MilliporeSigma, the U.S. and Canada life science business of Merck KGaA, Germany, says it has launched the first all-in-one, validated genetic stability assay of its kind. The Aptegra™ CHO genetic stability assay leverages whole genome sequencing and bioinformatics to significantly accelerate biosafety testing for clients and therefore, their move into commercial production, according to Benjamin Hein, head of life science services, the life science business of Merck.
“Driving innovation in biosafety testing is essential to bringing new therapies to patients faster,” said Hein. “CHO genetic stability testing has remained relatively unchanged for many years. The Aptegra platform transforms biosafety testing with a digital solution using next-generation sequencing.”
Currently, FDA guidance requires biotech companies to use multiple assays to address genetic stability requirements. This traditional package of assays is costly, time-consuming, and often results in data that need additional interpretation and support, explains Hein.
Pain points
“Aptegra addresses these pain points by replacing five different assays and four different technologies with one assay utilizing the next-generation sequencing technology platform,” he continues. “This approach reduces testing time by 66 percent and reduces costs by 43 percent compared to traditional methods. The platform meets all regulatory requirements for genetic stability assurance, including copy number assessment.”
MilliporeSigma has made investments over the last five years to expand its biosafety testing capabilities for clients across the globe. The company’s global biosafety testing network includes sites in Shanghai, China; Singapore; Stirling and Glasgow, U.K.; and Rockville, MD.
Q&A on the Aptegra Platform with Heather Ahlborn
What kinds of “safety issues” does biosafety testing address?
Genetic stability testing is included with cell-line characterization (CLC) when the cells being evaluated have been stably transfected with a genetic element that produces a biologically relevant product, like a monoclonal antibody or its related subunits. The entirety of the CLC testing package is applied to master cell banks and repeated for cell banks that are expanded from this principal material. The tests performed include methods to establish:
- Identity: Authenticate and identify the species of cells used for production
- Purity: Test cell lines, cell banks, and raw materials for contaminants
- Genetic stability: Test for potential instability of the gene expression system
What are the five different assays that are traditionally used for biosafety testing AND the four technologies are ordinarily required but are being replaced with Aptegra?
The traditional genetic stability testing package is performed using:
- Sanger sequencing to analyze the gene of interest (GOI) and flanking regions (i.e., these are performed as two separate assays, since they require different primer sequences for analysis)
- Droplet Digital™ PCR (ddPCR) to establish the gene copy number integrated into the host cell genome
- Southern blot restriction enzyme analysis to assess presence/absence of the intact vector and any large structural variants
- Fluorescence in situ hybridization (FISH) analysis to determine the general location and sites of vector integration into the host genome
Can you provide a brief description how Aptegra uses next gen sequencing to provide a less costly and less time consuming operation that traditionally requires using the technologies that have been replaced?
Our innovative Aptegra platform was developed as a collaboration between bench scientists and bioinformaticians to deliver a highly advanced tool that provides extremely comprehensive results for genetic stability testing using a single test. The Aptegra CHO genetic stability assay can be performed in 30 days, which is a significant savings over the three to five months (minimum) that are required for testing using traditional methods. Furthermore, traditional methods must be performed in duplicate using different primers for each of the heavy and light chain subunits encoding the monoclonal antibody; the Aptegra assay does not have this limitation and is sequence agnostic, meaning we can analyze multiple genes encoded on a single-vector expression system in one run with one test.
We provide a comprehensive, GMP-validated genetic stability assay based on whole genome sequencing—the first of its kind. We offer not only integration analysis and sequencing analysis to detect variants within the sequence, but also the capability to assess copy number. Copy number assessment is a significant differentiator for us. This is a unique feature that the industry has not yet explored in the context of whole genome sequencing. As a fully validated assay to GMP quality standards, the Aptegra platform offers a more complete, reliable and trustworthy solution to our clients.
Heather Ahlborn is head of contract testing services, Millipore Sigma.
