Standard Operating Procedure for Granulation Process for Immediate Release Tablets

1. Purpose

To establish the granulation process for immediate release tablets, ensuring uniformity, stability, and compliance with GMP requirements.

2. Scope

This SOP applies to the granulation of immediate release tablets, covering raw material handling, equipment setup, and granule preparation.

3. Responsibilities

• Manufacturing Personnel: Follow instructions for equipment setup, material handling, and process execution.
• QC: Conduct in-process checks and ensure the granules meet quality specifications.
• QA: Ensure compliance with SOP and review batch records for approval.

4. Accountability

The Production Manager is responsible for implementation; the QA Manager ensures compliance and approval.

5. Procedure

5.1 Receiving and Preliminary Inspection

1. Inspect all raw materials upon receipt.
2. Verify packaging, labeling, and documentation such as Certificates of Analysis (CoA).
3. Store materials under specified conditions.

5.2 Equipment Setup

1. Inspect and calibrate the granulation equipment, including the mixer and dryer.
2. Ensure all instruments (e.g., moisture analyzers, sieves) are in working order.

5.3 Granulation Process

1. Load the dry powder mixture (API and excipients) into the granulator.
2. Prepare and add the binder solution to the powder mixture while stirring continuously.
3. Granulate the mixture until the desired granule size is achieved. Adjust parameters like speed, time, and binder addition based on the material’s response during the process.
4. Ensure uniform wetting of the powder blend to form uniform granules. Continue mixing until the mixture reaches the required consistency, as per the formulation specifications.
5. Verify the process by monitoring granule size using a sieve or particle size analyzer. Continue adjusting as necessary to ensure uniformity.

5.4 Screening and Drying

1. Screen the granulated mixture to ensure uniformity of granule size. Discard oversized or undersized granules.
2. Dry the granules in the fluidized bed dryer, checking moisture content regularly with a moisture analyzer to achieve the desired moisture level.

5.5 Final Quality Control

1. Perform particle size distribution analysis and moisture content tests on the granules.
2. Ensure granules meet the required quality specifications for use in tablet compression.
3. Take necessary corrective actions if any parameters fall outside acceptable limits.

5.6 Documentation and Record-Keeping

1. Record all process parameters in the batch record, including mixing times, binder amounts, and granule characteristics.
2. Log in-process checks and test results in the QC Log (Annexure-1), ensuring traceability of all batch details.
3. Maintain batch records for reference during future production runs or audits.

6. Abbreviations

• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Granulation Batch Record (Annexure-1)
2. Granule Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Granulation Batch Record

Annexure-2: Granule Quality Control Log

Revision History:

Standard Operating Procedure for Wet Granulation Equipment Setup and Operation

1. Purpose

To establish a standardized, GMP-compliant method for setting up and operating the wet granulation equipment, ensuring optimal granule formation and product quality.

2. Scope

This SOP applies to the setup, calibration, and operation of the wet granulation equipment used in the tablet manufacturing process. It covers the preparation and granulation of active pharmaceutical ingredients (APIs) and excipients using wet methods.

3. Responsibilities

• Manufacturing Personnel: Set up and operate wet granulation equipment, monitor the process, and ensure correct material handling.
• Quality Control (QC): Ensure granulation meets specifications, monitor in-process quality, and perform equipment checks.
• Quality Assurance (QA): Oversee compliance with SOP and GMP guidelines and approve operational procedures.

4. Accountability

The Production Manager is responsible for ensuring the proper setup and operation of the wet granulation equipment. The QA Manager ensures the equipment meets compliance standards and approves operational procedures.

5. Procedure

5.1 Equipment Inspection and Preparation

1. Inspect all components of the wet granulation equipment, including the granulator, mixer, spray system, and drying system, to ensure they are clean and functioning correctly.
2. Verify that the equipment is free of residues from previous batches. Clean and sanitize all parts that will come into contact with the materials to prevent cross-contamination.
3. Check the calibration status of all instruments, including the spray system, temperature controls, and moisture analyzers, and document the calibration dates.

5.2 Material Preparation

1. Ensure that all materials for granulation, including active ingredients, excipients, and binder solution, are available and meet the specifications.
2. Verify the identity, batch number, and certification of all incoming raw materials (e.g., Certificate of Analysis, Safety Data Sheets).
3. Weigh and prepare the appropriate quantities of materials according to the batch formulation sheet.
4. Prepare the binder solution, ensuring it is mixed to the correct concentration and is free from impurities.

5.3 Granulation Setup

1. Load the dry powder blend (API and excipients) into the granulator, ensuring uniform distribution of all ingredients.
2. Start the equipment and adjust the mixing parameters, including speed and duration, according to the formulation requirements.
3. Slowly add the binder solution to the dry mixture while the equipment is running. Ensure the binder is evenly distributed to form a wet mass.
4. Monitor the granulation process, adjusting the addition of binder and mixing speed as necessary to achieve the desired granule consistency and size.

