1. Objective

Demonstrate that the proposed purified water generation and distribution system is designed, specified and documented such that, when built and operated as designed, it will consistently produce Purified Water that meets USP requirements and is suitable for its intended pharmaceutical uses.

2. Scope

Applies to design activities for the entire purified water system including feedwater pretreatment, generation (RO/DI/other), storage, distribution loop(s), point-of-use connections, instrumentation, controls, and utilities required for operation within (facility name). Includes documentation, drawings, materials, monitoring, and sampling points required for qualification and handover to Validation/QA.

3. References (key)

• USP General Chapter 〈1231〉 “Water for Pharmaceutical Purposes.”

• USP General Chapters 〈61〉 and 〈62〉 (Microbial and Antimicrobial) — methods used for monitoring.

• USP 〈643〉 Total Organic Carbon (TOC) — guidance for TOC control/measurement for bulk waters.

• FDA “High-Purity Water System” inspection guidance.

• ISPE / industry best practice guidance on design & operation of purified water and WFI systems.

4. Design Basis & Quality Attributes

List the product/quality attributes the system must achieve (to be completed with project-specific numbers where required):

• Purified Water definition / compliance: System must produce water meeting USP Purified Water monograph and informational chapter 〈1231〉.Microbiological control: System must be designed to support monitoring and control to meet USP microbial expectations using methods in 〈61〉/〈62〉; system design must minimise biofilm formation and allow effective sanitization.

• Organic contamination (TOC): System design and monitoring strategy must support TOC control and measurement per USP 〈643〉 recommendations for bulk waters.

• Conductivity / Resistivity: System instrumentation must provide online conductivity/resistivity monitoring with alarm limits defined in the design specification (refer to project-specific setpoints). (Use USP/PDG guidance for conductivity measurement methods such as 〈644〉 where applicable).

• Materials of construction: All wetted materials must be compatible with purified water and cleanable (e.g., stainless steel 316L electropolished for distribution, hygienic polymers where applicable).

5. System Overview (to be populated with site-specific items)

• Feed water source and mains quality (typical incoming potable water parameters and pretreatment needs).

• Pretreatment units: multimedia filters, activated carbon, softener or antiscalant, cartridge filtration, chlorine removal as required.

• Primary purification train: reverse osmosis (RO) + appropriate polishing units (mixed bed/EDI or continuous electrodeionization) and final polish (UV at 185 nm for TOC, 254 nm for microbiological control) or other validated technologies.

• Storage: recirculating stainless-steel storage tank with level controls and sanitary connections.

• Distribution: continuously recirculated loop(s) sized for velocity to minimise stagnation and biofilm (design velocity and dead-leg elimination).

• Instrumentation: continuous conductivity/resistivity, flow, temperature (for sanitization cycle verification), TOC online analyzer, pressure, and sample points.

• Control system: PLC/DCS with SCADA logging, alarms, automated sanitization scheduling, and PQ/validation-friendly data export.

(Design drawings / P&IDs, equipment datasheets and instrument lists to be attached.)

6. Critical Design Requirements (examples)

1. Hygienic piping layout: No dead legs; self-draining where possible; Tri-clamp or sanitary butt-weld fittings; slope to drain at low points.

2. Materials: All pipework and storage in SS 316L; surface finish and passivation per spec; polymer components must be USP-classified where required.

3. Recirculation velocity: Maintain design velocity (site to fill) to prevent microbial colonization (document rationale and calculations).

4. Sanitization capability: Provide hot-water and/or chemical sanitization routes and instrumentation to verify sanitization (temperature, contact time, chemical concentration).

5. Instrumentation redundancy: Critical parameters (TOC, conductivity) must have validated instruments with calibration and maintenance provisions; arrange failover alarms.

7. Risk Assessment

Perform a design-stage risk assessment (e.g., FMEA or HAZOP) to identify failure modes that could affect water quality (microbial ingress, dead legs, thermal gradients, material incompatibility, power/interruption). Document mitigation measures and acceptance criteria.

8. Sampling Plan & Monitoring Points (minimum)

Define sample locations on P&ID and on distribution loop for:

• Feed water (incoming potable).

• Post-pretreatment / RO feed.

• RO permeate.

• Final polish outlet.

• Storage tank outlet and inlet.

• Distribution loop mid-point and furthest point(s).

• Typical POU sample ports near critical production areas.

Monitoring frequency and tests: include online continuous monitoring (conductivity, TOC) and microbiological sampling plan using USP 〈61〉/〈62〉 methods and acceptance/action/alert levels per site procedures and USP guidance.

9. Acceptance Criteria (Design)

The system meets the DQ when:

• Vendor equipment, P&IDs, and datasheets match design requirements and material specifications.

• Instrumentation and control logic support all quality attribute monitoring and alarms.

• Sanitization and maintenance provisions are present and accessible.

• Sampling points located as per plan and permit aseptic sampling.

• Risk assessment closed with actions or noted residual risks.

Final numeric acceptance limits (e.g., conductivity, TOC, microbial Alert/Action levels) must be specified in the project’s Design Specification (DS) and based on USP guidance and site risk assessment. For microbiological and TOC testing approach use USP 〈61〉/〈62〉 and 〈643〉 respectively.

10. Deliverables (from design/vendor)

• Detailed P&IDs and isometrics.

• Material certificates (wetted materials).

• Instrument/dataflow diagrams.

• Instrument calibration/calibration plan.

• Sterilization / sanitization procedures and design calculations.

• Validation Master Plan (VMP) and commissioning/qualification protocol outlines (IQ/OQ/PQ).

• Operations & maintenance manuals, spare parts list.

• FAT/SAT documentation and vendor test certificates.

11. Responsibilities

• Engineering: ensure design meets DQ requirements and deliver P&IDs, datasheets.

• QA/Validation: review/approve design, lead qualification execution.

• Utilities/Maintenance: ensure installation and periodic maintenance.

• Microbiology/Lab: establish sampling & analytical method suitability and hold test responsibilities.

12. Next steps (qualification path)

1. Approve DQ and issue purchase orders.

2. On receipt, perform FAT per approved test scripts.

3. Install and execute IQ/OQ (include verification of materials of construction, instrument calibration, control logic, alarms).

4. Execute PQ under routine conditions with the established sampling plan (demonstrate stable control of TOC, conductivity, microbiology) — follow USP testing frequency and methods.

13. Annexes (to be attached)

• Annex A: Design Specification (numeric setpoints & limits).

• Annex B: P&IDs & routing.

• Annex C: Sampling map & schedule.

• Annex D: Instrument list & calibration plan.

• Annex E: Risk assessment (FMEA/HAZOP).

• Annex F: Vendor datasheets & certificates.

Quick checklist (for DQ reviewers)

• USP 〈1231〉 referenced in DS and design.

• TOC & conductivity online monitoring present and specificationed.

• Microbial monitoring & sample points defined per 〈61〉/〈62〉.

• Sanitization strategy and demonstration capability included.

• Materials and cleanability documented (SS316L electropolished where required)