Standard Operating Procedure for Scale-Up Studies in Cream Manufacturing

Department	Creams
SOP No.	SOP/CRM/029/2025
Supersedes	SOP/CRM/029/2022
Page No.	Page 1 of 7
Issue Date	20/07/2025
Effective Date	25/07/2025
Review Date	20/07/2026

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to outline the process for conducting scale-up studies in cream manufacturing. Scale-up studies ensure that the cream formulation, initially developed at a laboratory or pilot scale, can be successfully reproduced at a larger production scale while maintaining product quality, consistency, and compliance with regulatory standards.

2. Scope

This SOP applies to all cream formulations that are transitioning from pilot-scale or laboratory-scale production to full-scale manufacturing. It covers the processes, procedures, and testing requirements for scaling up cream formulations in the Creams Department.

3. Responsibilities

• Formulation Development Team: Responsible for providing the formulation details, assisting with scale-up procedures, and ensuring the consistency of the final formulation at larger production scales.
• Production Team: Responsible for implementing the scale-up process, coordinating equipment setup, and ensuring that the manufacturing conditions are optimized for larger batches.
• Quality Control (QC): Responsible for performing all necessary tests, including physical, chemical, and stability testing, to evaluate whether the scaled-up product meets the required specifications.
• Quality Assurance (QA): Ensures that the scale-up process is in compliance with GMP standards, oversees the documentation, and approves the final scaled-up formulation for commercial production.
• Regulatory Affairs: Ensures that the scaled-up process complies with regulatory requirements and guidelines for manufacturing and labeling the cream formulation in the target market.

4. Accountability

The Head of Creams Manufacturing is responsible for overseeing the scale-up process. The QA Manager is accountable for ensuring that the scaled-up batch is consistent with the pilot batch and complies with regulatory and quality standards.

5. Procedure

5.1 Pre-Scale-Up Preparations

1. Review the laboratory or pilot-scale batch records to ensure that the formulation and process are well-documented and optimized.
2. Select the appropriate manufacturing equipment for scale-up based on the batch size and production requirements. Consider factors such as mixing efficiency, heat transfer, and homogenization capacity.
3. Verify that the required raw materials, including APIs and excipients, are available in the necessary quantities for the larger batch production. Ensure that all raw materials meet the necessary quality standards.
4. Conduct a risk assessment to identify any potential challenges or critical factors that may affect the scale-up, such as ingredient compatibility, processing parameters, or equipment limitations.

5.2 Scale-Up Batch Production

1. Begin the scale-up process by manufacturing a small batch or pilot batch at the chosen production scale. Follow the same process steps used in the laboratory or pilot scale, ensuring that all critical process parameters are documented and monitored closely.
2. Monitor and adjust key process parameters (e.g., mixing speed, temperature, processing time, and viscosity) to maintain product consistency and quality during the scale-up process.
3. Ensure that the production team follows the established manufacturing procedures and protocols as per the formulation’s specifications.

5.3 Testing of Scale-Up Batch

1. Conduct a comprehensive set of tests on the scale-up batch to assess its quality and consistency. These tests include:
   • Viscosity Testing: Measure the viscosity to ensure it matches the desired product characteristics.
   • pH Testing: Verify that the pH is within the acceptable range for the intended skin application.
   • Stability Testing: Perform accelerated stability tests under various environmental conditions to simulate the product’s shelf life.
   • Active Ingredient Content: Ensure that the API concentration is within the acceptable range.
   • Microbial Testing: Conduct microbial tests if necessary to confirm the product is free from contamination.
2. Document the results of all tests and compare them to the specifications set for the formulation. If the results meet the desired criteria, proceed with the next steps. If any issues are identified, adjust the formulation or manufacturing process and repeat testing.

5.4 Process Optimization

1. After conducting the initial tests on the scale-up batch, analyze the results to identify any areas for improvement in the process. Common issues may include inadequate mixing, incorrect viscosity, or formulation instability.
2. Adjust the process parameters or formulation ingredients as necessary to optimize the product’s performance and ensure it meets all specifications.
3. Repeat the production and testing steps until the scale-up batch consistently meets all required specifications.

5.5 Documentation and Approval

1. Document all activities related to the scale-up process, including batch records, process parameters, test results, and any changes made to the formulation or production process.
2. Prepare a Scale-Up Report (Annexure-1) that includes:
   • Details of the formulation and production process
   • Test results from the scale-up batch
   • Any adjustments made during the scale-up process
   • Final approval status from the QA team
3. Submit the Scale-Up Report to the QA team for review and approval. Once approved, the formulation is ready for full-scale commercial production.

5.6 Finalization for Commercial Production

1. After the successful completion of scale-up studies, finalize the production parameters and manufacturing process for full-scale commercial production.
2. Ensure that all documentation, including process validation and batch records, is up to date and ready for regulatory submission, if required.
3. Communicate the results of the scale-up study to the production and quality teams, ensuring that the process is fully standardized for commercial manufacturing.

6. Abbreviations

• QC: Quality Control
• QA: Quality Assurance
• GMP: Good Manufacturing Practices
• API: Active Pharmaceutical Ingredient
• R&D: Research and Development

7. Documents

1. Scale-Up Report (Annexure-1)
2. Batch Records (Annexure-2)
3. Process Validation Report (Annexure-3)

8. References

• Good Manufacturing Practices (GMP) Guidelines – 21 CFR Part 211
• International Conference on Harmonisation (ICH) Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• FDA 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: Scale-Up Report

Batch Number	Production Parameters	Test Results	Approval Status
67890	Mixing Time: 30 mins, Temperature: 65°C	Viscosity: Pass, pH: Pass, Stability: Pass	Approved

Annexure-2: Batch Records

Batch Number	Production Date	Ingredients Used	Process Parameters	Operator
67890	20/07/2025	Water, Glycerin, Hyaluronic Acid	Mixing, Heating, Homogenization	John Doe

Annexure-3: Process Validation Report

Batch Number	Validation Tests	Test Results	Approval Status
67890	Stability, Viscosity, pH	Pass	Approved

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/03/2024	1.0	Initial Version	New SOP Creation	QA Head
01/03/2025	2.0	Format Revision and Updates	Standardization of Document	QA Head