Standard Operating Procedure for Capsule Polishing Procedures

1. Purpose

The purpose of this SOP is to describe the procedure for polishing capsules during the manufacturing process. Capsule polishing enhances the appearance of capsules, removes any dust or residues, and ensures smooth, shiny, and uniform capsules for final packaging.

2. Scope

This SOP applies to all capsules that require polishing as part of the post-manufacturing process. It covers the equipment, materials, procedures, and documentation related to capsule polishing.

3. Responsibilities

• Manufacturing Team: Responsible for executing the capsule polishing procedures according to this SOP. Ensure that the polishing process is carried out safely and efficiently.
• Quality Control (QC) Team: Responsible for verifying the appearance and quality of capsules after polishing and ensuring that polishing parameters are within specifications.
• Quality Assurance (QA) Team: Ensures compliance with the SOP and reviews records related to the polishing process. Ensures that the process meets GMP and regulatory requirements.
• Maintenance Team: Responsible for ensuring that polishing equipment is regularly maintained and calibrated for optimal performance.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring the proper execution of the polishing procedure. The QA Manager is responsible for overseeing the entire process and ensuring that quality and compliance standards are maintained.

5. Procedure

5.1 Pre-Polishing Preparation

Before beginning the capsule polishing process, ensure the following preparations are made:

1. Equipment Setup
   1. Ensure that the polishing machine is clean and free from any residues from previous batches. Perform a thorough inspection of the polishing equipment, including rollers, brushes, and other components.
   2. Set up the polishing machine according to the manufacturer’s instructions. Verify that all settings, such as speed and temperature, are in compliance with the specifications for the current batch of capsules.
2. Polishing Materials
   1. Ensure that all materials used in the polishing process, such as polishing powder, wax, or vegetable-based lubricants, are approved for use and stored appropriately. Use only the recommended materials for the specific capsule type.
3. Documentation
   1. Document all preparation activities, including the setup of equipment and materials, in the batch production record (BPR). Note any deviations from the standard procedure.

5.2 Capsule Polishing Process

Follow these steps to polish the capsules:

1. Loading Capsules
   1. Carefully load the capsules into the polishing machine hopper, ensuring that the capsules are properly aligned to prevent damage during polishing.
   2. Do not overfill the hopper to avoid blockages or uneven polishing.
2. Polishing Action
   1. Start the polishing machine and allow it to operate according to the specified settings. During the polishing process, capsules will pass through rotating rollers or brushes coated with polishing materials.
   2. Monitor the capsules during the process to ensure uniform polishing. The machine speed should be adjusted as necessary to achieve the desired finish without causing damage to the capsules.
3. Polishing Material Application
   1. Ensure that the polishing material is applied evenly and that excess powder or wax is removed after polishing. Adjust the amount of polishing material if necessary to avoid over-coating the capsules.
4. Inspection
   1. After polishing, visually inspect the capsules for uniformity in appearance, shine, and smoothness. Capsules should be free from dust or residual polishing materials. Any defects should be recorded, and defective capsules should be segregated for rework or disposal.

5.3 Post-Polishing Actions

After the polishing process is complete, perform the following actions:

1. Final Inspection
   1. Inspect the polished capsules for the desired appearance, including a smooth, shiny surface free from blemishes, scratches, or foreign particles. Ensure that the capsules meet all visual standards.
   2. Check for any remaining polishing material on the surface of the capsules and remove any excess residue using an air blower or brush.
2. Segregation of Defective Capsules
   1. Immediately segregate any defective capsules identified during the final inspection. Place them in a “Rejected” container and document the defects for further action.
3. Documentation
   1. Document the polishing process in the batch production record (BPR), including the number of capsules polished, any defects found, and any corrective actions taken. Record the batch number and date of the polishing operation.
4. Packaging
   1. Once capsules have passed the final inspection, transfer them to the packaging area for further processing. Ensure that the polished capsules are carefully handled and properly stored until they are ready for packing.

5.4 Cleaning and Maintenance of Polishing Equipment

After completing the polishing process, ensure the polishing equipment is cleaned and maintained to prevent contamination in future batches:

1. Cleaning
   1. Clean all parts of the polishing machine, including rollers, brushes, and hoppers, to remove any remaining polishing powder or wax. Use approved cleaning agents and follow the manufacturer’s cleaning instructions.
2. Inspection
   1. Inspect the polishing equipment for wear and tear, and ensure that all moving parts are functioning smoothly. Replace any worn-out components as needed.
3. Documentation
   1. Document the cleaning and maintenance activities in the maintenance log. Record the date of cleaning, maintenance tasks performed, and any parts replaced or repaired.

5.5 Documentation and Record-Keeping

Ensure proper documentation of all polishing activities:

1. Batch Production Record (BPR)
   1. Document the polishing procedure in the BPR, including the batch number, quantity of capsules polished, any defects observed, and any corrective actions taken.
2. Inspection Log
   1. Maintain a log of all inspections performed during the polishing process, including the date, operator, and results of the inspection. Note any capsules that were rejected or reworked.
3. Maintenance Log
   1. Document any maintenance or cleaning activities performed on the polishing equipment, including the tasks completed, parts replaced, and the date of completion.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• BPR: Batch Production Record

7. Documents

1. Capsule Polishing Log (Annexure-1)
2. Polishing Defect Report (Annexure-2)
3. Equipment Maintenance Log (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Capsule Polishing Log

Annexure-2: Polishing Defect Report

Annexure-3: Equipment Maintenance Log

Revision History:

Standard Operating Procedure for Capsule Batch Number Allocation and Tracking

1. Purpose

The purpose of this SOP is to define the procedure for allocating and tracking batch numbers for capsules produced during manufacturing. A systematic approach to batch number allocation ensures traceability, compliance with regulatory requirements, and effective quality control throughout the production process.

2. Scope

This SOP applies to all capsule production batches within the manufacturing facility. It covers the procedures for assigning batch numbers, documenting batch information, and maintaining records for tracking and traceability purposes.

3. Responsibilities

• Manufacturing Team: Responsible for ensuring that the correct batch numbers are assigned to the capsules during production and that batch records are accurately maintained.
• Quality Control (QC) Team: Responsible for verifying the batch number allocation and ensuring that proper documentation is maintained to facilitate traceability and auditing processes.
• Quality Assurance (QA) Team: Ensures compliance with the SOP, reviews batch records, and oversees the traceability system to ensure it meets regulatory requirements.
• IT and Records Management Team: Responsible for maintaining electronic systems and records to ensure accurate batch tracking and retrieval.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that batch numbers are allocated correctly and that proper tracking procedures are followed. The QA Manager is responsible for reviewing batch records and ensuring compliance with regulatory standards.

