# Sensitive and spatially-selective quantification of oxygen in the headspace of pharmaceutical vials

> **NIH NIH R43** · PHYSICAL SCIENCES, INC · 2022 · $262,962

## Abstract

Project Summary/Abstract
 Physical Sciences Inc. (PSI) is developing a head space analyzer (HSA) to accurately measure 0.01%
of O2 in the head space of pharmaceutical vials at a speed of 600 vials per minute. The measurement
approach is non-destructive and selectively measures only oxygen in the vial head space. HSA is used in
the pharmaceutical industry to evaluate the closed container integrity (CCI) of packaging against air
ingress. The presence of oxygen in the head space indicates compromised packaging of a drug product,
potentially reducing the shelf life and efficacy and voiding the sterility. This is particularly true for biologic
drugs, the fastest growing pharmaceutical market segment valued at $90B/year, that are highly susceptible
to oxygen-induced degradation. The current standard for non-destructive HSA is based on laser
absorption spectroscopy. Laser-based HSA requires an active nitrogen purge to mitigate the signal
contribution of ~20% oxygen present in room air. The reliability of head space measurements with laser-
based HSA critically relies on the efficacy of a nitrogen purge. PSI's proposed HSA approach does not
require a nitrogen purge removing a mode of failure, and will be an order of magnitude more sensitive than
conventional laser-based HSAs. More sensitive detection of oxygen will lead to improved product shelf-life
and a reduction in the shortages of biologics and other classes of drugs that are vulnerable to oxidation.
 During the Phase I program PSI will demonstrate the feasibility of the new HSA approach in a series of
benchtop experiments with standard pharmaceutical vials of different sizes. These studies will
demonstrate the capability of the technology to selectively quantify oxygen to 0.01% levels in the vial head
space with detection limits better than what are achieved with conventional laser-based HSAs. The
experimental studies will also demonstrate the capability of the HSA approach to be operated without an
active nitrogen purge. Knowledge gained from the Phase I studies will guide the development of a
fieldable prototype design to be fabricated during the Phase II program. In the Phase I program PSI will
establish a collaboration with a company that manufactures and sells vial inspection instrumentation. The
industry collaborator will provide a location for field testing of a prototype system fabricated in the Phase II
program.

## Key facts

- **NIH application ID:** 10545821
- **Project number:** 1R43GM148094-01
- **Recipient organization:** PHYSICAL SCIENCES, INC
- **Principal Investigator:** Brian E Brumfield
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $262,962
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545821

## Citation

> US National Institutes of Health, RePORTER application 10545821, Sensitive and spatially-selective quantification of oxygen in the headspace of pharmaceutical vials (1R43GM148094-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10545821. Licensed CC0.

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