Sampling, Testing and Release of Water and Pure Steam

SOP for Sampling, Testing and Release of Pharmaceutical Water and Pure Steam in Pharmaceutical Industries.

SOP Covers below points:

• Types of Water Samples
• Water Sampling Procedure
  • Water Sampling precautions
  • Water Sampling quantity
• Testing of Water
• Release of Water
• Trends of Water analysis data
• Water Sampling Points
• Protocol for purified water and water for injection

1.0 OBJECTIVE :

• To lay down a procedure for sampling, testing and release of Potable Water, Purified Water, Water for Injection and Pure Steam.

2.0 SCOPE :

• This SOP is applicable for sampling of water from various points for chemical testing and release of water and pure steam.

3.0 RESPONSIBILITY :

• The QC Staff shall be responsible for:
  • To follow the procedure of sampling, testing and release of various type of water.
  • Maintenance of documents
• The Individual Head shall be responsible for:
  • To train the subordinates of that department to follow the SOP.
  • To checking of documents.
• The Head QC shall be responsible for:
  • Ensuring compliance of the SOP
• The Head QA shall be responsible for:
  • Documents review

4.0 ACCOUNTABILITY:

• QC Head and Head QA shall be accountable for this SOP.

5.0 PROCEDURE :

5.1 Type of Water Samples

• Water for Injection
• Pure Steam
• Purified Water
• Potable Water
• DM Water

5.2 Sampling of Water

• Apparatus required
  • Screw capped glass bottles.
  • Amber colored air tight glass bottles for TOC
• Glassware preparation
  • Wash the sampling bottles thoroughly with water for injection.
  • For TOC analysis sampling bottles are then treated with nitric acid that will remove organic matter.
  • Use milli-Q/ultra pure type-I water for the final rinse of the sampling bottles.
• Sampling Quantity
  • Sampling quantity for Pure Steam for all sampling points.
    • Sampling quantity for chemical analysis: 500 ml
    • Sampling quantity for TOC analysis: 125 ml
  • Sampling quantity for purified water and water for injection for all sampling points except sampling points of storage tank and return line: 1000 ml
    • Sampling quantity for chemical analysis: 1000 ml
  • Sampling quantity for purified water and water for injection for sampling points of storage tank and return line: 1125 ml
    • Sampling quantity for chemical analysis: 1000 ml
    • Sampling quantity for TOC analysis: 125 ml
  • Sampling quantity for Raw Water and DM Water: 1250 ml.
• Sampling procedure of water
  • Wear hand gloves and remove the cap from bottle just prior to obtaining a sample.
  • Avoid direct contact of hand to mouth of bottle.
  • Open the sampling valve and drain the water to be tested for about 1 to 2 minutes by opening the valve fully.
  • Rinse the sampling bottle by water to be tested.
• Sample for chemical analysis
  • Collect the water from all sampling points to be tested in glass bottle.
  • Cap the bottle.
• Sample for TOC analysis
  • Collect carefully the water to be tested about 125 ml in amber coloured tight Glass bottle with minimum head space.
  • Keep the Stopper immediately with no head space.
  • Examine it with minimum delay.
• The points which are difficult to collect sample by QC Chemist, sample of that point shall be collected with the help of user department or Engineering Department.
• Extreme precaution when obtaining samples for TOC analysis.
  • Sampling bottle must be filled to the top (no head space) with tight fitting stopper.
  • Take care to avoid contamination of the sample with organic substances.
  • As far as possible, try to analyze sample immediately.
  • Storage should be avoided. This is due to oxidation or bacterial activity.
  • Sample should be protected from sunlight and atmospheric oxygen.
  • Sample should be kept at 4°C.
  • In instances, where analysis cannot be performed within two hours from the time of sampling, the sample is acidified to pH lower than 2 by hydrochloric acid.
• Sample from storage tank and return line of Purified water, and Storage Tank and return line for Water for Injection shall be sampled and analyzed daily and all other User’s points shall be analyzed on rotation basis.
• The sampling of water shall not be carried out on weekly off and on holidays. However the sampling points of water to be sampled, falling on weekly off and Holidays, shall be sampled and analyzed on previous day.
• In case of changes in the weekly off, sampling points of water to be sampled in current weekly off shall be replaced with that of new weekly off.
  • For e.g. Changes in weekly off from Sunday to Monday, then Monday sampling points shall be covered in Sunday.
• Perform the sampling of various type of water as per sampling plan.
• Affix the label on the bottle with details such as;

• Bring the sample to Quality Control Department.