5. Procedure

5.1 Allocation of Batch Numbers

The following steps should be followed for allocating batch numbers during capsule production:

1. Batch Number Format
   1. Define the batch number format based on company standards. A typical format includes information such as the product code, production date, and a unique batch number (e.g., PROD-20250201-001).
   2. Ensure that the format is consistent across all batches to allow for easy identification and tracking.
2. Assignment of Batch Number
   1. Assign a unique batch number to each production batch. The batch number should be linked to the production record, raw material lot numbers, and other relevant manufacturing details.
   2. Batch numbers should be assigned in a sequential manner to prevent duplication and ensure traceability.
3. Record the Batch Information
   1. Record the batch number, product details, date of manufacture, and operator information in the batch production record (BPR). This will provide a comprehensive log of each batch produced, facilitating traceability.

5.2 Tracking of Batch Numbers

Once the batch number is assigned, ensure that the batch is tracked throughout the production and distribution process:

1. Documentation of Batch Details
   1. Ensure that all batch details, including the batch number, product specifications, raw material lot numbers, and equipment used, are documented in the batch production record and related documentation.
2. Batch Number on Packaging
   1. Ensure that the batch number is printed on the packaging of the capsules, including primary, secondary, and tertiary packaging, to ensure full traceability during distribution.
3. Real-Time Tracking System
   1. If available, use a computerized system to track batch numbers in real time. The system should be updated throughout the production process to provide immediate access to batch information for QC, QA, and regulatory purposes.
4. Inventory and Distribution Tracking
   1. Track each batch from production through to distribution, ensuring that the batch number is recorded at each stage of the supply chain. This includes storage, shipping, and delivery to customers or distributors.

5.3 Batch Number Traceability and Retrieval

Ensure that batch numbers can be traced and retrieved quickly for quality control, auditing, or regulatory inspections:

1. Batch Record Retrieval
   1. Maintain an organized system for storing batch records and related documents. Ensure that batch numbers are easily searchable and that records can be retrieved promptly upon request.
2. Audit Trail
   1. Maintain an audit trail for each batch, documenting any deviations, corrective actions, or changes made during the production process. This ensures transparency and traceability in case of any issues.
3. Regulatory Compliance
   1. Ensure that the batch tracking system complies with regulatory requirements, including FDA, EMA, or other relevant authorities, by providing access to batch records when requested.

5.4 Batch Number Reconciliation

To ensure accuracy in batch tracking, perform regular batch number reconciliation:

1. Reconciliation After Production
   1. Once a batch is completed, perform a reconciliation process to ensure that all materials used and capsules produced are accounted for under the correct batch number.
2. Reconciliation with Inventory Records
   1. Reconcile batch production records with inventory and distribution records to ensure that all capsules are properly accounted for and no discrepancies exist between the number of capsules produced and the number recorded in the system.

5.5 Batch Number Modifications

If any changes or modifications to the batch number are required, follow these procedures:

1. Documentation of Changes
   1. Any changes to batch numbers should be documented in the batch record, including the reason for the change and who authorized it. Ensure that all changes are made in compliance with GMP and regulatory standards.
2. Approval for Changes
   1. Changes to batch numbers should only be made with the approval of the QA Manager or another authorized individual to ensure traceability and prevent confusion or errors in batch tracking.

5.6 Documentation and Record-Keeping

Ensure proper documentation of all batch numbers and related activities:

1. Batch Production Records
   1. Maintain detailed batch production records for each batch produced, including batch number, raw materials, production conditions, and any deviations or issues encountered.
2. Batch Tracking Log
   1. Maintain a batch tracking log that documents all batch numbers, the status of each batch, and any actions taken throughout the production and distribution process.
3. Retention of Records
   1. Ensure that all batch production records and tracking logs are retained for the required period, in compliance with regulatory requirements, to allow for audits or inspections.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• BPR: Batch Production Record

7. Documents

1. Batch Production Record (Annexure-1)
2. Batch Tracking Log (Annexure-2)
3. Batch Number Allocation Form (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Batch Production Record

Annexure-2: Batch Tracking Log

Annexure-3: Batch Number Allocation Form

Revision History:

Standard Operating Procedure for Preventive Maintenance of Capsule Manufacturing Equipment

1. Purpose

The purpose of this SOP is to establish a preventive maintenance program for the capsule manufacturing equipment to ensure its optimal performance, reduce downtime, and extend its operational life. Regular preventive maintenance is essential to minimize equipment failure and maintain product quality.

2. Scope

This SOP applies to all capsule manufacturing equipment, including capsule filling machines, gelatin preparation systems, capsule inspection systems, drying equipment, and sealing machines. It covers the preventive maintenance tasks, frequency, and documentation required to maintain equipment functionality.

3. Responsibilities

• Manufacturing Team: Responsible for notifying the maintenance team when equipment is due for maintenance and assisting with equipment shutdowns if required.
• Maintenance Team: Responsible for conducting regular preventive maintenance on all capsule manufacturing equipment, ensuring that the equipment is cleaned, calibrated, and operational.
• Quality Control (QC) Team: Responsible for ensuring that the equipment is functioning properly during production and that any maintenance issues that impact product quality are documented and addressed.
• Quality Assurance (QA) Team: Ensures that preventive maintenance activities are performed according to this SOP, verifies maintenance records, and ensures compliance with regulatory standards.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that preventive maintenance activities are carried out as scheduled. The QA Manager is responsible for ensuring compliance with this SOP and reviewing maintenance documentation.

5. Procedure

5.1 Pre-Maintenance Preparation

Before beginning any preventive maintenance task, ensure the following steps are completed:

1. Equipment Shutdown
   1. Ensure that the equipment to be serviced is properly shut down and that all safety procedures are followed. Disconnect electrical power if necessary and lock out/tag out the equipment to prevent accidental start-up.
2. Review Maintenance Schedule
   1. Review the maintenance schedule to ensure that the correct tasks are being performed on the equipment at the correct intervals. Maintenance schedules should be based on the manufacturer’s recommendations and the operating history of the equipment.
3. Tools and Spare Parts
   1. Ensure that all necessary tools, spare parts, and lubricants are available before beginning the maintenance work. Use only approved parts and materials for repairs or replacements.

5.2 Preventive Maintenance Tasks

Perform the following preventive maintenance tasks at the recommended intervals to ensure optimal performance of capsule manufacturing equipment:

1. Cleaning
   1. Clean all equipment parts, including capsule filling machines, hoppers, and capsules inspection units. Use approved cleaning agents and follow cleaning procedures to prevent contamination and ensure smooth operation.
2. Lubrication
   1. Lubricate all moving parts, including gears, motors, and conveyor systems, according to the manufacturer’s specifications. Use appropriate lubricants and check for signs of wear or damage to moving parts.
3. Inspection and Calibration
   1. Inspect equipment for wear, corrosion, or other damage. Calibrate systems such as weight sensors, filling mechanisms, and sealing units to ensure that the equipment operates within specified tolerances.
4. Check Electrical Systems
   1. Inspect all electrical connections, circuits, and components for signs of damage or overheating. Test the electrical systems to ensure proper functionality.
5. Inspect Air and Gas Systems
   1. Inspect pneumatic systems, air filters, and gas lines for leaks or blockages. Replace filters as needed to ensure a constant supply of clean air to the equipment.
6. Check for Alignment and Calibration
   1. Check the alignment of all mechanical components, including the capsule filling stations and sealing mechanisms. Ensure that all components are correctly aligned to prevent misalignment during production runs.

