List Of SOPs

1.0 PURPOSE

The Purpose of this Standard Operating Procedure is to provide guideline for Validation of Purified Water Generation and Distribution System.

2.0 SCOPE

This Standard Operating Procedure is applicable to Purified Water Generation and Distribution Systems installed in Utility Area

5.0 PROCEDURE

5.1 Introduction

5.1.1 Qualification focuses on those aspects that directly affects water quality in a direct impact system, while commissioning ensures that the system is fully operational, robust, and challenged from an engineering perspective (paying close attention to quality and safety aspects); important concepts include:

Significance of commissioning and qualification in the validation life cycle
Boundary limits of the direct impact water system
Indirect and no impact systems associated with direct impact water system
Impact assessment of process steps and / or components
Critical and non-critical components of a process step
Critical quality attributes and critical process operating parameters
Project scope activities associated with qualification of water systems

5.1.2 This SOP addresses compliance with pharmaceutical regulations and guidelines for water systems, and considers new systems and extensions to existing ones and existing validated systems to be maintained.

Benefits and attributes of this policy include:

Listing of URS, System Design, DQ, IQ, OQ and PQ
Critical Quality Attributes measure and monitor quality, while critical process operating parameters are established.
“Risk Based” approach to the qualification of direct impact system.
Efficient and cost effective use of resources and minimum overlap in validation.
Effective focus on objectives and deliverables through the entire life cycle.

5.1.3 A validation program qualifies and documents the design, installation, operation, and performance of the system. Validation is accomplished through the use of a structured, documented process as individual protocols for each phase, or integrated into variations of a DQ/IQ/OQ/PQ combined document format.

5.2 User requirement Specifications (URS)

5.2.1 The URS should be developed during the conceptual design phase and must be reviewed and updated throughout the lifecycle of the project.

5.2.2 URS describes the overall capability and capacity of the water system. This specification provide the critical quality attributes, including water quality specifications, such as Total Organic Carbon (TOC), conductivity, microbial and microbial endotoxin, etc.

5.2.3 The identification of system design requirements may be directly influenced by feed water quality and seasonal influences and intended purpose.

5.2.4 Feed water quality should be defined and included in system design document.

5.2.5 The URS specifies what the direct impact water system is required to do. Items recorded in this specification should be tested and verified during PQ. Testing requirement should be specified. Following Requirements shall be considered while defining User Requirement Specifications for Water Purification System (Not Limited To):

5.2.5.1 Process Requirements

Consider capacity of water system based on quantity of water requirement, Peak load which includes number of users, use points and usage priorities, as applicable.
Consider what water quality the system needs to produce.
Consider variations in incoming water quality.
Consider available support utilities (incoming water, compressed air, steam, power, drainage, etc.) up front.
Space layout where system will be installed – considering access to normal operation and maintenance activities.
Sanitization of water system.
Distribution system requirement (Ambient, Hot and Cold loop)

5.2.5.2 Mechanical Requirements

Piping standard(s) like material of construction and surface finish
Usage of sanitary components (valves, pumps including standby pump, tri-clamp connections, etc.)
Vent filter requirement
Spray ball requirement with provision to ensure spray ball type need to be considered (dynamic / static)
Type of storage vessel required like jacketed tank for sanitization
Welding requirements
Air break in floor drains to prevent contamination
Piping slope requirements
Piping dead-leg requirements (Dead leg should not significantly exceed 3 times of the branch diameter as measured from the Inner diameter pipe wall to center line of point of use valve)
System drain ability
Inline monitoring requirements
Sampling location
Flow rate
Calculations for Minimum velocity maintained in return loop considering user points in operation at a time.
The distribution loop shall be able to deliver 95 L / min (25 gpm) at three points of use, while maintaining 2.8 kg/ sqcm (40 psig) at the spray nozzle inlet (return to vessel) during normal operation (Ref. ISPE Good practice Guide: Approaches to Commissioning and Qualification of Pharmaceutical water and Steam System).
Requirements for stand by pump and spare parts

5.2.5.3 Automation Requirements

Requirement of automation hardware. E.g. PLC /HMI
Software Design Specification (SDS)
Controller/HMI interface with existing plant automation
Alarm/interlock requirements
Required automation for usage of user point at a time
Data storage requirement – Existing / Historical
Requirement of other interfaces
21 CFR Part 11 Compliance as applicable
Online Monitoring Requirement in generation and distribution system like flow meter, PH meter, conductivity meter, temperature sensor, ORP meter, level transmitters, intensity meter in case of UV etc.
On-line “end of loop” instrument measurements for chemical attributes such as TOC and conductivity proves to provide accurate depictions of water quality at water use points in the distribution system.

