Residual DNA and host-cell proteins
Although traditional small-molecule drugs are made through chemical synthetic routes, many biologic and biotechnology products
are made using recombinant technologies in host cells designed to produce a genetically engineered therapeutic protein. These
recombinant products are often transcribed from human DNA sequences that are placed into host cells such as mouse cell lines,
yeast cells, or Escherichia coli. After the cells produce the proteins, they are purified and characterized. Manufacturers of these protein products must be
able to demonstrate that their final products contain very low levels of host-cell DNA and proteins because there could be
a risk of tumorigenicity or immunogenicity, respectively, from these materials when given to the patient. Currently, USP is
developing a chapter on residual DNA, and at least two material reference standards will be available to support the chapter.
USP also is developing a general information chapter containing best practices for critical reagent development and characterization
as well as development, validation, and use of host-cell protein measurement procedures.
In June 2013, USP will cohost a workshop with the BioPharmaceutical Emerging Best Practices Association (BEBPA) focused on
the measurement of residual DNA and host-cell proteins in biotechnology products. The meeting will feature current industry
practices and provide perspectives from the regulatory community. For a workshop description and registration information,
Regarding elemental impurities, USP has developed two relevant general chapters—<232> Elemental Impurities—Limits and <233> Elemental Impurities—Procedures. General Chapter <232> specifies limits for selected elemental impurities, including limits for mercury, cadmium, arsenic,
and lead—toxic elements commonly found in the environment. In General Chapter <233>, procedures for identifying impurities
using inductively couple plasma technology are described. In addition, General Chapter <233> provides validation criteria
should a manufacturer choose to use procedures other than the one described in the new general chapters. As is the case with
residual solvents, the elemental impurities chapters will be applied to articles recognized in USP–NF by means of a General Notices provision, expected to be proposed in January 2013 in Pharmaceutical Forum and become official May 1, 2014. For updated information about the current status of USP's standards on elemental impurities,
Maura Kibbey, PhD, is senior scientific liaison, Antonio Hernandez-Cardoso, MSc, is senior scientific liaison, and Kahkashan Zaidi, PhD, is senior scientific liaison, all with the US Pharmacopeial Convention (USP).