Evidence map›Paper›PMID 31229435›Full record

ArticleJournal of pharmaceutical sciences2020

DEHP Nanodroplets Leached From Polyvinyl Chloride IV Bags Promote Aggregation of IVIG and Activate Complement in Human Serum.

Jared R Snell, Connor R Monticello, Cheng Her, Emma L Ross, Ashley A Frazer-Abel, John F Carpenter, Theodore W Randolph

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of pharmaceutical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 13% of its field
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 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. How are we handling protein drugs in hospitals? A human factors and systems engineering approach to compare two hospitals and suggest a best practice.International journal for quality in health care : journal of the International Society for Quality in Health Care · 2024
    Observational
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

7 authors at 3 institutions in 1 country.

Jared R SnellDepartment of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
Connor R MonticelloDepartment of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
Cheng HerDepartment of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045.
Emma L RossDepartment of Pharmacy, Children's Hospital Colorado, Anschutz Medical Campus, Aurora, Colorado 80045.
Ashley A Frazer-AbelExsera BioLabs, Anschutz Medical Campus, Aurora, Colorado 80045.
John F CarpenterDepartment of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045.
Theodore W RandolphDepartment of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309. Electronic address: theodore.randolph@colorado.edu.
University of Colorado Boulder · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · US

Funding

Biotechnology Research Partnerships Renewal: Aggregation of Therapeutic ProteinsR01EB006006 · NIBIB · UNIVERSITY OF COLORADO · PI RANDOLPH, THEODORE W · 2006 to 2017
$7.2M
NIBIB NIH HHS R01 EB006006
6 · The paper itself

Abstract

Concerns regarding the impact of subvisible particulate impurities on the safety and efficacy of therapeutic protein products have led manufacturers to implement strategies to minimize protein aggregation and particle formation during manufacturing, storage, and shipping. However, once these products are released, manufacturers have limited control over product handling. In this work, we investigated the effect of di(2-ethylhexyl) phthalate (DEHP) nanodroplets generated in polyvinyl chloride (PVC) bags of intravenous (IV) saline on the stability and immunogenicity of IV immunoglobulin (IVIG) formulations. We showed that PVC IV bags containing saline can release DEHP droplets into the solution when agitated or transported using a pneumatic tube transportation system in a clinical setting. We next investigated the effects of emulsified DEHP nanodroplets on IVIG stability and immunogenicity. IVIG adsorbed strongly to DEHP nanodroplets, forming a monolayer. In addition, DEHP nanodroplets accelerated IVIG aggregation in agitated samples. The immunogenicity of DEHP nanodroplets and IVIG aggregates generated in these formulations were evaluated using an in vitro assay of complement activation in human serum. The results suggested DEHP nanodroplets shed from PVC IV bags could reduce protein stability and induce activation of the complement system, potentially contributing to adverse immune responses during the administration of therapeutic proteins.

Indexed as

Protein AggregatesComplement ActivationComplement C3aComplement C4aDiethylhexyl PhthalateDrug ContaminationDrug PackagingDrug StabilityGas Chromatography-Mass SpectrometryHumansImmunoglobulins, IntravenousImmunologic FactorsNanoparticlesParticle SizePlasticizersPolyvinyl ChlorideComplement C3aComplement C4aDiethylhexyl PhthalateImmunoglobulins, IntravenousImmunologic FactorsPlasticizersPolyvinyl ChlorideProtein Aggregatesimmunogenicitymicroparticle(s)nanoparticle(s)protein aggregationstability

Identifiers

PMID31229435
PMCPMC6951798
OpenAlexW2949741757

What OpenQuestion holds

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Registered trials

None linked

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.