Standard Operating Procedure for Testing Thickness of Enteric Coating in Process

1. Purpose

To establish the procedure for measuring and ensuring the correct thickness of the enteric coating applied to tablets during the production process.

2. Scope

This SOP applies to the measurement of enteric coating thickness on tablets during the coating process, ensuring that the tablets meet product specifications for uniformity and quality.

3. Responsibilities

• Quality Control (QC): Responsible for performing the thickness testing of the enteric coating on tablets, documenting results, and ensuring that the coating meets specified thickness standards.
• Production Operator: Responsible for ensuring that the tablet coating process is performed according to the batch record and notifying QC when tablets are ready for thickness testing.
• Quality Assurance (QA): Ensures that the coating thickness testing procedure is followed according to the SOP and reviews the documentation for compliance.

4. Accountability

The QC Manager is accountable for ensuring that the enteric coating thickness test is performed as required and that any deviations from the specification are properly addressed. The QA Manager ensures compliance with this SOP and approves corrective actions when necessary.

5. Procedure

5.1 Preparation for Thickness Testing

1. Ensure that the enteric coating equipment is properly set up and calibrated before starting the coating process.
2. Verify that the batch of tablets is ready for coating, with all required excipients and active ingredients in place.
3. Ensure that the required tools and instruments for measuring coating thickness (e.g., micrometers or specialized coating thickness gauges) are available and calibrated.
4. Confirm that the coating pan and drying system are operating within the specified parameters, such as temperature and airflow, to ensure uniform coating application.

5.2 Sampling of Tablets

1. Take a representative sample of tablets from the batch after the enteric coating process has been completed. Typically, 5 to 10 tablets should be sampled for testing, or as per the batch record.
2. Label the samples with batch information, date, and time of sampling to ensure traceability.
3. Ensure that the tablets are at room temperature and have not undergone any further processing, such as packaging, before testing.

5.3 Measuring Coating Thickness

1. Measure the thickness of the enteric coating on each tablet using an appropriate measuring instrument (e.g., micrometer, coating thickness gauge, or other methods as approved by QC).
2. For manual measurement, select random areas on the tablet surface and record the thickness at these points. Ensure that the measurements are taken at multiple locations to confirm uniformity of the coating.
3. For automated systems, ensure that the equipment is calibrated and functioning properly, and record the measurements from the system.
4. Document the measured values in the batch record (Annexure-2) and calculate the average thickness for the sampled tablets.

5.4 Documentation of Results

1. Record the measured thickness values, average thickness, and any deviations from the acceptable thickness range in the batch record (Annexure-2).
2. If the measured thickness exceeds the specified limits, initiate a deviation report (Annexure-1) and investigate the cause of the variation.
3. Ensure that all results are signed by the responsible QC personnel and reviewed by QA.

5.5 Corrective Actions for Coating Thickness Deviations

1. If the coating thickness exceeds or falls short of the acceptable limits, investigate the cause of the deviation. Possible causes may include incorrect coating solution viscosity, inadequate pan speed, or improper application of the coating.
2. Adjust the coating process parameters, such as the solution viscosity, spray rate, or pan speed, to bring the thickness back within specifications.
3. Re-sample and re-test the batch to confirm that the coating thickness is now within the required range.
4. Record all corrective actions in the deviation report and the batch record.

5.6 Acceptance Criteria

1. The batch is considered acceptable if the measured coating thickness is within the predefined limits specified in the batch record (typically ±10% of the target thickness).
2. If more than 2 tablets in the sample fail the thickness test, initiate a deviation report and further investigation into the root cause of the variation.

5.7 Post-Testing Actions

1. If the batch passes the coating thickness test, proceed with the next step in the tablet manufacturing process, such as drying or packaging.
2. If the batch fails, perform corrective actions, rework the batch if necessary, and re-test the tablets to ensure the coating meets the required specifications.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Tablet Coating Specifications
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Tablet Manufacturing Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for Weight Variation Control in Extended Release Tablets

1. Purpose

To establish a standardized procedure for controlling and monitoring weight variation in extended-release tablets, ensuring that each tablet meets the required weight specifications and remains consistent during production.

2. Scope

This SOP applies to the production of extended-release tablets, focusing on monitoring and controlling weight variation to ensure uniformity and compliance with product specifications during tablet manufacturing.