5.3 Post-Maintenance Verification

After completing the preventive maintenance tasks, perform the following steps:

1. Equipment Testing
   1. Test the equipment to ensure that it is functioning correctly after maintenance. Run a test batch of capsules to verify that the machine is operating smoothly and within specified parameters.
2. Verification of Adjustments
   1. Verify that any adjustments made during maintenance (e.g., machine settings, calibration) are correct. Document the adjustments made and any changes to equipment parameters.
3. Documentation
   1. Document all preventive maintenance activities in the equipment maintenance log. Include the date, tasks performed, parts replaced, and any issues identified during the maintenance process. Include the results of post-maintenance testing and verification.

5.4 Frequency of Preventive Maintenance

The frequency of preventive maintenance tasks depends on the manufacturer’s recommendations, equipment usage, and criticality. Ensure the following tasks are performed at regular intervals:

1. Daily
   • Visual inspection of equipment for damage or wear
   • Cleaning of equipment surfaces and components
   • Lubrication of moving parts as required
2. Weekly
   • Calibration checks on weight sensors, filling mechanisms, and sealing machines
   • Inspection of air filters and pneumatic systems
3. Monthly
   • Full system inspection, including electrical systems and mechanical components
   • Replacement of worn parts and filters

5.5 Emergency Maintenance

In case of unexpected breakdowns or equipment failure, follow these steps:

1. Shutdown and Isolation
   1. Immediately shut down the equipment and isolate it from the production line to prevent further damage or safety hazards. Ensure that all electrical power is disconnected and the equipment is locked out for safety.
2. Assessment and Repair
   1. Assess the cause of the breakdown and repair the equipment as quickly as possible. If necessary, call in specialized maintenance personnel to address the issue.
3. Post-Repair Testing
   1. Once repairs are made, test the equipment to ensure that it is fully operational and that no further issues exist. Verify that the equipment is running smoothly and within the specified operational parameters.
4. Documentation
   1. Document the cause of the breakdown, the repair actions taken, and the outcome of the post-repair testing. Include any adjustments made to the equipment during repairs.

5.6 Documentation and Record-Keeping

It is essential to maintain accurate records of all preventive maintenance activities:

1. Equipment Maintenance Log
   1. Document all preventive maintenance activities in the equipment maintenance log, including the tasks performed, parts replaced, and any corrective actions taken.
2. Maintenance Request Form
   1. For any non-routine maintenance or repairs, complete a maintenance request form detailing the issue, the urgency of the repair, and any necessary parts or tools.
3. Calibration and Inspection Records
   1. Keep records of all calibration and inspection activities for each piece of equipment, including the results and any corrective actions taken.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Equipment Maintenance Log (Annexure-1)
2. Maintenance Request Form (Annexure-2)
3. Calibration and Inspection Records (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Equipment Maintenance Log

Annexure-2: Maintenance Request Form

Annexure-3: Calibration and Inspection Records

Revision History:

Standard Operating Procedure for Handling Rejected Capsules During Manufacturing

1. Purpose

The purpose of this SOP is to define the procedure for handling rejected capsules during the manufacturing process. Rejected capsules must be properly identified, segregated, and disposed of or reworked in accordance with established procedures to maintain product quality and comply with regulatory standards.

2. Scope

This SOP applies to all capsule manufacturing processes where capsules are rejected due to quality issues, such as defects in filling, sealing, weight, or appearance. It includes the steps for segregation, documentation, and disposal or rework of rejected capsules.

3. Responsibilities

• Manufacturing Team: Responsible for identifying and segregating rejected capsules during production, ensuring that they are handled as per this SOP.
• Quality Control (QC) Team: Responsible for inspecting rejected capsules, determining the cause of rejection, and ensuring that rejected capsules are disposed of or reworked as appropriate.
• Quality Assurance (QA) Team: Ensures that rejected capsules are handled according to SOP, investigates root causes of rejection, and ensures compliance with GMP regulations.
• Maintenance Team: Ensures that any equipment or machine malfunctions contributing to capsule rejection are promptly addressed and documented.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the rejected capsules are properly handled, segregated, and documented. The QA Manager is responsible for overseeing the rejection handling process and ensuring that all deviations are investigated and addressed appropriately.

5. Procedure

5.1 Identification of Rejected Capsules

During the manufacturing process, capsules may be rejected due to various reasons such as defects in fill weight, misalignment, sealing issues, or other quality problems. The following steps should be followed to identify rejected capsules:

1. Routine Inspections
   1. Conduct visual inspections and quality checks at regular intervals throughout the production process to identify defective capsules. Inspections should focus on visual defects, improper fill, damaged capsules, and other obvious issues.
2. Sampling
   1. Perform sample checks to detect potential defects. Rejected capsules should be marked immediately upon detection.
3. Defects to Look for
   1. Cracked or damaged shells
   2. Improperly filled or empty capsules
   3. Poorly sealed capsules
   4. Discoloration or contamination

5.2 Segregation of Rejected Capsules

Once capsules are identified as rejected, the following steps should be taken:

1. Immediate Segregation
   1. Immediately separate rejected capsules from the acceptable batch to prevent contamination or mixing with good capsules. Use designated bins or containers clearly marked as “Rejected” to segregate the defective capsules.
2. Labeling and Documentation
   1. Label the rejected capsules with the reason for rejection and batch number. Maintain records of rejected capsules, including the quantity and specific defect type. This should be documented in the batch production record and in a separate rejection log.
3. Regular Inspection
   1. Ensure that the rejected capsules are inspected regularly to prevent further contamination or mismanagement. Maintain clear separation between rejected and non-rejected capsules in the storage area.

5.3 Investigation of Rejected Capsules

If a significant number of capsules are rejected, a thorough investigation should be conducted to determine the root cause of the problem:

1. Root Cause Analysis
   1. Perform a root cause analysis to identify the underlying issue that caused the rejection. Common causes could include equipment malfunction, improper formulation, or human error.
2. Corrective Action
   1. Based on the investigation, take corrective actions to address the root cause. This may include equipment calibration, adjustments to machine settings, improved operator training, or changes to the raw materials.
3. Rework or Rejection
   1. Once the issue is identified and corrected, evaluate the rejected capsules to determine if they can be reworked or if they need to be discarded. For reworkable capsules, establish the process for reworking them to meet the required quality standards.

