Monitoring impurities in biopharmaceuticals produced by recombinant technology

DiPaolo, Byron; Pennetti, Aniello; Nugent, LaDonna; Venkat, K.

doi:10.1016/s1461-5347(99)00120-0

Cited by 30 publications

(27 citation statements)

References 67 publications

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“…The first one is the PicoGreen method. In this approach, a dye called PicoGreen® binds to double stranded DNA and generates fluorescence, whereas unbound dye emits little fluorescence (DiPaolo et al, 1999). The advantage of the PicoGreen® method is its ease of use and low cost, and has some utility for samples with relatively high levels of DNA (e.g., upstream bioprocess samples).…”

Section: Traditional Rdna Analysismentioning

confidence: 99%

Residual DNA analysis in biologics development: Review of measurement and quantitation technologies and future directions

Wang

Morgan

Gan

et al. 2011

Biotech & Bioengineering

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Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and longer length molecules originating from the host organism that may be present in samples from recombinant biological processes. Although similar in basic structural base pair units, rDNA may exist in different sizes and physical forms. Interest in measuring rDNA in recombinant products is based primarily on demonstration of effective purification during manufacturing, but also on some hypothetical concerns that, in rare cases, depending on the host expression system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV virus and the Ras oncogene, respectively). Recent studies suggest that a sequence known as long interspersed nucleotide element-1 (LINE-1), widely distributed in the mammalian genome, is active as a retrotransposon that can be transcribed to RNA, reverse-transcribed into DNA and inserts into a new site in genome. This integration process could potentially disrupt critical gene functions or induce tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand, could add to risk of immunogenicity to the target recombinant protein being expressed, due to the high CpG content and unmethylated DNA sequence. For these and other reasons, it is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm low levels in the final drug substance using an appropriately specific and quantitative analytical method. The heterogeneity of potential rDNA sequences that might be makes the testing of all potential analytes challenging. The most common methodology for rDNA quantitation used currently is real-time polymerase chain reaction (RT-PCR), a robust and proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR is limited by the sequences to which the primers are directed. To address this, primase-based whole genome amplification is introduced herein. This paper will review the recent advancement in rDNA quantitation and recent findings regarding potential risks of immunogenicity, infectivity, and oncogenicity of rDNA.

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Section: Traditional Rdna Analysismentioning

confidence: 99%

Residual DNA analysis in biologics development: Review of measurement and quantitation technologies and future directions

Wang

Morgan

Gan

et al. 2011

Biotech & Bioengineering

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“…Protein therapeutics produced by recombinant technology are almost inevitably heterogeneous due to the biotechnological mode of manufacturing. In addition, potential chemical and physical changes may be introduced from the raw materials, the host cells, and the manufacturing and storage processes . The chemical changes are covalent changes, for example, amino acid sequence variants are often produced in the biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

“…To ensure the safety, quality, integrity, and efficacy of a therapeutic protein, which is usually of extreme structural complexity, it is critical to characterize and monitor the product‐related variants throughout the discovery and quality control processes. A wide range of analytical techniques have been applied .…”

Section: Introductionmentioning

confidence: 99%

Applications of capillary electrophoresis in characterizing recombinant protein therapeutics

Zhao

Chen

2013

Electrophoresis

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The use of recombinant protein for therapeutic applications has increased significantly in the last three decades. The heterogeneity of these proteins, often caused by the complex biosynthesis pathways and the subsequent PTMs, poses a challenge for drug characterization to ensure its safety, quality, integrity, and efficacy. CE, with its simple instrumentation, superior separation efficiency, small sample consumption, and short analysis time, is a well-suited analytical tool for therapeutic protein characterization. Different separation modes, including CIEF, SDS-CGE, CZE, and CE-MS, provide complementary information of the proteins. The CE applications for recombinant therapeutic proteins from the year 2000 to June 2013 are reviewed and technical concerns are discussed in this article.

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“…[1,8]. Protein nature of EP determines the only administration route (parenteral) and the risk of a variety of side effects and complications [6,[10][11][12] related to immunogenicity of a linearly restricted growth factor for erythroid hemopoietic cells [2,3]. Protein toxicity can be reduced by immobilization on lowmolecular-weight polyethylene glycol by using exposure to ionizing radiation.…”

mentioning

confidence: 99%

Hemostimulating Effects of Erythropoietin Immobilized by the Nanotechnology Method of Electron-Beam Synthesis

et al. 2011

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The hemostimulating effect of erythropoietin immobilized by the nanotechnology method of electron-beam synthesis was studied on the model of carboplatin-induced myelosuppression. Subcutaneous injection or oral administration of immobilized erythropoietin was followed by stimulation of erythropoiesis. The effect was most pronounced after parenteral treatment with this agent. The increase in proliferative activity and maturation of erythroid precursor cells serve as a factor determining acceleration of reparative processes in the hemopoietic tissue.

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Monitoring impurities in biopharmaceuticals produced by recombinant technology

Cited by 30 publications

References 67 publications

Residual DNA analysis in biologics development: Review of measurement and quantitation technologies and future directions

Residual DNA analysis in biologics development: Review of measurement and quantitation technologies and future directions

Applications of capillary electrophoresis in characterizing recombinant protein therapeutics

Hemostimulating Effects of Erythropoietin Immobilized by the Nanotechnology Method of Electron-Beam Synthesis

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