EXPERT FOCUS
PROCESS MEASUREMENT POINTS
MEETING THE GLOBAL
PHARMACOPEIA CHALLENGE
MEDICAL GAS PRODUCERS FOLLOW REGIONAL VARIATIONS IN QUALITY REQUIREMENTS.
Medical gases are regulated under the same
rules as medicines. For Europe and the United
States, these rules are covered in an official
publication known as a Pharmacopeia. The
European Pharmacopeia (EP) and the US
Pharmacopeia (USP) are different, but they
do share some of the same rules.
Each medical gas has its own set of rules
known as a monograph, which provides
an official definition of the medical gas. It
also states the typical production process,
acceptable purity level of the gas (known
as “assay”), what impurities must be
measured, official measurement methods
for assay and impurities, and the required
technical specifications for the analyzer.
Medical gas can be supplied in bulk for high-
usage hospitals, where the gas is supplied in
a large cryogenic tank. The gas composition
is measured at the source and the gas
quality is measured before and/or after the
bulk gas delivery. In the case of European
Pharmacopeia (EP), dedicated tankers do not
need to be sampled after filling a customer
cryogenic vessel, provided a certificate of
analysis is supplied with the delivery.
The different filling gases are delivered to
the filling plant – either via pipeline from
an ASU or from a tanker – in a liquified
form and stored in a cryogenic tank. The
liquified gas is then vaporized into the gas
phase and pumped to the filling manifold.
The gas quality delivered is usually at a
high enough standard to ensure that no
further purification is required.
Medical air
The monograph will also specify the
calibration gases for the gas analyzers.
Where references are provided (i.e. 2.5.24
for carbon dioxide Infrared analyzer),
these relate to the required technical
specification for the gas analyzer.
EUROPEAN PHARMACOPEIA (EP) MONOGRAPH FOR OXYGEN
DEFINITION
Content:
Minimum 99.5 per cent V/V of O 2
CHARACTER
Appearance:
Colorless gas
Solubility:
At 20 o C and at a pressure of
101kPa, 1 volume dissolves in
about 32 volumes of water
PRODUCTION
Medical oxygen
O 2
O 2 93%
Medical N 2
Oxygen is produced by a purification process followed by cryodistillation
of the ambient air
Carbon dioxide:
Maximum 300ppm V/V
determined using an Infrared
analyzer (2.5.24)
Carbon monoxide:
Maximum 5ppm V/V determined
using an Infrared analyzer (2.5.25)
Servomex sensing technology continues to meet the EP and USP
requirements for monitoring medical gases, providing a wide
range of solutions for impurity and assay measurements.
P14
Air, synthetic medicinal
N 2 97%
Water:
Maximum 67ppm V/V determined
using an electrolytic hygrometer
(2.5.28)
Assay:
Determine the concentration of
oxygen using a Paramagnetic
analyzer (2.5.27)
ANALYTE
Most cylinder filling plants have a manifold
system allowing the simultaneous filling of
multiple cylinders. In the case of a single
medicinal gas being filled into multiple
cylinders via a multi-cylinder manifold, the
gas from at least one cylinder from each
manifold filling cycle is tested for identity
and assay each time the cylinders are
changed. SERVOPRO MultiExact 4100
For plants where a single medicinal gas
is filled into cylinders one at a time, the
gas from at least one cylinder of each
uninterrupted filling cycle should be tested
for identity and assay. servomex.expert/multiexact4100
Air is classed as a single gas as long it is not
mixed using N 2 and O 2 . In the case of the
EP, when two or more gases are mixed to
produce medicinal gas, the gas from every
cylinder should be tested for identity and
assay of each component gas. For the USP,
the identity and assay of one gas less than
total component gases must be measured,
e.g. one of two gases or two of three gases.
When filling single gases, there must be a
dedicated manifold for each gas (e.g. an
oxygen-only manifold) and a dedicated
mixture manifold for two or more gases
(e.g. 50% N 2 O and 50% O 2 mixture for
analgesia). There are exceptions to this;
GAS MIXTURE
control procedures must be in place and
certified to prevent cross-contamination.
RECOMMENDED
SERVOMEX ANALYZERS
ASSAY OR
IMPURITY MEASUREMENT
TECHNOLOGY
SERVOPRO Chroma
servomex.expert/chroma
ACCEPTABLE
ACCEPTABLE
CONCENTRATION CONCENTRATION
(EP)
(USP/NF 3 )
O 2 Assay Paramagnetic 20.4-21.4% 19.5-23.5%
CO Impurity Infrared Gfx 1 <5ppm <10ppm
CO 2 Impurity Infrared Gfx <500ppm <500ppm
O 2 Assay Paramagnetic 21-22.5% N/A
1
O 2 Assay Paramagnetic >99.5% >99.0%
CO Impurity Infrared Gfx 1 <5ppm <10ppm
CO 2 Impurity Infrared Gfx 1 <300ppm <300ppm
O 2 Assay Paramagnetic 90-96% 90-96%
CO Impurity Infrared Gfx <5ppm <10ppm
CO 2 Impurity Infrared Gfx 1 <300ppm <300ppm
N 2 Assay TCD >99.5% >99.0%
1
CO Impurity Infrared Gfx <5ppm <10ppm
CO 2 Impurity Infrared Gfx <300ppm N/A
1
1
CO Impurity Infrared Gfx N/A <10ppm
CO 2 Impurity Infrared Gfx 1 N/A <300ppm
Helium CH 4 Impurity Infrared Gfx <50ppm N/A
Argon O 2 Impurity Paramagnetic Not O 22 N/A
N 2 O Assay Infrared Gfx >98% N/A
N 2 O Assay TCD N/A >98.0%
CO 2 Impurity TCD <300ppm N/A
Nitrous oxide
The detector tube is the measurement technology for impurities in the USP. Gas analyzers can be used as an alternative method if supported by validation tests.
For medical argon, Servomex provides a solution that confirms it is not oxygen before it is measured using gas chromatography.
3
The National Formulary (NF) provides standards for medicinal N 2 and 93% N 2 in the US.
1
2
Find out more about our Pharmacopeia-compliant medical gas
measurement solutions: servomex.expert/contact-us
P15
P3