Evidence map›Paper›PMID 29404710›Full record

ArticlePharmaceutical research2018

The Impact of Inadequate Temperature Storage Conditions on Aggregate and Particle Formation in Drugs Containing Tumor Necrosis Factor-Alpha Inhibitors.

N D Vlieland, M R Nejadnik, H Gardarsdottir, S Romeijn, A S Sediq, M L Bouvy, A C G Egberts, B J F van den Bemt, W Jiskoot

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Trial
  2. Impact of Climate Change on Rheumatology Care: A Global Perspective.Rheumatic diseases clinics of North America · 2026
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  5. Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  6. Article
  7. Article
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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

9 authors.

N D VlielandDepartment of Clinical Pharmacy, Division Laboratory and Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
M R NejadnikDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
H GardarsdottirDepartment of Clinical Pharmacy, Division Laboratory and Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands. H.Gardarsdottir@umcutrecht.nl.
S RomeijnDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
A S SediqDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
M L BouvyDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
A C G EgbertsDepartment of Clinical Pharmacy, Division Laboratory and Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
B J F van den BemtDepartment of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands.
W JiskootDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes.

methodsTNF-α inhibitors in their original primary and secondary packaging were exposed to 32 freeze-thaw cycles (-10°C for 120min/5°C for 60 min) or continuous low storage temperature (-20°C for 96 h) before thawing at 2-8°C. Non-stressed products were used as controls. The products were analyzed by high pressure size exclusion chromatography (HP-SEC), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), micro-flow imaging (MFI) and second derivative ultraviolet (UV) spectroscopy.

resultsTen out of twenty-one stressed product samples (47.6%) showed increased particle numbers in the submicron and micron size range when compared to controls. For each product, DLS, MFI and NTA detected an increase in particle level in at least one stressed syringe (both continuous freezing and freeze-thaw), whereas HP-SEC and UV spectroscopy showed no differences between stressed and non-stressed products.

conclusionTNF-α inhibitors are relatively resistant to freezing temperatures similar to storage conditions previously observed in patients' homes. However, almost half of the stressed product samples showed formation of particles in the submicron and micron size range.

Indexed as

Protein AggregatesAdalimumabAnti-Inflammatory AgentsBiological FactorsCertolizumab PegolChemistry, PharmaceuticalDrug StorageEtanerceptFreezingParticle SizeTumor Necrosis Factor-alphaAdalimumabAnti-Inflammatory AgentsBiological FactorsCertolizumab PegolEtanerceptProtein AggregatesTNF protein, humanTumor Necrosis Factor-alphaaggregation of antibodiesdrug product characterizationfreezing stress conditionshome storageTNF-α inhibitors

Identifiers

PMID29404710
PMCPMC5799349

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Registered trials

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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.