Procedure for Managing Change Control Records

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for managing change control records in pharmaceutical manufacturing. Change control ensures that all proposed changes to processes, equipment, documents, and materials are evaluated, approved, and documented before implementation to maintain compliance with Good Manufacturing Practices (GMP) and regulatory requirements.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), Production, and Regulatory Affairs departments responsible for initiating, reviewing, approving, and maintaining change control records.

3. Responsibilities

• Change Requestor: Initiates a change control request and provides justification.
• QA Officer: Reviews change requests for impact assessment.
• QC Analyst: Evaluates potential effects on product quality.
• Regulatory Affairs Officer: Assesses regulatory implications.
• Change Control Committee (CCC): Approves or rejects change requests.
• QA Manager: Ensures proper documentation and implementation.

4. Accountability

The QA Manager and Change Control Committee (CCC) are accountable for ensuring that all change control records comply with GMP, FDA, ICH, and WHO guidelines.

5. Procedure

5.1 Types of Changes Requiring Change Control

Change control is required for:

• Process Changes: Modifications in manufacturing, testing, or cleaning processes.
• Equipment Changes: Installation, replacement, or modification of machinery.
• Material Changes: Changes in raw materials, suppliers, or packaging components.
• Document Changes: Revisions to SOPs, batch records, and validation documents.
• Facility Changes: Modifications in manufacturing or laboratory areas.
• Regulatory Changes: Updates due to new compliance requirements.

5.2 Initiating a Change Control Request

• A Change Control Request (CCR) must be initiated using the **Change Control Request Form (Annexure-1).**
• The requestor must provide:
  • Reason for change.
  • Impact on product quality, process, or regulatory compliance.
  • Proposed implementation timeline.
• The form must be submitted to **QA for preliminary review.**

5.3 Risk and Impact Assessment

• QA must conduct a **Risk and Impact Assessment** to evaluate:
  • Potential impact on product safety and efficacy.
  • Need for revalidation or additional testing.
  • Effect on regulatory filings and approvals.
• QC must assess potential effects on raw materials, in-process controls, and finished product specifications.
• The assessment must be documented in the **Change Control Evaluation Report.**

5.4 Approval Process

• The **Change Control Committee (CCC)** must review the request and risk assessment.
• Approval categories:
  • Approved: Change can be implemented with conditions.
  • Approved with Modifications: Implementation requires further review.
  • Rejected: Change poses unacceptable risk.
• Final approval must be provided by the **QA Manager.**

5.5 Implementation of Change

• Once approved, the change must be implemented as per the **Change Implementation Plan.**
• Training sessions must be conducted if procedural changes are involved.
• All implementation actions must be recorded in the **Change Implementation Log (Annexure-2).**

5.6 Verification and Effectiveness Check

• QA must conduct a **post-implementation review** within **30 days** to verify effectiveness.
• Key verification steps:
  • Review of manufacturing and laboratory records.
  • Evaluation of process performance.
  • Regulatory compliance check.
• If issues arise, further corrective actions must be taken.

5.7 Archiving and Retention of Change Control Records

• All change control records must be archived in the **Change Control Master File.**
• Retention periods:
  • Major changes – **Minimum 10 years.**
  • Minor changes – **Minimum 5 years.**
• Records must be available for audits and regulatory inspections.

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• CCC – Change Control Committee
• CCR – Change Control Request
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• Change Control Request Form (Annexure-1)
• Change Implementation Log (Annexure-2)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO Guidelines on Change Management
• US FDA Guidance on Change Control

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Change Control Request Form

Annexure-2: Change Implementation Log

12. Revision History

Procedure for Recording and Investigating Non-Conformance Reports

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for recording and investigating non-conformance reports (NCRs) in pharmaceutical manufacturing. Proper documentation and investigation of non-conformances ensure compliance with Good Manufacturing Practices (GMP) and regulatory requirements while maintaining product quality.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), and Production departments responsible for identifying, documenting, investigating, and resolving non-conformances observed in materials, processes, equipment, and final products.

3. Responsibilities

• Production Supervisor: Identifies non-conformances and initiates NCRs.
• QC Analyst: Evaluates non-conformances related to product quality and testing.
• QA Officer: Reviews NCRs and initiates investigations.
• CAPA Coordinator: Implements corrective and preventive actions.
• QA Manager: Approves NCR resolutions and ensures compliance.