5.2.5.4 Validation Requirements

Requirement of Validation Plan
System Qualification Plan
Ongoing monitoring Plan

5.2.5.5 Safety / Ergonomic Requirements

Pressure relief devices
Considerations for ease of operation and maintenance
Insulation of piping that may be hot
Guarding of moving parts (e.g. pumps, motors)
Required signage (Identification and marking)
Flow Direction
Height/accessibility requirements for sample valves

5.2.5.6 Electrical Requirements:

NEMA (National Electrical Manufacturers Association), CSA (Canadian Standards Association) standards as applicable to pumps, electrical panel etc.
As per vendor’s requirement

5.2.5.7 Documentation Requirements

User Guide
As-built P&IDs
Schematic Diagram
Panel layout and electrical diagrams
Isometric piping diagrams
Operation &Maintenance manuals
Documentation of piping leak testing
Documentation of sanitary welds (weld logs, coupons, welder qualification, weld inspection, boroscopy documentation, hydro test report, passivation report, slop report, dead leg report, Identification of weld, Date wise Identification)
User point and sampling layout
Layout of ID’s of joints, boroscopy and radiography.

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1.0 PURPOSE

The primary objective of this Standard Operating Procedure (SOP) is to establish a comprehensive Alarm Life Cycle Management strategy for the equipment employed in the GxP process control system. This SOP delineates a systematic approach encompassing the definition, categorization, evaluation, monitoring, assessment, maintenance, change management, and periodic review of alarms. The overarching aim is to ensure a robust and efficient management framework that aligns with regulatory standards and best practices within the GxP environment, thereby contributing to the overall reliability, safety, and compliance of the process control system.

2.0 SCOPE

This SOP is applicable to the definition, categorization, evaluation, monitoring, assessment, maintenance, change management, and periodic review of alarms generated within the GxP process control system for product manufacturing, packing, and Utility Equipment (Building Management System-BMS and Purified Water System)

This SOP encompasses all alarms notified during the manufacturing process on various equipment, including but not limited to Rapid Mixer Granulator (RMG), Fluid Bed Dryer (FBD)/Fluid Bed Exchanger (FBE), Blender, Compression Machine, Auto Coaters, Inspection Machine, as well as Packing and Utility Equipment.

5.0 Procedure

5.1 Alarms shall be approached as a life cycle model i.e., the management of alarms shall be planned from the inception of a system, are designed to the plan, and then the system shall be continuously developed during operation.

5.2 Effective and continuous operation of alarm shall be ensured e.g. UPS system shall be provided for continuous operation of alarm system.

5.3 When operating effectively alarm system performs following tasks:

Alerts the operators that important change has occurred. This could be as abnormal process condition or an equipment malfunction.
Informs the operator of the nature of the change.
Guides the operator to take appropriate corrective action.
Provides fault data to maintenance systems

5.4 Alarm life cycle management shall consist of following phases:

5.4.1 Alarm management

Alarm shall include type of alarms like process control alarms, safety alarms etc. and strategy for classification of each alarm (risk assessment).
Equipment shall be classified based on PLC type as Type – 1 and Type – 2 used to operate the machine.
List of critical and non-critical alarms of each equipment shall be prepared by engineering department, reviewed by User department and approved by quality assurance.

5.4.2 Identification, implementation and rationalization of alarms

The Engineering department shall list out an audible and/or visible alarm for the respective equipment before equipment qualification based on qualification documents provided by the equipment /system manufacturer.
All the listed alarms with verification procedure shall be incorporated in the operational qualification protocol and shall be challenged during qualification activity.
Each alarm shall be categorized as critical and non-critical based on significance of each alarm. The categorization to be done as per Annexure no. JSA/QA/052/F-01/00 -“List of Critical alarms/Non critical alarms with Impact of alarm – Template”. Use this annexure as a template to perform categorization of alarm system. These categorization shall include minimum, alarm message, alarm code (if any), alarm interpretation (audio/ visual/ audio and visual), description of alarm, cause, corrective action and impact of alarm.

