Potency evaluation of a formulated drug product containing 150-kd botulinum neurotoxin type A.
OBJECTIVE
To assess the potency of a formulated drug product containing 150-kd botulinum toxin type A (BoNT/A) as the active pharmaceutical ingredient.


METHODS
Potencies of 3 unexpired lots of a commercially available BoNT/A drug product, reportedly devoid of complexing proteins (Xeomin), were determined using an approved in-house potency bioassay by injecting mice intraperitoneally and recording percent-mortality across dilutions. For each test session, duplicate sets of dilutions were performed for each lot alongside a 900-kd BoNT/A (BOTOX) potency reference standard. A relative potency for each 150-kd BoNT/A preparation was determined using this potency reference standard. A standard normalized potency estimate for each lot of 150-kd BoNT/A was calculated by multiplying the relative potency by the nominal value for the reference standard. The average potency for each 150-kd BoNT/A lot was calculated using a weighted combination of assay results and compared against the labeled potency of 100 U per vial. Similar follow-on testing was performed 1 year later to assess stability.


RESULTS
The average potencies for the 3 lots of 150-kd BoNT/A product were 69 (95% confidence interval [CI], 65-73), 75 (95% CI, 70-80), and 78 (95% CI, 70-87) U per vial. Follow-on testing produced even lower potency results for all 3 lots.


CONCLUSIONS
The potency of the drug product containing 150-kd BoNT/A (Xeomin) measured substantially lower than the labeled 100 U per vial when tested in a potency assay approved for release testing of an established drug product containing 900-kd BoNT/A (BOTOX).
Hunt
Terrence
T
Department of Biological Sciences, Allergan, Inc, Irvine, CA, USA. hunt_terrence@allergan.com
Clarke
Kenneth
K
D000826:Animal Testing Alternatives; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D051379:Mice; D008970:Molecular Weight; D009498:Neurotoxins / Q000633:toxicity*; D016019:Survival Analysis
D009498:Neurotoxins; D019274:Botulinum Toxins, Type A