5.4 Disposal of Rejected Capsules

Once the rejection process is complete, the capsules must be properly disposed of if they cannot be reworked:

1. Segregation for Disposal
   1. Rejected capsules that cannot be reworked must be segregated for disposal. Place them in sealed containers and ensure that they are not accessible to production or quality control personnel.
2. Disposal Methods
   1. Ensure that the disposal of rejected capsules complies with environmental and safety regulations. Use approved disposal methods, such as incineration or disposal at certified waste management facilities.
3. Document Disposal
   1. Document the disposal of rejected capsules, including the quantity, reason for rejection, and disposal method. Ensure the record is kept for future reference and audit purposes.

5.5 Rework of Rejected Capsules

If the rejected capsules are reworkable, ensure the following steps are followed:

1. Rework Identification
   1. Determine if the rejected capsules can be reworked without compromising their quality or integrity. Common rework actions include refilling, resealing, or relabeling capsules.
2. Rework Process
   1. Follow the appropriate procedure for reworking the capsules. Document each step of the rework process, including adjustments made to the machine settings or formulation.
3. Re-inspection
   1. After rework, re-inspect the capsules to ensure that they meet the required quality specifications. Perform visual and weight checks to confirm that the capsules are now acceptable.

5.6 Documentation and Record-Keeping

Proper documentation is crucial for the traceability of rejected capsules:

1. Rejection Log
   1. Maintain a log of all rejected capsules, including the batch number, reason for rejection, and corrective actions taken. This log should be reviewed periodically for any trends or recurring issues.
2. Batch Production Records
   1. Document all rejection details in the batch production record, including the number of rejected capsules, reasons for rejection, and the actions taken to address the issue.
3. Deviation Reports
   1. For significant deviations, document a formal deviation report that includes a root cause analysis, corrective actions, and any impact on product quality.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Rejected Capsule Report (Annexure-1)
2. Deviation and Corrective Action Report (Annexure-2)
3. Rework Documentation Log (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Rejected Capsule Report

Annexure-2: Deviation and Corrective Action Report

Annexure-3: Rework Documentation Log

Revision History:

Standard Operating Procedure for Ensuring Uniform Gelatin Shell Thickness

1. Purpose

The purpose of this SOP is to define the procedure for ensuring uniform gelatin shell thickness during the capsule manufacturing process. Achieving consistent shell thickness is crucial for maintaining capsule integrity, ensuring consistent drug release, and complying with product specifications.

2. Scope

This SOP applies to all capsule manufacturing processes involving gelatin shell formation. It includes the procedures for monitoring, adjusting, and verifying the uniformity of gelatin shell thickness during production.

3. Responsibilities

• Manufacturing Team: Responsible for ensuring that the gelatin shell thickness is uniform and meets the required specifications during production. They must also monitor shell thickness and make necessary adjustments.
• Quality Control (QC) Team: Responsible for performing periodic checks to ensure uniform gelatin shell thickness and verifying that the shells meet the required thickness specifications.
• Quality Assurance (QA) Team: Ensures that the procedure for controlling gelatin shell thickness is followed and that any deviations are documented and addressed.
• Maintenance Team: Ensures that the equipment used to produce the gelatin shells is properly calibrated and functioning to produce capsules with uniform shell thickness.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that uniform gelatin shell thickness is maintained throughout the production process. The QA Manager is responsible for ensuring compliance with this SOP and reviewing the inspection results.

5. Procedure

5.1 Pre-Production Setup

Before starting the production process, ensure the following steps are completed:

1. Machine Setup
   1. Ensure that the capsule filling machine is clean and free from residues from previous batches. Perform a thorough inspection of the machine, particularly the parts responsible for gelatin shell formation.
   2. Set up the gelatin preparation system, ensuring that the correct formulation (e.g., gelatin type, plasticizer content, and moisture level) is used to achieve the desired shell properties.
2. Gelatin Solution Preparation
   1. Prepare the gelatin solution according to the formulation and temperature requirements. Ensure that the gelatin concentration and viscosity are within the specified limits to ensure proper shell formation.
3. Documentation
   1. Document the setup parameters, including gelatin solution details, capsule size, and machine settings in the batch production record.

5.2 Monitoring Gelatin Shell Thickness During Production

During the production process, monitor the gelatin shell thickness to ensure uniformity:

1. Regular Thickness Measurements
   1. Use calibrated micrometers or automated thickness measurement systems to check the shell thickness at regular intervals during production. Measure a sample of capsules from the start, middle, and end of the production run.
2. Acceptable Thickness Range
   1. The gelatin shell thickness must fall within the specified range, typically ±0.05 mm of the target thickness. If capsules fall outside this range, take corrective action immediately.
3. Inspection Points
   1. Inspect the shell thickness from various locations around the capsule (e.g., at the top, middle, and bottom) to ensure uniformity. Any significant variation in thickness must be addressed.
4. Automated Monitoring
   1. If available, use automated systems to continuously monitor the shell thickness throughout the production run. Set up alerts to notify operators if the thickness deviates from the acceptable range.

5.3 Adjusting Parameters to Maintain Uniformity

If the shell thickness deviates from the acceptable range, follow these steps:

1. Adjust Machine Settings
   1. Adjust the temperature or speed of the gelatin casting and drying process to control the shell thickness. Typically, increasing the gelatin temperature or slowing down the machine speed may increase the shell thickness.
2. Gelatin Solution Adjustments
   1. If the thickness variation is due to the gelatin solution, adjust its concentration or viscosity. Ensure the solution is mixed properly to prevent inconsistent shell thickness.
3. Re-Check Thickness
   1. After making adjustments, continue measuring the thickness of capsules to ensure that the modifications have successfully brought the shell thickness within the desired range. Verify that the shell thickness is consistent across all sample points.

5.4 Post-Production Review

After completing the production run, perform the following checks:

1. Review Thickness Data
   1. Review the recorded thickness measurements to ensure that they meet the required specifications. Ensure that no deviations were left unaddressed during the production process.
2. Confirm Compliance
   1. Ensure that the final batch of capsules meets the required shell thickness specifications and that any deviations from the specified range were corrected during the production process.
3. Documentation
   1. Document the final shell thickness measurements in the batch production record, including any corrective actions taken during production.

5.5 Equipment Maintenance and Calibration

Ensure that the equipment used to measure and adjust shell thickness is properly maintained:

1. Routine Equipment Calibration
   1. Perform regular calibration of all thickness measurement tools, including micrometers and automated systems. Ensure that calibration is performed according to the manufacturer’s specifications.
2. Maintenance of Manufacturing Equipment
   1. Ensure that all equipment involved in the gelatin shell formation process, such as the capsule filling machine, is well-maintained and regularly serviced. Perform checks on temperature controls, the dosing system, and the drying system to ensure consistent operation.

