Evidence map›Paper›PMID 26658915›Full record

ArticlePharmaceutical research2016

Investigation of Color in a Fusion Protein Using Advanced Analytical Techniques: Delineating Contributions from Oxidation Products and Process Related Impurities.

Hangtian Song, Jianlin Xu, Mi Jin, Chao Huang, Jacob Bongers, He Bai, Wei Wu, Richard Ludwig, Zhengjian Li, Li Tao and 1 more

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

Hangtian SongBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Bloomsbury, New Jersey, USA. hangtian.song@bms.com.ORCID http://orcid.org/0000-0001-5924-2360
Jianlin XuBiologics Process Development, Bristol-Myers Squibb, East Syracuse, New York, USA.
Mi JinBiologics Process Development, Bristol-Myers Squibb, East Syracuse, New York, USA.
Chao HuangBiologics Process Development, Bristol-Myers Squibb, East Syracuse, New York, USA.
Jacob BongersBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Hopewell, New Jersey, USA.
He BaiBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Hopewell, New Jersey, USA.
Wei WuBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Bloomsbury, New Jersey, USA.
Richard LudwigBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Hopewell, New Jersey, USA.
Zhengjian LiBiologics Process Development, Bristol-Myers Squibb, Devens, Massachusetts, USA.
Li TaoBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Hopewell, New Jersey, USA.
Tapan K DasBiologics Molecular and Analytical Development, Bristol-Myers Squibb, Hopewell, New Jersey, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDiscoloration of protein therapeutics has drawn increased attention recently due to concerns of potential impact on quality and safety. Investigation of discoloration in protein therapeutics for comparability is particularly challenging primarily for two reasons. First, the description of color or discoloration is to certain extent a subjective characteristic rather than a quantitative attribute. Secondly, the species contributing to discoloration may arise from multiple sources and are typically present at trace levels. Our purpose is to development a systematic approach that allows effective identification of the color generating species in protein therapeutics.

methodsA yellow-brown discoloration event observed in a therapeutic protein was investigated by optical spectroscopy, ultra-performance liquid chromatography, and mass spectrometry (MS).

resultsMajority of the color generating species were identified as oxidatively modified protein. The location of the oxidized amino acid residues were identified by MS/MS. In addition, the impact of process-related impurities co-purified from media on discoloration was also investigated. Finally a semi-quantitative scale to estimate the contribution of each color source is presented, which revealed oxidized peptides are the major contributors.

conclusionsA systematic approach was developed for identification of the color generating species in protein therapeutics and for estimation of the contribution of each color source.

Indexed as

AnimalsCHO CellsChromatography, High Pressure LiquidColorCricetulusDrug ContaminationHistidineOxidation-ReductionPeptidesPharmaceutical PreparationsProteinsRecombinant Fusion ProteinsTandem Mass SpectrometryTryptophanHistidinePeptidesPharmaceutical PreparationsProteinsRecombinant Fusion ProteinsTryptophancolorhistidinemass spectrometryoxidationprocess developmenttryptophanultra-performance liquid chromatography

Identifiers

PMID26658915

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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.