There are no limits for Endotoxins in Purified Water as per USP and EP (Ph.Eur). However the EMA (European Medicines Agency) Guideline for Quality of Water for Pharmaceutical use require that Purified Water is to be used in the manufacture of active substances intended for use in parenteral products. The EMA guidance also specifies that appropriate specifications for endotoxins be set for the active substance intended to be used in parenteral products. The WHO GMP Guidance Water for pharmaceutical use (Annexure 3: TRS 970), also suggest that production, storage and distribution of water should have controls for endotoxins where appropriate considering the properties of use. The WHO guideline for Good Manufacturing Practices for Active Pharmaceutical Ingredients (Annexure 2; TRS 957, Clause 4.34) specifies water used in the final isolation and purification of active substances intended to be used for sterile finished products should be monitored and controlled for microbial counts and endotoxins. Accordingly, it will be prudent to monitor Endotoxins in Purified Water during qualifications of the water system, if the water is used in the production of active substances used in parenteral and sterile / injectable products. Purified Water shall also be monitored and trended for Endotoxins in the quarterly Water Trend Analysis reports. Typical limits applied for Endotoxins in Purified Water could be 0.25IU/ml, same as that for Water for Injection (WFI).
Reference:
1. Guideline on the quality of water for pharmaceutical use (EMA).
2. Annex 2 WHO good manufacturing practices for active pharmaceutical ingredients
3. Good manufacturing practices: Water for pharmaceutical use (Annexure 3: TRS 970)
There are no limits for Endotoxins in Purified Water as per USP and EP (Ph.Eur). However the EMA (European Medicines Agency) Guideline for Quality of Water for Pharmaceutical use require that Purified Water is to be used in the manufacture of active substances intended for use in parenteral products. The EMA guidance also specifies that appropriate specifications for endotoxins be set for the active substance intended to be used in parenteral products. The WHO GMP Guidance Water for pharmaceutical use (Annexure 3: TRS 970), also suggest that production, storage and distribution of water should have controls for endotoxins where appropriate considering the properties of use. The WHO guideline for Good Manufacturing Practices for Active Pharmaceutical Ingredients (Annexure 2; TRS 957, Clause 4.34) specifies water used in the final isolation and purification of active substances intended to be used for sterile finished products should be monitored and controlled for microbial counts and endotoxins. Accordingly, it will be prudent to monitor Endotoxins in Purified Water during qualifications of the water system, if the water is used in the production of active substances used in parenteral and sterile / injectable products. Purified Water shall also be monitored and trended for Endotoxins in the quarterly Water Trend Analysis reports. Typical limits applied for Endotoxins in Purified Water could be 0.25IU/ml, same as that for Water for Injection (WFI).
Reference:
1. Guideline on the quality of water for pharmaceutical use (EMA).
2. Annex 2 WHO good manufacturing practices for active pharmaceutical ingredients
3. Good manufacturing practices: Water for pharmaceutical use (Annexure 3: TRS 970)
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