Water Technologies & Solutions

application note

best practice for analyzing compendia water samples on the

Sievers* M9 Total Organic Carbon (TOC) Analyzer with conductivity
This document is intended to provide best practice
guidance on how to measure simultaneous TOC and
conductivity of compendia water samples on the
Sievers M9 TOC Analyzer with conductivity.
sampling
The critical components for successful implementation
of compendia water testing on the M9 with conductivity
are:
1. Good sampling technique
2. Use of a Dual Use Conductivity and TOC (DUCT)
vial
guidance for both TOC and conductivity testing on the
M9 is a minimum of four repetitions with one reject.
Stage 1 conductivity testing uses raw conductivity and
temperature data so selecting a compensating
algorithm is not required. The M9 will give a raw
conductivity value, a temperature value, and a
temperature compensated value. For compendia
water samples, the raw conductivity value and
temperature should be reported. Acceptance criteria
should be determined by Table 1 in USP <645>, Stage
1 – Temperature and Conductivity Requirements.
Based on the measured temperature, the
corresponding conductivity value is the limit for
compendia water samples. 1

According to USP <645>, “Stage 1 conductivity may be

performed offline in a suitable container.” A suitable
1

container for simultaneous testing is one that does not

contribute either TOC or conductivity when in contact
with the sample. Sievers DUCT vials, caps, and septa
have demonstrated that with good sampling technique,
there is no significant TOC or conductivity contribution
for up to five days.
2,3

Sievers DUCT vials are cleaned and certified to less Figure 1: Method Conditions
than 10 ppb TOC, eliminating the need for any vial pre-
Set the acid and oxidizer flow rates for compendia
rinse steps. Best practices for sampling are:
water samples below 500 ppb TOC to 1.0 µL/min acid
1. Do not rinse vials prior to use. and 0.0 µL/min oxidizer. These flow rates ensure
complete carbon oxidation in the UV reactor while
2. To avoid contamination, do not touch the inside
avoiding over-oxidation of the sample.
of the vial, cap, or septa.
An additional method consideration is the use of the
3. Fill the DUCT vial once, completely full, with no
optional Inorganic Carbon Remover (ICR). If the IC
headspace and avoid turbulent flow when
measurement is approximately ten times greater in
filling the vial.
magnitude or more than the TOC measurement, use
4. Immediately cap the vial. of the ICR is recommended as best practice to
5. Do not reuse DUCT vials. improve TOC measurement stability and precision. 4,5

In the event of a Stage I conductivity failure, proceed

instrument method conditions to Stage II testing per USP <645>.

