Standard Operating Procedure for Validating Granulation Process in Tablet Manufacturing
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process validation procedure for the granulation process in tablet manufacturing. This SOP ensures that the granulation process consistently produces granules that meet the required quality specifications, including uniformity, strength, and flowability. Proper validation ensures that critical parameters such as mixing time, granulation speed, and binder concentration are optimized to produce high-quality tablets in compliance with regulatory standards.
2) Scope
This SOP applies to the granulation process used in the manufacturing of tablets within the facility. It covers the process validation activities for both new formulations and existing formulations undergoing significant process changes. This SOP ensures that all critical parameters in the granulation process, from mixing to drying, are validated to achieve consistent and reliable results. The SOP is applicable to both wet and dry granulation processes.
3) Responsibilities
Operators: Responsible for performing granulation tasks according to the approved protocol and ensuring that all critical process parameters are monitored and recorded.
Quality Assurance (QA): Ensures that the granulation process is validated in compliance with this SOP and that all documentation and validation reports are reviewed and approved.
Production Supervisors: Oversee the granulation process and ensure that it is carried out according to the approved protocol and that operators follow all required procedures.
Validation Team: Develops the granulation process validation protocol, executes the validation runs, and analyzes the results.
Maintenance Personnel: Ensures that the equipment used in the granulation process is properly calibrated and maintained to meet operational standards.
4) Procedure
The following steps should be followed for the validation of the granulation process in tablet manufacturing:
1. Preparation for Validation:
1.1 Review batch records to identify critical process parameters (CPPs) for each step in the granulation process, such as granule size, binder concentration, and drying time.
1.2 Develop a process validation protocol that includes the objectives, scope, equipment, process flow, and personnel involved in the validation process.
1.3 Ensure that all equipment, such as blenders, granulators, fluidized bed dryers, and sieving machines, are calibrated and operational before initiating the validation process.
2. Validation Protocol:
2.1 Protocol Design: The validation protocol should be based on the formulation of the tablets and the specific granulation process used, whether wet or dry.
2.2 Defining Acceptance Criteria: Establish acceptance criteria for critical parameters such as granule size distribution, uniformity, and moisture content. The criteria should also include parameters such as binder concentration, mixing time, and granulation speed.
2.3 Risk Assessment: Conduct a risk assessment to identify critical quality attributes (CQAs) and corresponding critical process parameters (CPPs). This ensures that potential risks to product quality are identified and mitigated effectively.
3. Execution of Validation:
3.1 Granule Mixing: Validate the mixing process to ensure uniform distribution of active ingredients, excipients, and binder. This includes controlling the mixing time and speed to achieve consistent granule formation.
3.2 Granulation (Wet or Dry): If wet granulation is used, validate the addition of the binder solution to ensure that the correct amount is applied to the powder mixture. If dry granulation is used, ensure proper compression and size reduction.
3.3 Drying: Validate the drying process to ensure that granules are dried to the required residual moisture content. Control drying temperature, humidity, and time to avoid over-drying or under-drying of the granules.
3.4 Sieving: Validate the sieving process to ensure that the granules are of the correct size for tablet compression and that they meet the required uniformity criteria.
3.5 Storage and Handling: Validate the storage and handling of the granules to prevent contamination and ensure that the granules retain their properties for subsequent compression into tablets.
4. Documentation and Reporting:
4.1 Record all data during the validation process, including batch records, equipment logs, process parameters, and testing results.
4.2 Ensure that all forms, reports, and certificates are completed and signed by the responsible personnel.
4.3 Perform statistical analysis on the collected data to assess process capability and ensure that the granulation process consistently meets the acceptance criteria.
4.4 Prepare a final validation report summarizing the results, including any deviations from the acceptance criteria and corrective actions taken, if necessary.
5. Revalidation:
5.1 Revalidate the granulation process if there are significant changes to the formulation, equipment, or critical process parameters.
5.2 Conduct periodic revalidation to ensure continued compliance with regulatory requirements and confirm that the granulation process consistently meets the required quality specifications.
5) Abbreviations
- QA: Quality Assurance
- CPP: Critical Process Parameter
- CQA: Critical Quality Attribute
- SOP: Standard Operating Procedure
6) Documents
- Process Validation Protocol
- Batch Production Records
- Equipment Calibration Logs
- Process Validation Reports
- Raw Material Certificates of Analysis
- Statistical Analysis Data
7) Reference
- International Council for Harmonisation (ICH) Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
- FDA Guidance for Industry: Process Validation
- ISO 9001: Quality Management Systems – Requirements
8) SOP Version
Version 1.0 – Effective Date: DD/MM/YYYY
Annexure
Template 1: Granule Mixing Process Record
| Date | Time | Operator Initials | Mixing Duration | Remarks |
|---|---|---|---|---|
| DD/MM/YYYY | HH:MM | Operator Name | Duration in minutes | Process completed as per SOP |
Template 2: Granulation Process Record
| Batch No. | Granulation Date | Binder Solution Amount | Operator Initials | Supervisor Signature |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Binder Volume in mL | Operator Name | Supervisor Name |
Template 3: Drying Process Record
| Batch No. | Drying Date | Drying Temperature | Drying Duration | Residual Moisture |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Temperature in °C | Duration in minutes | Moisture in % |
Template 4: Sieving Process Record
| Batch No. | Sieving Date | Sieve Size | Operator Initials | Supervisor Signature |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Sieve Mesh Size | Operator Name | Supervisor Name |
Template 5: Final Granule Quality Check Record
| Batch No. | Test Date | Granule Size | Granule Uniformity | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Size Range (mm) | Pass/Fail | Operator Name |
Template 6: Statistical Analysis Data
| Sample ID | Test Type | Mean | Standard Deviation | Result |
|---|---|---|---|---|
| Sample Number | Test Name | Mean Value | Standard Deviation | Pass/Fail |
