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Conductivity

and TOC Sampling


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Standard Operating Procedure (SOP)

Analytical Instruments

www.geinstruments.com
300 00314 Rev. A

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

Table of Contents
CONDUCTIVITY AND TOC SAMPLING SOP
FOR PHARMACEUTICAL GRADE ULTRAPURE WATER
1 PURPOSE .............................................................................................................................................................. 3
2 SCOPE .................................................................................................................................................................... 3
3 RESPONSIBILITIES............................................................................................................................................. 3
4 DEFINITIONS ....................................................................................................................................................... 3
5 ENVIRONMENTAL, HEALTH AND SAFETY ............................................................................................... 3
6 EQUIPMENT AND MATERIALS ...................................................................................................................... 3
7 PROCEDURE ........................................................................................................................................................ 4
8 SUPPORTING DATA .......................................................................................................................................... 6
9 REFERENCES ....................................................................................................................................................... 7

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300 00314 Rev. A


GE Analytical Instruments 2015

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

CONDUCTIVITY AND TOC SAMPLING SOP


FOR PHARMACEUTICAL GRADE ULTRAPURE WATER
1 PURPOSE
1.1. This procedure describes best practices for collecting and storing ultrapure water samples to be tested for
conductivity and total organic carbon using a GE Sievers M9 Series Analyzer.
2 SCOPE
2.1. This procedure covers sampling and storing primary and reserve samples collected from sample ports on
a purified water (PW), water for injection (WFI), or other ultrapure water system.
3 RESPONSIBILITIES
3.1. It is the responsibility of the analyst to follow this procedure, all required support SOPs relevant to this
procedure, and to perform the tasks in accordance with GMP.
3.2. It is the responsibility of the functional team manager to provide the relevant training and materials for
this procedure.
4 DEFINITIONS
4.1. Pure or Ultrapure Water = Deionized (DI) Water, Milli-Q Water, Reverse Osmosis (RO), Purified Water (PW),
Water for Injection (WFI), or other suitably purified water.
4.2. DUCT vials = Dual Use Conductivity and TOC vials supplied by GE Analytical Instruments.
4.3. PP = Polypropylene
5 ENVIRONMENTAL, HEALTH AND SAFETY
5.1. Wear required PPE (personal protective equipment) that is suitable or necessary to perform the task.
5.2. Refer to the relevant MSDS (material safety data sheets) for any chemicals.
5.3. Refer to the operating instructions for the equipment and instrumentation.
5.4. Perform a risk assessment as required by local/site rules.
5.5. Observe all warning and hazard signs for the equipment, chemicals and area.
5.6. Dispose of waste in accordance with site, local and national guidelines and regulations.
5.7. Consider whether materials are corrosive, toxic, flammable and if any incompatibilities exist with the
surrounding environment.
5.8. Key risks: Sample water temperature for hot WFI water systems.
6 Equipment and Materials
6.1. Sievers M9 Series TOC Analyzer supplied by GE Analytical Instruments with optional conductivity feature
installed.
6.2. Routine sample containers: Glass DUCT vials (certified low TOC/Conductivity) supplied by GE Analytical
Instruments. Part number: HMI 77500-01 (30 vials).

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GE Analytical Instruments 2015

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

6.3. Reserve sample containers: 250mL Thermo Scientific Nalgene or Cole-Parmer polypropylene containers.
Thermo Scientific Nalgene PP bottle part number: 2105-0008 (12 pk). Cole Parmer brand PP bottle part
number: 06045-62 (12 pk).
7 Procedure
7.1. Information
7.1.1. DUCT vial samples are taken for the purpose of performing TOC and/or USP Stage 1 conductivity as
described in the current USP monograph, sections <643> and <645>. This procedure may also be
used to sample water for equivalent testing as described in the European, Japanese, Chinese,
Korean, or other harmonized pharmacopeias.
7.1.2. Reserve sample containers are used to collect sufficient sample from a representative sample
location to complete conductivity stage 2 or additional TOC analyses should an out of specification
result occur. Reserve samples may be taken at each point of use or a location that is
representative of the water system as a whole. This will typically be a worst-case location either
based on past data or a measurement point on the return loop after all points of use, but before the
loop water storage tank. A risk assessment may be necessary to determine the most suitable
sampling location.
7.2. Sampling Area Check
7.2.1. Check the sampling point and sampling area is suitable for sampling.
7.2.2. Ensure that there is minimal activity at the time of sampling to minimize risk of contaminating
samples such as construction, maintenance, or chemical usage.
7.2.3. If sample points are routinely sanitized with alcohol, note that alcohols contain high concentrations
of organic carbon and may contaminate samples. Any sanitizer containing organic carbon should
be allowed to fully evaporate from the port and sample port flush times may need to be increased.
7.3. Sample Order
7.3.1. Samples should be taken in the following order/sequence (TOC and conductivity will be measured
from the same vial or reserve container)
7.3.1.1. Other samples such as Bioburden or Endotoxin
7.3.1.2. Conductivity and TOC samples
7.3.1.3. Conductivity and TOC reserve sample(s)
7.4. Sample Point Preparation
7.4.1. The sample point should be flushed by opening the sample valve and allowing water to flush
for a minimum of 10 seconds. Note that a flush of up to 2 minutes may be necessary if organic
sanitizing agents are used on or near the sample port.
7.4.2. After flushing, reduce the sample port flow to avoid splashing or turbulent flow that may
contaminate the sample with atmospheric carbon dioxide.
7.5. DUCT Vial Sampling
7.5.1. Do not rinse vials prior to use.

