Evidence mapPaperPMID 40730690Full record

ArticlePharmaceutical research2025

Investigating Zinc Migration from Rigid Needle Shield to Drug Formulation in Needle Tip of Pre-filled Syringe.

Guangli Hu, Chengbei Li, Kaitlin Wang, Yongchao Su, William Forrest, Jeffrey Givand, Dario Ferreira Sanchez, Margie Olbinado, Matthias Wagner, Christian Grünzweig and 1 more

Abstract read
In one paragraph

Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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.

Guangli HuPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA. guangli.hu@merck.com.ORCID http://orcid.org/0009-0001-9717-4765
Chengbei LiAnalytical Research & Development, Merck & Co., Inc, Rahway, NJ, 07065, USA.
Kaitlin WangPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA.
Yongchao SuPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA. yongchao.su@merck.com.ORCID http://orcid.org/0000-0001-5063-3218
William ForrestPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA.
Jeffrey GivandPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA.
Dario Ferreira SanchezPaul Scherrer Institute, Forschungsstrasse 111, 5232, Villigen PSI, Switzerland.
Margie OlbinadoANAXAM, Park Innovaare, Parkstrasse 1, CH-5234, Villigen, Switzerland.
Matthias WagnerANAXAM, Park Innovaare, Parkstrasse 1, CH-5234, Villigen, Switzerland.
Christian GrünzweigANAXAM, Park Innovaare, Parkstrasse 1, CH-5234, Villigen, Switzerland.
Vladimir NovakANAXAM, Park Innovaare, Parkstrasse 1, CH-5234, Villigen, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study investigates the underexplored mechanisms of needle clogging in pre-filled syringes (PFSs), focusing on zinc (Zn) ions, which have been reported to promote protein gelation and increase formulation viscosity. We present direct evidence of Zn migration from the rigid needle shield (RNS) into drug products, aiming to elucidate the migration pathways and the role of Zn in clogging.

methodsPre-filled syringes containing a therapeutic monoclonal antibody (mAb) were stored at 5°C and subjected to stress conditions at 40°C for up to six months. Inductively coupled plasma mass spectrometry (ICP-MS) measured metal ion levels, while synchrotron-based X-ray phase-contrast computed tomography (SR-XPCT) and X-ray fluorescence (SR-XRF) provided in situ visualization of Zn distribution in dry materials under stress.

resultsWe found that Zn leaches from the RNS into the drug formulation during liquid-RNS contact. ICP-MS revealed higher Zn levels, along with aluminum and titanium, in clogged needles compared to clean ones. SR-XRF identified Zn hot spots within the dried drug product, while SR-XPCT displayed 3D visualization of Zn particle accumulation at the needle tip. Notably, Zn migration accelerated at 40°C, with minimal detection at 5°C, indicating the significant influence of temperature.

conclusionsThis study offers the first experimental evidence of Zn migration from the RNS into drug formulations within staked-in-needle PFSs. While Zn is not solely responsible for needle clogging, its presence in both RNS and the drug suggests a contributory role. These insights can inform strategies for improving PFS performance and reliability.

Indexed as

Antibodies, MonoclonalNeedlesSyringesZincChemistry, PharmaceuticalDrug CompoundingAntibodies, MonoclonalZincCloggingHigh concentration biologicsPre-filled syringesRigid needle shieldZinc

Identifiers

PMID40730690
PMCPMC12405019

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.