5.6 Documentation and Record-Keeping

Ensure proper documentation of all activities related to gelatin shell thickness:

1. Thickness Measurement Records
   1. Document all shell thickness measurements, including the results of the sample capsules taken during the production run. Include the batch number, machine settings, and any corrective actions taken.
2. Deviation and Corrective Action Records
   1. Document any deviations from the target shell thickness and the corrective actions taken. Include the time, cause of deviation, and actions implemented to restore uniformity.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Shell Thickness Measurement Log (Annexure-1)
2. Deviation and Corrective Action Report (Annexure-2)
3. Calibration and Maintenance Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Shell Thickness Measurement Log

Annexure-2: Deviation and Corrective Action Report

Annexure-3: Calibration and Maintenance Record

Revision History:

Standard Operating Procedure for Visual Inspection of Capsules During Production

1. Purpose

The purpose of this SOP is to outline the procedure for performing visual inspection of capsules during production to ensure that they meet the required quality standards. This is critical for identifying defects such as cracks, improper sealing, or contamination before the capsules are released for further processing.

2. Scope

This SOP applies to all capsules produced within the manufacturing facility. It covers the visual inspection process of capsules during production to ensure that they meet the necessary specifications for quality, integrity, and appearance.

3. Responsibilities

• Manufacturing Team: Responsible for performing the visual inspection of capsules, following the procedures outlined in this SOP, and segregating defective capsules.
• Quality Control (QC) Team: Responsible for overseeing the visual inspection process, ensuring compliance with quality standards, and verifying that all identified defects are recorded and addressed.
• Quality Assurance (QA) Team: Ensures that the SOP is followed during capsule production and inspects the documentation for compliance with GMP standards.
• Maintenance Team: Responsible for ensuring that the visual inspection equipment, such as inspection cameras or lights, is properly maintained and functioning.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the visual inspection process is carried out effectively. The QA Manager is responsible for reviewing the inspection records and ensuring that all deviations are appropriately addressed and documented.

5. Procedure

5.1 Pre-Inspection Preparation

Before starting the inspection process, ensure the following steps are completed:

1. Equipment Setup
   1. Ensure that the visual inspection area is well-lit and free from any obstructions that may hinder the inspection process.
   2. Verify that inspection equipment, such as cameras or magnification tools, is calibrated and in good working condition. Clean the equipment before use to prevent contamination.
2. Material and Capsule Preparation
   1. Ensure that the capsule shells are properly formed and free from any physical damage or deformities before beginning the filling process.
   2. Prepare the capsules for inspection by transferring them to the inspection station, ensuring that they are handled properly to avoid contamination.
3. Documentation
   1. Document the batch information, including capsule size, fill material, and inspection parameters, in the batch production record.

5.2 Visual Inspection Process

During production, the following steps should be taken to inspect the capsules visually:

1. Continuous Monitoring
   1. Perform visual inspections on capsules during production at regular intervals to ensure they meet the required specifications. Check for defects such as cracks, dents, discoloration, improper filling, or any other visible defects.
2. Inspection Criteria
   1. Examine each capsule for the following defects:
      • Cracks or chips on the capsule shell.
      • Uneven or incomplete filling of the capsule.
      • Missing or poorly sealed capsule halves.
      • Discoloration or contamination on the capsule surface.
3. Defective Capsule Segregation
   1. Immediately segregate any defective capsules identified during the visual inspection. Place them in a designated area or container marked as “Rejected” to avoid cross-contamination with good capsules.
4. Inspection Frequency
   1. Inspect a sample of capsules from each batch at the start, middle, and end of the production run to ensure consistency in quality throughout the process.

5.3 Post-Inspection Actions

After completing the visual inspection, the following actions should be taken:

1. Defective Capsule Documentation
   1. Document the total number of defective capsules identified during the inspection, including the type of defect (e.g., cracks, underfilled capsules, etc.). Record this information in the inspection log or batch production record.
2. Rejection and Disposal
   1. If the number of rejected capsules exceeds an acceptable threshold, stop the production process and investigate the cause. Document the reason for the rejection and take corrective actions if necessary.
   2. Dispose of defective capsules in accordance with environmental and safety regulations. If rework is possible, initiate the rework process based on the severity of the defect.
3. Verification and Rework
   1. If the number of defective capsules is within the acceptable range, verify that the corrective actions were effective, and restart the production process. Perform further visual inspections if necessary to ensure continued product quality.

5.4 Documentation and Record-Keeping

Document all visual inspection activities to ensure traceability and compliance:

1. Inspection Logs
   1. Maintain a log of all visual inspections performed, including the number of capsules inspected, the number of defective capsules identified, and any corrective actions taken.
2. Quality Control Records
   1. Ensure that QC records include details of the inspection, including the batch number, operator name, and inspection results. Any deviations from the standard should be noted, along with the corrective actions taken.
3. Deviation Reports
   1. Document any deviations from the standard visual inspection criteria, including the cause of the defect and any steps taken to resolve the issue. Include the impact of the deviation on the production process.

5.5 Equipment Maintenance

Ensure that all visual inspection equipment is properly maintained:

1. Routine Maintenance
   1. Perform routine maintenance on all inspection equipment, including visual inspection cameras, lighting, and magnification tools. Ensure that these tools are calibrated and free from defects.
2. Calibration
   1. Calibrate inspection tools and equipment at regular intervals to ensure accuracy and reliability. Record all calibration activities in the equipment log.

5.6 Training and Competency

Ensure that all operators involved in visual inspection are properly trained:

1. Training
   1. Provide training to all manufacturing and QC personnel on the visual inspection process, including how to identify common defects and the importance of accurate inspection. Ensure that operators understand the criteria for acceptable and rejected capsules.
2. Competency Verification
   1. Verify the competency of operators by conducting periodic assessments and providing feedback based on their inspection performance. Ensure that any deficiencies are addressed through additional training or support.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Capsule Visual Inspection Log (Annexure-1)
2. Defective Capsule Report (Annexure-2)
3. Calibration and Maintenance Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Capsule Visual Inspection Log

Annexure-2: Defective Capsule Report

Annexure-3: Calibration and Maintenance Record

Revision History:

Standard Operating Procedure for Adjusting Capsule Filling Machine Parameters

1. Purpose

The purpose of this SOP is to provide a standardized procedure for adjusting the parameters of the capsule filling machine to ensure consistent capsule fill weight, capsule size, and proper capsule closure. These adjustments are critical for ensuring that all capsules meet the required quality standards and regulatory requirements.

2. Scope

This SOP applies to all capsule filling operations within the manufacturing facility where the capsule filling machine is used. It covers the procedure for adjusting key parameters of the machine, including fill weight, capsule alignment, capsule closure, and the operational settings for different types of capsules.

