What is the visible/subvisible particulate profile (USP <788>) of IV fluids in bags with vs without overwrap?

Abstract

Intravenous fluid studies show only limited, non‐standardized observations related to visible or subvisible particulates as defined by USP <788> in bags with versus without overwrap. Fekete et al. (2014) noted that an overpouch can allow migration of a slip additive (erucamide) during autoclaving, manifesting as opalescence, yet no particulate counts were provided. Gabay and von Martius (2008) reported that fully collapsible bags revealed no visible particulates by visual inspection, whereas one study measuring microplastics/nanoplastics (Mou et al., 2024) found levels of 1.0 ± 0.7 μg/L in bags and 8.4 ± 3.6 μg/L in tubing. Signoretti et al. (1988) documented particulate contamination in large volume injectables—with 20% of samples showing particles exceeding 20 μm—and identified fibers, manufacturing debris, and other materials as contaminants.

None of the reviewed abstracts employed USP <788> methods or directly compared particulate profiles in IV bags with versus without overwrap in a quantitative, standardized fashion.

Methods

We analyzed 5 sources from an initial pool of 998, using 7 screening criteria. Each paper was reviewed for 5 key aspects that mattered most to the research question.

Papers identified with Elicit search

• n = 998
• Papers screened using: Comparison Groups, Container Type, Outcome Measurement, Measurement Methodology, Clinical Relevance, Study Design, Particulate Source
• n = 998
• Papers screened out
• n = 993
• Papers included for extraction
• n = 5

Paper search

Using your research question "What is the visible/subvisible particulate profile (USP <788>) of IV fluids in bags with vs without overwrap?", we searched across over 126 million academic papers from the Semantic Scholar corpus. We retrieved the 998 papers most relevant to the query.

Screening

We screened in sources based on their abstracts that met these criteria:

• Comparison Groups: Does the study compare IV fluid bags with overwrap versus those without overwrap?
• Container Type: Does the study examine intravenous fluids stored in flexible bags or containers?
• Outcome Measurement: Does the study measure visible and/or subvisible particulate matter?
• Measurement Methodology: Does the study use USP <788> methodology or equivalent international standards?
• Clinical Relevance: Does the study involve commercially available IV solutions or clinically relevant formulations?
• Study Design: Is the study an experimental study, observational study, systematic review, or meta-analysis?
• Particulate Source: Does the study focus on particulate matter related to packaging/storage factors?

Data extraction

We asked a large language model to extract each data column below from each paper:

• Study Design:

Describe the specific type of study design used. Possible designs include:

• Observational study

• Experimental study

• Comparative study

• Laboratory analysis

• Particulate Matter Analysis Method:

Identify and describe the specific method used to analyze particulate matter:

• Specify the exact analytical technique (e.g., visual inspection, light obscuration, microscopic counting)

• If USP <788> is explicitly mentioned, highlight this

• Packaging Conditions:

Describe the specific packaging conditions being compared:

• Types of IV fluid bags (fully collapsible, semi-rigid, etc.)

• Presence/absence of overwrap

• Particulate Profile Characteristics:

Extract detailed information about the particulate profile:

• Total number of particles
• Particle size ranges

Results

Characteristics of Included Studies

Particulate Levels in Overwrapped Versus Non-Overwrapped Containers

Material Migration and Contamination Sources

Summary of findings across studies:

• Container configuration: No mention found for 2 studies; 1 study examined overpouch; 1 study compared fully collapsible and semi-rigid containers.
• Particulate concentration: 3 studies had no mention; 1 study reported no visible particulates.
• Particle size range: 4 studies with no mention; 1 study reported contaminants >20 μm.
• Contamination source: Tubing identified as a predominant source in one study.

Synthesis and Limitations

• Limited evidence base: most studies focused on qualitative data rather than quantitative.
• Overwrap and particulate profile: only one study directly addressed overwrap.
• Sources of contamination: included manufacturing and packaging processes.
• Container performance: results based on visual methods rather than standardized methods.

Overall, the literature does not provide a quantitative answer regarding the visible/subvisible particulate profile as per USP <788> for intravenous fluids in bags with and without overwrap. The evidence is limited to qualitative findings.