A new STAT3-based potency assay for human G-CSF analog therapeutics.

Tao Xie, Weiming Ouyang, Yaqin Zhang, Phillip Angart, Patrick J Lynch, David M Frucht

Abstract read

In one paragraph

Article in Journal of pharmaceutical and biomedical analysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Tao XieOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: tao.xie@fda.hhs.gov.

Weiming OuyangOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

Yaqin ZhangOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

Phillip AngartOffice of Product Quality Assessment III, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

Patrick J LynchOffice of Product Quality Assessment III, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

David M FruchtOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: david.frucht@fda.hhs.gov.

Funding

Intramural FDA HHS FD999999

6 · The paper itself

Abstract

Human granulocyte colony-stimulating factor (G-CSF) is the primary cytokine promoting the development and function of neutrophils. More than a dozen recombinant human G-CSF (rhG-CSF) therapeutic originator or biosimilar products (e.g., filgrastim and pegfilgrastim) have been developed and are widely used to treat and prevent neutropenia, especially following chemotherapy for cancer. Published analytical methods described for assessing the bioactivities of rhG-CSF products are primarily based on G-CSF-induced proliferation of the murine myeloblastic NSF-60 or its variant cell lines. These cell proliferation assays are reported to exhibit large variability in assay performance between laboratories. Moreover, the biological action initiated by the interaction of human G-CSF with the murine G-CSF receptor expressed on NFS-60 cells does not fully reflect the action of the product in humans because of interspecies differences between the G-CSF receptors. We describe herein the establishment of a new 293-CSF3R-STAT3Luc reporter cell line that constitutively expressed the human G-CSF receptor and inducibly expressed luciferase in response to STAT3 activation. This cell line selectively responded to stimulation by rhG-CSF. Using this cell line, we developed and qualified a reporter-based potency bioassay for PEG-rhG-CSF products. This new potency reporter assay was linear and accurate over the range of 25-200 % of the reference material potency, and the assay demonstrated acceptable specificity, precision, and robustness. This reporter cell assay platform may also be applied to develop assays for potency determinations of other therapeutics in the rhG-CSF class.

Indexed as

Granulocyte Colony-Stimulating FactorSTAT3 Transcription FactorAnimalsBiological AssayBiosimilar PharmaceuticalsCell ProliferationFilgrastimHEK293 CellsHumansLuciferasesMicePolyethylene GlycolsReceptors, Granulocyte Colony-Stimulating FactorRecombinant ProteinsBiosimilar PharmaceuticalsFilgrastimGranulocyte Colony-Stimulating FactorLuciferasesPolyethylene GlycolsReceptors, Granulocyte Colony-Stimulating FactorRecombinant ProteinsSTAT3 protein, humanSTAT3 Transcription FactorBioassayG-CSFG-CSF-RPegfilgrastimPotencySTAT3

Identifiers

PMID40645038

DOI10.1016/j.jpba.2025.117056

PMCPMC12520044

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.