5.4 In-Process Monitoring

1. Monitor the temperature, humidity, and moisture content of the granulating mass throughout the process.
2. Perform regular checks for uniformity of the wet granules, ensuring they meet the size and consistency specifications.
3. If necessary, adjust the binder flow rate or granulation time to maintain uniform granule size and avoid over-wetting.

5.5 Granule Drying

1. Once granulation is complete, transfer the granules to the drying system.
2. Set the drying parameters (e.g., temperature, airflow) to ensure that the granules dry to the desired moisture content.
3. Regularly monitor the drying process by checking moisture levels at intervals using a moisture analyzer. Ensure that the moisture content meets the required specification.

5.6 Equipment Shutdown and Cleaning

1. After the granulation and drying process is complete, turn off the equipment and document the completion of the batch in the equipment log.
2. Clean and sanitize all parts of the wet granulation equipment that came into contact with the raw materials, following the approved cleaning procedure.
3. Inspect the equipment again after cleaning to ensure no residues remain and that all parts are in good working condition for the next batch.

5.7 Documentation and Record-Keeping

1. Document all setup, operational, and cleaning activities in the batch record, including material lot numbers, equipment settings, and any deviations.
2. Record all in-process quality checks, including moisture content, granule size, and equipment calibration results in the QC log (Annexure-1).
3. Ensure that all records are signed by the responsible personnel and stored as per regulatory requirements for future audits and reference.

6. Abbreviations

• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Wet Granulation Equipment Setup Log (Annexure-1)
2. Granulation Batch Record (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Wet Granulation Equipment Setup Log

Annexure-2: Granulation Batch Record

Revision History:

Standard Operating Procedure for Dry Granulation Method for Tablets

1. Purpose

To define the procedure for the dry granulation method in tablet manufacturing, ensuring uniformity, integrity, and compliance with GMP standards.

2. Scope

This SOP applies to the dry granulation process for tablet production, including powder blending, compaction, and granule processing.

3. Responsibilities

• Manufacturing Personnel: Operate the dry granulation equipment, monitor the process, and ensure material handling is correct.
• Quality Control (QC): Perform in-process checks and verify that the granules meet the required specifications.
• Quality Assurance (QA): Ensure compliance with SOP, GMP standards, and regulatory requirements.

4. Accountability

The Production Manager is responsible for ensuring the correct operation of the dry granulation method. The QA Manager ensures adherence to SOPs and regulatory compliance.

5. Procedure

5.1 Equipment Inspection and Setup

1. Inspect all dry granulation equipment, including the roller compactor, mills, and sieves, to ensure cleanliness and proper working order.
2. Ensure that all components are free from contaminants and have been cleaned according to the cleaning SOP.
3. Check calibration of all measurement instruments such as the weight scales and compaction pressure gauge.

5.2 Material Preparation

1. Verify all raw materials, including active pharmaceutical ingredients (APIs) and excipients, for compliance with specifications (e.g., Certificates of Analysis, batch numbers).
2. Weigh all materials according to the formulation requirements, ensuring that the proportions align with the approved batch formula.
3. Ensure that the materials are free-flowing and do not require additional powder blending before the granulation process.

5.3 Dry Granulation Process

1. Load the pre-weighed material into the roller compactor.
2. Set the appropriate compaction force based on the material specifications to form the compacted ribbons.
3. Ensure uniformity of ribbon thickness and appearance. If ribbons are not uniform, adjust the equipment settings (e.g., roller gap, force) accordingly.
4. Once the ribbons are formed, feed them into the mill to break them into smaller granules of the desired size.
5. Monitor the granule size distribution using a sieve or particle size analyzer. Adjust milling conditions if the size does not meet the required specification.

5.4 In-Process Monitoring

1. Regularly monitor the granulation process, checking parameters such as compaction pressure, ribbon quality, and granule size.
2. Document all in-process parameters, including compaction pressure, roller speed, and granule size.
3. Verify that the moisture content of the granules remains within the acceptable limits to prevent clumping or uneven compaction.

5.5 Final Quality Control

1. Once the granules have been produced, perform quality control tests on granule uniformity, size distribution, and moisture content.
2. If the granules do not meet the specifications, evaluate potential adjustments to the equipment settings or material formulation.
3. Document all testing results and any corrective actions taken in the batch records.

5.6 Equipment Shutdown and Cleaning

1. After the granulation process, power off the equipment and disconnect from the main power supply.
2. Perform a thorough cleaning of the granulation equipment, including the rollers, mills, and sieves, using the approved cleaning SOP.
3. Inspect the equipment post-cleaning to ensure all parts are free of residues and ready for the next batch.