4. Accountability

The QA and Production Managers are accountable for ensuring that all non-conformance reports are documented, investigated, and resolved in compliance with GMP, FDA, ICH, and WHO regulations.

5. Procedure

5.1 Identification of Non-Conformances

Non-conformances can occur at various stages of manufacturing and include:

• Material Non-Conformance: Raw materials or packaging materials that do not meet specified standards.
• Process Non-Conformance: Deviations from standard operating procedures (SOPs) in manufacturing.
• Product Non-Conformance: Finished products failing to meet quality standards.
• Equipment Non-Conformance: Malfunctions or deviations in equipment performance.
• Documentation Non-Conformance: Errors or omissions in records and logbooks.

5.2 Initiating a Non-Conformance Report (NCR)

• Any personnel identifying a non-conformance must report it to the **Production Supervisor or QA Officer** immediately.
• An **NCR Form** must be completed, capturing the following details:
  • Date and time of occurrence.
  • Location and process step affected.
  • Description of the non-conformance.
  • Immediate actions taken.
  • Person reporting the issue.
• The NCR form must be submitted to QA within **24 hours** of identification.

5.3 Investigation of Non-Conformance

• QA must initiate an **investigation within 48 hours** of receiving an NCR.
• Investigation steps include:
  • Reviewing batch records and process logs.
  • Conducting interviews with personnel involved.
  • Analyzing raw material and finished product test results.
  • Inspecting equipment and calibration records.
• The **Root Cause Analysis (RCA)** must be documented in the **NCR Investigation Report.**
• Critical non-conformances must be escalated to senior management.

5.4 Corrective and Preventive Action (CAPA)

• Based on the investigation findings, a **CAPA Plan** must be developed.
• Corrective Actions:
  • Immediate measures to correct the identified non-conformance.
  • Batch rejection or product recall if necessary.
  • Training of personnel if human error is identified.
• Preventive Actions:
  • Updating SOPs and work instructions.
  • Enhancing equipment calibration and maintenance programs.
  • Implementing additional quality control checks.
• The CAPA plan must be reviewed and approved by the **QA Manager.**

5.5 Implementation and Verification of CAPA

• The CAPA Coordinator must track the implementation of corrective and preventive actions.
• A **CAPA Effectiveness Check** must be conducted **one month after implementation.**
• QA must verify that the non-conformance has not recurred.

5.6 Closure and Documentation of NCRs

• QA must ensure all NCRs are properly documented and closed within the required time frame.
• NCR reports and CAPA records must be reviewed **monthly.**
• All NCRs must be archived for **a minimum of 5 years.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• NCR – Non-Conformance Report
• CAPA – Corrective and Preventive Action
• RCA – Root Cause Analysis
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• Non-Conformance Report Template (Annexure-1)
• CAPA Implementation Log (Annexure-2)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO Guidelines on Deviation and CAPA Management
• US FDA Guidance on CAPA Implementation

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Non-Conformance Report Template

Annexure-2: CAPA Implementation Log

12. Revision History

Procedure for Documentation of Calibration Activities

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic method for documenting calibration activities in pharmaceutical manufacturing. Proper documentation ensures compliance with Good Manufacturing Practices (GMP), regulatory requirements, and equipment reliability for accurate measurements.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), and Engineering departments responsible for calibrating, maintaining, and documenting calibration records for all measuring instruments and equipment used in production, laboratory testing, and quality control processes.

3. Responsibilities

• Calibration Technician: Performs calibration and records results.
• Engineering Department: Ensures calibration schedules are maintained.
• QA Officer: Reviews calibration reports for compliance.
• QA Manager: Approves and ensures adherence to calibration procedures.

4. Accountability

The QA and Engineering Managers are accountable for ensuring that all calibration activities and documentation meet GMP, FDA, ICH, and WHO requirements.

5. Procedure

5.1 Types of Equipment Requiring Calibration

The following types of equipment must be included in the calibration program:

• Weighing Balances: Analytical and precision balances used in laboratories and production.
• pH Meters: Instruments used to measure acidity/alkalinity of solutions.
• Thermometers and Hygrometers: Devices used to monitor environmental conditions.
• Pressure Gauges: Instruments used to measure pressure in vessels and pipelines.
• HPLC and GC Instruments: Analytical instruments used in QC testing.
• UV-Visible Spectrophotometers: Used for absorbance and purity testing.

