Residual Host Cell DNA Quantitation Regulatory Compliance

To verify product quality, the amount of residual DNA in a drug's final dosage form must meet regulatory guidelines established by the various regulatory agencies. Each regulatory agency has specific guidelines for acceptable limits, ranging from 10 pg to 10 ng DNA per therapeutic dose depending on the product and therapeutic modality. The Applied Biosystems resDNASEQ Quantitative DNA solution was specifically developed to help meet these regulatory guidelines, such as the ones below:

• DNA content in the final product should be less than 10 ng per therapeutic dose (WHO)
• DNA content in the final product should be as low as possible, as determined by a highly sensitive method (FDA)
• It is suggested that a method with a sensitivity of 10 pg be used to determine DNA levels (FDA)
• An appropriately conducted clearance study for DNA removal may be an acceptable substitute for lot-to-lot testing (FDA)
• USP (United States Pharmacopeia) general chapter <509>: Residual DNA Testing, details the application of quantitative PCR for measurement of residual host cell DNA levels during manufacturing of biopharmaceuticals

Validation of residual host cell DNA assays may vary by regulatory agency, but the general expectation is to meet validation requirements outlined in ICH Harmonised Tripartite Guideline Validation of Analytical Procedures Q2(R1) (ICHQ2R1).

Here we share validation data from our resDNASEQ host cell DNA quantitation kits, focusing on some of the most challenging validation parameters including sensitivity by limit of quantitation (LOQ), specificity, and accuracy.