5.7 Documentation and Record-Keeping

1. Record all operational steps, including material used, equipment settings, and any deviations or adjustments made during the process in the batch record.
2. Document all quality control results (granule size, moisture content, etc.) in the QC Log (Annexure-1).
3. Ensure all records are reviewed, signed, and stored according to regulatory requirements for traceability and audits.

6. Abbreviations

• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Dry Granulation Batch Record (Annexure-1)
2. Granule Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Dry Granulation Batch Record

Annexure-2: Granule Quality Control Log

Revision History:

Standard Operating Procedure for Binder Preparation for Granulation Process

1. Purpose

The purpose of this SOP is to define the process for preparing the binder solution used in the granulation of tablets. It ensures that the binder is prepared in a consistent manner, meeting the required quality standards and facilitating uniform granule formation.

2. Scope

This SOP applies to the preparation of binder solutions used in tablet granulation processes. It covers the materials, equipment, and procedures required for binder preparation.

3. Responsibilities

• Manufacturing Personnel: Responsible for the accurate preparation of the binder solution according to the formulation and ensuring that all equipment is set up and calibrated correctly.
• Quality Control (QC): Responsible for verifying the quality of the binder solution, ensuring compliance with specifications, and testing the binder for consistency and performance.
• Quality Assurance (QA): Responsible for ensuring compliance with this SOP and overseeing batch record reviews and approvals.

4. Accountability

The Production Manager is accountable for the preparation of the binder solution. The QA Manager is responsible for ensuring adherence to this SOP and regulatory requirements.

5. Procedure

5.1 Material Verification

1. Verify the required binder materials are available and meet the specified quality standards. Materials should be approved by the quality assurance team and should be from approved vendors.
2. Check the batch numbers, Certificates of Analysis (CoA), and storage conditions of all raw materials.

5.2 Binder Solution Preparation

1. Calculate the required amount of binder solution based on the batch size and formulation requirements.
2. Measure the appropriate quantity of the binder material (e.g., PVP, starch solution, or any other binder) according to the formulation recipe.
3. Heat the solvent (usually water or an alcohol-based solution) to the required temperature as per the formulation guidelines. Ensure that the temperature is within the range specified in the formulation procedure.
4. Add the binder material to the solvent while stirring continuously. Ensure the binder material is fully dissolved or dispersed as required.
5. Monitor the viscosity of the binder solution to ensure it is within the desired specifications. If necessary, adjust the concentration by adding more binder material or solvent.

5.3 Binder Solution Homogeneity

1. Ensure that the binder solution is homogeneous by stirring continuously. If necessary, use an agitator or mixing equipment to achieve a uniform solution.
2. Check for the absence of lumps, undissolved particles, or air bubbles in the binder solution.

5.4 Quality Control Checks

1. Take a sample of the binder solution for quality control testing. Perform tests such as viscosity, pH, and appearance checks to confirm that the solution meets the required specifications.
2. If the solution passes all quality control tests, it is ready for use in the granulation process.
3. If the solution fails any test, investigate the issue and rework the solution if necessary, or prepare a fresh batch.

5.5 Equipment Cleaning

1. Clean all equipment used in the binder preparation process, including mixing tanks, pumps, and measuring instruments, as per the equipment cleaning SOP.
2. Ensure that no binder residues are left in the equipment to prevent cross-contamination in future batches.

5.6 Documentation and Record-Keeping

1. Document all activities in the batch record, including material lot numbers, preparation conditions (e.g., temperature, time), and any deviations.
2. Sign off on the batch record to confirm that the binder solution was prepared according to the SOP.

6. Abbreviations

• SOP: Standard Operating Procedure
• CoA: Certificate of Analysis
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Binder Solution Batch Record (Annexure-1)
2. Quality Control Test Results (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Binder Solution Batch Record

Annexure-2: Quality Control Test Results

Revision History:

Standard Operating Procedure for Screening and Milling of Granules for Tablets

1. Purpose

To outline the procedure for screening and milling granules for tablet manufacturing, ensuring uniform particle size distribution and optimal processing for the subsequent tablet compression step.

2. Scope

This SOP applies to the screening and milling of granules following granulation, including the use of sieves and mills to achieve the desired granule size and uniformity for tablet production.

3. Responsibilities

• Manufacturing Personnel: Operate the screening and milling equipment, ensuring granules meet size specifications.
• Quality Control (QC): Perform checks on granule size, particle uniformity, and moisture content to ensure quality standards are met.
• Quality Assurance (QA): Oversee compliance with SOP and ensure all equipment is operating within regulatory requirements.

4. Accountability

The Production Manager is accountable for the proper operation of the screening and milling equipment. The QA Manager ensures compliance with this SOP and GMP standards.

