Evidence map›Paper›PMID 41291196›Full record

ArticleScientific reports2025

Root cause analysis investigation of visible particulates in therapeutic protein drug products using morphologically directed Raman spectroscopy.

Isabella F de Luna, Srivalli N Telikepalli, Michael Carrier, Dean Ripple, Charudharshini Srinivasan, Thomas O'Connor, Scott Lute, Ashwinkumar Bhirde

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PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. 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. Review
  2. Review
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

8 authors.

Isabella F de LunaDivision of Pharmaceutical Quality Research VI, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Srivalli N TelikepalliBiomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
Michael CarrierBiomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
Dean RippleBiomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
Charudharshini SrinivasanDivision of Product Quality Assessment II (DPQAII), Office of Product Quality Assessment (OPQA I), Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Thomas O'ConnorDivision of Pharmaceutical Quality Research VI, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Scott LuteDivision of Pharmaceutical Quality Research VI, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Ashwinkumar BhirdeDivision of Pharmaceutical Quality Research VI, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Ashwinkumar.Bhirde@fda.hhs.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Visible particulate (VP) matter in therapeutic protein drug products (DPs) is a quality attribute that can impact product efficacy and patient safety across the product lifecycle. This study evaluates Morphologically Directed Raman Spectroscopy (MDRS) for detecting and characterizing VPs in therapeutic protein DPs. MDRS combines morphological and chemical analyses, which are essential for root cause analysis (RCA) during incident investigations of VP formation. We evaluated MDRS using polystyrene (PS) microsphere standards, candidate reference materials from the US National Institute of Standards and Technology (NIST), and stressed therapeutic protein DPs, insulin lispro and rituximab. Using MDRS, VPs were imaged and chemically characterized in insulin or rituximab drug products with varying morphologies and ranged from 100 to 400 μm in diameter. The intensity of Raman spectral peaks varied with VP size, transparency, morphological complexity, and between therapeutic protein drug classes. Principal component analysis (PCA) of morphological features (e.g., size, shape, and transparency) revealed that NIST ethylene tetrafluoroethylene (ETFE) particles displayed a range of morphologies, akin to stressed therapeutic protein VPs. These results highlight the potential of combining morphological analysis with Raman spectroscopy to support RCA in therapeutic protein DPs for both pre- and post-market quality assessments.

Indexed as

Particulate MatterRituximabSpectrum Analysis, RamanHumansPrincipal Component AnalysisParticulate MatterRituximabBiopharmaceutical characterizationImaging methodsInsulinMonoclonal antibodiesMorphologyParticle sizePrincipal component analysisProtein aggregationRaman spectroscopy

Identifiers

PMID41291196
PMCPMC12657923

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