SOP ON ESTABLISHMENT OF ALERT LIMIT AND ACTION LIMIT

SOP ON ESTABLISHMENT OF ALERT LIMIT AND ACTION LIMIT

PURPOSE: To lay down a procedure for the establishment of an Alert Limit and Action Limit.

SCOPE: This SOP applies to critical stages of the system, analytical test / Microbial test, online results regarding water system, process, product and environmental condition of clean room like Temperature, Relative Humidity etc. but limited to wherever cGMP Limits are applicable.

REFERENCE(S): In house

CROSS-REFERENCE DOCUMENTS:

• Documents and data control
• Training Programme And Management
• Preparation, Review, Approval, issuance & Retrieval of standard operating procedure
• SOP on Monitoring Temperature, Relative Humidity, and Pressure Difference
• Corrective Action and Preventive Action (CAPA)
• SOP on Investigations

ATTACHMENTS

DEFINITIONS:

• Alert limit: The alert limit is reached when the normal operating range of a critical parameter has been exceeded, indicating that corrective measures may need to be taken to prevent the action limit being reached.
• Action limit: The action limit is reached when the acceptance criteria of a critical parameter has been exceeded. Results outside these limits will require specific action and investigation.
• Design condition: Design condition relates to the specified range or accuracy of a controlled variable used by the designer as a basis for determining the performance requirements of an engineered system.
• Normal operating range: The range that the manufacturer selects as the acceptable values for a parameter during normal operations. This range must be within the operating range.
• Operating range: Operating range is the range of validated critical parameters within which acceptable products can be manufactured.

RESPONSIBILITY

1. QA-Executive / Designee

• Shall be responsible for co-ordinate, review and verifies the action limit and alert limit.

 2. User Department shall be responsibility for:

• To evaluating the criticality of process based on risk.
• To find the action and alert limits on the basis of calculation and average of obtained data.

3. QA-Head / designee

• Shall be Responsible for approved the proposed action and alert limit.

OTHER RESOURCES: MFR OF BURN RELIEF CREAM

PROCEDURE:

SAFETY/PRECAUTION/EHS:

• Environmental monitoring programs may have alert/action limits established based on review of historical data.
• Once alert and/or action limits have been established, they should be periodically reviewed as part of routine trend analysis. They should be revised to reflect improvements, advances in technology, changes in use patterns, or other changes.
• Alert and Action Limits should be measures designed to signal potential or actual drift from historical or design performance characteristics.
• Alert and Action Limits should not be extension of product specifications, but are intended to standard changes so that corrective action may be taken before product quality is adversely affected.
• The application of alert and/ or action limits should be following written procedures and be employed in a consistent, non-arbitrary manner.
• To create consistency in treatment of alert and/or action limits, logical investigatory and/or corrective action steps should be followed.

Alert limit:

• When limit of established normal operating range of critical parameter(s) shown a potential drift from normal operating conditions.
• Alert Limit is usually based upon historical information gained from the routine operation of the process in a specific controlled environment, analysis and system.
• Immediate inform to department head and QA head and take prompt follow-up that should be including sampling plan modification.
• There no documented justification required for proposed corrective action.
• Exceeding of Alert Limit usually lead to alerting of personnel involve in operating, analysis and monitoring.
• When exceeding of alert limit then operating personnel and QA should be required additional monitoring system with more intense.
• The Normal Distribution Approach used to establish the Alert Limit and may be calculated on the basis of following formula.
•   Alert Limit = Average + 2 X SD …………………… equation (1)

Action Limit:

• When the limit of normal operating range of critical parameter(s) of validated system is exceeded it should be requires immediate follow-up and with corrective action.
• Immediate inform to department head and QA head and take prompt a documented follow-up and investigation.
• When exceeding the Action Limit, justification required for proposed corrective action and preventing.
• The Normal Distribution Approach has been used to establish the Action Limit and may be calculated on the basis of following formula.
•          Action Limit = Average + 3 X SD………………… equation (2)
• When the specified limit of a controlled environment, analysis report and system is exceeded, then deviation should be raised by concern department with proposed corrective action and preventive action as per CAPA SOP.
• Based on the review of the investigation data and testing results of system operating range, the significance of the specified limit being exceeded and the acceptability of the operations or products processed under that condition may be established.
• The information should be collect by investigator and evaluate the information’s and based on the information assign the route cause, especially when the Action Limit is exceeded.
• Any investigation and the rationale for the course of action should be documented and included as part of the overall quality management system.
• The environmental control program includes an appropriate limit of identification of the flora obtained from sampling.
• System operating range: The relationships between design conditions, operating condition and validated acceptance criteria are given in below figure.

Acceptance Criteria:

• Alert Limit and Action Limit should be establish based on the result of analysis of process, product, controlled environment, system and specific critical parameter which directly and or indirectly affect total attributes.
• Water System: On completion of Phase – I study a provisional Alert Limit and Action Limit should be established & on completion of Phase – II studies, Alert Limit and Action Limit for microbial count and other critical parameter(s) should be revised as per equation 1 and 2. Subsequent to successful completion of the Phase – III studies, the Alert Limit and Action Limit for critical parameter(s) shall be again revised as per equation 1 and 2, based on the completion data obtained during phase – I, Phase – II and Phase – III.
• Microbiological environmental monitoring of clean area and core functional area: A provisional Alert Limit and Action Limit should be established based on the data obtained from initial environment monitoring studies and limits should be revised as per equations 1 and 2, based on sufficient data collection. When the specified microbial limit of a controlled environment, the limit of the critical parameters of the water system, and the analysis of the product process, and system are exceeded, a documentation review and investigation should take place as per the investigation SOP.
• Data required: Alert Limit and Action Limit should be established based on at least one month’s data of test results. Test result data record as mentioned in Attachment-I
• Alert Limit and Action Limit shall be prepared in soft copy as per Attachment-I by the user department.

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