3. Responsibilities

• Quality Control (QC): Responsible for performing weight variation testing, documenting results, and ensuring that tablets meet the specified weight limits.
• Production Operator: Responsible for maintaining consistent tablet weight during the compression process and notifying QC when weight variation testing is required.
• Quality Assurance (QA): Ensures that weight variation control procedures are followed according to this SOP and reviews the documentation for compliance.

4. Accountability

The QC Manager is accountable for ensuring that weight variation testing is conducted regularly and that any deviation from the weight specifications is properly addressed. The QA Manager ensures that the procedure is followed according to this SOP and approves corrective actions as necessary.

5. Procedure

5.1 Preparation for Weight Variation Testing

1. Ensure the tablet compression machine is set correctly for extended-release tablet production, maintaining the appropriate compression pressure.
2. Verify that the batch of materials is ready for compression, including the appropriate excipients and API.
3. Ensure that the necessary equipment for weight variation testing, such as analytical balances and sampling containers, is available and calibrated.

5.2 Sampling of Tablets

1. Sample at least 20 tablets from each batch or according to the specified sample size in the batch record.
2. Ensure that tablets are sampled randomly from the tablet press to provide a representative sample of the batch.
3. Label the samples with the batch information and ensure they are properly documented.

5.3 Weight Variation Testing

1. Weigh each tablet individually on a calibrated analytical balance to the nearest milligram.
2. Record the weight of each tablet and calculate the average weight of the sample.
3. Check the weight variation against the specified limits outlined in the product’s quality specifications. The acceptable variation is typically ±5% of the average weight for extended-release tablets.
4. If the variation exceeds the permissible limits, the batch will be considered out of specification (OOS) and corrective actions must be taken.

5.4 Documentation of Results

1. Document the individual weights of the sampled tablets, the average weight, and the results of the weight variation test in the batch record (Annexure-2).
2. Note any deviations from the acceptable weight variation limits and indicate corrective actions taken in the deviation report (Annexure-1).

5.5 Corrective Actions for Weight Variation Issues

1. If weight variation exceeds the acceptable limits, investigate potential causes such as incorrect formulation, issues with tablet compression, or worn-out tooling.
2. Adjust the tablet compression settings, such as the die and punch alignment, tablet press speed, or compression pressure.
3. If the issue is related to formulation, review the excipient composition and ensure uniform distribution of the active ingredient.
4. After making adjustments, re-sample the batch and perform weight variation testing again to confirm that the issue has been resolved.

5.6 Acceptance Criteria

1. The batch is considered acceptable if the weight variation for at least 95% of the sampled tablets falls within the predefined limits (typically ±5%).
2. If more than 2 tablets in the sample fail the weight variation test, the batch should be rejected, and a deviation report should be created.

5.7 Post-Testing Actions

1. If the batch passes the weight variation test, proceed with the next step in the tablet manufacturing process, such as coating or packaging.
2. If the batch fails, take corrective actions as outlined in the deviation report and rework or reject the batch as necessary.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• OOS: Out of Specification

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Uniformity of Dosage Units
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Guidelines for Tablet Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for In-Process Uniformity of Blend Testing

1. Purpose

To define the procedure for conducting in-process testing of blend uniformity during tablet manufacturing to ensure that the mixture of ingredients is consistent and within the specified quality standards.

2. Scope

This SOP applies to the testing of blend uniformity during the tablet manufacturing process, ensuring uniform distribution of active pharmaceutical ingredients (APIs) and excipients throughout the blend.

3. Responsibilities

• Quality Control (QC): Responsible for conducting the blend uniformity test and documenting results. QC will also recommend corrective actions if deviations are observed.
• Production Operator: Responsible for ensuring that the blend is prepared as per the batch record and notifying QC when the blend is ready for testing.
• Quality Assurance (QA): Ensures that the blend uniformity testing process is compliant with SOP requirements and reviews the results for consistency with product specifications.

4. Accountability

The QC Manager is accountable for ensuring that the blend uniformity testing is conducted regularly during the manufacturing process. The QA Manager ensures the procedure is followed and results are documented appropriately.

5. Procedure

5.1 Preparation for Testing

1. Verify that the blending equipment has been cleaned and calibrated according to the SOP for equipment qualification.
2. Ensure that the batch of materials is ready for blending, including proper mixing of active ingredients and excipients.
3. Prepare the required testing equipment, including sampling tools, scales, and containers for blend sampling.
4. Confirm that the blend is prepared in accordance with the batch record and formulation requirements.

