Design Considerations for WFI

Distillation Systems Part 3

ISPE May 13, 2016 Design Considerations for WFI Distillation Systems Part 32016-0526T09:54:06+00:00 Knowledge, Pharmaceutical Engineering Magazine No Comment
Design Considerations for Water for Injection (WFI) Distillation Systems for Improving
Quality, Project Performance, and Equipment Life Cycle Cost Reduction was featured
in the September/October 2015 issue of Pharmaceutical Engineering magazine.
This four-part series presents and discusses a number of key requirements and
design, quality, and engineering considerations that have high importance in enduser usability, cost control and end-product quality that help manage risks in Water
for Injection production and processes. Part three reviews:

Should you expand your current facility or build a new one?

Typical Utility Connections for WFI distillation systems

Efficacy of High Temperature and Particle Separation of WFI Process

F0 of WFI Process

Expand Existing Production or Build a New Facility?

A new facility gives more freedom in equipment and process design in comparison
to upgrading or expanding existing production capacity. With existing equipment,
the impact of existing validation-procedure requirements on the upgrade process
must be considered; having to redefine validation procedures due to major
equipment upgrades can be time-consuming as well as resource-consuming.
When a completely new facility and equipment are being designed, it is
recommended to discuss with management any expansion plans that may help
prepare for increased capacity, such as reserving extra space for additional
equipment or sizing the unit so that there is extra space for future use. A backup
plan in terms of ensuring available capacity using duplicated processing units or
dividing capacity over two or more units can be worth the investment in true 24/7
operating production facilities that allow minimal or no downtime. Duplicating
equipment is a big investment, but it may be just a fraction of lost production
capacity in a situation where there is prolonged downtime. Dividing the WFI
production capacity from one big central unit to two smaller units may increase the

investment cost but never by a factor of two. This solution can guarantee the
minimum of half-capacity at all times and provide flexibility for planned downtime
arrangements, such as periodic preventive equipment maintenance.
Along with the redundancy scenario considerations, it is important to acknowledge
that a simpler system is better and more reliable. Do not fall into the trap of overengineering that can compromise the reliability of the system and have negative
implications on the quality of production. Unnecessarily complicated processes
require more maintenance, more spare parts, more validation, more testing, and
more documentation and can lead to an increased number of welds, connections,
and ports that can compromise the WFI process.
If pure steam is required, consider whether an independent unit is needed or should
the distillation unit be equipped with a pure steam generator operation,
simultaneous steam generation, or a simple pure steam outlet port. One has to
remember that a pure steam generator operation isolates the rest of the unit and
produces only pure steam at the time of use. Simultaneous operations are typically
not designed for central autoclave pure steam supply but for other smaller needs.
A combination-type unit means that the WFI is still equipped with a significantly
bigger first column followed by a number of smaller distillation columns to be able to
run steam generation for larger steam header systems with distillation
simultaneously and without risk of process fluctuations.

Typical Utility Connections for WFI Distillation Systems

The following utilities are typical for WFI distillation systems:

Feed water to unit (ambient temperature, sufficient supply pressure)

Cooling water (supply pressure and temperatures according to open- or

closed-loop system)

Plant steam supply (typically three to eight bars, depending on the system)

Atmospheric drain connection for blowdown and other reject waters

Plant steam condensate return to heating system

Three-phase electrical connection

One-phase electrical connection (typically in case of additional peripheral

devices)

Ethernet connection wiring from the units control system to the facility BMS
system for data collection and remote start/stop

Dry contact wiring for possible handshake signals (for example, from the
pretreatment system or WFI storage tank)

With multiple-effect water distillation systems, the steam utility line size may be
bigger compared to a vapor compression steam connection. On the other hand, the
electrical-connection power requirement for cable and main fuse size for a vapor
compression system is significantly bigger. Multiple-effect systems require threephase electricity merely for the feed-water pump and control system, while a vapor
compression system requires high electrical power for its compressor. Cooling-water
connection size and need depends directly on the cooling-water loop temperatures
available, as well as the number of effects applied to the MWS or the cooling-water
needs of the vapor compressor.

Efficacy of High Temperature and Particle Separation of

WFI Process
The greatest means of risk mitigation with high-temperature distillation systems that
employ separation of impurities is the safety they provide from contamination by
microorganisms or their particles. Just as important is the removal of nanometer- or
smaller-size particles that could affect patients when they are injected into the body.
Microbial contamination in WFI cannot be detected by any sensor during on-line
production. Conductivity of water can be one indicator of WFI quality and low
conductivity to indicate sufficient quality of WFI, along with periodical off-line
sampling for endotoxins. However, overlooking the highest risk of microbial
contamination by small particulate presence in WFI can cause risks affiliated with
patient safety and especially with patients who have an infection or who are
undergoing treatments that lower their resistance. Therefore, any considerations of
not having sufficient microbial-controlled WFI production should be ruled out.

F0 of WFI Process
Heat is an effective means of microbial control. Heat sterilizes the water through the
different stages of the heat distillation process, starting with heating up the feed
water in the condenser, going through column pre-heaters in each stage and finally
ending in the first column, which operates with plant steam and exposes incoming
water to the highest temperature. Following the route of feed water to flash
vaporization and condensing to final distillate takes place in each column, ending at
the condenser outlet, typically at 95C to 99C for the MWS. Typical maximum
operating pressure for plant steam is eight bar, and this respectively equals to a

temperature of 175C. The WFI processing temperature or the exposure

temperature of feed water and WFI throughout the process of MWSs is typically
between 143C and 175C. In comparison, the typical operating temperature in
processing WFI with vapor compression technology is significantly lower: between
100C and 105C. This means that in a multiple-effect distillation process, the F 0
exceeds the equal sterilization batch exposure time significantly, where the vapor
compression distillation process does not reach F0 = 15 at any stage of the process.
Water dwell time in this process is too short, and the temperature too low.
Since the exposure time of water passing through the equipment is measured in
seconds instead of minutes, the high temperature in exposure is critically important
to achieving acceptable sterility levels that ensure a Sterility Assurance Level (SAL) of
10-6.
This is a key element for safety of any such production, and calculating the F0 value
for the WFI system is critical. The heat exposure of water is not only estimated in the
highest temperature of the first column but the F0 accumulates in every part of the
process where the exposure temperature exceeds 100C.
The F0 accumulation is exponential, and this shows when looking at water exposure
in the WFI process at higher temperatures than the reference point of 121.1C. For
example, in the first column the feed-water temperature can rise to 170C when
running at eight bar of plant steam pressure. To achieve the same F 0 at 160C that
equals to 15 minutes at 121.1C, only 0.12 s is required. See the time/temperature
correlation table for reference (Table B).