Long-term stability of reconstituted incobotulinumtoxinA: how can we reduce costs of botulinum toxin therapy?

Botulinum neurotoxin (BNT), the biologically active component of botulinum toxin (BT), is a large double-stranded protein susceptible to various physical and chemical influences. All BT type A (BT-A) drugs are stored as powders allowing shelf lives from 24 to 36 months. After reconstitution, the specified shelf life is reduced to 8-24 h. Some studies, however, suggest longer shelf life. We wanted to test the long-term stability of reconstituted BT-A drugs in the hemidiaphragm assay (HDA), a high quality BT potency test. For this incobotulinumtoxinA (INCO) was reconstituted and stored in at 4-8 °C, whilst at various points of time probes of it were taken and potency tested with the HDA. Altogether 18 measurements were performed throughout a period of 52.1 weeks. The paralysis time in the HDA was 67.3 ± 5.2 min (min. 59 min, max. 76 min). The linear regression line was described by y = -0.0163x + 67.582. The paralysis time measured during the first 10 weeks (n = 11) was 67.5 ± 5.3 min, during the last 10 weeks (n = 7) 67.1 ± 4.9 min. Reconstituted INCO does not show reduction of potency throughout 52 weeks as tested by the high quality HDA. Lack of complexing proteins does not de-stabilise INCO. Our data allow un-used reconstituted INCO to be stored for further use. This may have a considerable impact on the costs of BT therapy. Further studies will have to demonstrate sterility of the reconstituted BT drug beyond the so far reported 6 weeks.