5.2 Sampling of the Blend

1. Take a sample of the blend from different points within the blending equipment to ensure that the sample is representative of the entire batch.
2. Follow the sampling plan for the number of samples to be taken and the locations from which the samples should be collected.
3. Ensure that the samples are properly labeled with batch information and time of sampling to ensure traceability.

5.3 Blend Uniformity Testing

1. Weigh each sample of the blend and test for uniformity using a method approved by the QC department (e.g., content uniformity or weight variation test).
2. For content uniformity testing, check the active ingredient concentration in the sample to ensure it is within the specified range.
3. If the testing method is weight variation, ensure that each sample meets the predetermined weight variation criteria specified in the batch record.
4. If an automated system is used for testing, ensure the system is calibrated and functioning properly before testing the samples.

5.4 Documentation of Results

1. Record the results of the blend uniformity testing in the batch record (Annexure-2), including the test method used, the results for each sample, and any deviations from the specification.
2. For failed tests, initiate a deviation report (Annexure-1) and document the cause of the failure and any corrective actions taken.
3. Ensure that the documentation includes relevant details such as sample locations, batch number, test conditions, and any corrective measures taken.

5.5 Corrective Actions for Blend Uniformity Issues

1. If the blend uniformity test results do not meet the specifications, investigate the cause. Potential causes could include inadequate mixing, equipment malfunction, or incorrect formulation.
2. Adjust the blending process as needed, including adjusting mixing time, speed, or batch size, and re-sample the blend for further testing.
3. If the issue persists, consider reworking the batch or investigating other potential causes, such as raw material quality issues.
4. Ensure that all corrective actions are documented and reviewed by the QA team for approval.

5.6 Acceptance Criteria

1. The blend is considered acceptable if the test results fall within the established limits for uniformity, as defined in the batch record and specifications.
2. If more than a specified percentage (e.g., 2%) of the samples fail to meet the uniformity specifications, initiate a full investigation and corrective actions.

5.7 Post-Testing Actions

1. If the blend is acceptable, proceed with the next step in the tablet manufacturing process, such as tablet compression or coating.
2. If the blend is rejected, review the blending process, investigate the root cause, and take corrective actions as necessary. Re-sample and retest the blend before proceeding with tablet manufacturing.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Uniformity of Dosage Units
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Guidelines for Tablet Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for Monitoring Drying Time in Sugar-Coating Process

1. Purpose

To define the procedure for monitoring and controlling drying time during the sugar-coating process to ensure uniformity in coating thickness and to avoid defects like peeling or uneven coating.

2. Scope

This SOP applies to the sugar-coating process for tablets, specifically to monitoring and controlling the drying time to ensure product quality and consistency during production.

3. Responsibilities

• Coating Operator: Responsible for ensuring the sugar-coating process is conducted properly and for monitoring drying time during the process.
• Quality Control (QC): Responsible for verifying that the drying time parameters are followed and ensuring the tablets meet the quality specifications.
• Quality Assurance (QA): Ensures compliance with the SOP and verifies the correctness of the drying time monitoring process through periodic reviews and audits.

4. Accountability

The Coating Supervisor is accountable for ensuring that the drying time monitoring during the sugar-coating process is accurate and complies with quality specifications. The QA Manager ensures that the process is followed according to this SOP.

5. Procedure

5.1 Preparation for Monitoring Drying Time

1. Ensure that the coating pan, airflow, and drying system are calibrated and functioning properly before starting the coating process.
2. Verify that the sugar-coating solution is prepared according to the formulation and that the required coating viscosity is achieved.
3. Ensure that the batch of tablets is ready for coating and that all required parameters (e.g., tablet weight, size) are within specifications.

5.2 Monitoring the Drying Time

1. Start the sugar-coating process and monitor the drying time continuously. Record the time spent on each drying stage in the batch record (Annexure-2).
2. Use the automatic or manual system to measure the drying time based on the environmental conditions (e.g., temperature, humidity) and coating thickness.
3. Ensure the coating pan rotation speed is optimal to achieve an even coating and facilitate proper drying during each stage.

5.3 Drying Time Adjustments

1. If the drying time is too long or too short, adjust the airflow and temperature settings to maintain the ideal drying time, typically between 15-30 minutes, depending on the coating thickness.
2. Monitor the temperature and humidity levels in the coating area to ensure they are within the specified range for efficient drying.
3. If necessary, adjust the pan speed to ensure proper tablet exposure to the airflow while maintaining an optimal drying time.