3. Responsibilities

• Manufacturing Team: Responsible for operating the capsule filling machine, adjusting machine parameters as per the SOP, and ensuring proper documentation of adjustments.
• Quality Control (QC) Team: Responsible for verifying the accuracy of the machine parameters during production runs and ensuring the adjusted parameters meet the required specifications for capsule quality.
• Quality Assurance (QA) Team: Ensures compliance with this SOP and reviews the adjustment records to verify that all adjustments align with regulatory and GMP standards.
• Maintenance Team: Responsible for ensuring that the capsule filling machine is properly maintained and calibrated, including the adjustment of machine parameters when required.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the capsule filling machine parameters are adjusted and maintained according to this SOP. The QA Manager is responsible for reviewing records and ensuring compliance with regulatory requirements.

5. Procedure

5.1 Pre-Adjustment Preparation

Before adjusting the machine parameters, ensure the following steps are completed:

1. Equipment Inspection
   1. Ensure the capsule filling machine is clean and free from any previous batch residues. Inspect all parts of the machine, including the hopper, dosing system, and capsule alignment mechanisms, for signs of wear or damage.
   2. Verify that the filling machine is properly calibrated and operating within the specified parameters set by the manufacturer.
2. Material Preparation
   1. Ensure that the capsule fill material is prepared according to the product specifications, including the correct viscosity, particle size, and moisture content.
   2. Check that the capsules (shells) are of the correct size and in proper condition for filling.
3. Documentation
   1. Record the initial machine settings, including the capsule size, fill weight, and other key parameters, in the batch production record.

5.2 Adjusting Capsule Filling Machine Parameters

Once pre-adjustment preparation is completed, follow these steps to adjust the machine parameters:

1. Set Fill Weight
   1. Adjust the fill weight by changing the volume of material dispensed into each capsule. This is done by adjusting the dosing system on the machine.
   2. Ensure that the fill weight is set according to the target specification. Perform a weight check on a sample of capsules to verify that the fill weight is within the acceptable range (±5% of the target weight).
2. Adjust Capsule Alignment
   1. Ensure that the capsules are aligned correctly within the filling machine. Misalignment can cause issues with capsule filling and closure. Adjust the alignment mechanisms as needed to ensure that the capsules are properly seated in the filling and closing areas of the machine.
3. Set Capsule Closure
   1. Adjust the sealing system to ensure that the capsules are properly closed after filling. The closure should be tight and uniform to prevent leakage of the fill material.
   2. Verify that the closure is secure by inspecting a sample of capsules for any signs of improper sealing, such as broken or poorly closed capsules.
4. Adjust Machine Speed
   1. Adjust the machine speed based on the production requirements. Ensure that the speed is set to allow for optimal capsule filling without compromising the accuracy of the fill weight or closure.

5.3 Verifying Adjustments

After making adjustments to the capsule filling machine parameters, follow these steps to verify that the changes are correct:

1. Perform Weight Checks
   1. Weigh a sample of filled capsules to ensure that the fill weight is within the acceptable range. This check should be done regularly throughout the production run to confirm that the adjustments have achieved the desired results.
2. Visual Inspection
   1. Perform a visual inspection of the capsules to ensure that they are properly aligned and that the closures are secure. Reject any capsules that show signs of misalignment or poor sealing.
3. Functional Test
   1. Test the filling and sealing functions of the machine by running a small test batch of capsules. Inspect the test batch to ensure that the capsules meet the required specifications for fill weight, size, and closure.

5.4 Post-Adjustment Documentation

After adjusting the machine parameters and verifying their accuracy, ensure the following documentation is completed:

1. Machine Setting Records
   1. Record the final machine settings, including the fill weight, capsule alignment, closure settings, and machine speed in the batch production record.
2. Quality Control Records
   1. Document the results of the weight checks, visual inspections, and functional tests. Include any deviations from the target specifications and the corrective actions taken to resolve them.
3. Deviation Reports
   1. Document any deviations from the required machine parameters and the corrective actions implemented to address the issue.

5.5 Maintenance and Calibration

Ensure that the machine remains in good working condition to maintain the accuracy of the filling and sealing process:

1. Routine Maintenance
   1. Perform routine maintenance on the capsule filling machine, including cleaning, lubrication, and inspection of key components such as the dosing system, capsule feeder, and sealing mechanism.
2. Calibration
   1. Ensure that the machine is calibrated at regular intervals as per the manufacturer’s guidelines. Verify that the fill weight, capsule alignment, and sealing parameters are within the specified limits.

5.6 Documentation and Record-Keeping

Maintain accurate records of all adjustments made to the capsule filling machine:

1. Adjustment Logs
   1. Document all adjustments made to the machine, including the date, the operator performing the adjustment, and the reason for the change. Include the final machine settings and any observations made during the process.
2. Deviation and Corrective Action Records
   1. Maintain records of any deviations from the target settings, the corrective actions taken, and the final outcome after the corrections are implemented.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Machine Adjustment Log (Annexure-1)
2. Quality Control Test Record (Annexure-2)
3. Deviation and Corrective Action Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Machine Adjustment Log

Annexure-2: Quality Control Test Record

Annexure-3: Deviation and Corrective Action Record

Revision History:

Standard Operating Procedure for Controlling Temperature and Humidity in Manufacturing Areas

1. Purpose

The purpose of this SOP is to ensure proper control of temperature and humidity levels in the manufacturing areas to maintain the quality and stability of the capsule formulation. This is essential to meet regulatory standards and ensure the proper functioning of the capsule production process.

2. Scope

This SOP applies to all capsule manufacturing areas, including production rooms, drying areas, and storage areas for raw materials and finished products. It covers the procedures for monitoring, controlling, and documenting temperature and humidity levels during the manufacturing process.

3. Responsibilities

• Manufacturing Team: Responsible for maintaining the proper temperature and humidity settings in the production areas, ensuring that equipment is functioning properly, and addressing any deviations promptly.
• Quality Control (QC) Team: Responsible for monitoring temperature and humidity levels regularly and conducting audits to ensure compliance with the required specifications.
• Quality Assurance (QA) Team: Ensures that temperature and humidity controls are maintained according to GMP guidelines, reviews documentation, and verifies compliance during audits.
• Maintenance Team: Responsible for maintaining and calibrating temperature and humidity control systems and ensuring that they are functioning correctly.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that temperature and humidity levels in manufacturing areas are controlled according to this SOP. The QA Manager is responsible for ensuring compliance with this procedure and reviewing records for regulatory compliance.

5. Procedure

5.1 Pre-Production Setup

Before starting production, ensure the following steps are completed to control temperature and humidity:

1. Temperature and Humidity Settings
   1. Set the temperature and humidity levels according to the requirements for the specific manufacturing process. Typical temperature ranges are between 20°C and 25°C, with humidity levels ranging from 30% to 60%, depending on the material and process requirements.
   2. Check that the temperature and humidity control equipment is properly calibrated before starting production.
2. Environmental Equipment Inspection
   1. Inspect HVAC (Heating, Ventilation, and Air Conditioning) systems, humidifiers, dehumidifiers, and thermostats to ensure they are in good working condition. Ensure that backup systems are available in case of failure.
3. Documentation
   1. Document the target temperature and humidity settings for each production area, and ensure that all relevant equipment is listed in the batch production records.