5. Procedure

5.1 Equipment Preparation

1. Inspect all screening and milling equipment, including sieves, mills, and any auxiliary components, to ensure they are clean, calibrated, and in proper working condition.
2. Check that the sieves are correctly sized for the required granule particle size, and verify that milling equipment is free from residue from previous batches.
3. Ensure the area around the equipment is clean and organized to prevent cross-contamination between materials.

5.2 Granule Screening

1. Transfer the granules from the granulation process into the screening area.
2. Place the appropriate sieve or mesh size into the screening equipment to achieve the desired particle size for the granules.
3. Use mechanical vibration or manual agitation to pass the granules through the sieve, ensuring the larger and smaller particles are separated effectively.
4. Discard oversized and undersized granules, and collect the properly sized granules for the next processing step.
5. Monitor the process for uniformity, and adjust equipment settings if necessary to ensure consistency in granule size distribution.

5.3 Granule Milling

1. Transfer the screened granules into the milling equipment (e.g., oscillating granulator or hammer mill).
2. Adjust the milling settings, including the mesh size of the screen or sieve used within the mill, to achieve the desired particle size.
3. Begin milling the granules, and monitor the granule size distribution to ensure it falls within the required specifications for tablet compression.
4. Periodically check the size of the milled granules to ensure uniformity and the desired consistency. Take samples for QC testing if necessary.
5. Stop milling once the required granule size is achieved, and proceed with the next steps in the tablet manufacturing process.

5.4 In-Process Quality Control

1. After screening and milling, perform in-process checks on granule size and particle uniformity.
2. Test a sample of the granules for moisture content using a moisture analyzer, ensuring it falls within the required specifications.
3. Document all quality control test results and observations in the batch record and QC log (Annexure-1).
4. If granule size or moisture content does not meet specifications, evaluate the process and make necessary adjustments to the equipment or procedure.

5.5 Equipment Shutdown and Cleaning

1. After completing the screening and milling process, turn off the equipment and clean the sieves, mills, and other components according to the cleaning SOP.
2. Ensure all equipment is thoroughly cleaned to prevent contamination in future batches. Remove any leftover granules from the equipment and dispose of them according to the waste disposal procedure.
3. Record the cleaning and maintenance activities in the equipment log to ensure traceability and compliance with GMP guidelines.

5.6 Documentation and Record-Keeping

1. Record all operational steps in the batch record, including equipment settings, granule sizes, and in-process checks.
2. Document any deviations from the standard process and actions taken to correct them.
3. Sign off on the batch record to confirm that the screening and milling process was completed in compliance with the SOP.

6. Abbreviations

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

7. Documents

1. Granule Screening and Milling Batch Record (Annexure-1)
2. Granule Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Granule Screening and Milling Batch Record

Annexure-2: Granule Quality Control Log

Revision History:

Standard Operating Procedure for Lubrication of Tablet Granules

1. Purpose

To establish a standardized method for the lubrication of tablet granules to ensure smooth tablet compression, preventing sticking and improving tablet flowability during the compression process.

2. Scope

This SOP covers the lubrication of tablet granules in the tablet manufacturing process, including the selection, preparation, and application of lubricants to the granules.

3. Responsibilities

• Manufacturing Personnel: Responsible for applying the lubricant correctly, ensuring proper mixing, and handling the granules as per the SOP.
• Quality Control (QC): Ensure that the lubricant is properly applied and the granules meet the required quality specifications.
• Quality Assurance (QA): Oversee compliance with this SOP and ensure that all procedures are followed according to GMP standards.

4. Accountability

The Production Manager is accountable for ensuring the proper application of lubricant to the granules. The QA Manager ensures the process adheres to the SOP and GMP standards.

5. Procedure

5.1 Selection of Lubricant

1. Choose an appropriate lubricant based on the formulation requirements. Common lubricants include magnesium stearate, stearic acid, or talc.
2. Ensure that the lubricant is compatible with the active pharmaceutical ingredient (API) and excipients, and confirm that it is approved for use by quality assurance.
3. Verify the batch number, Certificate of Analysis (CoA), and expiration date of the lubricant before use.

5.2 Lubricant Preparation

1. Weigh the appropriate amount of lubricant as per the formulation requirements.
2. If required, dissolve or disperse the lubricant in a small amount of a suitable solvent or mixture, ensuring uniform consistency.
3. Ensure that the lubricant is prepared at the correct temperature, if applicable, as per the formulation guidelines.

5.3 Lubrication Process

1. Transfer the lubricant to the granules in a manner that ensures even distribution. This can be done using a suitable blending equipment like a high shear mixer or ribbon blender.
2. Blend the granules and lubricant for the prescribed time, ensuring that the lubricant is uniformly distributed throughout the granule mass.
3. Ensure that the mixing speed and time are optimized to avoid over-lubrication or under-lubrication, which can affect tablet compression or granule flow.

5.4 In-Process Quality Control

1. Monitor the lubrication process by checking the uniformity of the granules for consistency in appearance and texture.
2. Perform a test on a sample of the lubricated granules to check the flow properties and ensure that they meet the specifications for compression.
3. If the granules fail the QC checks (e.g., poor flow properties, irregular texture), adjust the lubrication process, such as increasing mixing time or adjusting the lubricant concentration.

5.5 Lubrication Verification

1. Verify the final granule mixture by performing a quality check, including flowability tests (e.g., Carr’s index, angle of repose) and moisture content.
2. Document the results of all quality checks in the batch record and QC log (Annexure-1).

5.6 Equipment Cleaning

1. After completing the lubrication process, clean all equipment, including mixers, granulation pans, and containers, according to the cleaning SOP to prevent cross-contamination.
2. Ensure that all lubricant residues are removed from equipment surfaces to avoid contamination of subsequent batches.

5.7 Documentation and Record-Keeping

1. Record the complete lubrication process in the batch record, including the lubricant batch number, quantities used, and any deviations from the standard procedure.
2. Ensure that all in-process checks, such as flowability tests, are documented and signed off by the responsible personnel.
3. Ensure that all records are stored according to regulatory requirements for traceability and future reference.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Lubrication Batch Record (Annexure-1)
2. Granule Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Lubrication Batch Record

Annexure-2: Granule Quality Control Log

Revision History:

Standard Operating Procedure for Tablet Compression Process

1. Purpose

To establish a standardized procedure for the tablet compression process, ensuring that tablets are compressed to the required weight, hardness, and other quality specifications.

2. Scope

This SOP applies to the tablet compression process, including machine setup, tablet compression, and monitoring of tablet quality during the process.

3. Responsibilities

• Manufacturing Personnel: Responsible for setting up and operating the tablet compression machine, ensuring proper tablet compression parameters are followed.
• Quality Control (QC): Responsible for performing in-process checks on tablet weight, hardness, and other specifications during the compression process.
• Quality Assurance (QA): Responsible for overseeing the compliance with this SOP and ensuring the tablet compression process meets regulatory and internal quality standards.

4. Accountability

The Production Manager is accountable for the proper execution of the tablet compression process. The QA Manager ensures compliance with this SOP and regulatory standards.

5. Procedure

5.1 Tablet Compression Machine Setup

1. Ensure the tablet compression machine is clean and free of any previous product residue.
2. Verify that the die and punch sizes correspond to the specifications required for the current batch.
3. Check that the tablet press is calibrated and operational, including ensuring proper pressure and speed settings are in place.
4. Ensure all settings, such as tablet weight, hardness, and thickness, are input into the system and aligned with the formulation specifications.

5.2 Loading Granules into Compression Machine

1. Transfer the lubricated granules into the hopper of the tablet compression machine.
2. Ensure the granules are evenly distributed in the hopper, preventing blockages or uneven filling of the tablet dies.
3. Check that the granules have the correct consistency and moisture content for tablet compression. If necessary, adjust the formulation or parameters before loading.

5.3 Tablet Compression

1. Start the tablet compression process and monitor the machine to ensure tablets are being compressed properly.
2. Adjust the compression pressure if necessary to achieve the desired tablet hardness. Maintain consistency in the tablet weight and size throughout the process.
3. Ensure that the tablet edges are smooth and free from defects such as capping or lamination.
4. Perform regular checks on the compression force to ensure it remains within the specified range.

5.4 In-Process Quality Control

1. Monitor the tablet compression process regularly, checking the weight, hardness, and appearance of tablets at defined intervals.
2. Perform in-process checks for tablet weight, hardness, and thickness using calibrated instruments, and compare with specifications.
3. Take sample tablets for disintegration and dissolution testing, if required by the formulation guidelines.
4. Record all results from in-process quality checks in the batch record (Annexure-1).
5. If any abnormalities are detected, adjust machine parameters accordingly and document any deviations from the standard process.

5.5 Monitoring Tablet Quality

1. During the compression process, monitor tablet characteristics such as weight variation, hardness, and thickness to ensure consistency.
2. Ensure that tablets meet the required hardness range as per the formulation requirements.
3. Document any corrective actions taken if the tablet quality does not meet specifications.

5.6 Tablet Collection and Storage

1. Once the tablets are compressed, collect them in designated bins or containers for the next processing step (e.g., coating or packaging).
2. Ensure that tablets are stored in a clean, dry environment to avoid contamination or degradation before further processing.

5.7 Equipment Shutdown and Cleaning

1. Once tablet compression is complete, shut down the machine and clean it according to the approved cleaning SOP.
2. Ensure that all parts that come into contact with the product are thoroughly cleaned to prevent cross-contamination between batches.

