GMP Guidelines for Semi-Solid Manufacturing: What You Must Know

In the early days of pharmaceutical preparation, a compounding pharmacist's skill was the ultimate guarantee of safety. Creams and ointments were prepared in small batches using manual techniques, each tailored to patient need. But today, with large-scale manufacturing and international distribution, that model no longer works.

To ensure every tube of cream or jar of ointment is safe, effective, and consistent, pharmaceutical manufacturers must adhere to strict Good Manufacturing Practices (GMP). And for semi-solid dosage forms, GMP compliance is far more than a checklist—it's a critical pillar that affects every phase from facility design to final release.

This article is your complete guide to GMP requirements for semi-solid manufacturing in 2025 and beyond.

Understanding Semi-Solid Dosage Forms

Semi-solids include:

• Creams (O/W and W/O emulsions)
• Ointments (oleaginous, absorption, or water-soluble bases)
• Gels (hydrogels and organogels)
• Pastes (thicker formulations with a high solid content)

These products present unique GMP challenges due to:

• Complex emulsification and rheology
• Heat and shear-sensitive APIs
• Contamination risks in open systems
• Stability and uniformity requirements

Regulatory Framework for Semi-Solid GMP

Regulators across the globe expect adherence to ICH Q8–Q10, emphasizing Quality by Design (QbD), risk management, and continuous improvement.

Facility & Equipment Requirements

1. Cleanroom Classification

2. Equipment Design Principles

• Closed systems preferred over open processing
• All contact surfaces: SS 316L, electropolished
• Vacuum emulsifiers with CIP/SIP integration
• Automation & SCADA systems for traceability

Facilities must also separate zones by pressure differentials and include dedicated HVAC filters.

Personnel and Hygiene Practices

Personnel handling semi-solids must:

• Follow Grade D gowning procedures
• Undergo periodic GMP & hygiene training
• Avoid direct hand contact with product areas

In sterile environments:

• Strict access control and airlock protocols
• Routine microbiological monitoring of garments and gloves

Process Validation: IQ, OQ, PQ

GMP mandates three layers of equipment and process qualification:

1. Installation Qualification (IQ): Is the equipment installed correctly per specifications?
2. Operational Qualification (OQ): Does the equipment operate within defined parameters?
3. Performance Qualification (PQ): Can the process produce consistent product quality at scale?

Each step includes:

• Documented protocols
• Test results
• Deviation handling
• Final approval sign-offs

In-Process Controls (IPC) and Quality Assurance

Key IPC checkpoints in semi-solid manufacturing:

• Mixing time & temperature (critical for emulsification)
• Viscosity checks (rheology consistency)
• pH measurement (especially for topical APIs)
• Homogeneity sampling (uniform drug distribution)
• Visual inspection (color, texture, particulate)

QA oversight ensures:

• Compliance with batch manufacturing records
• Root-cause analysis of any deviation
• Lot release based on in-process and finished product testing

Microbial and Stability Testing Requirements

Since many semi-solids contain water, microbial control is vital.

Microbiological Testing

• TAMC & TYMC counts
• Absence of pathogens (Pseudomonas, S. aureus)
• Preservative efficacy testing (PET) for creams

Stability Protocols (per ICH Q1A)

• Accelerated: 40°C / 75% RH
• Long-term: 25°C / 60% RH
• Intermediate (if needed): 30°C / 65% RH

Stability samples must be packaged identically to market product.

Documentation and Record Keeping

GMP requires:

• SOPs for every process and equipment
• Master Formula Record (MFR) for each product
• Batch Manufacturing Records (BMR) updated in real time
• Logbooks for cleaning, maintenance, calibration
• Change Control & CAPA systems

Records must be:

• Legible, signed, and dated
• Archived per retention timelines
• Available for regulatory audit

Emerging GMP Trends in Semi-Solid Manufacturing

• Paperless GMP: Electronic batch records (EBRs)
• Inline PAT tools: Real-time viscosity & pH monitoring
• Continuous Manufacturing: Pilot use for semi-solids
• Remote audits and virtual validation walkthroughs
• Green GMP: Energy-efficient HVAC and water-saving CIP systems

Conclusion:

A century ago, ointments were made by instinct and touch. Today, we manufacture millions of sterile creams, hormone gels, and medicated pastes under controlled conditions that leave no room for error.

GMP compliance is not merely regulatory—it is foundational to patient safety and business integrity. For pharmaceutical companies manufacturing semi-solids, the future belongs to those who embed quality in every valve, protocol, and pixel of data.

Because when it comes to topical formulations, it’s not just what heals the skin—it’s what happens behind the scenes that matters most.

FAQs

1. What are GMP requirements for cream manufacturing?

GMP requires classified cleanrooms, validated equipment, SOPs, in-process controls, and microbiological testing.

2. What cleanroom grade is needed for non-sterile ointments?

Typically, ISO 8 (Grade D) is required when processed in closed equipment.

3. How is homogeneity ensured in semi-solid products?

By using high-shear mixers or vacuum homogenizers and validating with in-process sampling.

4. What tests are performed on creams under GMP?

Viscosity, pH, drug content, microbial load, stability, and visual characteristics.

5. What is the role of IQ, OQ, and PQ in GMP?

They qualify equipment and ensure that it performs consistently to produce high-quality products.