Tablets: SOP for End-Point Detection in Mixing Process – V 2.0

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Tablets: SOP for End-Point Detection in Mixing Process – V 2.0

Standard Operating Procedure for End-Point Detection in Mixing Process

Department Tablet
SOP No. SOP/TAB/166/2025
Supersedes SOP/TAB/166/2022
Page No. Page 1 of 6
Issue Date 01/03/2026
Effective Date 06/03/2026
Review Date 01/03/2027

1. Purpose

To define the procedure for detecting the end-point of the mixing process during tablet manufacturing, ensuring the uniformity and quality of the blended material before proceeding to the next manufacturing step.

2. Scope

This SOP applies to the mixing process during tablet manufacturing, where the end-point of mixing is critical to ensuring uniform distribution of active pharmaceutical ingredients (API) and excipients in the blend.

3. Responsibilities

  • Production Operator: Responsible for monitoring and detecting the end-point of the mixing process, ensuring that the blending is complete before proceeding to the next step.
  • Quality Control (QC): Responsible for verifying the end-point detection method, ensuring consistency and uniformity in the blend and conducting final checks on blend quality.
  • Quality Assurance (QA): Ensures that the end-point detection procedure is followed according to this SOP and approves the final blend for further processing.

4. Accountability

The Production Supervisor is accountable for ensuring the end-point detection process is followed properly. The QC Manager is responsible for verifying the end-point and ensuring the mix is consistent and uniform before moving forward.

5. Procedure

5.1 Preparation for End-Point Detection

  1. Ensure that the mixing equipment is set up and calibrated correctly, including verifying the mixer speed, time settings, and any other process parameters defined in the batch record.
  2. Check that the appropriate materials (API, excipients, lubricants) are prepared and ready for mixing as per the batch record.
  3. Review the batch record to confirm the target blend uniformity and the process limits for the end-point detection, such as the mixing time and visual appearance of the blend.
  4. Verify that all required monitoring tools (e.g., sampling equipment, humidity meters, temperature sensors) are available and ready for use during the mixing process.
See also  Tablets: SOP for Inspecting Equipment After Each Stage of Manufacturing - V 2.0

5.2 Monitoring the Mixing Process

  1. Start the mixing process as per the established parameters (e.g., mixer speed, time). Monitor the mix regularly to ensure the consistency of the material.
  2. Take periodic samples during the mixing process to check the uniformity of the blend and ensure that the API is evenly distributed across the excipients.
  3. Document the times at which samples are taken in the batch record (Annexure-2). Ensure the sampling time intervals follow the plan outlined in the batch record.
  4. If automated monitoring equipment is used, check that the system is recording data correctly, such as mixing time, temperature, and other relevant parameters.

5.3 Detecting the End-Point

  1. The end-point of the mixing process is detected when the following conditions are met:
    • The blend is visually homogeneous, with no visible powder clumps or segregation of materials.
    • The sample tested for uniformity passes the required tests for API distribution, such as content uniformity or blending uniformity tests.
    • The mixer has run for the pre-determined time, or the batch record specifies that the desired blend uniformity has been reached.
  2. Once the end-point is reached, stop the mixing process and document the time and parameters in the batch record (Annexure-2).
  3. Verify that the blend meets the required specifications for uniformity and quality before moving to the next manufacturing stage.
See also  Tablets: SOP for End-Point Determination in Granulation Process - V 2.0

5.4 Documentation of Results

  1. Record the time of end-point detection, the sampling results, and any observations made during the process in the batch record (Annexure-2).
  2. If the mixing process does not meet the required blend uniformity or any other end-point criteria, document this in the batch record and initiate corrective actions.
  3. Ensure that all data related to the mixing process, including the sampling results, are reviewed and signed off by the QC personnel before proceeding to the next stage of manufacturing.

5.5 Corrective Actions for End-Point Deviations

  1. If the end-point is not achieved as expected (e.g., blend uniformity failure), initiate corrective actions such as:
    • Re-mixing the batch to achieve the desired blend uniformity.
    • Adjusting the mixing parameters (e.g., time, speed) to improve blend quality.
    • Verifying that all raw materials were properly prepared and weighed.
  2. Document all corrective actions taken in the deviation report (Annexure-1) and initiate a review with the QA team to determine the impact on product quality.

5.6 Acceptance Criteria

  1. The batch is considered acceptable for the next manufacturing stage if the following criteria are met:
    • Uniform distribution of API across the blend, as verified by sample testing.
    • The visual appearance of the blend is homogeneous, with no clumps or segregation.
    • All process parameters (time, speed) are within the specified limits.
  2. If the batch fails to meet any of these criteria, re-mixing and re-sampling may be required before continuing to the next manufacturing step.
See also  Tablets: SOP for Ensuring Weight Uniformity in Tablets - V 2.0

5.7 Post-Testing Actions

  1. If the end-point is successfully achieved, proceed with the next step in the tablet manufacturing process, such as compression or granulation.
  2. Ensure that all documentation is complete and stored according to the company’s document retention policy for audit purposes.

6. Abbreviations

  • SOP: Standard Operating Procedure
  • GMP: Good Manufacturing Practice
  • QC: Quality Control
  • QA: Quality Assurance
  • API: Active Pharmaceutical Ingredient
  • 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 Mixing and Blending Processes

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Deviation Report

Deviation Date Batch Number Deviation Description Corrective Action Responsible Person
15/12/2025 Batch 001 Blend uniformity failure Re-mixed batch and adjusted mixing time John Doe

Annexure-2: Batch Record

Time Sample Number Blend Uniformity Result Tested By
08:00 AM Sample 1 Pass 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 sample frequency and end-point criteria Improved process control QA Head
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