Qvents Template

Risk Assessment Template for Process Water (Potable Water / Purified Water / WFI)

Type of Water	Potable / Purified / WFI
Source of Raw Water	Ground Water / Municipal Supply / Others
Briefly describe the Water system / Treatment

S. No.	Questions	Options	Answer
1.	Is Nitrates controlled in water by specification	Yes ¨ / No ¨ / Not sure ¨
2.	Can there be amines in water due to leaching from quarternary ammonium anion in the ion exchange resins	Yes ¨ / No ¨ / Not sure ¨
3.	Does Water purification process involve chloramine treatment which can leave chloramine residue in water	Yes ¨ / No ¨ / Not sure ¨
4.	Is there possibility of residual chlorine to be present in the water due to Chlorination for disinfection (f there a dichlorination process in the water treatment, possibility for residual chlorine to be present is practically NIL)	Yes ¨ / No ¨ / Not sure ¨
5.	Does Water treatment process involve Ozonisation	Yes ¨ / No ¨ / Not sure ¨

Risk assessment for Nitrosamines in Water
1.	Risk for Nitrosamines to be present in Water	High ¨ / Moderate ¨ / Minor ¨ / Nil ¨	· High if Chloramine residues are possible in water and amines are possible in water · Moderate If Nitrates are not present but controlled and amines are possible in water · Moderate if Ozone treatment is performed on water and amines are present in water. · Moderate if residual chlorine can be present in water along with amines and Nitrates are not controlled in water · Nil if amines are not possible in water.
· Note 1: Risk of Formation of Nitrosamines / NDSRIs due to Water in the drug product shall be evaluated in each product separately · Note 2: Specification control for Nitrites / Nitrosating agents / Amines in Water to be implemented based on the Nitrosamines and NDSRI Risk Assessment of Drug Products

Overall Risk Categorization & Actions

Based on the Nitrosamine Risk Assessment of Process water take actions as below..

Risk Category	Action
High	Identify the potential Nitrosamine impurity that can be present Monitor water for Nitrosamine impurity Initiate measures for mitigation of the nitrosamines in Process water Establish specification limits for the Nitrosamine impurity in the drug product and control. Continue monitoring the Nitrosamines in water and establish scientifically sound alert and action limits. Alert and action limit shall be useful for reviewing effectiveness of mitigation measures in Water and specification controls on drug product,
Moderate	Identify the potential Nitrosamine impurity that can be present Monitor water for Nitrosamine impurity Initiate measures for mitigation of the nitrosamines in Process water Monitor Nitrosamines in drug product batches If nitrosamine levels in the drug product are not more than 10% of the recommended Acceptable Intake (AI) limit, a formal specification limit is not needed in drug product. If nitrosamines exceed 10% but are still within the AI limit, specifications should be established for controlling the impurity in the drug product Continue monitoring the Nitrosamines in water and establish scientifically sound alert and action limits for water above which drug product batches will be tested for the Nitrosamines.
Minor	Identify the potential Nitrosamine impurity that can be present Evaluate water samples for Nitrosamine impurity and establish a trend If detectable amount of Nitrosamines are observed in water, continue to monitor Process Water for nitrosamine impurities. Monitor Nitrosamines in drug product batches If nitrosamine levels in the drug product are not more than 10% of the recommended Acceptable Intake (AI) limit, a formal specification limit is not needed in drug product. If nitrosamines exceed 10% but are still within the AI limit, specifications should be established for controlling the impurity in the drug product If during evaluation of water samples no detectable amount of Nitrosamines are observed in water, no regular monitoring of water for Nitrosamines is warranted. Or else continue monitoring the Nitrosamines in water and establish scientifically sound alert and action limits for water above which drug product batches will be tested for the Nitrosamines. Initiate measures for mitigation of the nitrosamines in Process water
Nil	Nil Risk Document the risk assessment with all supporting documents. No further evaluation of water samples for nitrosamines are necessary