5.8 Documentation and Record-Keeping

1. Document all tablet compression parameters, including compression pressure, speed, tablet weight, and hardness, in the batch record.
2. Sign off on the batch record to confirm the completion of the tablet compression process.
3. Maintain detailed records of in-process checks, deviations, and any corrective actions taken during the tablet compression process.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Tablet Compression Batch Record (Annexure-1)
2. Tablet Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Tablet Compression Batch Record

Annexure-2: Tablet Quality Control Log

Revision History:

Standard Operating Procedure for Monitoring Tablet Hardness during Compression

1. Purpose

This SOP defines the procedure for monitoring the hardness of tablets during the compression process, ensuring tablets meet the required hardness specifications for optimal product quality and performance.

2. Scope

This SOP applies to the monitoring and control of tablet hardness during the compression process in tablet manufacturing, including the use of hardness testers and adjustment of compression force.

3. Responsibilities

• Manufacturing Personnel: Operate tablet compression machines, monitor tablet hardness, and report any deviations to the QA team.
• Quality Control (QC): Perform hardness testing at defined intervals during the compression process and ensure tablets meet the required hardness specifications.
• Quality Assurance (QA): Ensure compliance with this SOP and regulatory requirements, review quality control data, and approve any adjustments made during the process.

4. Accountability

The Production Manager is accountable for ensuring the proper monitoring and control of tablet hardness during compression. The QA Manager is responsible for ensuring adherence to this SOP and reviewing the quality data.

5. Procedure

5.1 Tablet Hardness Monitoring Setup

1. Ensure that the tablet hardness tester is calibrated and in good working condition. Record the calibration data in the equipment log.
2. Check the compression machine to ensure it is properly set up for the required tablet weight, thickness, and hardness specifications.
3. Set the hardness tester to measure the required tablet hardness range (e.g., 4–8 kg). Ensure that the tester is positioned properly to avoid measurement inaccuracies.

5.2 Tablet Hardness Testing

1. During the compression process, test tablet hardness at regular intervals (e.g., every 30 minutes or every 100 tablets) using the hardness tester.
2. Measure the hardness of tablets from different positions in the batch to ensure uniformity. Perform at least three measurements per sample.
3. Ensure that the hardness is consistent with the target specifications for the formulation. If the hardness deviates from the acceptable range, adjust the compression force on the tablet press accordingly.

5.3 Recording Hardness Data

1. Record the tablet hardness measurements in the batch record (Annexure-1) and the QC log (Annexure-2).
2. Include relevant details such as the batch number, tablet hardness values, and any adjustments made to the compression force.
3. Ensure that all records are signed off by the responsible personnel and stored in compliance with regulatory requirements.

5.4 Adjusting Compression Force

1. If the tablet hardness does not meet the required specifications, adjust the compression force on the tablet press.
2. Increase or decrease the force as needed and recheck the tablet hardness after making adjustments.
3. Repeat the hardness test at regular intervals to ensure that the new settings produce tablets within specification.
4. If issues persist, stop the process, investigate potential causes, and rectify them. Document any troubleshooting actions taken in the batch record.

5.5 In-Process Quality Control

1. Ensure that tablets are tested for other critical parameters (e.g., weight, disintegration) in addition to hardness during the compression process to ensure overall tablet quality.
2. Monitor the tablet appearance for any issues such as capping, lamination, or uneven compression. If issues are detected, stop the process and troubleshoot the equipment.

5.6 Tablet Collection and Storage

1. Once the tablets meet the required hardness and other specifications, collect them in containers or bins for the next processing stage (e.g., coating or packaging).
2. Store tablets in a clean, dry environment to prevent degradation or damage before further processing.

5.7 Equipment Shutdown and Cleaning

1. After completing the tablet compression process, shut down the machine and clean the equipment according to the cleaning SOP.
2. Ensure that all components in contact with the tablets are cleaned thoroughly to avoid cross-contamination.

5.8 Documentation and Record-Keeping

1. Document the tablet hardness results, any deviations, and actions taken in the batch record.
2. Ensure all records are reviewed, signed, and retained according to regulatory requirements.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Tablet Hardness Monitoring Batch Record (Annexure-1)
2. Tablet Quality Control Log (Annexure-2)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Tablet Hardness Monitoring Batch Record

Annexure-2: Tablet Quality Control Log

Revision History:

Standard Operating Procedure for Troubleshooting Capping and Lamination Issues in Tablets

1. Purpose

To provide a standardized approach for troubleshooting and resolving capping and lamination issues during the tablet compression process, ensuring that all tablets meet the required quality specifications.

2. Scope

This SOP applies to the troubleshooting of capping and lamination issues during tablet compression, focusing on identifying causes and corrective actions to improve tablet integrity.

