Optimal bioreactor purity.

Accelerated downstream processing. 

Unprocessed bulk (UPB) is the material collected directly from the bioreactor in which genetically engineered cells grow and produce product. Low levels of adventitious agents such as bacteria, yeast, fungi, moulds, mycoplasma and viruses that bypass detection during raw materials testing may grow to detectable levels under the highly enriching conditions of the bioreactor. This is the ideal point in the process to test for adventitious agents in the UPB, which is a regulatory requirement.

The streamlined, cGMP approach to UPB testing developed by the Eurofins BPT network of laboratories ensures product purity and the ability to move into downstream purification faster, with less risk of contamination.

The recommended testing package includes bioburden testing, mycoplasma testing, in vitro viral screening, transmission electron microscopy (TEM), and virus-specific qPCR assays. All of these can be performed in 21 or 35 calendar days, while the testing package can be tailored to meet each client’s unique specifications.

35-day-chart-upb-testing

The 35-day release testing programme is the traditional approach, utilising the longer test methods. The table below outlines the test methods, turnaround times, and sample requirements. 

21-day-chart-upb-testing

The 21-day release testing program utilises the shorter in vitro adventitious agent test method (14-day), and uses the molecular-based PCR approach to mycoplasma testing. The table below outlines the test methods, turnaround times, and sample requirements. Consultation with your regulatory reviewer is recommended if the shorter UPB test approach is preferred. 

*TEM testing should be performed on three lots of UPB to assess retroviral load to help design the IND or BLA viral clearance study. After three lots have been tested, the TEM assay is no longer required.

The MMV interference and mycoplasmastasis test methods only need to be performed once for early stage clinical trials. For late stage/commercialisation, product-specific qualifications (multiple lots, multiple spike controls) should be considered.

Why so many global clients choose Eurofins BPT for UPB 

Retroviral-like particles (RVLPs) released into the media during the manufacturing process must be quantified to help determine the log reduction value (LRV) of clearance required to obtain a safe product. This is where Eurofins BPT can provide support:

  • Fully validated GMP TEM service: Provides streamlined, reliable, and consistent unprocessed bulk testing for mAb and ADC biologics
  • Real-time access to experts and online access to raw data and images: Provides confidence to move from UPB to viral clearance in the same laboratory
  • Specialised sample delivery and receipt process: Ensures seamless communication between the Eurofins BPT network of laboratories and your own to expedite processing within days of receipt
  • Individual or Summary Certificate of Analysis provided within 21 or 35 calendar days
  • Experienced project management
  • Dedicated technical teams
  • Single-source testing solution
  • Secure 24/7 online data portal to access test results