Note: Following are the guidance which can be used to categorize the alarm as critical and non-critical alarm. The following are a series of question which can be used to define the category of alarm.

Does the alarm need manual intervention for change in settings or correction which may impact on product quality?
Does the occurrence of alarm impact on safety, integrity, strength, purity and quality of the product?
Does the occurrence of alarm create interlock condition which may affect the product quality?
Does the occurrence of alarm indicate possible safety risk to the operating personnel?

In addition to that, the following can be considered during categorization of alarm based on equipment functionality:

If alarm having interlocking with machine and machine stopped immediately as soon as alarm occurred, without impacting on product quality then it shall not be considered as critical.
If the alarm generated and machine stops however if it impact on quality of product then it shall be considered as critical alarm as interlocking not able to prevent the product quality.

The categorization of alarms shall be done by cross functional team which includes user, engineering and QA as a minimum. Where appropriate, IT and function or OEM shall be consulted to classify the alarm. The categorization of Alarm in List shall be done by engineering and finally reviewed by User Department and approved quality assurance. The product quality impacting alarms shall be considered as critical alarms

5.5 Categorization based on Equipment Functionality:

Critical Alarms: Alarms that have significant impact on the Product (Strength, Identity, Safety, Purity and Quality).
Process / System Alarms: An alarm whose failure may affect the equipment performance or system performance but does not directly impact on the Product quality or personnel safety.
Non Critical Alarms: Alarms do not have impact on the Product (Strength, Identity, Safety, Purity and Quality).
Quality Categorization of Alarm based on impact of the alarm on quality of product:

Quality Impacting: The alarms which may have impact on product quality and CQAs.
Quality Non Impacting: The alarms which are may not have any impact on product quality and CQAs.

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1.0 PURPOSE

The objective of this Standard Operating Procedure is to lay down procedure for Equipment / Instrument and Utility Decommissioning from site.

2.0 SCOPE

This Standard Operating Procedure is limited up to decommissioning of equipment / instrument, Utilities (water system, AHU etc.) and all support systems installed in the facility.

3.0 PROCEDURE

Validation is a regulatory requirement that provides operational benefits in that reliable, understood and compliant premises, utilities, equipment, laboratories and processes (hereafter collectively referred to as ‘systems’) form the basis for effective manufacturing and supply operations. It is essential that controls are in place to ensure systems are fit for purpose.

For Equipment’s / Instruments, retirement is end of lifecycle. A systematic, standardized and effective approach to ‘Decommissioning’ is required in order to provide a consistent approach to validation and to ensure validated systems are decommissioned in a controlled manner.

Retirement / Decommissioning of an equipment or instrument shall always be triggered by an Investigation or up gradation plan of existing equipment / instrument and shall be executed through an approved change management. Following conditions (not limited to) can be considered for retirement of equipment.

5.1 Identification criteria for decommissioning

The reason for decommissioning may be but not limited to;

Old technology
Frequent / major break down
Higher maintenance cost
Malfunctioning of equipment
Non- availability of spare parts
Less Output
Repetitive market complaints
No longer meeting current or emerging business needs / regulatory requirements
Not supported by the supplier for servicing and maintenance
Facility obsolescence
Site or Department closures / facility shutdown

5.2 Initiation of change control

5.2.1 The section QA shall ensure at a minimum following members are part of CFT

5.2.2 The section QA in consultation with the user department head shall identify the CFT members required for the assessment of decommissioning.

5.2.3 Change control shall be reviewed by the department head. The department head shall prepare the risk assessment and forward the change to section QA.

5.2.4 The change control request shall contain a list of interfacing systems.

5.2.5 The decommissioning shall be done through the change control procedure initiated by functional owner (user). Annexure III shall be refer for pre requisite checklist for initiation of change control for decommissioning.