When analyzing compendia water samples on the M9, it

is important to evaluate multiple repetitions of the
determining frequency of verification
sample for statistical robustness and for additional Challenging the instrument and method with known
measurement stability confidence. Best practice standards provides confidence in each measurement.
Verify the nominal performance of the method on the
instrument by using TOC system suitability and
conductivity verification standards on a frequency
determined via risk assessment. Standards passing the
acceptance criteria give a high degree of assurance that
the analysis of unknown water samples complies with
the compendia requirements for pharmaceutical grade
bulk water. 1,6
The compendia specify the periodic use of conductivity
verification and system suitability standards as a
method verification, though the frequency of
verification is not specified. Frequency should be
determined by assessing the risk and potential impact
unique to each process. Risk management requires
clearly defining and assessing all variables and their
impact to the process. Factors to consider include
frequency of use, sample time, risk of system suitability
or verification failures, likelihood of out-of-
specification (OOS) results, and/or time constraints. As
specific frequencies are not prescribed by USP <643>
and <645>, it is the responsibility of each facility to have
robust processes and procedures that manage risk
unique to the process. It is important to establish the
use of conductivity verification and system suitability
standards on a practical and defensible frequency while
simultaneously meeting minimum requirements of
USP <643> and <645>.
TOC system suitability standards verify the relative
recovery capability of the instrument at the compendia
upper limit of 500 ppb TOC. System suitability ensures
suitable recovery of TOC, providing confidence in the
ability to analyze unknown water samples. The
conductivity verification standard verifies the accuracy
of conductivity measurements taken on the M9.
Conductivity verification standards performed at a
justified frequency ensure accurate measurements of
unknown water samples while meeting compendia
requirements.
To limit variation as much as possible, it is
recommended to use Sievers standards and vials from
SUEZ as consistent and certified consumables. It is best
practice to use the Sievers system suitability and
conductivity verification standards shown in Table 1.
When using the consumables in Table 1, companies
can take advantage of SUEZ’s OOS investigation
support. In the event of a sample, system suitability or
verification failure, the SUEZ quality team will
troubleshoot and thoroughly investigate inhouse
variables and onsite instrument performance,
discussing the findings in the failure analysis report.
Table 1: Best Practice Consumables
Product Description Part Number
System Suitability Set STD 31004-01
100µS/cm KCl Conductivity STD 77050-01
Verification
DUCT Vials for Dual TOC and HMI 77500-01
Conductivity Analysis
Lastly, it is best practice to always leave the
instrument with water in the flow path. Following the
last standard, a syringe flush should be performed
using DI or MilliQ water. This will purge the
instrument of all previous sample and replace it with
water.
troubleshooting/maintenance
Due to the method sensitivity and the low-level
acceptance criteria for offline Stage 1 conductivity
testing, many users have a dedicated Sievers M9 TOC
Analyzer with conductivity for offline TOC and
conductivity measurements. An M9 used for both
7
compendia and non-compendia testing (e.g., cleaning
validation samples) may require additional steps to
minimize carry-over between the two sample types.
These steps are unique to the types of non-
compendia samples being analyzed. For more
information on such precautions please see Tech Tip
UPW 07-10. Instrumentation should be maintained
8
and verified per our operating and maintenance
manual for optimal performance.
conclusion
Implementing proper sampling technique, method
conditions, and justified verification frequencies will
ensure a high degree of confidence in TOC and
conductivity measurements using the Sievers M9
Analyzer. Execution of best practices outlined in this
document will allow for simultaneous analysis of TOC
and conductivity while meeting compendia specified
requirements.
References
1. USP <645> Water Conductivity. Retrieved February 14, 2019 from
https://hmc.usp.org/sites/default/files/documents/HMC/GCs-
Pdfs/c645.pdf
2. Sievers Lean Lab: Simultaneous Stage 1 Conductivity and TOC Lab
Testing of Pharmaceutical Water (300 40030). Retrieved February 14,
2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Applic
ation%20Notes_Cust/Americas/English/ANai_300_40030_EN.pdf
300 00124 EN Rev. C
3. DUCT Vial Performance and Stability (300 00297). Retrieved February 14,
2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Technica
l%20Bulletins_Cust/Americas/English/TBai_300_00297_EN.pdf
4. Reserve Sample Bottles for Conductivity and TOC (300 00299). Retrieved
February 14, 2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Technica
l%20Bulletins_Cust/Americas/English/TBai_300_00299_EN.pdf
5. Sievers Inorganic Carbon Remover (ICR) (300 00109). Retrieved February
14, 2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Applicati
on%20Notes_Cust/Americas/English/ANai_300_00109_EN.pdf
6. USP <643> Total Organic Carbon. Retrieved July 25, 2019 from
https://hmc.usp.org/sites/default/files/documents/HMC/GCs-
Pdfs/c643.pdf
7. Low Level Linearity Conductivity Study on the Sievers M9 TOC Analyzer
(300 00339). Retrieved February 14, 2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Applicati
on%20Notes_Cust/Americas/English/ANai_300_00339_EN.pdf
8. UPW 07-10 Multiple Products Biological Contamination (800 19025)
Retrieved February 14, 2019 from
https://www.suezwatertechnologies.com/kcpguest/documents/Technica
l%20Bulletins_Cust/Americas/English/ai_UPW_07-10_EN.pdf

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