Pharmaceutical water is the “blood” of pharmaceutical production. From raw material cleaning and formulation preparation to injectable production, different processes have strict requirements for water purity, microbial limits, and endotoxin levels (e.g., the United States Pharmacopeia (USP) and European Pharmacopeia (EP) specify that the endotoxin level of Water for Injection (WFI) shall be ≤ 0.25 EU/ml). As the “conveyance channel” for pharmaceutical water, the design of the pipeline system directly determines whether the water quality can consistently meet standards – improper design may easily lead to dead-end fouling, microbial growth, and even drug contamination. Therefore, the design of pharmaceutical water pipelines must focus on the four core goals of “no dead ends, easy cleaning, anti-contamination, and verifiability”, and build a safety system by combining regulatory requirements with production practices.

 

Core Design Goals: Guided by Water Quality Safety and Compliance

The essential difference between pharmaceutical water pipelines and ordinary industrial pipelines lies in the need to meet both “process requirements” and “regulatory compliance”:

• Process Requirements: Avoid secondary contamination of water quality (such as excessive microorganisms and ion leaching) and no impurity generation (such as pipeline corrosion debris) during conveyance;
• Regulatory Compliance: Comply with Good Manufacturing Practice (GMP), USP, EP, FDA 21 CFR Part 211 and other requirements, and the design must pass Design Qualification (DQ), Installation Qualification (IQ), and Operational Qualification (OQ).

Three principles must be followed throughout the design:

• Eliminate “stagnant water” to prevent microbial growth;
• The materials of pipelines and fittings are compatible with the water used (potable water, purified water, water for injection), with no leaching or adsorption;
• Support Clean-in-Place (CIP) and Sterilize-in-Place (SIP), with verifiable effectiveness.

 

1. Key Design Principle 1: Material Selection – Controlling Contamination at the Source

Materials must meet the requirements of “inertness, corrosion resistance, and no leaching”, and different water qualities correspond to different materials:

Water Quality Grade	Recommended Materials	Core Advantages	Application Scenarios
Potable Water (DW)	304 Stainless Steel	Low cost, corrosion resistance meets the needs of potable water	Pipelines for raw material cleaning and equipment cooling water
Purified Water (PW)	316L Stainless Steel / PVDF (Polyvinylidene Fluoride)	316L contains molybdenum for acid resistance; PVDF has stronger inertness and no metal leaching	Pipelines for oral formulation preparation and sterile API cleaning
Water for Injection (WFI)	316L Low-Carbon Stainless Steel	Carbon content ≤ 0.03% to prevent intergranular corrosion, and resistant to 121°C pure steam sterilization	Pipelines for injectable formulation and sterile filling water

Note: 316L stainless steel must be “pharmaceutical-grade”, with inner walls polished by electropolishing (Ra ≤ 0.4μm for WFI pipelines); PVDF has poor high-temperature resistance (≤ 80°C) and is only suitable for purified water pipelines that do not require high-temperature SIP.

 

 

 

 

2. Key Design Principle 2: Hydraulic Design – Eliminating Dead Ends

 

The core is “uniform water flow, no dead ends, no stagnation”, with key focuses on:

• Pipe Diameter: Calculated based on “maximum water consumption + minimum flow rate”. The normal flow rate of purified water/WFI pipelines shall be ≥ 1.0 m/s (≥ 1.5 m/s for circulation pipelines) to avoid microbial sedimentation due to excessively low flow rate;
• Slope: The slope of purified water/WFI pipelines shall be ≥ 0.5%, facing the drainage point to eliminate water accumulation;
• Dead End Control: Follow the “3D Principle” (dead end length ≤ 3 times the inner diameter of the pipeline). For WFI pipelines, the standard can be upgraded to the “2D Principle”, and blind pipes are prohibited;
• Circulation System: Purified water/WFI adopts a full-circulation design. WFI pipelines maintain circulation above 80°C (or insulation at 65°C + regular sterilization), and purified water pipelines maintain 25-40°C.

 

3. Key Design Principle 3: Connections and Fittings – Reducing Contamination Nodes

• Connection Methods: For purified water/WFI pipelines, the main pipes and branch pipes shall be connected by stainless steel automatic orbital welding (with smooth welds and no weld beads, and passivation after welding); sanitary quick-connect fittings (with silicone gaskets) shall be used for connections with valves and instruments, and threaded and flange connections are prohibited;
• Fitting Selection: Diaphragm valves (with EPDM/PTFE diaphragms) are preferred for valves; sanitary centrifugal pumps (with mechanical seals) are selected for pumps; 0.22μm microporous filters (supporting CIP/SIP) are installed at key nodes.

4. Key Design Principle 4: Cleaning and Sterilization – Verifiable Contamination Control

• CIP: The process is “pre-rinsing → alkaline cleaning → intermediate rinsing → (optional) acid cleaning → final rinsing”. Control the temperature (50-60°C for alkaline cleaning) and flow rate (≥ 1.5 m/s) to ensure turbulent flow (Re ≥ 4000), and set sampling points at hard-to-clean locations;
• SIP: Use pure steam meeting USP/EP standards. WFI pipelines require 121°C for ≥ 30 minutes (or 132°C for 5 minutes), monitor the temperature of the “cold spot”, and drain condensed water after sterilization.

 

 

5. Regulations and Verification: The Design Defense Line

• DQ: Confirm that the design meets regulatory and process requirements;
• IQ: Verify that materials, welding, slope, etc., meet standards;
• OQ: Confirm CIP/SIP parameters through simulated operation;
• PQ: Monitor water quality (microorganisms, TOC, etc.) in actual production to confirm long-term stability.

Conclusion

The design of pharmaceutical water pipelines is a systematic project integrating “technology + regulations”, and every detail must be controlled to prevent contamination. With the deepening of the “Quality by Design (QbD)” concept, the design will pay more attention to foresight and traceability, ensure water quality safety by relying on digital tools (such as BIM modeling), and ultimately safeguard drug quality.