Reduce unprocessed bulk testing from 35 to 21 days

by Stan Prince, Senior Scientific Advisor, Eurofins BioPharma Product Testing

Monoclonal Antibodies (mAb’s) are manufactured from genetically engineered cells using varying bioreactor sizes (depending on the size of the clinical trial or commercial market). Chinese Hamster Ovary (CHO) cells are commonly used to produce the mAb drug product.

The bioreactors used can be a breeding ground for microbial and viral organisms. These organisms are commonly referred to as adventitious agents and can include bacteria, yeast, fungi, molds, mycoplasma, and viruses.

Contaminants can enter from the raw materials used in the manufacturing process. Raw materials should be tested for microbial and viral contamination. However, there can be times where a contaminant may go unnoticed in the test method. This is why unprocessed bulk (UPB) testing is critical to assess the purity of the bioreactor harvest
material.

The common tests performed on UPB samples include:

• Bioburden
• Mycoplasma (compendial or PCR)
• In vitro Adventitious Agent (IVAA)
• MMV PCR
• TEM

Traditionally the above tests took approximately 35 days to complete. However, with newer technologies and with proper risk assessments, including raw material testing plans and viral clearance studies, the above testing can be reduced to 21 days for the final certificate of analyses.

Phase appropriate qualification/validation should also be considered when running UPB testing. GMP validated platform methods are appropriate for use for early stage clinical trials. When companies are progressing to larger Phase III and commercialization of the mAb, Product Specific Qualification (PSQ) studies should be considered to qualify the mAb and matrix into the GMP platform methods.

Eurofins is here to help with any UPB testing questions and provide the GMP services needed to ensure product safety. Most importantly, always consult with your regulatory reviewer on your final UPB testing strategy.