cGMP Clean Steam and CSG: Critical Differences Between Clean Steam and Industrial Steam in the Pharmaceutical Sector

In the modern pharmaceutical sector, where regulations are extremely strict and quality requirements are stringent, steam represents a critical element for numerous processes. However, not all steam is the same: the differences between clean steam and industrial steam are fundamental, both from a technical and regulatory standpoint. In this context, the role of steam generators such as the CSG (Clean Steam Generator) is central to ensuring compliance with cGMP (current Good Manufacturing Practices), guaranteeing purity, data integrity, and process control.

The critical importance of steam in pharmaceutical processes

Steam is used in several phases of pharmaceutical production, including:

• Sterilization: Of surfaces, instruments, components, and equipment.
• Washing and disinfection: To ensure aseptic environments and equipment.
• Thermal reactions: Used as a medium for specific production processes.
• Thermal energy generation: For heat exchange in various systems.

In tutti questi scenari, la qualità del vapore incide direttamente sulla qualità del prodotto finale, sulla sicurezza del processo e sulla conformità normativa. Le autorità regolatorie, infatti, richiedono livelli di qualità del vapore differenti in base all’uso previsto, con parametri specifici per purezza, controllo microbiologico e assenza di contaminanti.

What is industrial steam?

Industrial steam is generally produced by boilers for generic energy purposes. Its main characteristics include:

• Large-scale production: Intended for general thermal uses.
• Potential contaminants: It may contain micro-particulates, chemical residues, or other impurities resulting from water treatment or pipe corrosion.
• No microbiological control: It is not subject to systematic microbiological monitoring.

Although it can reach high pressures and temperatures, industrial steam is not designed or qualified for direct pharmaceutical uses, where purity and absence of contaminants are essential requirements.

What is clean steam?

Clean steam is a type of steam produced, treated, and controlled specifically for pharmaceutical and biotechnological applications. Its key features are:

• Origin from purified water: Generated from purified water (PW – Purified Water) or Water For Injection (WFI), depending on the type of process supplied (aseptic, non-aseptic) and risk assessment.
• Absence of contaminants: Characterized by the absence of microbiological contaminants, endotoxins, and chemical residues.
• Continuous monitoring and traceability: Critical process parameters are continuously monitored and recorded, ensuring repeatability and full traceability.

Clean steam production requires dedicated generators, integrated water treatment systems, and distribution networks built with GMP-compliant materials and components, such as stainless steel according to ASME BPE.

Industrial steam vs. Clean Steam: main technical and regulatory differences

The distinctions between industrial steam and clean steam are numerous and concern crucial aspects for the pharmaceutical industry:

Clean steam is specifically designed for critical applications, with automated control systems, parameter recording, and compliance with ALCOA+ data integrity requirements.

Why Clean Steam is an essential requirement in cGMP environments

Under cGMP, steam quality is not only a technical requirement but a regulatory expectation. Guidelines require:

• Microbiological purity: Absence of microorganisms and endotoxins.
• Full traceability: Of all critical process parameters.
• Validated systems: Ensuring reproducibility and reliability.

The use of clean steam ensures that sterilization and washing processes are not compromised by contaminants and that cycles are repeatable, monitorable, and verifiable during audits and inspections. It also contributes to process consistency, contamination risk reduction, and documented proof of regulatory compliance.

Steam quality and sampling: how Clean Steam is demonstrated

For cGMP compliance it is not enough to “produce clean steam”: its quality must be demonstrated with objective criteria, both during qualification (DQ/IQ/OQ/PQ) and during operation. In practice, clean steam is assessed through targeted sampling and testing activities defined on a risk-based basis depending on use (direct contact vs indirect).

What is typically verified (steam quality testing):

• Dryness fraction: Indicates how much of the flow is actually steam and how much is entrained water (wet steam).
  • Non-condensable gases (NCG): Presence of air/gases that reduce sterilization efficiency and heat transfer.
  • Superheat: Excessively superheated steam can compromise correct heat release and cycle reproducibility.
  • Chemical and particulate contaminants: Possible residues from water treatment, corrosion, and plant materials (to be excluded in critical applications).
  • Microbiological/endotoxin aspects: Evaluated when steam may contact critical surfaces/equipment or product (depending on process).
  • Trends and data integrity: Recording, audit trail, and review of critical parameters to ensure traceability and deviation investigation.

Sampling must be properly designed (representative sampling points, steady-state conditions, suitable instrumentation, and documented procedures). This allows steam quality to be robustly linked to process and audit requirements, avoiding theoretical conclusions unsupported by evidence.

The crucial role of the CSG in cGMP systems

The Clean Steam Generator (CSG) is the central component for clean steam production in pharmaceutical plants. It uses high-purity water as input and integrates advanced systems for:

• Impurity separation: To remove any residual contaminants.
• Thermodynamic control: To maintain optimal generation conditions.
• Continuous monitoring: Of steam quality parameters.

A CSG system ensures the continuous production of steam that meets the required purity specifications, reliably supporting sterilization processes (SIP – Sterilization In Place) and other critical systems.

Main functions of a CSG

The key functions of a CSG include:

• Generation of steam from purified water (PW or WFI).
• Separation of condensate and impurities.
• Precise control of pressure and temperature.
• Automatic recording of process data (audit trail).
• Integration with sterile distribution systems.

These elements are essential to ensure process stability and regulatory compliance.

Technical characteristics required for a cGMP-compliant CSG
A CSG designed for cGMP environments must include specific technical features:

• Certified materials: Such as stainless steel (e.g., AISI 316L).
• Polished internal surfaces: To prevent contaminant adhesion.
• Automatic drainage systems: To avoid stagnation.
• Integrated sensors and data recording: With audit trail functionality for traceability.
• Qualification and validation readiness: According to IQ (Installation Qualification), OQ (Operational Qualification), and PQ (Performance Qualification) protocols.

IQ/OQ/PQ Validation and Integration into the QMS

The integration of a CSG into the company Quality Management System (QMS) requires a complete qualification pathway:

• Installation Qualification (IQ): Verifies the correct installation of the equipment.
• Operational Qualification (OQ): Confirms that the CSG operates within the defined limits.
• Performance Qualification (PQ): Demonstrates system performance under real operating conditions.

The documentation generated during these phases must be complete, traceable, and readily available for audits and inspections, in line with data integrity principles (ALCOA+).

Conclusions: Technology, Compliance, and Competitive Advantage

The clear distinction between industrial steam and cGMP clean steam has direct implications for the quality, safety, and compliance of pharmaceutical products. The CSG represents a strategic asset in modern pharmaceutical infrastructures, as it ensures:

• Controlled purity: Essential to prevent contamination.
• Data traceability: Fundamental for regulatory compliance.
• Validation support: Simplifies qualification processes.
• Integration into quality systems: Contributes to a robust QMS.

Adopting cGMP-compliant clean steam systems is not only a regulatory requirement but also a technological and competitive choice that enables pharmaceutical companies to operate with greater reliability, reduce risk, improve process consistency, and ultimately strengthen their market position. Investing in clean steam solutions means investing in product quality and safety, which are core pillars of the pharmaceutical industry.

In this scenario, LAST Technology positions itself as a strategic partner, offering state-of-the-art CSG clean steam generators designed and manufactured to meet the most stringent cGMP requirements. In addition to CSG units (clean steam generators), LAST Technology also provides complementary solutions such as RSA saturated steam sterilizers and UCW washing and disinfection machines, which directly benefit from clean steam quality. LAST Technology solutions not only ensure the continuous production of very high-quality clean steam—essential for sterilization and critical processes—but also integrate advanced control systems, full data traceability, and hygienic design compliant with pharmaceutical standards. This approach enables LAST Technology customers not only to meet regulatory requirements, but also to gain a competitive advantage through process optimization, reduced contamination risk, and assured final product quality, strengthening their leadership in the pharmaceutical sector.

Essential glossary

Clean steam (or pure steam): Steam produced from pharmaceutical-grade water (typically PW or WFI) and generated under controlled conditions, suitable for use in critical applications and/or in direct contact with the product or process surfaces.

Utility steam (industrial steam): Service steam generated from non-pharmaceutical water and intended for general utilities (e.g., heating). It is not designed to ensure the purity requirements and controls typical of clean steam.

CSG – Clean Steam Generator: A clean steam generator designed to produce clean/pure steam in compliance with cGMP requirements, with appropriate materials, hygienic design, and control systems.

PW – Purified Water: Purified water used in the pharmaceutical field as a process utility; it can be used as feed water for clean steam depending on intended use and risk assessment.

WFI – Water For Injection: Water for injectable preparations, with stricter microbiological and endotoxin requirements than PW; often required as feed water when clean steam is used in highly critical applications.

SIP – Steam In Place: In-place sterilization of equipment and lines using steam; requires steam with controlled quality and repeatable performance.

ALCOA+: Data integrity principles: data must be Attributable, Legible, Contemporaneous, Original, Accurate, plus Complete, Consistent, Enduring, and Available.

Steam quality testing: A set of targeted tests intended to demonstrate steam quality (e.g., dryness fraction, non-condensable gases, superheat) and its suitability for the intended use, both during qualification and periodic monitoring.