Head of the user department
Representative of quality assurance
Representative of engineering department
Representative of regulatory department (wherever applicable)

5.2.6 Section QA shall submit the change control for assessment.

5.2.7 CFT members shall do the assessment which should include the followings,

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1.0 PURPOSE

The objective of this Standard Operating Procedure is to lay down procedure for selection, evaluation & approval of vendors.

2.0 SCOPE

This Standard Operating Procedure is covers vendors of raw materials, packing materials and consumables for all products currently manufactured.

5.0 PROCEDURE

5.1 Need for inclusion of new vendor: The need to induct a new vendor to APC may arise due to the following reasons: -

5.1.1 New product initiation / business development plan

5.1.2 New raw materials, packing materials identified for procurement from a new source / existing source.

5.1.3 Adding a new source for raw materials, packing materials to the list of approved vendors.

5.2 Process for selection & evaluation of vendor:

5.2.1 New /Alternate source identified for procurement of material for existing commercial products or adding a new source to the list of approved vendors:

Responsibility:

Vendor Identification - Procurement Department.

Assessment of Pre-shipment samples – QCD.

Vendor Evaluation based on Quality Matrix – QA

Updation of Approved Vendor List for Commercial batch – QA

5.2.2 The vendor selection process will be carried in the following steps:

5.2.2.1 The addition of new vendor or change in vendor for the existing material in a product shall be routed through Change control procedure.

5.2.2.2 Procurement Department. shall assess the identified vendor capabilities by sending a copy of VSF (Annexure-1, 2, 3 & 4) and get the feedback with all necessary supporting documents from the vendor. This includes pre-shipment samples from the vendor.

5.2.2.3 The Samples from 3 consecutive Lots/Batches required as pre-shipment samples from the vendor and the number/quantity of sample shall be based on the product/material specification required for the analysis.

5.2.2.4 Vendor also provide the evidence for testing elemental impurities with COA of the material.

5.2.2.5 QC personal shall check the analysis results of elemental impurities in vendor COA.

5.2.2.6 Pre-shipment samples shall be sent by Procurement department to QCD for assessment as per specification and suitability wherever applicable.

5.2.5.7 If samples (For Example; expensive materials) are purchased by Procurement Dept., the sample shall be sent to the respective location warehouse. Warehouse shall inward the material through GRN and shall send to QCD for assessment.

5.2.5.8 After analyzing the RM samples (if any) & trials conducted for packaging pre-shipment samples, Plant QA / QC shall provide a feedback.

5.2.5.9 During procurement for commercial batch, the following documents but not limited to shall be forwarded by Procurement dept to QA for updating the AVL:

Vendor documents comprises of the following

Duly signed VSF
Copy of pre-shipment sample analysis report
COAs including of results of elemental impurities
MSDS
Product List

5.3 The above mentioned documents can be varied based on the type or the nature of the material i.e; API, excipients and packaging material, etc.

5.4 QA will evaluate the vendor documents based on quality matrix (Annexure-4) and update the Approved Vendor List (AVL) before the material is used for commercial batch.

5.5 QA will evaluate the vendor for audit, if it’s required it will planed accordingly.

5.6 In case of critical observation reported during the audit which may lead the adverse impact on safety, purity, efficacy, potency of material/product and patient health. The vendor shall not be qualified until the satisfactory compliance not submitted by the vendor against the observations

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1.0 PURPOSE

The objective of this Standard Operating Procedure is to establish and maintain a framework for Good Pharmacy Practice (GPP) that ensures the delivery of high-quality pharmacy services, compliance with national regulations, and continuous improvement in patient care

2.0 SCOPE

This SOP applies to all pharmacists, pharmacy technicians, and staff involved in pharmaceutical services within [Name of the Organization]. It encompasses the entire spectrum of pharmacy practice, including but not limited to medication preparation, dispensing, administration, and medication therapy management

3.0 RESPONSIBILITY

3.1 Pharmacists:

Ensure compliance with GPP standards outlined in this SOP.
Take a leadership role in the implementation of best practices in pharmacy services.
Uphold the ethical standards and code of conduct as outlined by [National Pharmacy Association].
Participate in ongoing professional development activities to enhance knowledge and skills.

3.2 Pharmacy Technicians:

Assist pharmacists in medication preparation, dispensing, and other pharmacy-related activities.
Adhere to established procedures for maintaining cleanliness and safety in medication preparation areas.
Comply with quality assurance principles during the procurement process.
Collaborate with pharmacists in the monitoring and management of medication inventories.

3.3 Management:

Provide necessary resources and support for the implementation of GPP standards.
Ensure that the pharmacy is equipped with appropriate facilities and technologies.
Oversee the development and implementation of contingency plans for medicine shortages and emergencies.
Encourage a culture of continuous improvement in pharmacy services.

3.4 Regulatory Compliance Officer:

Monitor adherence to national regulations and guidelines.
Conduct periodic audits to ensure compliance with GPP standards.
Investigate and address any deviations or non-compliance promptly.
Collaborate with pharmacists to update and revise SOPs as needed.

4.0 DEFINITION(S)

4.1 Good Pharmacy Practices: GPP is the practice of pharmacy that responds to the needs of the people who use the pharmacists’ services to provide optimal, evidence-based care.

5.0 PROCEDURE

5.1 Prepare, Obtain, Store, Secure, Distribute, Administer, Dispense, And Dispose Of Medical Products

5.1.1 Function A: Prepare Extemporaneous Medicine Preparations and Medical Products:

Design medicine preparation areas for ease of extemporaneous preparations.
Maintain cleanliness and safety in preparation areas.
Ensure compliance with written formulas and quality standards

5.1.2 Function B: Obtain, Store, and Secure Medicine Preparations and Medical Products:

Conduct transparent and ethical procurement processes.
Implement quality assurance principles during procurement.
Develop and implement contingency plans for medicine shortages.

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1.0 PURPOSE

The purpose of this SOP is to provide procedure for Analysis of Human Error.

2.0 SCOPE:

This SOP applicable to main plant for investigation of Human Errors

3.0 RESPONSIBILITY:

3.1 Quality Assurance

Part of investigation team and review HEAT form as a part investigation report approval.

3.2 Investigation owner

Evaluation of Human error by using the HEAT form

4.0 DEFINITIONS:

4.1 Human error: Inappropriate action or response by a person, resulting in undesired outcome.

5.0 PROCEDURE:

5.1 In case of OOS/OOT/Deviation/Market complaint/Lab incidence and any other non-compliance, the investigation concludes Human error as a root cause, further investigation of Human error shall be carried out.

5.2 Upon identifying the root cause for above mentioned quality indicators, respective department shall request QA to issue the Human Error Analysis Tool (HEAT) (Annexure. I)

5.3 Human Error Analysis shall be conducted by respective Investigation Owner of the incident by interviewing the identified employee.

5.4 In case of multiple people to be investigated separate Annexure shall be used and comprehensive summary of this investigation shall be included in Investigation report of OOS/OOT/Deviation/Market complaint/Lab incidence (Whichever is applicable).

5.6 There are two types of Human error

5.6.1 Intentional: Intentional human error is when an employee purposefully and knowingly takes an inappropriate action or response. This can be called intentional, misconduct or falsification. Behavioural gap comes under internal human error.

5.6.1.1 Behavioural Gap: It's a function of the environment and the behavior repertory of individuals.

5.6.2 Un-intentional: Un-intentional human error can result from incorrect decision, an incorrect action or both, therefore human error is broken down into following sub-categories

5.6.2.1 Learning Gap: Learning gap or knowledge gap is to assess whether employee has proper learning or knowledge to perform the task. Whether is not trained on the concerned topic or whether the employee handling task first time.

5.6.2.2 Application Gap: Application gap as difference between knowledge acquired and related activity execution emphasizing person has knowledge but applied incorrectly.

5.6.2.3 Attention Gap: A condition in which lack of attention or does not remember/Oversight/ Multitasking for task/performance/documentation even after having knowledge

5.6.2.4 Decision Gap: Decision gap is observed when wrong decision taken in a given situation provided has knowledge about process and system.

5.6.2.4 Procedure Gap: Procedure gap can occur due to inadequate/unclear procedures or due to incomplete procedures.

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ORAL DOSAGE FORM SOPs

List Of SOPs