5.4 Documentation of Drying Time

1. Document the drying time parameters and any adjustments made during the process in the batch record (Annexure-2).
2. Note any deviations from the expected drying time, including the causes and corrective actions taken.
3. If the drying time exceeds the allowable range, initiate a deviation report (Annexure-1) and take corrective action.

5.5 Quality Control Checks

1. Periodically check the tablets during the drying process for any signs of coating defects, such as peeling, uneven coating, or excess moisture.
2. Test a sample of the tablets after the drying stage to confirm that the moisture content and coating thickness are within the acceptable limits.
3. If any tablets are found to be defective, adjust the drying time, coating solution, or equipment settings to correct the issue.

5.6 Corrective Actions for Drying Time Deviations

1. If the drying time is found to be outside the expected range, initiate corrective actions by adjusting airflow, temperature, and pan speed settings.
2. Verify that the corrective actions have resolved the issue by re-monitoring the drying time and conducting visual inspections on the next set of tablets.
3. Record all corrective actions taken, including the cause of the deviation, adjustments made, and results of re-tests, in the batch record and deviation report.

5.7 Post-Drying Actions

1. After the drying process is completed, proceed with the next step in the production process, such as cooling, inspection, and packaging.
2. If any defects persist after adjusting the drying process, consult with the QA team for a detailed investigation and review of the procedure.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Tablet Coating Specifications
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Tablet Manufacturing Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for Testing Tablet Edges for Chipping in Process

1. Purpose

To define the procedure for testing tablet edges for chipping during the compression process to ensure that tablets meet the required specifications and are free from damage.

2. Scope

This SOP applies to testing tablet edges for chipping during the compression process, ensuring that the edges are intact and meet the quality standards set for tablet manufacturing.

3. Responsibilities

• Quality Control (QC): Responsible for performing the chipping test on tablets and documenting the results. QC is also responsible for taking corrective actions if excessive chipping is observed.
• Compression Operator: Responsible for ensuring the tablet compression machine is set correctly to minimize edge chipping and notifying QC when tablets are ready for inspection.
• Quality Assurance (QA): Ensures that the chipping test procedure is followed according to the SOP and reviews the documentation for compliance.

4. Accountability

The QC Manager is accountable for ensuring the chipping test is performed regularly and that any chipping-related defects are properly addressed. The QA Manager is responsible for ensuring compliance with this SOP and for approving corrective actions as necessary.

5. Procedure

5.1 Preparation for Testing

1. Ensure the inspection area is clean, well-lit, and equipped with magnification tools, such as a magnifying glass or tablet inspection machine, for accurate evaluation of tablet edges.
2. Verify that the tablet compression machine is set to the appropriate settings for tablet hardness and shape. This includes checking the die and punch alignment to prevent excessive pressure on tablet edges.
3. Collect a sample of tablets for inspection. The sample should be representative of the batch, typically 100 tablets or as per the sampling plan.

5.2 Testing Tablet Edges for Chipping

1. Visually inspect each tablet in the sample for chipping or cracks on the edges. Pay particular attention to the corners and perimeter of the tablet.
2. If using a magnifying tool, inspect the tablet edges for fine cracks, chips, or missing pieces of coating that may affect tablet integrity or appearance.
3. For automated systems, ensure that the tablet inspection machine is calibrated to detect edge defects, and review flagged tablets for manual verification.

5.3 Documentation of Results

1. Document the results of the edge inspection in the batch record (Annexure-2), including the number of defective tablets found, the type of defects observed, and the severity of the defects.
2. If a tablet has chipped edges, record whether the chipping is minor (cosmetic) or severe (functional impairment). For cosmetic defects, the batch may still be acceptable depending on the tolerance limits set.
3. If the number of chipped tablets exceeds the acceptance criteria (e.g., more than 2% of the sample), initiate a deviation report (Annexure-1) and investigate the root cause.

5.4 Corrective Actions

1. If excessive chipping is found, investigate the cause. Potential causes may include improper compression settings, worn-out tooling, or inappropriate tablet formulations.
2. Adjust the tablet compression machine settings, such as the pressure or tablet hardness, to reduce the likelihood of edge chipping in future batches.
3. Ensure that any corrective actions are documented in the deviation report and the batch record. Verify the effectiveness of the corrective actions by re-inspecting the tablets after changes are made.

5.5 Acceptance Criteria

1. The batch is considered acceptable if no more than 2% of the tablets in the sample show chipped edges that affect the tablet’s functional integrity.
2. Minor chipping that does not affect the tablet’s efficacy or appearance may be acceptable within predefined limits. However, significant chipping or damage to more than 2% of the tablets will require corrective actions.

5.6 Post-Testing Actions

1. If the batch passes the edge inspection, proceed with the next step in the production process, such as coating or packaging.
2. If the batch fails, perform a root cause analysis to determine the source of the problem and rework the batch or initiate a deviation report for further investigation.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Tablet Marking and Quality Specifications
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Tablet Manufacturing Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for Troubleshooting Coating Process Issues in Real-Time

1. Purpose

To establish a standardized procedure for real-time troubleshooting of coating process issues to ensure consistent tablet quality and to address any disruptions in the coating process promptly.

2. Scope

This SOP applies to troubleshooting activities during the coating process of tablets, covering issues such as coating uniformity, defects in coating, spray rate control, and any equipment-related issues.

3. Responsibilities

• Coating Operator: Responsible for identifying and reporting any issues in the coating process, monitoring real-time parameters, and notifying the QC or maintenance team for troubleshooting.
• Quality Control (QC): Responsible for assisting in troubleshooting activities, identifying quality defects, and providing solutions or recommendations to resolve issues during the coating process.
• Maintenance Team: Responsible for supporting troubleshooting efforts related to equipment malfunctions or setup issues in the coating process.
• Quality Assurance (QA): Ensures that all troubleshooting activities are documented, compliant with GMP, and lead to the correction of coating defects to meet product specifications.

4. Accountability

The Coating Supervisor is accountable for ensuring that real-time troubleshooting is executed effectively, ensuring that all equipment and processes are running optimally. The QC Manager and Maintenance Manager are responsible for addressing defects and implementing corrective actions as necessary.

5. Procedure

5.1 Identifying Process Issues

1. Monitor coating parameters such as spray rate, airflow, temperature, and tablet bed movement in real time.
2. Identify any inconsistencies or deviations in the coating process, such as uneven coating thickness, incomplete coating, excessive or insufficient spray rate, or equipment malfunctions.
3. Immediately flag any observations for further investigation, ensuring that the batch remains within specifications and does not compromise product quality.

5.2 Troubleshooting Spray Rate Issues

1. If the spray rate is too high or too low, verify the coating solution viscosity and adjust the spray rate control settings accordingly.
2. Check for any clogs in the spray nozzles or air spray system that could be affecting the coating distribution.
3. Ensure that the correct spray gun settings (e.g., air pressure and fluid pressure) are applied as per the specification.
4. If adjustments to the spray rate do not resolve the issue, consult the equipment manual for nozzle or spray system calibration.

5.3 Resolving Coating Defects

1. If defects such as peeling, cracking, or uneven coating are observed, stop the coating process and inspect the tablet bed for uniformity in tablet placement and rotation speed.
2. Check for any discrepancies in the coating pan speed or temperature that may cause non-uniform coating.
3. Verify the coating solution’s composition and viscosity. If the solution is too thick or too thin, adjust it according to the formulation requirements.
4. In case of spray gun malfunction, inspect the equipment for blockage, leaks, or misalignment. Clean or replace the nozzles as necessary.

5.4 Monitoring Equipment Performance

1. Regularly monitor the functioning of the coating equipment during production, checking for any unusual noises, irregular vibrations, or overheating that might indicate a mechanical failure.
2. In case of an equipment malfunction, immediately stop the process and notify the maintenance team to inspect the machine.
3. Ensure that all sensors, controllers, and related instruments are calibrated and functioning properly. Calibrate or replace faulty equipment as necessary.

5.5 Documentation of Issues and Actions

1. Document all identified issues and troubleshooting actions taken in the batch record (Annexure-2), including the type of issue, root cause (if identified), and corrective action implemented.
2. If a significant deviation occurs, generate a deviation report (Annexure-1) and submit it for further investigation and review.
3. Record any maintenance actions performed, including equipment servicing or calibration, in the maintenance log.

5.6 Corrective and Preventive Actions

1. After resolving the immediate issue, implement corrective actions to prevent recurrence. These actions might include training, equipment upgrades, or procedural changes.
2. If necessary, perform a root cause analysis to identify underlying problems that may require long-term solutions or process changes.
3. Verify the effectiveness of corrective actions by reviewing subsequent batches and ensuring the process runs without issues.