5.2 Continuous Monitoring of Temperature and Humidity

During production, continuously monitor the temperature and humidity levels in the manufacturing areas:

1. Continuous Monitoring
   1. Use automated temperature and humidity monitoring systems to continuously track environmental conditions in real time. Ensure that all monitoring devices are regularly calibrated.
2. Manual Inspections
   1. In addition to automated systems, conduct manual temperature and humidity checks at least once every 4 hours to verify the automated system readings. Record the results in the appropriate log.
3. Alarm Systems
   1. Ensure that alarm systems are in place to notify operators if temperature or humidity levels fall outside the acceptable range. The system should trigger an immediate investigation and corrective action.

5.3 Corrective Actions for Deviations

If temperature or humidity deviations occur, follow these steps:

1. Investigate the Cause
   1. Identify the cause of the deviation. Common causes may include HVAC system malfunction, material handling issues, or operator error.
   2. Check for any environmental disturbances, such as external weather conditions, which may be influencing the internal temperature or humidity.
2. Implement Corrective Action
   1. If the HVAC system is malfunctioning, immediately repair or adjust the system. If the deviation is due to other causes, address the issue accordingly (e.g., adjust the material handling process or relocate products to a more controlled area).
3. Verify Corrective Actions
   1. Once corrective actions are implemented, verify that temperature and humidity levels have returned to the acceptable range. Continue monitoring closely for several hours to ensure stability.
4. Documentation of Deviations
   1. Document any deviations, including the cause, corrective actions taken, and verification results. Include any impact on production and whether any product quality was affected.

5.4 Post-Production Review

After production, ensure the following checks are completed:

1. Environmental Records Review
   1. Review the environmental monitoring records to verify that temperature and humidity levels were maintained within the acceptable ranges during production. Ensure that all deviations have been properly documented and investigated.
2. Compliance Check
   1. Verify that all temperature and humidity records are in compliance with GMP standards and any relevant regulatory requirements (e.g., FDA, EMA, or ICH guidelines).

5.5 Equipment Maintenance and Calibration

Ensure that all environmental control equipment is properly maintained and calibrated:

1. Routine Maintenance
   1. Perform routine maintenance on temperature and humidity control equipment, including air conditioning, humidity controllers, and automated monitoring systems.
   2. Check all systems for proper functioning and replace any components that show signs of wear or malfunction.
2. Calibration
   1. Ensure that temperature and humidity sensors are calibrated at regular intervals, based on the manufacturer’s recommendations, or at least once every six months.

5.6 Documentation and Record-Keeping

Proper documentation of environmental controls is critical for regulatory compliance:

1. Environmental Monitoring Records
   1. Document all temperature and humidity readings, including any deviations and the corresponding corrective actions taken. Maintain these records in batch production files for traceability.
2. Calibration and Maintenance Records
   1. Maintain records of calibration and maintenance activities for temperature and humidity control equipment, including calibration certificates and maintenance logs.
3. Deviation Reports
   1. Document any deviations from the required environmental conditions, including the cause of the deviation, corrective actions, and verification results.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Temperature and Humidity Monitoring Record (Annexure-1)
2. Calibration and Maintenance Record (Annexure-2)
3. Deviation Report (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Temperature and Humidity Monitoring Record

Annexure-2: Calibration and Maintenance Record

Annexure-3: Deviation Report

Revision History:

Standard Operating Procedure for Ensuring Uniformity of Capsule Weight During Production

1. Purpose

The purpose of this SOP is to outline the process for ensuring uniformity of capsule weight during production. This is essential to meet regulatory standards, improve product quality, and maintain consistency across capsules in terms of both weight and active ingredient content.

2. Scope

This SOP applies to all capsule manufacturing processes, where the weight of the capsules is a critical quality attribute. It covers the methods for weight monitoring, sampling frequency, and corrective actions to ensure uniformity of capsule weight throughout production.

3. Responsibilities

• Manufacturing Team: Responsible for operating the capsule filling equipment and ensuring that the correct amount of material is dispensed into each capsule. They must also ensure the weight of the capsules meets the required specifications.
• Quality Control (QC) Team: Responsible for performing regular weight checks during the production process and ensuring that capsules meet the required weight specifications. QC will also investigate any deviations.
• Quality Assurance (QA) Team: Ensures that this SOP is followed and that all necessary records are maintained for traceability. QA also reviews any deviations and approves corrective actions.
• Maintenance Team: Responsible for ensuring that all equipment used in the filling process is calibrated and maintained properly to avoid issues related to inconsistent capsule weight.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring uniformity of capsule weight during production and for overseeing the proper implementation of this SOP. The QA Manager is responsible for reviewing the records and ensuring compliance with regulatory requirements.

5. Procedure

5.1 Pre-Production Setup

Before beginning the production process, ensure the following steps are completed:

1. Equipment Inspection
   1. Inspect the capsule filling machine for cleanliness and ensure it is calibrated properly. Ensure that all components of the machine are functioning correctly, including the filling system, dosing system, and weight monitoring system.
2. Material Preparation
   1. Ensure that the fill material is prepared and meets the required specifications (e.g., consistency, viscosity, and moisture content). Ensure the material is homogeneous before it is fed into the filling machine.
3. Documentation
   1. Document the batch information, including capsule size, fill material, and the expected fill weight. Ensure that this documentation is ready before starting the production run.

5.2 Weight Monitoring During Production

During the production process, the following steps should be taken to monitor and ensure capsule weight uniformity:

1. Sample Collection
   1. Collect capsule samples at regular intervals during production to monitor weight uniformity. The sample size should be determined based on the batch size and statistical sampling principles.
2. Weight Measurement
   1. Weigh each sample capsule using a calibrated analytical balance. Record the weight of each capsule and compare it with the target weight specified for the batch.
3. Acceptance Criteria
   1. The weight of each capsule must be within ±5% of the target weight. If the capsules fall outside this range, further investigation is needed.
4. Automated Weight Monitoring
   1. If an automated weight monitoring system is used, ensure it is continuously monitoring the capsule weight during production. Any deviation from the target weight should trigger an alert and initiate corrective actions.

5.3 Corrective Actions for Weight Deviations

If weight deviations are detected, follow these steps:

1. Investigate the Cause
   1. Investigate the cause of the weight deviation. Potential causes may include incorrect machine settings, material variations, or improper machine calibration.
2. Corrective Action
   1. Based on the investigation, implement the necessary corrective actions, such as adjusting the fill material flow rate, recalibrating the machine, or replacing any malfunctioning components.
3. Rework or Discard Capsules
   1. If a large number of capsules fall outside the acceptable weight range, they may need to be reworked or discarded, depending on the nature of the deviation and the production stage.
4. Restart Production
   1. Once the corrective actions are implemented, restart production and monitor capsule weight closely until uniformity is restored. Take additional samples to verify that the problem is resolved.

