: CD5 plusSwitch to manufacturing in dialysis tubing resulted in loss of efficacy9 10Development discontinued
Primatised αCD4: clenoliximabWorking cell bank switched to facilitate manufacturing scale-up. Resulted in CD4 T cell depletion and loss of efficacy9 10Development discontinued
Darbopoetinα: AranespBatches produced between 11/2008 and 4/2011 show different sialylation rate, suggesting a manufacturing change12Iterative manufacturing change
Rituximab: MabtheraVariation in batches with expiration dates between 9/2007 and 10/2011 suggests a manufacturing change12Iterative manufacturing change
p75TNF-R:Ig: etanercept: EnbrelMajor differences in glycosylation pattern after 2009 suggest a manufacturing change12Iterative manufacturing change
  • CHO, Chinese hamster ovary; EPO, erythropoietin.