Genetic Stability Testing

Genetic stability testing is required to demonstrate that the genetic sequence of an expression construct is stable throughout the production life cycle to ensure the quality and consistency of the product and production process.

Next Generation Sequencing (NGS) is now recognized as one of the most powerful and reliable tools for full genome sequencing. Using NGS for the cell line characterization purpose will allow you to run one study rather than performing multiple assays to achieve the same results.

Webinar: Using NGS to Characterize Cell Lines 

strand of DNA

Learn about the use of next generation sequencing technologies for the characterization of your cell lines and for verifying clonality and identity.

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Regulations for Genetic Stability Testing

According to ICH Q5B guidelines, regulating agencies request that cell substrates must be analyzed at two time points (i.e., on the level of the Master Cell Bank and on the level of the End of Production cells) to show their genetic stability. Methods must be applied to confirm the coding sequence of the expression construct or the corresponding RNA transcripts. The copy number of the transgene has to be determined, and its integrity and integration pattern must be demonstrated by restriction endonuclease mapping.

The strategy for genetic characterization and stability testing varies and depends on the production system and the project phase. Our regulatory experts can provide guidance to your program to meet regulatory requirements.

Genetic Stability Methods

Charles River applies the following methods to determine the genetic stability of recombinant production cell lines and to characterize plasmid products:

  • Restriction endonuclease mapping
  • Southern blotting
  • Northern blotting
  • Copy number determination by qPCR
  • DNA and RNA sequencing
  • Plasmid sequencing
  • Retention of recombinant construct

Charles River has partnered with PathoQuest, a genomics expert, to provide Next Generation Sequencing (NGS) services that can also be used for genetic stability testing. Our partnership can accelerate your drug development by offering quick and comprehensive testing.

Talk to a Genetic Stability Expert

Frequently Asked Questions (FAQs) About Genetic Stability