Development of a current Good Manufacturing Practice-compliant Process for Producing Cryptosporidium parvum oocysts...

Area of Science:

• Parasitology
• Infectious Diseases
• Drug Development

Background:

• Cryptosporidiosis is a major cause of severe diarrhea and death in young children, lacking vaccines or effective treatments.
• Cryptosporidium controlled human infection model (CHIM) studies in adults are crucial for evaluating new therapies before pediatric trials.
• Development of CHIM has been limited by the absence of current good manufacturing practice (cGMP)-compliant Cryptosporidium parvum oocysts for regulatory submissions.

Purpose of the Study:

• To establish a cGMP-compliant manufacturing process for Cryptosporidium parvum oocysts.
• To enable the use of these oocysts in Investigational New Drug (IND) applications and subsequent clinical trials.
• To facilitate the evaluation of novel therapeutics and vaccines for cryptosporidiosis.

Main Methods:

• Sourced well-characterized oocysts from neonatal calves under controlled non-GMP conditions.
• Implemented cGMP processing including peracetic acid surface sanitization and rigorous microbial testing.
• Released the product as a non-sterile oral product for human use after meeting stringent release criteria.

Main Results:

• Peracetic acid treatment (0.5% for 20 minutes) ensured microbial safety while preserving oocyst viability.
• Oocyst viability was confirmed through excystation, cell culture, and animal infectivity studies.
• cGMP-produced oocysts (ABO809) met all batch-release criteria and were successfully used in human challenge studies, inducing reliable infections.

Conclusions:

• A robust cGMP-compliant process for producing and qualifying Cryptosporidium parvum oocysts has been developed.
• This process enables CHIM studies in healthy adults, paving the way for new cryptosporidiosis treatments.
• The availability of cGMP oocysts opens avenues for evaluating novel therapeutics and vaccines against cryptosporidiosis.