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300 00314 Rev. A


GE Analytical Instruments 2015

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

7.5.2. The aim of a robust sampling procedure is to minimize carbon dioxide diffusing into the sample
once the water has exited the sample port
7.5.3. Avoid splashing or highly turbulent flow when filling the vial
7.5.4. Avoid re-using DUCT vials or DUCT vial caps and septa as there is a possibility that carbon dioxide
can permeate through pierced septa and increase conductivity
7.5.5. To avoid contamination, avoid touching the inside of the vial or cap/septa.
7.5.6. Fill the DUCT vial to the top of the vial to minimize headspace as carbon dioxide can dissolve into
the sample and increase conductivity. Do not overfill the vial. A properly filled vial will be full, but
will not have a curved meniscus of water above the top of the vial.
7.5.7. Screw the cap by hand onto the vial immediately after sampling. Do not overtighten.
7.6. Reserve Container Sampling
7.6.1. Rinse the container 3 times with the sample water prior to filling.
7.6.2. The aim of a robust sampling procedure is to minimize carbon dioxide diffusing into the sample
once the water has exited the sample port
7.6.3. Avoid splashing or highly turbulent flow when filling the container
7.6.4. To avoid contamination, avoid touching the inside of the container or cap
7.6.5. Fill the container to the top to minimize headspace
7.6.6. Screw the cap by hand onto the reserve sample container immediately after sampling
7.7. Sample Storage
7.7.1. If required, store samples up to 5 days from time of sampling (for DUCT vials) and up to 30 days (for
reserve containers)
7.7.2. Samples may be stored between 4 and 25 C. Avoid significant temperature cycling (if stored cold,
do not return samples to cold storage after they have been warmed)
7.7.3. Allow samples to warm to room temperature (approximately 18-25 C (64-77 F) prior to analysis
7.8. Analysis
7.8.1. Analyze samples for TOC and/or conductivity as required within 5 days. Samples stored in reserve
containers can be analyzed for TOC or conductivity for up to 30 days (see 8.2).

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GE Analytical Instruments 2015

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

8 SUPPORTING DATA
8.1. The following charts show the TOC and conductivity stability of various reserve sample containers after
one and five days of storage at room temperature (22 C/72 F). This data supports the use of
polypropylene (PP) containers for reserve sampling.

8.2. The following charts show the TOC and conductivity stability of reserve sample containers from two
separate manufacturing lots from the same manufacturer, and two manufacturers polypropylene
containers at one, five, and thirty days. Based on this data, samples in the recommended reserve
containers may be stored for up to 30 days at 4- 25 C (39-77 F).

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300 00314 Rev. A


GE Analytical Instruments 2015

Conductivity and TOC Sampling SOP


for Pharmaceutical Grade Ultrapure Water

8.3. The following chart shows that DUCT vials contribute equal or less TOC contamination to a sample than
the cleanest available certified low TOC vial commercially available (GE Part Number: HMI 90606).

20.0

TOC (ppb)

15.0
TOC Vials

10.0

DUCT Vials
5.0
0.0
0 hrs

24 hrs

48 hrs
96 hrs
Storage Time

10 days

8.4. The following chart shows the conductivity stability of DUCT vials compared to typical glass TOC vials.
Typical glass vials exceed pharmacopeia limits due to contamination within minutes, while DUCT vials are
stable for up to 10 days. In glass vials, this contamination is due to both exposure to atmospheric carbon
dioxide and sodium leaching from the glass surface.

Conductivity (S/cm)

5.0
4.0
3.0
TOC Vials

2.0

DUCT Vials

1.0
0.0
0 hrs

24 hrs

48 hrs
96 hrs
Storage Time

10 days

9 REFERENCES
9.1. Data Report: Duct Vial Performance and Stability. GE Document #300 00297 Rev A.
9.2. Test Report: Reserve Sample Bottles for Conductivity and TOC. GE Document #300 00299 Rev A.

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300 00314 Rev. A


GE Analytical Instruments 2015