5.7 Post-Troubleshooting Actions

1. After resolving the issues and ensuring the coating process is running smoothly, continue with the production process, ensuring that the batch is inspected for compliance with product specifications.
2. If issues persist, escalate the problem to the QA Manager for further review and additional corrective measures.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)
3. Maintenance Log (Annexure-3)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• USP <701> – Tablet Coating Specifications
• ISO 9001 – Quality Management Systems

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Annexure-3: Maintenance Log

Revision History:

Standard Operating Procedure for Sampling Granules from Fluidized Bed Process

1. Purpose

To define the procedure for sampling granules during the fluidized bed granulation process to ensure the granules meet quality standards and specifications before further processing.

2. Scope

This SOP applies to the sampling of granules produced in the fluidized bed process, ensuring uniformity in the granules’ size, moisture content, and other physical properties before proceeding with tablet compression or coating.

3. Responsibilities

• Quality Control (QC): Responsible for performing the sampling procedure, ensuring that samples are representative and testing them for granule quality parameters.
• Granulation Operator: Responsible for ensuring that the granulation process is conducted as per the SOP and assisting QC with the sampling of granules.
• Quality Assurance (QA): Ensures that the sampling process is compliant with the SOP and reviews the results for consistency with the product specifications.

4. Accountability

The QC Manager is accountable for ensuring that the granules are sampled at the correct times and in a manner that ensures accurate and representative testing. The QA Manager ensures that all steps of the process are followed correctly and approves the test results.

5. Procedure

5.1 Preparation for Sampling

1. Ensure that the sampling tools, such as clean sampling equipment, gloves, and containers, are prepared and ready for use.
2. Verify that the fluidized bed system is operating within the defined parameters for granulation, including airflow, temperature, and humidity.
3. Ensure that the sampling area is clean and appropriately designated for the sampling process.

5.2 Granule Sampling Method

1. Granules must be sampled from different points within the fluidized bed system to ensure that the sample is representative of the entire batch.
2. Sample granules from the top, middle, and bottom sections of the fluidized bed. At least three separate points should be sampled to get a homogeneous sample.
3. If the fluidized bed is equipped with an automatic sampling system, ensure that the system is calibrated and functioning properly. Otherwise, manual sampling should be performed at the specified intervals.

5.3 Sample Size

1. Sample a minimum of 1-2 kg of granules from each selected point (or as per the batch size and sampling plan).
2. The total sample size should be representative of the batch and adequate for further testing, such as moisture content, particle size distribution, and uniformity.

5.4 Sampling Interval

1. Samples should be taken at predefined intervals during the granulation process (e.g., every 30 minutes or as specified by the production batch parameters).
2. Ensure that samples are taken before any further processing steps, such as drying, to maintain the accuracy of the sample’s characteristics.

5.5 Documentation of Sample Collection

1. Document the sampling process in the batch record (Annexure-2), including the sample number, sampling point, date, time, and operator details.
2. Record the number of samples collected and any relevant observations regarding the granulation process.

5.6 Analysis of Granules

1. Perform the necessary analyses on the samples, including moisture content, particle size distribution, and uniformity testing.
2. Document the results of the analysis in the batch record, noting any deviations from the predefined specifications.

5.7 Corrective Actions

1. If the granules do not meet the quality specifications, initiate corrective actions such as adjusting the granulation parameters (e.g., drying time, temperature) or modifying the formulation.
2. Re-sample and analyze the granules after corrective actions have been implemented to confirm that the issue has been resolved.

5.8 Post-Sampling Actions

1. After successful sampling and analysis, proceed with the next stage of tablet manufacturing, such as drying or compression.
2. If issues persist, initiate a thorough review of the granulation process and make any necessary adjustments before continuing production.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• Moisture Content: The percentage of water present in the granules
• Particle Size Distribution: The distribution of particle sizes in the granules

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Granulation and Moisture Testing for Tablets
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Guidelines for Granulation and Tablet Production

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for Automated In-Process Data Review Systems

1. Purpose

To define the procedure for using automated in-process data review systems to monitor and review tablet manufacturing processes in real-time, ensuring data integrity and compliance with GMP standards.

2. Scope

This SOP applies to the use of automated data review systems for in-process monitoring during tablet manufacturing, including data related to weight, hardness, moisture content, and other critical process parameters.

3. Responsibilities

• Quality Control (QC): Responsible for configuring, monitoring, and reviewing automated data review systems for compliance with predefined specifications.
• Production Operator: Ensures that in-process data is captured in the automated systems and reports any deviations or alerts to QC.
• Quality Assurance (QA): Ensures the review system is functioning as per the SOP and that any issues are addressed through corrective actions and validation.

