ISO 22519:2023

Overview

ISO 22519:2023 - Membrane-based generation of water for injection (WFI) - is an international benchmark for designing, operating and assessing membrane-based WFI generation systems. Applicable to the design of new systems, it addresses the principles, process design, construction, operation, maintenance and control of membrane WFI systems. It does not cover validation activities or thermal distillation-based WFI generation.

Key topics and technical requirements

• System boundaries: The WFI generation system begins at the potable water inlet to pretreatment and ends at the inlet valve of the WFI storage tank or point-of-use; storage tanks and upstream industrial utilities are outside the scope.
• Feed water: Incoming feed should meet WHO potable water standards; if not, upstream treatment is required prior to the membrane WFI system.
• Process design: Systems must be designed to remain stable under worst-case conditions (seasonal changes, fluctuating feed quality, microbial loads). Critical feed parameters to consider include scale, TOC, silica, iron, manganese, dissolved and suspended solids, and residual disinfectants.
• Typical process stages (examples): sanitant dosing, multimedia/cartridge/UF filtration, anti-scaling (softeners/antiscalants), activated carbon or UV for dechlorination/TOC reduction, single- or double-pass RO, CEDI/EDI and polishing UF.
• Microbial control: A minimum of two membrane barriers for microbiological and endotoxin reduction is recommended (e.g., RO‑RO or RO‑UF). Where only one barrier exists, a documented risk assessment and additional controls are required.
• Instrumentation & monitoring: Minimum instrumentation includes conductivity sensors after RO and CEDI/EDI stages, final product conductivity measurement and TOC sample points or online TOC monitoring.
• Sanitization: Sanitization must be possible system‑wide. Hot water sanitization is preferred for the final membrane barrier; chemical or other validated methods are acceptable where appropriate. Activated carbon filters should be thermally sanitized when used.
• Construction: Hygienic design downstream of the final membrane barrier is required; practical hygienic principles should guide materials and layout.

Applications and users

ISO 22519 is intended for:

• Pharmaceutical and biotech engineering teams designing new membrane WFI systems
• Facility and utilities engineers specifying WFI equipment (RO, UF, EDI/CEDI)
• Quality assurance, regulatory and cGMP compliance teams benchmarking system design and operational controls
• Equipment manufacturers, system integrators and water treatment consultants

Use cases include selecting process configurations (RO-RO, RO-UF), defining sanitization strategies, setting monitoring requirements (conductivity/TOC), and preparing design risk assessments.

Related standards

• ISO 20670 (Water reuse - Vocabulary) is referenced for terminology.
  Note: At publication, most major pharmacopoeias allow non‑distillation WFI generation except the Chinese Pharmacopoeia; check local regulatory requirements when applying ISO 22519.

Keywords: ISO 22519, membrane-based WFI, water for injection, reverse osmosis, ultrafiltration, sanitization, TOC, conductivity, pharmaceutical water, cGMP.