Background
Oropharyngeal gonorrhoea plays a key role in transmission and acquisition of antimicrobial resistance in Neisseria gonorrhoeae. However, oropharyngeal gonorrhoea remains understudied due to a lack of in vitro and in vivo infection models, and antimicrobial and vaccine efficacy are not well studied at this site. An oropharyngeal N. gonorrhoeae controlled human infection model (CHIM) represents a promising tool to study pathogenesis and aid product development. Here we describe a process for challenge agent manufacture that features a scalable, tiered cell bank manufacturing protocol for production of single-use, cryopreserved inoculum vials at pre-determined doses, that require no further preparation at the study site before inoculum delivery at bedside. We describe the implementation of a quality control program that employs in-process and release testing at all stages of cell bank production to confirm identity, purity and potency of the challenge material prior to participant inoculation.
Methods
The microbiological performance of a cell bank manufacture method used to generate the challenge agent inoculum was assessed for reproducibility and feasibility.
Findings
The proposed challenge agent manufacture method was demonstrated to reliably and reproducibly generate doses suitable for direct inoculation into trial participants. Release testing of manufactured cell banks demonstrated acceptable identity (as determined by MALDI-TOF, microbial characterisation), microbial purity (specific pathogen testing, bioburden, total yeast and mold counts), dose (CFU enumeration), and antimicrobial susceptibility.
Conclusion
We demonstrate the feasibility of a challenge inoculum manufacture process in line with international best practice guidelines. The infectivity, safety and tolerability of the N. gonorrhoeae manufactured challenge inoculum are being tested in a clinical trial (ACTRN12626000436370) with the goal of establishing a robust and reliable human challenge model of oropharyngeal gonorrhoea.