4. Accountability

The QC Manager is accountable for ensuring the effective use of the automated in-process data review system. The QA Manager ensures the validation and compliance of the system with regulatory requirements.

5. Procedure

5.1 System Configuration

1. Ensure that the automated system is correctly configured to capture relevant process data such as tablet weight, hardness, moisture content, and other critical parameters during manufacturing.
2. Set up appropriate alarm thresholds for each parameter, including upper and lower limits, based on product specifications and regulatory guidelines.
3. Verify that all sensors, controllers, and data collection points are properly integrated with the system.

5.2 Data Capture

1. Ensure that the automated system continuously captures in-process data from the production line during tablet manufacturing.
2. Verify that data is recorded at regular intervals and is consistent with the predefined parameters for each tablet batch.
3. Check that the system logs any relevant events or changes in process conditions for further review.

5.3 Real-Time Monitoring and Alerts

1. Monitor the real-time data through the automated system interface to ensure that all parameters are within the acceptable range.
2. If any data point falls outside the predefined threshold, the system should trigger an automatic alert to notify the relevant personnel (QC, production operator, etc.)
3. Investigate any alerts immediately and determine if corrective actions are necessary to maintain process consistency.

5.4 Data Review and Documentation

1. Review the data collected by the automated system at the end of each production run to ensure it meets quality and process specifications.
2. Document any findings, deviations, or corrective actions taken in the batch record (Annexure-2).
3. Review data trends and compare them with historical data to identify any potential issues that may need further investigation.

5.5 Corrective Actions

1. If a process parameter is found to be out of specification or if an alert is triggered, initiate corrective actions as appropriate.
2. Adjust machine settings, calibrate equipment, or modify process conditions to bring the parameter back within the acceptable range.
3. Document all corrective actions taken and monitor the system to verify the effectiveness of the actions.

5.6 Validation and Calibration

1. Ensure that the automated data review system is validated before use, following the equipment qualification and validation procedures outlined in SOP/TAB/101/2025 (Equipment Qualification).
2. Calibrate all measurement devices and sensors connected to the system regularly to maintain accuracy and precision.
3. Perform revalidation of the system after any significant system upgrades or changes in the manufacturing process.

5.7 Post-Inspection Actions

1. After the review and necessary corrective actions, finalize the batch record and approve the data for further manufacturing steps such as packaging and labeling.
2. If the system identifies any recurrent issues, perform a detailed investigation to assess the root cause and take necessary actions to prevent recurrence.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CAPA: Corrective and Preventive Actions

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)
3. Calibration Log (Annexure-3)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• USP <701> – General Guidelines for Equipment and Instrumentation in Pharmaceutical Manufacturing
• ISO/IEC 17025 – General Requirements for the Competence of Testing and Calibration Laboratories

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Annexure-3: Calibration Log

Revision History:

Standard Operating Procedure for Tablet Marking Inspection During Compression

1. Purpose

To define the procedure for performing tablet marking inspection during the compression process to ensure that the markings on the tablets meet the required specifications for identification and branding.

2. Scope

This SOP applies to the inspection of tablet markings during the compression stage of tablet manufacturing, ensuring proper and consistent markings on all tablets.

3. Responsibilities

• Quality Control (QC): Responsible for inspecting tablet markings, ensuring that they are clear, legible, and consistent with the specified design.
• Compression Operator: Responsible for ensuring that the compression machine is set up properly to apply markings and notify QC when a batch is ready for inspection.
• Quality Assurance (QA): Ensures that the marking inspection process is followed correctly, reviews inspection results, and approves any corrective actions or deviations.

4. Accountability

The QC Manager is accountable for ensuring that tablet markings are inspected regularly during compression. The QA Manager ensures the marking inspection process is compliant with the SOP and approves any corrective actions or deviations.

5. Procedure

5.1 Preparation for Inspection

1. Ensure the inspection area is well-lit and clean to facilitate accurate inspection of tablet markings.
2. Verify that all inspection tools, such as magnifying glasses or automated tablet marking inspection systems, are properly calibrated and ready for use.
3. Confirm that the compression machine is properly set up to apply the required tablet markings according to the design specifications.

5.2 Marking Inspection Method

1. Inspect each tablet for the following:
   • Legibility of the marking (e.g., text, logo)
   • Consistency of the marking (e.g., uniformity of depth, size, and location)
   • Presence of any defects such as smudging, incomplete markings, or double markings
   • Correct positioning of the marking on the tablet surface
2. Inspect a representative sample from each batch of tablets. The sample size should be defined in the sampling plan (e.g., 100 tablets per batch).
3. If using an automated inspection system, verify that it is functioning correctly and flagging any tablets with defective markings.

