and documented.
Quality Assurance (QA): Ensures that the syrup manufacturing process is validated in compliance with this SOP and meets all regulatory and quality requirements. QA is also responsible for reviewing and approving all validation documentation and reports.
Production Supervisors: Oversee the syrup manufacturing process and ensure that it is performed according to the approved protocol, with operators following all required procedures.
Validation Team: Responsible for developing the syrup manufacturing process validation protocol, executing the validation runs, and analyzing the results.
Maintenance Personnel: Ensures that all equipment used in the syrup manufacturing process, such as mixing vessels, heating systems, filtration units, and packaging machines, is properly calibrated, maintained, and functioning during the validation process.

4) Procedure

The following steps should be followed for the validation of the syrup manufacturing process:

1. Preparation for Validation:
1.1 Review batch records and product specifications to identify critical process parameters (CPPs) for the syrup manufacturing process, such as ingredient concentration, pH, mixing speed, and heating temperature.
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 syrup manufacturing equipment, including mixing vessels, heat exchangers, filtration units, and packaging machines, are calibrated and operational before initiating the validation process.

2. Validation Protocol:
2.1 Protocol Design: The validation protocol should be designed based on the specific syrup formulation and the manufacturing equipment used.
2.2 Defining Acceptance Criteria: Establish acceptance criteria for critical parameters such as ingredient concentration, mixing uniformity, pH, viscosity, and the final syrup appearance. Criteria should also include parameters like stability and microbiological limits.
2.3 Risk Assessment: Conduct a risk assessment to identify critical quality attributes (CQAs) and corresponding critical process parameters (CPPs). This will help ensure that risks to product quality are identified and mitigated effectively.

3. Execution of Validation:
3.1 Ingredient Preparation: Validate the preparation of ingredients to ensure that all components, such as active pharmaceutical ingredients (APIs), excipients, and solvents, are measured and mixed according to the formulation specifications.
3.2 Mixing Process: Validate the mixing process to ensure that all ingredients are uniformly blended. This includes validating the mixing time, speed, and temperature to ensure the homogeneous distribution of the active ingredient.
3.3 Heating: Validate the heating process to ensure that the syrup is heated to the correct temperature and held for the specified time, avoiding degradation of heat-sensitive components.
3.4 Filtration: Validate the filtration process to ensure that any particulate matter is removed, and that the syrup meets clarity and microbial limits.
3.5 pH and Viscosity Control: Validate the pH and viscosity of the syrup to ensure that it meets the required specifications for product stability and performance.
3.6 Packaging: Validate the packaging process to ensure that the syrup is properly transferred into containers, sealed, and labeled in compliance with regulatory requirements.

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 collected data to assess process consistency and capability. This analysis should confirm that the syrup manufacturing process consistently produces syrups that meet the acceptance criteria.
4.4 Prepare a final validation report that summarizes the results of the validation, including any deviations, corrective actions, and conclusions regarding the syrup manufacturing process.

5. Revalidation:
5.1 Revalidate the syrup manufacturing process if there are significant changes to the formulation, equipment, or critical process parameters.
5.2 Periodically conduct revalidation to ensure continued compliance with regulatory requirements and confirm that the syrup manufacturing process consistently produces high-quality products.

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: Syrup Manufacturing Process Record

Date	Time	Operator Initials	Mixing Time	Ingredient Concentration
DD/MM/YYYY	HH:MM	Operator Name	Time in minutes	Concentration in %

Template 2: Syrup pH and Viscosity Record

Batch No.	pH Value	Viscosity (cP)	Test Date	Operator Initials
Batch Number	pH Value	Viscosity in cP	DD/MM/YYYY	Operator Name

Template 3: Syrup Filtration Record

Batch No.	Filtration Date	Filtration Method	Filter Type	Operator Initials
Batch Number	DD/MM/YYYY	Filtration Method	Filter Type	Operator Name

Template 4: Syrup Final Inspection Record

Batch No.	Test Date	Final Appearance	Operator Initials
Batch Number	DD/MM/YYYY	Pass/Fail	Operator Name

Template 5: Statistical Analysis Data

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