3. Responsibilities

• Manufacturing Personnel: Responsible for identifying signs of capping and lamination issues, adjusting machine settings, and following corrective procedures.
• Quality Control (QC): Monitor tablet quality, perform in-process checks, and identify defects related to capping and lamination during tablet production.
• Quality Assurance (QA): Ensure compliance with this SOP, perform audits, and approve corrective actions and process adjustments.

4. Accountability

The Production Manager is accountable for the resolution of capping and lamination issues and ensuring that the tablet compression process runs smoothly. The QA Manager ensures compliance with this SOP and regulatory standards.

5. Procedure

5.1 Identifying Capping and Lamination Issues

1. During the tablet compression process, observe any irregularities in tablet formation, particularly cracking, separation of tablet layers, or incomplete tablet formation.
2. Check for capping, which is when the upper surface of the tablet splits or separates, often due to high compression forces or improper granule flow.
3. Examine for lamination, where multiple layers of the tablet form due to excess lubrication, insufficient binder, or improper tablet press settings.
4. Note the frequency of these issues to identify whether they are isolated incidents or recurring problems that require immediate attention.

5.2 Potential Causes and Troubleshooting for Capping

1. Excessive Compression Force: If tablets are experiencing capping, check the compression force. If too high, decrease the force and test again. Document any changes.
2. Poor Granule Flow: If granules are not flowing properly, ensure they are adequately lubricated. Adjust the lubrication process to improve granule flow.
3. Moisture Content Issues: Low moisture content in the granules can result in brittle tablets. Ensure that the moisture content is within acceptable levels before compression.
4. Inadequate Pre-Compression: Ensure the tablet press is set to provide sufficient pre-compression to improve tablet bonding before main compression.
5. Adjust machine parameters and observe changes. Continue troubleshooting until tablet quality improves.

5.3 Potential Causes and Troubleshooting for Lamination

1. Excess Lubricant: Excess lubricant can cause lamination by preventing proper bonding of tablet layers. Reduce the amount of lubricant used in the granulation process.
2. Improper Binder: Check that the binder is correctly formulated and mixed. Insufficient binder can lead to weak tablets prone to lamination.
3. Granule Size Issues: Granules that are too fine or too large can cause uneven compression. Ensure the granule size is consistent and within specification.
4. Machine Settings: Adjust the speed and pressure of the tablet press. Higher speeds can lead to increased lamination issues, so reduce the speed and pressure to see if the problem improves.
5. Make adjustments and continue testing until the issue is resolved. Monitor tablet quality closely after each change.

5.4 In-Process Quality Control

1. Perform visual inspections of tablets throughout the compression process. Use a tablet hardness tester and visual inspection to detect any capping or lamination issues early on.
2. Perform regular checks for tablet weight, thickness, and appearance. Record results in the batch record (Annexure-1).
3. If a pattern of capping or lamination issues is observed, escalate to the QA team for a thorough investigation and to determine further corrective actions.

5.5 Machine Parameter Adjustments

1. If troubleshooting indicates the need for adjustments, reconfigure the tablet press settings. This may include altering compression force, tablet speed, or die settings.
2. After adjustments, run test batches to monitor if the capping and lamination issues have been resolved.
3. Document all adjustments made, including parameters changed and the outcome of the tests in the batch record.

5.6 Corrective Action and Documentation

1. If corrective actions are implemented, record the issue, cause, corrective action, and resolution in the batch record (Annexure-2).
2. Ensure all involved personnel sign off on the corrective actions taken, and provide detailed explanations of any deviations or unexpected results.
3. Review process parameters and tablet quality data to confirm that the capping and lamination issues have been resolved. Approve any changes in the process if necessary.

5.7 Documentation and Record-Keeping

1. Ensure that all troubleshooting activities, including observations, machine adjustments, and corrective actions, are documented in the batch record.
2. Sign and review all records to confirm that all issues have been addressed, and document final tablet quality in the quality control log (Annexure-3).
3. Maintain all records for future reference and in compliance with GMP regulations.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Tablet Compression Batch Record (Annexure-1)
2. Tablet Quality Control Log (Annexure-2)
3. Tablet Troubleshooting Log (Annexure-3)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Tablet Compression Batch Record

Annexure-2: Tablet Quality Control Log

Revision History:

Standard Operating Procedure for Coating Machine Calibration and Setup

1. Purpose

To outline the process for calibrating and setting up the coating machine, ensuring uniform coating of tablets, and that all operational parameters are met according to the product specifications.

2. Scope

This SOP applies to the calibration, setup, and operation of the coating machine for tablet coating, including the setup of equipment and verification of operational parameters.

3. Responsibilities

• Manufacturing Personnel: Responsible for setting up and operating the coating machine and ensuring correct calibration and machine settings during operation.
• Quality Control (QC): Responsible for verifying that the coating process is consistent with the defined specifications, performing quality checks on the coated tablets, and ensuring equipment calibration is accurate.
• Quality Assurance (QA): Responsible for overseeing the entire coating process, ensuring compliance with SOP, and reviewing and approving all records and deviations.

