Transmission Electron Microscopy

Comprehensive quality assessment with TEM testing

 

TEM provides high-resolution imaging that can detect and identify potential contaminants, ensuring the integrity and safety of biological materials (e.g., cell lines, virus seeds, bulk harvests) used in production. TEM testing enables visualization of virus particles, determination of particle size and morphology, identification of virus particle location, and quantification.

Viruses and virus-like particles (VLPs) are observed by TEM on thin sections of pelleted samples embedded in resin using positive staining. Furthermore, suspended viruses and VLPs can be analyzed in buffer or media supernatant using negative staining.

For the detection of retrovirus and other viral contaminants in cell substrates used in the manufacture of biopharmaceuticals, guidelines from the Federal Drug Administration (FDA), the Center of Biologics Evaluation and Research (CBER), and the European Medicines Agency (EMA), as well as ICH guideline Q5A (R2) recommend the use of TEM.

With our GMP-certified TEM testing, you gain access to a suite of advanced imaging and analysis tools tailored specifically for the biopharmaceutical industry. This includes TEM testing for GMP-compliant batch release.

From analyzing cell substrates used in the production of biologics to characterizing viral vectors and ensuring CMC, our GMP-compliant TEM testing provides the comprehensive insight you need to drive innovation and ensure regulatory compliance.

TEM

TEM applications for evaluation of biologic products

TEM is crucial for viral safety testing, facilitating the detection of adventitious agents and retrovirus-like particles (RVLPs) in biologic products, as required by regulatory guidelines. For genetically engineered viral vectors and viral vector-derived products, TEM addresses additional contamination risks, including defective particles and contaminations introduced by the expression system. Furthermore, TEM testing ensures comprehensive characterization of viral capsid integrity, purity, and population, meeting all regulatory requirements for the safe and effective release of gene therapy products, such as AAVs.

 

TEM for adventitious agents testing

TEM testing enables the detection of aggregates and contaminants, including adventitious agents (e.g., parvovirus, polyomavirus, picornavirus, reovirus, adenovirus) and retroviral particles (e.g., type-A and type-C), in bulk harvest samples, cell banks, or virus seed stocks. This assessment is critical for ensuring viral safety. As outlined in the ICH guideline Q5A (R2), TEM should be utilized on the cell substrate used in biologics production and on unprocessed bulk harvest samples to detect and quantify VLPs and other endogenous viruses or adventitious agents.