The A–Z of steam-in-place validation

Also read: Introduction to SIP validation

Glossary: SIP validation

A

Autoclave: A pressure chamber used to sterilize equipment via saturated steam. Unlike SIP, autoclaving requires the equipment to be disassembled.

Annex 15: Part of the EU GMP guidelines that covers qualification and validation, including SIP requirements.

B

Biological indicator (BI): A test system containing viable microorganisms used to validate sterilization cycles by confirming microbial lethality.

C

Commissioning, Qualification, and Validation (CQV): A structured approach to bringing equipment and systems into a validated state. SIP validation often forms part of the qualification phases in a CQV framework. Learn more about CQV in pharma

Clean-in-place (CIP): The process of cleaning internal surfaces of equipment with chemical solutions before SIP sterilization. Cold spot: The hardest-to-sterilize location in a system. Sensors or BIs are placed here to confirm the effectiveness of the SIP cycle.

D

Design Qualification (DQ): Verification that the design of equipment or systems meets process and regulatory requirements.

Dryness fraction: A measure of steam quality. SIP requires ≥90% dryness to ensure effective heat transfer.

F

F₀ value: A calculated sterilization value that represents equivalent lethality at 121 °C. Used to validate SIP cycle performance.

G

GxP: An umbrella term for 'Good Practice' quality guidelines and regulations in the pharmaceutical and biotech industries. GxP includes GMP, GDP, and others, and ensures processes are traceable, documented, and compliant with regulatory expectations.

GMP (Good Manufacturing Practice): Regulatory framework that governs sterile processing. SIP validation must meet GMP requirements.

I

Installation Qualification (IQ): Confirms that SIP-related equipment has been installed correctly according to design and specifications.

N

Non-condensable gases (NCGs): Air or other gases that do not condense at sterilization temperature. These reduce steam effectiveness and must be minimized.

O

Operational Qualification (OQ): Testing the SIP system under empty-load conditions to verify temperature, pressure, and cycle control.

P

Performance Qualification (PQ): Verifies SIP performance in real operating conditions, including use of BIs and temperature mapping. PIC/S: Pharmaceutical Inspection Co-operation Scheme. Sets harmonized GMP standards across multiple regulatory agencies.

S

Steam trap: A device that removes condensate from the steam system without releasing steam. Critical for maintaining sterilization temperatures.

Steam quality: A measure of steam purity and effectiveness, based on dryness, pressure, and absence of contaminants.

Sterilization hold time: The period during which the SIP system must maintain sterilizing temperature to ensure microbial inactivation.

T

Temperature mapping: Recording temperatures at various points during SIP to confirm uniformity and identify cold spots. This is a core part of temperature mapping and validation strategy in GxP environments at various points during SIP to confirm uniformity and identify cold spots.

V

Validation Master Plan (VMP): A document outlining all validation activities, including SIP protocols, acceptance criteria, and responsibilities.

Learn more: Complete guide to SIP validation