5.2 Calibration Schedule and Frequency

• Each instrument must have a **defined calibration schedule** based on manufacturer recommendations and regulatory requirements.
• Calibration frequency must be categorized as:
  • Daily – e.g., analytical balances.
  • Weekly – e.g., temperature monitoring probes.
  • Monthly – e.g., pH meters.
  • Quarterly – e.g., spectrophotometers.
  • Annually – e.g., HPLC and GC instruments.
• The calibration schedule must be maintained in a **Calibration Master Log.**

5.3 Calibration Procedure

• The Calibration Technician must follow a **predefined calibration protocol.**
• Calibration activities must include:
  • Instrument identification and serial number.
  • Calibration standards used.
  • Pre-calibration readings.
  • Adjustment and corrective actions taken.
  • Final calibration readings.
• All calibration data must be recorded in the **Calibration Log Sheet.**

5.4 Documentation and Record Keeping

• Calibration records must include:
  • Equipment name and location.
  • Calibration frequency.
  • Calibration date and next due date.
  • Calibration method and reference standards used.
  • Results and pass/fail status.
  • Technician signature and QA approval.
• Electronic records must be stored in a **validated document management system (DMS).**

5.5 Handling Out-of-Specification (OOS) Calibration Results

• If an instrument fails calibration, it must be **immediately taken out of service.**
• A **Deviation Report** must be initiated and sent to QA.
• Corrective actions may include:
  • Instrument recalibration.
  • Equipment maintenance or repair.
  • Replacement of instrument components.
• Recalibration must be performed before the instrument is used again.

5.6 Review and Approval of Calibration Records

• QA must review calibration logs **monthly.**
• Calibration certificates must be stored with batch records if applicable.
• Records must be archived for **a minimum of 5 years.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• DMS – Document Management System
• OOS – Out of Specification
• HPLC – High-Performance Liquid Chromatography
• GC – Gas Chromatography

7. Documents

• Calibration Master Log (Annexure-1)
• Calibration Log Sheet (Annexure-2)

8. References

• ICH Q7 – GMP for Active Pharmaceutical Ingredients
• WHO Guidelines on Calibration
• US FDA Guidance on Equipment Calibration

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Calibration Master Log

Annexure-2: Calibration Log Sheet

12. Revision History

Procedure for Preparing and Reviewing Standard Operating Procedures

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for preparing, reviewing, approving, and maintaining SOPs within pharmaceutical manufacturing. SOPs ensure standardization of processes, regulatory compliance, and effective training of personnel.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), Production, and other relevant departments responsible for drafting, reviewing, and maintaining SOPs.

3. Responsibilities

• Departmental Heads: Identify the need for new or revised SOPs and assign authors.
• SOP Author: Drafts the SOP following standard templates and guidelines.
• QA Officer: Reviews the SOP for compliance and clarity.
• QA Manager: Approves the final SOP for implementation.
• Training Coordinator: Ensures that relevant staff members are trained on new or revised SOPs.

4. Accountability

The QA Manager is accountable for ensuring that all SOPs are properly prepared, reviewed, and maintained in compliance with GMP, FDA, ICH, and WHO regulations.

5. Procedure

5.1 SOP Format and Structure

All SOPs must follow a standard format, which includes:

• Title: Clearly defines the purpose of the SOP.
• Version Number: Specifies the revision history.
• Scope: Defines the applicability of the SOP.
• Responsibilities: Identifies personnel responsible for execution.
• Procedure: Provides a step-by-step guide for performing the process.
• References: Lists regulatory and internal guidelines followed.
• Annexures: Includes templates, logs, or additional reference documents.

5.2 SOP Preparation

• The SOP author must draft the SOP using the **standard template**.
• Each SOP must be assigned a **unique identification number**.
• All procedures must be described in **clear and concise language**.
• The draft SOP must be **submitted to the department head for initial review**.

5.3 SOP Review and Approval Process

• The **QA team** must review the SOP for:
  • Compliance with GMP and regulatory standards.
  • Accuracy and completeness of instructions.
  • Consistency with existing procedures.
• The **QA Manager** must approve the SOP before implementation.
• The approved SOP must be:
  • Signed and dated by all relevant stakeholders.
  • Uploaded to the **document management system (DMS).**
  • Distributed to all applicable departments.