4. Accountability

The Production Manager is accountable for the proper operation and setup of the coating machine. The QA Manager is responsible for ensuring compliance with this SOP and regulatory standards.

5. Procedure

5.1 Equipment Inspection and Setup

1. Ensure the coating machine is clean and free from any residue from previous batches.
2. Inspect all components of the coating machine, including spray guns, air pressure regulators, and temperature controllers, to ensure they are properly functioning.
3. Verify that the machine is equipped with the correct tablet drum size and that the drum is properly aligned and free from damage.
4. Check for proper air filtration and circulation systems, ensuring no blockages or leaks.
5. Ensure that the coating material (e.g., sugar, film coating) is properly prepared and available for use.

5.2 Calibration of Coating Machine

1. Calibrate the spray nozzles according to the manufacturer’s specifications to ensure uniform and accurate coating distribution.
2. Verify the airflow rate, pressure, and temperature settings to ensure they are within the prescribed limits for the coating process.
3. Perform a test run without tablets to check the spray pattern and adjust as necessary to achieve a consistent coating spray.
4. Record calibration results in the equipment log for future reference and verification (Annexure-1).

5.3 Coating Material Preparation

1. Prepare the coating solution by mixing the coating agent with the appropriate solvent (e.g., water, ethanol) as per the formulation guidelines.
2. Ensure the coating material is filtered to remove any contaminants before it is loaded into the coating machine’s reservoir.
3. Verify that the coating material is the correct batch and within its expiry date, checking the Certificate of Analysis (CoA) for quality assurance.

5.4 Loading Tablets into the Coating Machine

1. Ensure that the tablets are properly prepared and free from defects (e.g., chips or cracks) before loading into the coating drum.
2. Carefully load the tablets into the coating drum, ensuring that they are evenly distributed and not overcrowded to allow for optimal coating.
3. Verify that the tablet feed mechanism is functioning properly to prevent blockage during the coating process.

5.5 Coating Process

1. Start the coating machine, ensuring that the spray system is activated and the tablets are tumbling evenly inside the drum.
2. Gradually introduce the coating material into the system, adjusting the flow rate to ensure a uniform coating.
3. Monitor the tablet surface throughout the process to check for uniformity and avoid over-coating or under-coating.
4. Adjust the airflow, temperature, and spray rate if needed to achieve the desired coating thickness.
5. Ensure that tablets are coated evenly and that there are no defects such as uneven coverage, drips, or streaks.

5.6 In-Process Quality Control

1. During the coating process, regularly sample the tablets and inspect them for uniformity, appearance, and coating thickness.
2. Perform physical tests, such as checking for coating defects, tablet integrity, and adhesion quality (e.g., peel resistance, gloss, etc.).
3. If any tablets show defects (e.g., uneven coating, cracks), stop the process and investigate possible causes. Make adjustments as necessary.
4. Record all in-process checks in the batch record (Annexure-2) and ensure that results are documented and signed off by the responsible personnel.

5.7 Final Coating Inspection and Drying

1. After completing the coating process, check the tablets for appearance and ensure the coating has dried properly without any tackiness.
2. If the coating appears wet, adjust the drying time or temperature settings to ensure complete drying of the tablets.
3. Perform the final inspection for coating defects and record the results in the batch record.
4. Ensure the tablets are stored in an appropriate environment until the next stage in the process (e.g., packaging).

5.8 Equipment Shutdown and Cleaning

1. Once the coating process is complete, turn off the machine and clean all parts that have come into contact with the coating material according to the cleaning SOP.
2. Ensure that the spray nozzles, drum, and other components are thoroughly cleaned to avoid cross-contamination in future batches.
3. Record cleaning details in the equipment log, including the date, cleaning method, and personnel responsible (Annexure-3).

5.9 Documentation and Record-Keeping

1. Ensure that all steps of the coating process, including calibration, machine settings, in-process checks, and adjustments, are documented in the batch record.
2. Sign off on the batch record to confirm the successful completion of the coating process, and store all records for regulatory compliance.
3. Ensure that all relevant quality control data is properly documented, including any deviations and corrective actions taken during the process.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance
• CoA: Certificate of Analysis

7. Documents

1. Coating Batch Record (Annexure-1)
2. Coating Quality Control Log (Annexure-2)
3. Equipment Cleaning Log (Annexure-3)

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (US FDA)
• EU GMP Guidelines Part I – Basic Requirements for Medicinal Products
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

9. SOP Version

Version: 2.0

10. Approval Section

11. Annexures

Annexure-1: Coating Batch Record

Annexure-2: Coating Quality Control Log

Annexure-3: Equipment Cleaning Log

Revision History: