Prior changes in manufacturing processes
| Product | Manufacturing change | Result |
|---|---|---|
| Interferon α2A | Biferonics biopartners had master cell bank but could not produce identical product. Inadequate validation, stability and impurities present formation of aggregates led to immunogenicity6 | No approval |
| Interferon β1A: Avonex | Produced by biogen in new mammalian cell line. The resulting product, Avonex, had reduced immunogenicity compared with that produced in original CHO cell line7 | Initial production stopped Subsequent product improved |
| rHuEPO: Eprex | 1998: 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 plunger7–10 | Aggregate formation led to formation of anti-EPO Abs and 175 cases of pure red cell aplasia 1998–2004 |
| p55TNF-R:Ig: lenercept | Manufacturing processes yielded product with differing glycosylation patterns, resulting in differences in pharmacokinetics and efficacy9–11 | Development discontinued |
| Muromonab aritox: CD5 plus | Switch to manufacturing in dialysis tubing resulted in loss of efficacy9 10 | Development discontinued |
| Primatised αCD4: clenoliximab | Working cell bank switched to facilitate manufacturing scale-up. Resulted in CD4 T cell depletion and loss of efficacy9 10 | Development discontinued |
| Darbopoetinα: Aranesp | Batches produced between 11/2008 and 4/2011 show different sialylation rate, suggesting a manufacturing change12 | Iterative manufacturing change |
| Rituximab: Mabthera | Variation in batches with expiration dates between 9/2007 and 10/2011 suggests a manufacturing change12 | Iterative manufacturing change |
| p75TNF-R:Ig: etanercept: Enbrel | Major differences in glycosylation pattern after 2009 suggest a manufacturing change12 | Iterative manufacturing change |
CHO, Chinese hamster ovary; EPO, erythropoietin.