GMP guidelines and reviews records for compliance with this SOP.

Maintenance Team: Responsible for ensuring that the mixing equipment is properly maintained and calibrated to function optimally during the production process.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that the semi-solid mixing process is carried out according to this SOP. The QA Manager is responsible for ensuring the overall compliance with quality standards and regulatory requirements during the mixing and filling processes.

5. Procedure

5.1 Pre-Mixing Preparation

Before beginning the mixing process, ensure the following preparations are completed:

1. Raw Material Verification
   1. Verify that all raw materials, including active pharmaceutical ingredients (APIs) and excipients, are approved by the QC department and meet the required specifications.
   2. Ensure that the materials are stored appropriately and are within the expiry dates.
2. Weighing of Materials
   1. Weigh the raw materials accurately using calibrated equipment. Ensure the weights are consistent with the batch recipe and documented in the batch production record (BPR).
   2. Double-check the material identification and weight before transferring them to the mixing area.
3. Equipment Setup
   1. Ensure that the mixing equipment is clean, calibrated, and suitable for processing semi-solids. Verify that all mixing vessels, agitators, and other tools are in proper working condition.
   2. Set up the equipment according to the batch requirements, ensuring that the speed, temperature, and mixing time are correctly adjusted.
4. Document Preparation
   1. Ensure all required documentation, including the BPR, material specifications, and test protocols, are available and up to date.
   2. Record the batch number, operator name, and date of preparation in the BPR before starting the mixing process.

5.2 Mixing Process

Follow these steps to properly mix the semi-solid material:

1. Loading of Ingredients
   1. Load the raw materials into the mixing vessel in the order specified by the batch formula. Begin with the larger excipients and gradually add the APIs and other additives.
   2. Ensure that each material is added evenly to avoid clumping or uneven distribution of ingredients.
2. Mixing
   1. Start the mixing process at a slow speed to allow the ingredients to blend together, then gradually increase the speed as needed to achieve the desired consistency.
   2. Monitor the consistency of the mixture throughout the process. The material should be smooth, homogenous, and free from lumps or air bubbles.
3. Temperature Control
   1. If the formulation requires heating, ensure that the temperature is carefully controlled and maintained throughout the mixing process. Use a thermometer or temperature sensor to monitor the temperature.
   2. Ensure that the temperature does not exceed the maximum allowed for the semi-solid materials to prevent degradation of the API or excipients.
4. Mixing Time
   1. Allow the mixing process to continue for the specified time to ensure thorough integration of all ingredients. Do not overmix, as this may introduce air or heat, which could affect the consistency of the final product.
5. Sampling
   1. During the mixing process, take samples of the semi-solid mixture at regular intervals to check for uniformity, consistency, and appearance. The samples should be checked for viscosity, texture, and any lumps or inconsistencies.

5.3 Quality Control During Mixing

Quality control (QC) checks should be performed during the mixing process to ensure the consistency and quality of the semi-solid mixture:

1. Viscosity Test
   1. Measure the viscosity of the semi-solid mixture using a viscometer. Ensure that the viscosity falls within the specified range for the product.
2. Homogeneity Test
   1. Check for uniformity in the appearance of the mixture. The semi-solid mixture should be smooth, without lumps, air pockets, or uneven color distribution.
3. Temperature Monitoring
   1. Monitor the temperature of the mixture throughout the process to ensure that it stays within the acceptable range. Excessive heating can cause the material to degrade.

5.4 Post-Mixing Process

After mixing, perform the following steps:

1. Final Inspection
   1. Inspect the semi-solid mixture for consistency, uniformity, and appearance. Ensure there are no visible defects, lumps, or inconsistencies in the formulation.
   2. Ensure that the mixture is at the correct temperature and consistency for capsule filling.
2. Transfer to Capsule Filling
   1. Once the mixture passes quality control checks, transfer the semi-solid material to the capsule filling equipment. Ensure that the material is loaded into the machine without contamination or damage.
3. Record-Keeping
   1. Document all details of the mixing process, including batch number, equipment used, material weights, mixing time, viscosity, and QC test results, in the batch production record (BPR).
   2. Ensure that all deviations or corrective actions taken during the mixing process are documented appropriately.

5.5 Equipment Cleaning and Maintenance

After the mixing process, ensure that all equipment is cleaned and maintained:

1. Cleaning
   1. Clean all mixing equipment thoroughly to remove any residual material. Use approved cleaning agents and follow the equipment manufacturer’s cleaning instructions.
2. Inspection and Maintenance
   1. Inspect the equipment for wear and tear. Ensure that all components are functioning properly and are free from any material build-up that could affect future batches.

6. Abbreviations

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

7. Documents

1. Batch Production Record (BPR) (Annexure-1)
2. Deviation Report (Annexure-2)
3. Inspection and Testing Log (Annexure-3)
4. Equipment Maintenance Log (Annexure-4)

8. References

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

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Batch Production Record (BPR)

Batch ID	Mixing Date	Raw Materials	Mixing Parameters	Operator Name
Batch 001	01/02/2025	API, Excipients	Speed: 150 rpm, Time: 30 min	John Doe

Annexure-2: Deviation Report

Deviation ID	Description	Corrective Action Taken	Operator Name
DEV-001	Inconsistent viscosity	Adjusted mixing speed	John Doe

Annexure-3: Inspection and Testing Log

Batch ID	Test Type	Result	Operator Name
Batch 001	Viscosity	Pass	John Doe

Annexure-4: Equipment Maintenance Log

Equipment ID	Maintenance Date	Tasks Performed	Technician Name
Mixer 1	01/02/2025	Calibrated and cleaned	Jane Smith

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated mixing process	Standardization	QA Head