5.3 Testing Of Water

• All tests mentioned in the specification except TOC test will be performed for the sample collected from all sampling points except sampling points of storage tanks and return lines.
• Record the result in respective protocol.
• The test TOC will be performed only for the sample collected from sampling points of storage tanks and return lines as per specification. Rest of all other sampling points will not be tested for TOC test.
• Perform the sampling of purified water, water for injection and pure steam as sampling plan.
• Testing should be performed within 2 hours from collection of samples, alternatively keep the samples in refrigerator at 2 – 8°C and analyze within 4 hours. (Allow the sample to cool room temperature before analyzing).
• In case of instrument breakdown, shortage of gases or other specific reason, alternative test shall be performed in urgency such as;

Sr. No.	Test	Alternative test
1.	Total Organic Carbon	Oxidisable substances

• In case of unavoidable circumstances, the testing parameter shall be performed in sister concern unit or other competent authorized testing laboratory.

5.4 Release of Water

• Water shall be released daily on the basis of result of Chemical Test and Bacterial Endotoxin Test.
• If any water quality parameter will be outside of the acceptance limits, consult with Department Head. The same shall be informed to Concern Department and Engineering Department.
• In case of instrument breakdown or shortage of gases, water shall be released on the basis of results of alternative test or on the basis of results of test(s) performed at sister concern unit or other competent authorized testing laboratory.
• Testing is performed by the assigned analyst and the results are entered after completion of testing in ERP system.
• Sample is reviewed by the reviewer and released.
• Release of water shall be informed to respective department as per Annexure No. 03.
• Print out of the report will be taken as and when required.
• Microbiological Limit test will be released after fifth day of testing.

5.5 Alert limit and action limit – TOC

• Alert limit and action limit are decided on the basis of water validation analytical data.
• Alert limit and action limit for TOC is as follows;

Samples	Alert limit	Action limit	Acceptance criteria
Water for injection	Not more than 0.3 mg/liter	Not more than 0.35 mg/liter	Not more than 0.5 mg/liter
Pure steam	Not more than 0.3 mg/liter	Not more than 0.35 mg/liter	Not more than 0.5 mg/liter
Purified water	Not more than 0.4 mg/liter	Not more than 0.45 mg/liter	Not more than 0.5 mg/liter

5.6 Sanitization of water system is carried out by engineering team on every weekly off irrespective of holidays.

5.7 Purified water and water for injection will be sampled after sanitization to check the pH from the return line of both the plants. Record shall be maintained by Engineering department.

5.8 Sample received from production

• At the time of manufacturing, production chemist will collect the sample of water for injection from the manufacturing tank and send to Quality Control for analysis with “INTIMATION SLIP FOR WATER SAMPLE”.
• The same water for injection shall be released on the basis of result of Chemical Test and Bacterial Endotoxin Test.
• If any out of specification is observed, inform to Concern Department.
• The signed Intimation Slip with all results shall be returned to Production Department.
• The complete analysis record shall be maintained by Quality Control Department

5.9 Trends of Water analysis data

• Trend of pH test, conductivity test and TOC test shall be prepared for Purified water and Water for injection.
• Frequency for trend charts preparation
  • Prepare monthly trends for water analysis data of all sampling points.
  • Prepare yearly trends for water analysis data of daily sampling points.
  • Prepare trends before 10^th working day of subsequent month.

5.10 Colors Coding

• Follow the colors code for different series in a trend chart as below:

Parameters	Colour code
Maximum counts	Green
Minimum counts	Blue
Alert limits	Pink
Action limits	Red
Recommended Limit	Brown
Other Contents	Black

5.11 Interpretations:

• Trends charts shall be interpreted as below:
  • Whether there is any specific / adverse trend or out of trend, out of specifications of trend data generated. Whether the data is well within the acceptance criteria.

5.12 Water sampling points:

• Sampling points of Water for injection

• Sampling points for Purified Water

• Sampling points for Raw Water

• Sampling points for demineralization water

• Sampling points for pure steam

 6.0 ABBREVIATIONS:

QA	Quality Assurance
SOP	Standard operating Procedure
DM	De mineralized
IPA	Isopropyl alcohol
NMT	Not more than
WFI	Water for injection
PW	Purified Water
PIC/S	Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme.
MHRA	Medicines and Healthcare products Regulatory Agency
USP	United State Pharmacopeia
BP	British Pharmacopeia
IP	Indian Pharmacopeia

7.0 ANNEXURES:

Annex. No.	Title
01	Protocol for purified water
02	Protocol for water for injection
03	Water Release Slip

8.0 SOP REFERENCES

• MHRA – Rules and Guidance for Pharmaceutical Manufacturers and Distributors – 2017.
• USP 36, NF 31 – Water for Pharmaceutical purposes <1231>
• BP 2018 – Monograph of Purified Water and Water for Injection
• IP 2014 – Monograph of Purified Water and Water for Injection

END OF THE SOP

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ANNEXURES :

Annex. No. 01 Protocol for purified water

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Annex. No. 02 Protocol for water for injection

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Annex. No. 03 Water Release Slip

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