5.4 SOP Implementation and Training

• All employees affected by the SOP must receive **formal training**.
• A **Training Record** must be maintained for each employee trained.
• The training coordinator must conduct **assessments** to ensure comprehension.

5.5 SOP Revision and Control

• SOPs must be reviewed **every two years** or when regulatory updates occur.
• Any revision must be documented in the **SOP Revision History Log.**
• Obsolete SOPs must be marked as **”Superseded”** and archived.

5.6 Archiving and Retention of SOPs

• All approved SOPs must be stored in a **secured archive.**
• Retention period:
  • Active SOPs – **Minimum 5 years.**
  • Superseded SOPs – **Minimum 10 years.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• DMS – Document Management System
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• SOP Preparation Checklist (Annexure-1)
• SOP Revision History Log (Annexure-2)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO Guidelines on SOP Management
• US FDA Guidance on Document Control

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: SOP Preparation Checklist

Annexure-2: SOP Revision History Log

12. Revision History

Procedure for Archiving Ointment Manufacturing Records

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic method for archiving ointment manufacturing records. Proper archiving ensures compliance with Good Manufacturing Practices (GMP), facilitates audits, and maintains traceability of batch production records, test reports, and regulatory documents.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), and Production departments responsible for maintaining, reviewing, and archiving ointment manufacturing records in both physical and electronic formats.

3. Responsibilities

• Production Officer: Ensures manufacturing records are compiled and submitted for archiving.
• QC Analyst: Provides laboratory test reports and analytical data for archiving.
• QA Officer: Reviews records for completeness and compliance before archiving.
• QA Manager: Approves the archiving of records and ensures compliance with regulatory retention policies.

4. Accountability

The QA and Production Managers are accountable for ensuring that all ointment manufacturing records are properly archived and maintained for the required retention period.

5. Procedure

5.1 Types of Ointment Manufacturing Records for Archiving

The following records must be archived:

• Batch Manufacturing Records (BMR): Contains details of batch processing, raw material usage, and in-process controls.
• Quality Control Test Reports: Includes analytical and microbial test results for raw materials, intermediates, and finished products.
• Cleaning and Sanitation Records: Documents cleaning schedules for equipment and manufacturing areas.
• Deviation and CAPA Reports: Contains information on any process deviations and corrective actions taken.
• Validation and Qualification Reports: Includes process validation, equipment qualification, and stability study reports.
• Regulatory Submission Documents: Includes regulatory approvals, compliance certificates, and audit reports.

5.2 Record Compilation and Review

• All manufacturing records must be compiled within **7 days** of batch completion.
• QA must review each record for:
  • Completeness of entries.
  • Signatures and authorizations.
  • Accuracy and compliance with GMP requirements.
• Any missing or incorrect entries must be corrected before archiving.

5.3 Record Categorization and Labeling

• Records must be categorized into **paper-based and electronic formats.**
• Each record must be labeled with:
  • Record type (e.g., BMR, QC Report, Validation Report).
  • Batch Number.
  • Retention Period.
  • Storage Location.

5.4 Physical Archiving of Paper Records

• Paper records must be stored in a **fireproof, humidity-controlled archive room**.
• Records must be stored in **labeled storage boxes** arranged systematically by:
  • Batch Number.
  • Year of Manufacture.
  • Record Type.
• Access to the archive must be **restricted** to authorized personnel only.
• A **record retrieval log** must be maintained to track document access.

5.5 Electronic Archiving of Records

• All electronic records must be stored in a **validated document management system (DMS).**
• Electronic records must be:
  • Scanned in **PDF format** for long-term preservation.
  • Digitally signed for authenticity.
  • Backed up on **secured servers** with controlled access.
• Audit trails must be enabled to track any modifications or access.
• Records must be periodically checked for **file integrity and readability.**

5.6 Retention Period and Disposal of Archived Records

• Retention periods must comply with **GMP and regulatory guidelines**:
• Batch Manufacturing Records – **Minimum 5 years**.
• QC Test Reports – **Minimum 7 years**.
• Validation Documents – **Minimum 10 years**.
• Regulatory Compliance Records – **Permanent Storage**.
• Records past the retention period must be **disposed of securely** following approval from QA.
• Record disposal must be documented in a **Record Destruction Log.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• BMR – Batch Manufacturing Record
• CAPA – Corrective and Preventive Action
• DMS – Document Management System
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• Record Retrieval Log (Annexure-1)
• Record Destruction Log (Annexure-2)

8. References

• ICH Q7 – GMP for Active Pharmaceutical Ingredients
• WHO Guidelines on Document Retention
• US FDA Guidance on Archiving and Record Management

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Record Retrieval Log

Annexure-2: Record Destruction Log

12. Revision History

Procedure for Ensuring Data Integrity in Documentation

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for ensuring data integrity in pharmaceutical documentation. Data integrity is essential for maintaining compliance with Good Manufacturing Practices (GMP), regulatory requirements, and audit readiness.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), Production, and IT departments responsible for maintaining, verifying, and reviewing electronic and paper-based documentation.

3. Responsibilities

• QA Officer: Ensures adherence to data integrity principles.
• QC Analyst: Verifies laboratory data for accuracy and completeness.
• Production Supervisor: Ensures real-time documentation of manufacturing processes.
• IT Department: Maintains security and audit trails for electronic records.
• QA Manager: Reviews and approves data integrity policies.

4. Accountability

The QA and IT Managers are accountable for ensuring data integrity compliance across all documentation and electronic systems.

5. Procedure

5.1 ALCOA+ Principles of Data Integrity

All data must adhere to the **ALCOA+ principles**, which ensure reliability and compliance:

• Attributable – Each entry must be linked to the person responsible.
• Legible – Data must be recorded clearly and permanently.
• Contemporaneous – Entries must be made in real-time.
• Original – Records must be the first recording (not transcribed or copied).
• Accurate – Data must be correct and free from manipulation.
• Permanent – Records must be durable and not altered.
• Available – Data must be accessible for review and audits.

5.2 Documentation Requirements

• Data must be recorded in **indelible ink** (for paper records) or **secure electronic systems**.
• All entries must include:
  • Full name and signature of the person making the entry.
  • Date and time of entry.
  • Reason for any data modifications.
• Corrections must follow **Good Documentation Practices (GDP)**:
  • Errors must be struck through with a single line.
  • Corrections must be initialed and dated.
  • Do not use correction fluid or erasers.

5.3 Ensuring Data Integrity in Electronic Records

• Electronic records must be stored in **validated systems** with controlled access.
• Systems must generate **audit trails** that track:
  • User logins and modifications.
  • Time-stamped changes to records.
  • Reasons for data entry modifications.
• Electronic signatures must comply with **21 CFR Part 11** regulations.
• Data backups must be performed **daily** and stored in a secure location.

5.4 Reviewing and Verifying Data Integrity

• QA must conduct **monthly audits** of documentation for data integrity compliance.
• QC must verify laboratory data before final approval.
• Production records must be reviewed **before batch release**.

5.5 Handling Data Integrity Violations

• Suspected data integrity issues must be **reported to QA immediately**.
• An **investigation** must be conducted to determine:
  • Root cause of the violation.
  • Extent of data falsification or errors.
  • Impact on product quality and regulatory compliance.
• Corrective actions may include:
  • Retraining employees on data integrity policies.
  • Implementing stricter access controls.
  • Revalidating affected systems.

5.6 Retention and Archiving of Records

• All paper records must be archived in a **fireproof storage area**.
• Electronic records must be stored with **secure encryption**.
• Retention periods:
  • Manufacturing records – **Minimum 5 years**.
  • QC test records – **Minimum 7 years**.
  • Audit trails – **Minimum 10 years**.

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• GDP – Good Documentation Practices
• CFR – Code of Federal Regulations
• IT – Information Technology

7. Documents

• Data Integrity Compliance Checklist (Annexure-1)
• Audit Trail Review Log (Annexure-2)

8. References

• ICH Q7 – GMP for Active Pharmaceutical Ingredients
• WHO Guidelines on Data Integrity
• US FDA Guidance on Data Integrity

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Data Integrity Compliance Checklist

Annexure-2: Audit Trail Review Log

12. Revision History

Procedure for Maintaining QA Approval Logs

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for maintaining Quality Assurance (QA) approval logs in pharmaceutical manufacturing. These logs provide traceability and ensure regulatory compliance for batch approvals, document verifications, deviation authorizations, and other QA-related activities.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), and Production departments responsible for recording, reviewing, and maintaining QA approval logs for manufacturing, validation, deviation approvals, and batch releases.

3. Responsibilities

• QA Officer: Updates QA approval logs with relevant details.
• QC Analyst: Provides verification data to support QA approvals.
• Production Supervisor: Ensures batch documents are submitted for QA approval.
• QA Manager: Reviews and approves QA logs for compliance.

4. Accountability

The QA Manager is accountable for ensuring that all QA approval logs are maintained in compliance with GMP, FDA, ICH, and WHO regulations.

5. Procedure

5.1 Types of QA Approval Logs

The following types of QA approval logs must be maintained:

• Batch Manufacturing Record (BMR) Approval Log: Documents approvals for batch processing.
• Deviation and CAPA Approval Log: Records QA approvals for deviations and corrective actions.
• Validation Approval Log: Maintains records of validation study approvals.
• Change Control Approval Log: Documents QA approvals for process or document changes.
• Vendor and Material Approval Log: Tracks approval of raw materials and vendor qualifications.

5.2 Recording QA Approvals

• QA approvals must be recorded in **real-time** to ensure traceability.
• The following details must be recorded for each approval:
  • Approval date and time.
  • Document reference number (Batch No., Deviation No., Validation No.).
  • Nature of approval (batch release, deviation clearance, validation sign-off).
  • QA Officer’s name and signature.
  • QA Manager’s authorization.
• Electronic logs must be maintained in a **validated document control system** with controlled access.

5.3 Review and Verification of QA Approval Logs

• QA must review approval logs **weekly** for completeness.
• Any discrepancies in approval logs must be investigated and corrected.
• QA logs must be **cross-verified with batch records, deviation reports, and validation documents**.

5.4 Archiving and Retention of QA Logs

• All QA logs must be archived in a **secure, fire-resistant storage area**.
• Retention period for QA logs:
  • Batch approvals – **Minimum 5 years**.
  • Deviation approvals – **Minimum 3 years**.
  • Validation approvals – **Minimum 5 years**.
• Archived QA logs must be **retrievable for regulatory audits**.

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• BMR – Batch Manufacturing Record
• CAPA – Corrective and Preventive Action
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• QA Approval Log Template (Annexure-1)
• QA Review Checklist (Annexure-2)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO Guidelines on QA Documentation
• US FDA Guidance on QA Oversight

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: QA Approval Log Template

Annexure-2: QA Review Checklist

12. Revision History

Procedure for Filing Validation Protocols

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic method for filing validation protocols in pharmaceutical manufacturing. Proper documentation of validation protocols ensures compliance with Good Manufacturing Practices (GMP), regulatory requirements, and traceability for audits and inspections.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Validation, Quality Control (QC), and Production departments responsible for preparing, reviewing, and filing validation protocols for processes, equipment, and systems.

3. Responsibilities

• Validation Officer: Prepares and reviews validation protocols for processes, equipment, and facilities.
• QA Officer: Ensures proper documentation and filing of validation protocols.
• QC Analyst: Verifies compliance with validation requirements.
• QA Manager: Approves and ensures compliance with validation protocols.

4. Accountability

The QA and Validation Managers are accountable for ensuring that validation protocols are prepared, filed, and maintained in compliance with GMP, FDA, ICH, and WHO regulations.

5. Procedure

5.1 Types of Validation Protocols

The following types of validation protocols must be maintained:

• Process Validation Protocol: Documents procedures to validate manufacturing processes.
• Equipment Qualification Protocol: Defines the qualification process for equipment (IQ, OQ, PQ).
• Cleaning Validation Protocol: Establishes procedures for verifying cleaning effectiveness.
• Analytical Method Validation Protocol: Ensures analytical methods provide reliable test results.
• Computer System Validation Protocol: Verifies compliance of computerized systems used in manufacturing.

5.2 Preparation of Validation Protocols

• The Validation Officer must draft validation protocols based on regulatory and organizational requirements.
• Protocols must include:
  • Objective and scope of validation.
  • Validation approach and acceptance criteria.
  • Equipment and materials required.
  • Execution plan and responsibilities.
  • Data collection methods and report format.
• Protocols must be reviewed and approved by the QA Manager before implementation.

5.3 Filing and Documentation of Validation Protocols

• Validation protocols must be assigned a unique identification number.
• Each protocol must be stored in a **Validation Master File (VMF).**
• Filing must be categorized based on validation type (Process, Equipment, Cleaning, Analytical, Computerized Systems).
• Electronic copies must be stored in a **secured document management system** with controlled access.

5.4 Implementation and Execution of Validation Protocols

• QA must ensure that validation protocols are followed during execution.
• All test results must be recorded in a **Validation Execution Report**.
• Any deviations or failures must be documented and investigated.

5.5 Review and Approval of Validation Reports

• QA must review validation execution reports for compliance.
• Final validation reports must be signed off by the QA Manager.
• Validation records must be **archived for a minimum of 5 years.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• VMF – Validation Master File
• IQ – Installation Qualification
• OQ – Operational Qualification
• PQ – Performance Qualification
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• Validation Protocol Template (Annexure-1)
• Validation Execution Report Template (Annexure-2)

8. References

• ICH Q2 – Validation of Analytical Procedures
• WHO Guidelines on Process Validation
• US FDA Guidance on Validation Principles

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Validation Protocol Template

Annexure-2: Validation Execution Report Template

12. Revision History

Procedure for Preparing Stability Study Reports

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for preparing Stability Study Reports in pharmaceutical manufacturing. Stability studies evaluate the effect of environmental factors such as temperature, humidity, and light on drug products to determine their shelf life and storage conditions.

2. Scope

This SOP applies to personnel in the Quality Assurance (QA), Quality Control (QC), and Research & Development (R&D) departments responsible for conducting stability studies, analyzing data, and preparing Stability Study Reports for regulatory compliance.

3. Responsibilities

• QC Analyst: Conducts stability tests and records analytical data.
• QA Officer: Reviews stability study reports for compliance.
• R&D Scientist: Designs and monitors stability studies.
• QA Manager: Approves final Stability Study Reports.

4. Accountability

The QA and R&D Managers are accountable for ensuring that Stability Study Reports comply with GMP, ICH, WHO, and FDA guidelines.

5. Procedure

5.1 Types of Stability Studies

Stability studies are classified into the following categories:

• Accelerated Stability Studies: Conducted at elevated temperature and humidity conditions to predict long-term stability.
• Long-Term Stability Studies: Conducted under normal storage conditions to determine real-time stability.
• Intermediate Stability Studies: Performed at conditions between long-term and accelerated studies.
• Photostability Studies: Evaluates the effect of light exposure on drug products.

5.2 Stability Study Protocol Development

• A Stability Study Protocol must be prepared before initiating stability testing.
• The protocol must include:
  • Purpose and scope of the study.
  • Batch details (Batch No., manufacturing and expiry date).
  • Storage conditions and test intervals.
  • Test parameters (e.g., assay, pH, viscosity, microbial limits).
  • Acceptance criteria and test methods.
• The Stability Study Protocol must be reviewed and approved by the QA Manager.

5.3 Sample Preparation and Storage

• Stability samples must be collected from representative batches.
• Samples must be labeled with:
  • Product name and batch number.
  • Storage condition and test interval.
  • Date of sample collection.
• Samples must be stored in **stability chambers** under defined conditions:
• Storage conditions:
  • Accelerated: **40°C ± 2°C / 75% RH ± 5% RH**
  • Long-Term: **25°C ± 2°C / 60% RH ± 5% RH**
  • Intermediate: **30°C ± 2°C / 65% RH ± 5% RH**
  • Photostability: **Light exposure per ICH guidelines**

5.4 Stability Testing and Data Recording

• QC must conduct tests at predefined intervals (e.g., 1 month, 3 months, 6 months, 12 months, 24 months).
• Tests include:
  • Physical tests (appearance, odor, color).
  • Chemical tests (assay, pH, degradation products).
  • Microbiological tests (total viable count, endotoxin levels).
• All test results must be recorded in the **Stability Testing Log.**

5.5 Preparation of Stability Study Reports

• The Stability Study Report must include:
  • Summary of stability testing results.
  • Trend analysis of critical parameters.
  • Degradation profile and extrapolated shelf life.
  • Recommendations on storage conditions and expiry period.
• The report must be reviewed by the **QA Manager** before submission.

5.6 Review and Approval of Stability Study Reports

• QA must review stability data monthly.
• Regulatory compliance must be ensured before final approval.
• Reports must be archived for **a minimum of 5 years.**

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• R&D – Research & Development
• RH – Relative Humidity
• ICH – International Council for Harmonisation

7. Documents

• Stability Study Protocol Template (Annexure-1)
• Stability Study Report Template (Annexure-2)

8. References

• ICH Q1A – Stability Testing of New Drug Substances
• WHO Guidelines on Stability Studies
• US FDA Guidance on Stability Testing

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Stability Study Protocol Template

Annexure-2: Stability Study Report Template

12. Revision History

Procedure for Recording Deviations and CAPA Reports

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the systematic approach for identifying, documenting, investigating, and addressing deviations in pharmaceutical manufacturing. It also outlines the Corrective and Preventive Action (CAPA) process to ensure continual improvement and compliance with Good Manufacturing Practices (GMP).

2. Scope

This SOP applies to all personnel in the Quality Assurance (QA), Quality Control (QC), and Production departments responsible for identifying deviations, recording them in deviation reports, and implementing CAPA procedures.

3. Responsibilities

• Production Supervisor: Identifies deviations and initiates deviation reports.
• QA Officer: Reviews deviations, conducts investigations, and proposes corrective actions.
• QC Analyst: Evaluates quality-related deviations and assesses potential product impact.
• CAPA Coordinator: Implements corrective and preventive actions.
• QA Manager: Approves deviation reports and CAPA plans.

4. Accountability

The QA and Production Managers are accountable for ensuring that all deviations are documented and addressed in compliance with GMP, FDA, ICH, and WHO regulations.

5. Procedure

5.1 Types of Deviations

Deviations are classified into three categories based on their impact on product quality and regulatory compliance:

• Critical Deviation: Any deviation that significantly impacts product quality, patient safety, or regulatory compliance (e.g., microbial contamination, incorrect formulation, equipment failure).
• Major Deviation: A deviation that does not directly impact product quality but may affect process efficiency (e.g., exceeding temperature limits, incomplete documentation).
• Minor Deviation: A minor procedural deviation with no significant effect on product quality (e.g., slight delay in record entry, minor errors in labeling).

5.2 Identifying and Documenting Deviations

• Any personnel identifying a deviation must report it to the **Production Supervisor or QA Officer** immediately.
• A **Deviation Report** must be initiated, capturing the following details:
  • Date and time of deviation occurrence.
  • Location and process step affected.
  • Detailed description of the deviation.
  • Immediate corrective actions taken.
  • Name of the person reporting the deviation.
• The deviation report must be submitted to QA within **24 hours** of detection.

5.3 Investigation of Deviations

• QA must initiate a **Root Cause Analysis (RCA)** within **48 hours** of receiving a deviation report.
• Investigation methods include:
  • Review of batch records and process logs.
  • Interviews with personnel involved.
  • Analysis of equipment calibration and environmental monitoring records.
• The investigation findings must be recorded in the **Deviation Investigation Report**.
• Critical deviations must be escalated to senior management.

5.4 Corrective and Preventive Action (CAPA) Process

• Based on the deviation investigation, a **CAPA Plan** must be developed.
• Corrective Actions:
  • Immediate steps to rectify the identified deviation.
  • Product recall or batch rejection if necessary.
  • Training of personnel if human error is identified.
• Preventive Actions:
  • Revising SOPs and work instructions.
  • Enhancing equipment calibration and maintenance schedules.
  • Implementing additional quality control checks.
• The CAPA plan must be reviewed and approved by the QA Manager.

5.5 Implementation and Monitoring of CAPA

• The CAPA Coordinator must track the implementation of corrective and preventive actions.
• A **CAPA Effectiveness Check** must be conducted **one month after implementation**.
• QA must verify that no recurrence of the deviation has been observed.

5.6 Review and Approval of Deviation Reports and CAPA

• QA must review all deviation reports monthly.
• CAPA reports must be reviewed quarterly for effectiveness.
• Deviation records and CAPA reports must be archived for a **minimum of 5 years**.

6. Abbreviations

• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• CAPA – Corrective and Preventive Action
• RCA – Root Cause Analysis
• FDA – Food and Drug Administration
• ICH – International Council for Harmonisation

7. Documents

• Deviation Report Template (Annexure-1)
• CAPA Implementation Log (Annexure-2)

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO Guidelines on Deviation and CAPA Management
• US FDA Guidance on CAPA Implementation

9. SOP Version

Version 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report Template

Annexure-2: CAPA Implementation Log

12. Revision History