and meets regulatory requirements. QA also reviews and approves all validation documentation and reports.
Production Supervisors: Oversee the validation process, ensuring proper execution and providing support to operators.
Validation Team: Responsible for designing the validation protocol, executing the validation runs, and analyzing the results.
Maintenance Personnel: Ensures that all manufacturing equipment used in the process is properly calibrated, functioning, and maintained to avoid any process deviations during validation.

4) Procedure

The following steps should be followed for the validation of API manufacturing processes:

1. Preparation for Validation:
1.1 Review batch records to identify critical process parameters (CPPs) for each stage in the API manufacturing process.
1.2 Develop a process validation protocol, which includes objectives, scope, equipment, process flow, and personnel involved in the validation process.
1.3 Ensure that all equipment used in the manufacturing process, such as reactors, filtration units, drying units, and packaging lines, are properly calibrated and operational before initiating the validation process.

2. Validation Protocol:
2.1 Protocol Design: The validation protocol should be designed based on the formulation of the API and the specific manufacturing process involved in its production.
2.2 Defining Acceptance Criteria: Establish acceptance criteria for critical parameters such as yield, purity, content uniformity, and residual solvents. This should include specifications for intermediates and the final API product.
2.3 Risk Assessment: Conduct a risk assessment to identify critical quality attributes (CQAs) and corresponding critical process parameters (CPPs). The goal is to ensure that risks to product quality are identified and mitigated effectively.

3. Execution of Validation:
3.1 Raw Material Validation: Ensure that raw materials, such as reagents, solvents, and excipients, meet quality specifications before use in the manufacturing process.
3.2 Synthesis Validation: Validate the chemical synthesis process to ensure that all reactions proceed as intended and that the correct intermediates are produced. Monitor critical parameters such as temperature, pressure, and reaction time.
3.3 Purification: Validate the purification process to ensure that all impurities are removed to meet the required purity specifications. This includes validating steps such as filtration, chromatography, and crystallization.
3.4 Drying: Validate the drying process to ensure that the API is dried to the required residual moisture content without degradation of the product.
3.5 Packaging: Validate the packaging process to ensure that the API is securely packaged, protected from contamination, and that the packaging material is suitable for the intended use. Ensure that all containers are properly labeled and sealed.

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 of the data to assess the process capability and confirm that the 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 process if there are significant changes to the formulation, raw materials, equipment, or critical process parameters.
5.2 Conduct periodic revalidation to ensure continued compliance with regulatory requirements and confirm that the process consistently meets the acceptance criteria for product quality.

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: Raw Material Certificate of Analysis

Material ID	Supplier	Batch No.	Test Result	Approved By
Material Number	Supplier Name	Batch Number	Test Result	QC Name

Template 2: Synthesis Process Record

Batch No.	Synthesis Date	Temperature	Reaction Time	Operator Initials
Batch Number	DD/MM/YYYY	Temperature in °C	Time in hours	Operator Name

Template 3: Purification Process Record

Batch No.	Purification Date	Purification Method	Purity Level	Operator Initials
Batch Number	DD/MM/YYYY	Chromatography/Filtration	Purity in %	Operator Name

Template 4: Drying Process Record

Batch No.	Drying Date	Temperature	Drying Time	Residual Moisture
Batch Number	DD/MM/YYYY	Temperature in °C	Time in hours	Moisture in %

Template 5: Packaging Process Record

Batch No.	Packaging Date	Container Type	Operator Initials	Supervisor Signature
Batch Number	DD/MM/YYYY	Container Type	Operator Name	Supervisor Name

Template 6: Statistical Analysis Data

Sample ID	Test Type	Mean	Standard Deviation	Result
Sample Number	Test Name	Mean Value	Standard Deviation	Pass/Fail