5.4 Post-Production Review

After completing the production run, perform the following steps:

1. Data Review
   1. Review all the capsule weight data collected during the production run, including individual weights, average weight, and standard deviation. Ensure that all capsules meet the required weight specifications.
2. Documentation
   1. Document the final weight results, including the average weight, standard deviation, and any corrective actions taken. Include this information in the batch production record.

5.5 Equipment Maintenance and Calibration

Ensure that the capsule filling equipment is properly maintained to ensure consistent weight uniformity:

1. Routine Maintenance
   1. Perform routine maintenance on the capsule filling machine, including cleaning, calibration, and inspection of critical components such as the dosing system and weight monitoring equipment.
2. Calibration
   1. Ensure that all measurement equipment, including balances and automated weight monitoring systems, are calibrated regularly according to the manufacturer’s specifications.

5.6 Documentation and Record-Keeping

Ensure thorough documentation of all weight monitoring and corrective actions:

1. Weight Monitoring Records
   1. Document the results of all weight monitoring activities, including the average capsule weight, individual weights, and any deviations observed during the production run.
2. Deviation Reports
   1. Document any deviations from the target weight specifications and the corrective actions taken to resolve them. Include the root cause analysis and any preventive measures implemented.
3. Calibration and Maintenance Records
   1. Maintain records of all equipment calibration and maintenance activities, including the date of calibration, the technician involved, and any corrective actions taken to ensure proper functioning.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Capsule Weight Monitoring Record (Annexure-1)
2. Deviation Report (Annexure-2)
3. Calibration and Maintenance Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Capsule Weight Monitoring Record

Annexure-2: Deviation Report

Annexure-3: Calibration and Maintenance Record

Revision History:

Standard Operating Procedure for Handling Overfilled or Underfilled Capsules

1. Purpose

The purpose of this SOP is to outline the procedures for identifying and handling overfilled or underfilled capsules during the manufacturing process. This ensures that all capsules meet the required fill weight specifications, maintaining the quality and integrity of the final product.

2. Scope

This SOP applies to all capsule manufacturing operations where capsules are filled with material. It covers the identification, segregation, and appropriate corrective actions for overfilled or underfilled capsules to ensure quality standards are met.

3. Responsibilities

• Manufacturing Team: Responsible for identifying overfilled or underfilled capsules during the filling process, following the necessary steps to segregate them, and providing relevant details for further investigation and correction.
• Quality Control (QC) Team: Responsible for verifying that the capsules meet the fill weight specifications and ensuring that all non-conforming capsules are segregated and properly documented.
• Quality Assurance (QA) Team: Ensures that this SOP is adhered to and verifies that the necessary corrective actions are implemented in case of overfilled or underfilled capsules.
• Capsule Manufacturing Supervisor: Oversees the capsule filling process and ensures the proper handling and documentation of overfilled or underfilled capsules, ensuring that the appropriate corrective actions are taken.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that overfilled or underfilled capsules are properly identified and handled according to this SOP. The QA Manager is responsible for ensuring compliance with this procedure and reviewing records for regulatory compliance.

5. Procedure

5.1 Identification of Overfilled or Underfilled Capsules

During the filling process, capsules may be overfilled or underfilled. Follow these steps to identify such capsules:

1. Visual Inspection
   1. Conduct visual inspection of capsules during the filling process to identify any that appear too full (overfilled) or too empty (underfilled). Pay particular attention to size and symmetry.
2. Weight Inspection
   1. Perform regular weight checks on a sample of capsules throughout the filling process. Use calibrated weighing scales to measure capsule weight and compare the results to the target weight specifications.
   2. If the average weight is outside of the acceptable range (typically ±5% of the target weight), investigate the issue further.
3. Automated Inspection Systems
   1. If an automated weight inspection system is available, use it to continuously monitor the fill weight of capsules during the production process. The system should flag any capsules that deviate from the specified weight range.

5.2 Segregation of Overfilled or Underfilled Capsules

Once overfilled or underfilled capsules are identified, follow these steps:

1. Segregation of Defective Capsules
   1. Immediately remove any overfilled or underfilled capsules from the production line to prevent contamination with correctly filled capsules.
   2. Place defective capsules in a designated container or area clearly marked as “Rejected.” Ensure the area is secure to avoid accidental contamination of non-defective capsules.
2. Identification and Labeling
   1. Label the containers or storage areas containing rejected capsules with clear information, such as the batch number, defect type (overfilled or underfilled), and the number of capsules removed.

5.3 Investigation and Corrective Actions

After identifying and segregating defective capsules, follow these steps to investigate the cause and implement corrective actions:

1. Root Cause Analysis
   1. Investigate the cause of overfilling or underfilling. Potential causes may include inconsistent fill material, equipment malfunction, or improper machine settings.
   2. Perform a detailed investigation to identify whether the issue is isolated to a specific batch or if it represents a systematic problem in the filling process.
2. Corrective Actions
   1. If the issue is equipment-related, schedule immediate maintenance and calibration of the filling machine to ensure that the fill material is dispensed accurately.
   2. If the issue is related to material properties (e.g., inconsistent viscosity or moisture content), adjust the material formulation or handling procedures.
   3. After corrective actions are taken, restart the filling process and perform additional checks to verify that the issue has been resolved.

5.4 Rework or Disposal of Defective Capsules

After identifying the cause and implementing corrective actions, the following steps should be followed for the defective capsules:

1. Rework
   1. If the overfilled or underfilled capsules can be reworked (e.g., by adjusting the fill weight or resealing), follow the appropriate procedures for rework and documentation.
2. Disposal
   1. If the capsules cannot be reworked, dispose of them in accordance with environmental and safety regulations. Ensure that all disposed capsules are documented and the disposal method is compliant with regulatory guidelines.

5.5 Documentation and Record-Keeping

Ensure proper documentation of all actions taken during the handling of overfilled or underfilled capsules:

1. Segregation and Investigation Records
   1. Document all overfilled or underfilled capsules, including the number of defective capsules, the batch number, and the cause of the issue.
2. Corrective Action Records
   1. Document any corrective actions taken, including the maintenance or calibration performed, material adjustments made, or any other actions taken to prevent recurrence.
3. Deviation Reports
   1. Document any deviations from the specified fill weight, including the corrective actions taken, and the outcome of the rework or disposal process.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Capsule Fill Weight Record (Annexure-1)
2. Deviation Report (Annexure-2)
3. Corrective Action Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Capsule Fill Weight Record

Annexure-2: Deviation Report

Annexure-3: Corrective Action Record

Revision History: