What is steam-in-place (SIP) validation?

What is steam-in-place (SIP) validation?

Steam-in-place (SIP) validation is a critical process in pharmaceutical and biotech operations that ensures sterile conditions within production systems – without disassembling equipment. It uses clean, saturated steam to sterilize internal surfaces of tanks, piping, valves, and other hard-to-reach areas after cleaning-in-place (CIP). This form of sterilization is essential for maintaining GxP compliance and protecting product integrity in highly regulated environments.

Unlike dry heat or autoclaving, SIP sterilizes non-portable equipment while it remains connected. The process must prove that steam reliably reaches and maintains at least 121 °C (250 °F) throughout the system for a specified duration. While a typical benchmark is 30 minutes, the actual hold time depends on achieving an F₀ value of at least 12 minutes – a measure of microbial lethality at 121 °C (250 °F).

Also read: Complete guide to steam-in-place validation in GxP environments

Who needs SIP validation – and when?

Steam-in-place validation is not necessary in every pharmaceutical or logistics operation. It is typically required in environments where microbial control and sterility are essential, and where in-place sterilization of equipment is more practical than disassembly.

You need SIP validation if you operate:

• Sterile or aseptic processing environments (e.g., biologics, vaccines, injectables)
• **Sterile fill-finish lines **where product-contact surfaces must be sterilized regularly
• Bioreactors and fermenters used in sensitive biotech production
• Multi-product systems requiring validated sterilization between campaigns
• Pharmaceutical-grade cleanrooms in logistics setups handling bulk drug substances or sterile transport tanks

SIP is likely not required if you:

• Manufacture non-sterile oral solid dosage forms (e.g., tablets, capsules)
• Use manual or autoclave-based sterilization with removable components
• Operate logistics sites without sterile handling or cleanroom areas

Determining whether SIP validation is needed depends on your facility design, regulatory classification, and the level of microbial control required by your processes.

How SIP validation works

At a high level, SIP validation ensures that clean steam is effectively delivered to all relevant surfaces and held at the required temperature for a validated period.

Some of the key parameters include:

• Uniform steam delivery to all product-contact surfaces
• Temperature monitoring to confirm target hold times (commonly 121 °C / 250 °F)
• Sensor placement in worst-case cold spots, often upstream of steam traps

Also read: Where to place data loggers during temperature mapping?

While the technical validation steps – such as temperature mapping, sensor calibration, and steam quality testing – are vital, these will be covered in more depth in our complete SIP validation guide.

Regulatory and audit expectations for SIP validation

Depending on your operation, SIP validation must meet standards such as: GMP Annex 15 (qualification and validation guidance) ISO 17665 and EN 285 (moist heat sterilization requirements) FDA 21 CFR Part 211 (current good manufacturing practices for finished pharmaceuticals)

These define expectations for lethality values, equipment design, documentation, and periodic revalidation.

Also, check out our SIP glossary to get a quick overview and understanding of the terminology used in SIP validation.