5.3 Documentation of Inspection Results

1. Document the results of the marking inspection in the batch record (Annexure-2), noting the type and number of defects found, if any.
2. If defects are found, document the nature of the defects, including whether they are isolated occurrences or affect the entire batch.
3. If defects exceed acceptable limits, generate a deviation report (Annexure-1) and initiate an investigation.

5.4 Corrective Actions

1. If defects are found, take corrective actions such as adjusting the compression machine settings or modifying the tablet design or marking process.
2. After corrective actions are taken, perform further inspection to verify that the defects have been resolved.
3. Document any corrective actions taken and verify their effectiveness through further inspections or tests.

5.5 Acceptance Criteria

1. The batch of tablets is considered acceptable if the marking defects do not exceed the predefined threshold (e.g., no more than 2% of the tablets from the sample show defects).
2. Minor defects, such as slight smudging that does not affect tablet identification, may be acceptable within predefined limits.

5.6 Post-Inspection Actions

1. If the batch passes the inspection, proceed with further tablet manufacturing steps, such as drying, coating, or packaging.
2. If the batch fails, perform a root cause analysis, modify the marking process, and re-inspect until the correct marking quality is achieved.

6. Abbreviations

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

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Tablet Marking Specifications
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Guidelines for Tablet Marking

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History:

Standard Operating Procedure for End-Point Testing During Drying Process

1. Purpose

To define the procedure for performing end-point testing during the drying process of tablet granules to ensure that they reach the desired moisture content before further processing.

2. Scope

This SOP applies to the drying process of tablet granules, specifically focusing on the testing performed to determine when the granules have reached the optimal moisture content.

3. Responsibilities

• Quality Control (QC): Responsible for performing the end-point testing on granules to verify that the moisture content is within acceptable limits.
• Drying Operator: Responsible for ensuring the drying process is carried out according to the prescribed parameters and for notifying QC when testing is required.
• Quality Assurance (QA): Ensures that end-point testing procedures are followed correctly, reviews test results, and approves corrective actions if necessary.

4. Accountability

The QC Manager is accountable for ensuring that the end-point testing is carried out regularly during the drying process. The QA Manager reviews the test results and approves corrective actions as needed.

5. Procedure

5.1 Sampling

1. Collect representative samples of granules from the drying bed or drying equipment at defined intervals during the drying process.
2. Ensure that samples are taken from different points within the batch to accurately reflect the moisture content across the entire batch.

5.2 Moisture Content Testing

1. Perform moisture content testing on the collected samples using an appropriate method, such as a moisture analyzer or oven-drying method.
2. Ensure the test method used is validated for the specific granules being tested.
3. Test moisture content at least twice per batch or as per established sampling plan.

5.3 End-Point Determination

1. Compare the results of the moisture content testing to the acceptable moisture content range for the granules. This range should be predefined based on the formulation requirements.
2. The batch is considered dried when the moisture content falls within the specified range, typically between 2-5% for most tablet formulations.
3. If the moisture content is outside the acceptable range, the granules should be returned to the dryer for further drying, and additional testing should be conducted.

5.4 Documentation

1. Document the results of the moisture content testing in the batch record (Annexure-2), including the moisture content percentage, the sampling time, and the method used for testing.
2. Note any deviations or corrective actions taken, such as further drying if the moisture content is too high.

5.5 Corrective Actions

1. If the moisture content is found to be outside the acceptable limits, initiate corrective actions such as adjusting the drying time, temperature, or airflow in the drying equipment.
2. After corrective actions are taken, perform further testing to verify that the moisture content falls within the acceptable range before proceeding with tablet compression.

5.6 Post-Testing Actions

1. If the batch passes the end-point testing and meets the desired moisture content, proceed with further tablet manufacturing steps, such as granulation or compression.
2. If the batch fails, perform a root cause analysis, modify the drying process, and re-test until the correct moisture content is achieved.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• Moisture Content: The amount of water present in the granules, typically expressed as a percentage of the total weight.

7. Documents

1. Batch Record (Annexure-2)
2. Deviation Report (Annexure-1)

8. References

• USP <701> – Moisture Testing for Granules
• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• European Pharmacopoeia (EP) – Guidelines for Moisture Testing

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Deviation Report

Annexure-2: Batch Record

Revision History: