Controlled human infection model (CHIM) inoculum production in Malawi using principles of good manufacturing practice

Background Controlled Human Infection Models (CHIM) are an important tool in biomedical research in which pathogens are inoculated into human volunteers to study pathogenesis and test vaccines or treatments. Production of CHIM inoculum, however, presents specific challenges in safety, reproducibility and replication of the desired dose. The principles of Good Manufacturing Practice (GMP) developed for production of medications can be applied to the preparation of CHIM inocula, but licensed GMP facilities are scarce in low resource settings. 

Methods We applied GMP principles to develop protocols for CHIM inocula production at Liverpool School of Tropical Medicine, UK and subsequently at Malawi-Liverpool Wellcome Programme, Malawi. We used published guidelines to evaluate these protocols and to advise selection, characterisation, manufacture, quality control and storage. We established in-house production of Streptococcus pneumoniae serotypes 3 and 6B for use in Experimental Human Pneumococcal Challenge models. 

Results The manufacturing process underwent regulatory review in both the UK and Malawi. CHIM inocula production in Malawi was approved by the National Health Sciences Research Committee after written and oral submission. We successfully implemented our procedure and manufactured batch lots of Streptococcus pneumoniae serotype 3 ( n = 2) and serotype 6B (n = 2). We safely, accurately and successfully inoculated participants in CHIM studies and achieved experimental human pneumococcal carriage with both serotype strains. 

Discussion CHIM inoculum manufacture of pneumococcus was feasible in Malawi. This allowed the Malawi scientific ecosystem to demonstrate scientific and regulatory autonomy as well as having the potential to improve operational efficiency compared to importation of challenge agents.