CRB SME's Rob Boulanger, Marc Pelletier, and Alejandro Kaiser

Boulanger, Pelletier, and Kaiser featured in BioProcess International

Oct 22, 2021

The need for biotech labs to prevent contamination during mammalian cell cultivation cannot be understated. There are vast risks and implications associated with a viral infection contaminating this delicate process. CRB’s Rob Boulanger, Marc Pelletier and Alejandro Kaiser, along with additional industry experts, thoroughly examine bioprocessing procedures alongside a real-world contamination case in BioProcess International’s article, “Spontaneous Infection: Did You Leave the Back Door Open to Your Cultivation Suite?

Contamination risks

“The need to ensure viral safety during production is well recognized by biomanufacturers and regulatory agencies around the world.”

As the necessary filtration-based sterilization practices for cell culture media differs from that of thermal sterilization techniques for typical microbial cultivation, there lies a greater potential for viral contamination of cell cultures. Beyond this risk factor are potential risk events within manufacturing, storage, and the product’s final use. Cell culture operations require more than standard preparations and procedures to be met; they require an acute understanding of all the risks at hand. The team brings this point into focus as they review a case of contaminated cell cultures where “standard procedures were followed for media-preparation operations, yet subsequent cell culture operations were contaminated because of a failure to understand all risks inherent to the production process.”

A case study on contaminated cell cultures

“A source of contamination was not identified during initial risk assessment of the biomanufacturing process.” An oversight that caused multiple campaign batches to fail with a significant monetary impact to the biomanufacturing company.

The case study presented in the article investigates a contamination outbreak within a baculovirus expression vector system (BEVS) to locate the source of contamination as well as the measures needed to mitigate and prevent recurrences. To do so, the team reviewed:

  • Sampling and testing from media batches
  • Facility layout and media segmentation
  • Media preparation and harvest operations
  • Operator processes and workflows

In the end, an operator’s outer garments were the culprit. “Lack of appropriate controls led to concentrated virus being introduced into the host-cell media-preparation area. Once they were introduced into the media, latent viruses could not be removed by sterile filtration, so subsequent host-cell cultures failed. That resulted in multiple batch-campaign failures.”

“Setting up clear rules on transitioning between functional areas and providing airlock gowning-change stations at transition points reduces the likelihood of such contamination events. Making the right thing to do also the easy thing to do always improves compliance with standard operating procedures (SOPs).”

A detailed account of the investigation and the team’s recommendations can be found within the full article here.