Procedure for Scaling Up Formulations from Lab to Pilot Scale

Department	Research and Development (R&D)/Quality Assurance (QA)/Quality Control (QC)/Manufacturing
SOP No.	SOP/Ointment/189
Supersedes	V 1.0
Page No.	Page X of Y
Issue Date	[Insert Issue Date]
Effective Date	[Insert Effective Date]
Review Date	[Insert Review Date]

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish a systematic approach for scaling up pharmaceutical ointment formulations from laboratory-scale development to pilot-scale production. This process ensures consistency, reproducibility, and compliance with regulatory guidelines while optimizing manufacturing parameters.

2. Scope

This SOP applies to all personnel involved in formulation development, process optimization, quality control, and scale-up activities in the Research and Development (R&D), Quality Assurance (QA), and Quality Control (QC) departments.

3. Responsibilities

• Formulation Scientist: Develops and optimizes the formulation scale-up process.
• Process Engineer: Ensures transfer of process parameters to pilot-scale production.
• QA Officer: Ensures adherence to GMP and validation requirements.
• QC Analyst: Conducts analytical and stability testing for scaled-up batches.
• Manufacturing Supervisor: Monitors process feasibility and equipment performance.
• Regulatory Affairs Specialist: Ensures documentation complies with global regulatory requirements.

4. Accountability

The R&D Manager is accountable for ensuring that all scale-up activities comply with GMP, FDA, ICH, WHO, and company policies.

5. Procedure

5.1 Pre-Scale-Up Assessment

• Review **lab-scale formulation** for:
  • API solubility and stability.
  • Homogeneity and viscosity.
  • Excipients compatibility.
• Identify **Critical Process Parameters (CPPs)**:
  • Mixing time and speed.
  • Shear force during emulsification.
  • Temperature control.
• Perform **Risk Assessment** to anticipate scale-up challenges.
• Document findings in the **Pre-Scale-Up Report (Annexure-1).**

5.2 Selection of Pilot-Scale Equipment

• Select pilot-scale equipment that **mirrors lab-scale processes**, including:
  • Mixing tanks with controlled agitation.
  • Homogenizers for emulsification.
  • Vacuum deaerators to remove air bubbles.
• Ensure equipment **calibration and validation** before scale-up.
• Record equipment details in the **Equipment Qualification Log (Annexure-2).**

5.3 Scale-Up Batch Production

• Develop a **Batch Manufacturing Record (BMR)** for pilot-scale production.
• Follow these steps during scale-up:
  • Weigh and dispense raw materials under **controlled conditions.**
  • Mix ingredients in a **pre-determined sequence.**
  • Monitor **temperature, mixing speed, and shear force.**
  • Conduct **intermediate quality checks** for homogeneity and viscosity.
• Document observations in the **Scale-Up Production Log (Annexure-3).**

5.4 In-Process Quality Control (IPQC) and Testing

• Perform **real-time monitoring** of:
  • pH, viscosity, and spreadability.
  • Particle size distribution.
  • Microbial contamination.
• Record all in-process test results in the **IPQC Log (Annexure-4).**

5.5 Stability Testing and Process Validation

• Conduct **accelerated and real-time stability studies.**
• Compare results with **lab-scale stability data.**
• Validate:
  • Content uniformity.
  • Drug release profile.
  • Batch reproducibility.
• Record validation data in the **Scale-Up Stability Report (Annexure-5).**

5.6 Documentation and Regulatory Compliance

• QA must review and approve all scale-up data.
• Ensure compliance with **ICH Q8 – Pharmaceutical Development.**
• Maintain records for **five years** for regulatory audits.

6. Abbreviations

• API – Active Pharmaceutical Ingredient
• GMP – Good Manufacturing Practices
• QA – Quality Assurance
• QC – Quality Control
• ICH – International Council for Harmonisation
• FDA – Food and Drug Administration

7. Documents

• Pre-Scale-Up Report (Annexure-1)
• Equipment Qualification Log (Annexure-2)
• Scale-Up Production Log (Annexure-3)
• IPQC Log (Annexure-4)
• Scale-Up Stability Report (Annexure-5)

8. References

• ICH Q8 – Pharmaceutical Development Guidelines
• FDA Guidance on Scale-Up and Post-Approval Changes (SUPAC)
• WHO Guidelines on Pharmaceutical Scale-Up

9. SOP Version

Version 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Pre-Scale-Up Report

Date	Batch No.	Key Findings	QC Review
02/02/2025	OINT-1001	Optimal viscosity achieved	Approved

Annexure-2: Equipment Qualification Log

Date	Equipment Name	Calibration Status	QA Approval
02/02/2025	Homogenizer	Validated	Approved

12. Revision History

Revision Date	Revision No.	Details	Reason	Approved By
02/02/2025	2.0	Expanded Scale-Up Process	Improved Compliance	QA Head