eBook: Analytical Method and QC Testing Strategies for Biologics Production - 10

Validation Guidance for Residual
Host Cell DNA Testing of Biologics
Mike Brewer
Introduction
Development of a manufacturing process for a
biotherapeutic that ensures consistent quality, purity
and safety is a critical step in successfully developing
the drug, getting it approved by regulatory agencies,
and bringing it to the market.
Most biological drugs, such as antibodies, recombinant
proteins, and vaccines, are produced in bacterial, yeast,
or animal cell lines and may still contain trace amounts
of DNA from the host cells, even after a rigorous
purification process. The presence of residual host cell
DNA molecules in a biotherapeutic could potentially
cause an adverse event or present a safety issue.
Because of these potential risks to patient safety,
regulatory authorities have set requirements to
demonstrate that the levels of host-cell DNA in
products manufactured in cell cultures are below
certain limits established globally.
Guidance from Regulatory Agencies
Quantitation of residual
host
product. Over the past decade, methods using realtime
quantitative polymerase chain reaction (qPCR)
have become a staple in quantitatively measuring
nucleic acid-based impurities (e.g., residual host cell
DNA). The US Pharmacopeia chapter 509 provides
guidance on use of qPCR as the preferred method for
highly sensitive, specific, and accurate quantitation of
host-cell DNA in biopharma manufacturing.
Quality control
(QC) methods using these assays
require validation per International Conference on
Harmonization guidelines, ICH Q2(R1), 'Validation of
Analytical Procedures', to ensure that the analytical
procedure is suitable for the intended use. Following
the ICH guidance, manufacturers typically develop
their own standard operating procedures (SOP) for
executing analytical
tests
for parameters such as
cell DNA requires
a method with a level of sensitivity that enables
meeting or exceeding the regulatory specifications
for acceptable levels of host cell DNA in a dose of the
specificity, sensitivity, or limit of quantitation.1,2
" The testing is generally done during the purification
process for two reasons: 1) to develop a thorough
understanding of the capability of the purification
process to remove the host-cell DNA; and 2) to
understand the level of DNA that's present at the end
of the purification process, " says Mike Brewer, Director
and Global Principal Consultant (Regulatory) for the
BioProduction Division at Thermo Fisher Scientific.
10
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