BACKGROUND: For regulatory approval, consistency in manufacturing of vaccine 
lots is expected to be demonstrated in confirmatory immunogenicity studies using 
two-sided equivalence trials. This randomized, double-blind study (NCT01323972) 
assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from 
commercial-scale purified antigen bulk lots in terms of anti-CS-responses 
induced.
METHODS: Healthy children aged 5-17 months were randomized (1:1:1:1) to receive 
RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen 
bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a 
comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 
litres-fermentation scale; pilot-scale lot). The co-primary objectives were to 
first demonstrate consistency of antibody responses against circumsporozoite 
(CS) protein at one month post-dose 3 for the three commercial-scale lots and 
second demonstrate non-inferiority of anti-CS antibody responses at one month 
post-dose 3 for the commercial-scale lots compared to the pilot-scale lot. 
Safety and reactogenicity were evaluated as secondary endpoints.
RESULTS: One month post-dose-3, anti-CS antibody geometric mean titres (GMT) for 
the 3 commercial scale lots were 319.6 EU/ml (95% confidence interval (CI): 
268.9-379.8), 241.4 EU/ml (207.6-280.7), and 302.3 EU/ml (259.4-352.3). 
Consistency for the RTS,S/AS01 commercial-scale lots was demonstrated as the 
two-sided 95% CI of the anti-CS antibody GMT ratio between each pair of lots was 
within the range of 0.5-2.0. GMT of the pooled commercial-scale lots (285.8 
EU/ml (260.7-313.3)) was non-inferior to the pilot-scale lot (271.7 EU/ml 
(228.5-323.1)). Each RTS,S/AS01 lot had an acceptable tolerability profile, with 
infrequent reports of grade 3 solicited symptoms. No safety signals were 
identified and no serious adverse events were considered related to vaccination.
CONCLUSIONS: RTS,S/AS01 lots formulated from commercial-scale purified antigen 
bulk batches induced a consistent anti-CS antibody response, and the anti-CS GMT 
of pooled commercial-scale lots was non-inferior to that of a lot formulated 
from a pilot-scale antigen bulk batch.