HIGH PURITY WATER FOR

BIOPHARMACEUTICAL
FACILITIES

Presenter: Steve Peck

Introduction to Biotechnology
Manufacturing
Winter Quarter 2004
 Water Purity Regulations and Guidance

• Official Monographs in U.S. Pharmacopoeia, USP27,

1/2004
- Codified through Food, Drug, and Cosmetic Act
•Title 21 CFR Parts 210 and 211 (cGMPs)
•FDA Guide to Inspections of High Purity Water Systems
•FDA Biotechnology Inspection Guide
•Parental Drug Association’s Technical Report No. 4 -
Design Concepts for the Validation of Water for Injection
System
•International Society of Pharmaceutical Engineers (ISPE) -
Baseline Water and Steam Systems Guide
 USP Regulates:
• Compendial Water Grades (6 monographs)
– Purified Water (PW)
– Water for Injection (WFI)
• Specific Quality Parameters
– Total Organic Carbon
– Conductivity
– Endotoxin
• Test Procedure Methods
– Online Measurements
– Offline Measurements
 Uses of High Purity Water in
Biopharmaceutical Facilities
• Production
• Processing - CBER requires WFI
• Formulation - Cold WFI
• Cleaning - PW
• Rinsing - PW
USP PW and WFI Quality Requirements

PARAMETER UNITS USP PURIFIED USP WATER

WATER FOR
INJECTION
Total Organic g/L (ppb) 500 500
Carbon
Conductivity @ S/cm 1.3 Online 1.3 Online
25C
Resistivity @ Mohm-cm 0.77 0.77
25C
Endotoxin EU/mL NA 0.25
(Endotoxin Units)
Bacteria CFU/mL 100 0.1
(Colony Forming (Action Limit) (Action Limit)
Units)
Potable Water  PW  WFI
•Purified water is prepared from potable
water meeting Drinking Water Standards
(MCLs)
•Purified Water contains no added
substance
•WFI is prepared from Purified Water
•WFI must be prepared using either
distillation or reverse osmosis
 Typical USP
PW/WFI System

Source: Pharmaceutical
Engineering, Sept/Oct. 2001

MMF - Multimedia Filtration

ACF - Activated Carbon Adsorption
RO - Reverse Osmosis
CEDI - Continuous Electrodeionization
 Factors Affecting Water Quality in
Storage and Distribution Systems
• Prevention of ionic contamination
(increase in water conductivity)
• Prevention of physical entry of foreign
particles and microorganisms
• Prevention of microbial growth
 Material Selection & Sanitary Design
Considerations
• Stainless Steel vs. Thermoplastics (PVDF)
• Use of highly polished sanitary tubing
• Welded joints and no threaded fittings
• Piping sloped to assure complete drainage
• Turbulent flow in the circulation loop
• Limit piping “dead legs” at the water use
points
 Performance Qualification

• For WFI >> FDA Guide Recommends:

– Daily Samples from One Point of Use
– Weekly Samples from All Points of Use
• Season Variation in the Potable Water
Supply - full years worth of data
– Concurrent validation