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One Hundred Pharmaceutical Water Systems Pitfalls

Tue, 01/22/2008 - 9:35am
Part 1 - Feed Water Supplies and Pretreatment Equipment

By William V. Collentro


There are several factors that should be considered during the design, engineering, commissioning, start-up, operation, and maintenance of pharmaceutical water systems. This first article in the series will discuss pitfalls associated with feed water supply characteristics, monitoring, design, operation, maintenance and other important factors to be considered for pretreatment components.
1. Monitoring of Physical, Inorganic, Organic, Microbial, and Disinfecting Agent Parameters in Raw Water Supplies
During the design phase, it is critical to compile as much information as possible regarding the feed water supply to a system. A single analysis is not adequate. Historical data must be reviewed and evaluated. Further, a visit to the local municipal treatment facility (for public feed water supplies) is suggested. This allows a system designer to review treatment techniques including chemical addition for control of undesirable impurities. The ultimate source of feed water is critical. In general, water from a surface water source will exhibit both seasonal and climatic changes in characteristics. Water from a ground water source tends to be more stable than a surface water source. However, during periods of excessive rainfall or drought, ground water supplies may exhibit quality changes since "vertical mixing" within an aquifer is very slow. Certain ground water supplies are "influenced" by surface water supplies. This may not be readily apparent to a designer reviewing an analysis. As an example, the presence of even trace amounts of bacteria, bacterial endotoxins, Total Organic Carbon (TOC), and/or disinfection byproducts in a raw water supply from a ground water source could indicate influence by surface water. Finally, some municipalities will use feed water from multiple sources, from ground to surface, or from another municipal source. All of the indicated factors, coupled with a program to periodically monitor the feed water parameters, must be considered.
2. Chloramines
The use of chlorine (hypochlorous and hypochlorite ion) for effective disinfection of water has been used in the United States since the early 1900's. However, chlorine will oxidize heavy molecular weight naturally occurring organic material (NOM) present in surface water supplies and ground water supplies influenced by surface water supplies, producing lighter molecular weight chlorinated organic compounds such as chloroform. These compounds are known carcinogens and are regulated by the United States Environmental Protection Agency's National Primary Drinking Water Regulations. To suppress formation of these disinfection byproducts in the distribution system from a municipal treatment facility, ammonia is introduced, after treatment, but prior to distribution. Ammonia reacts with the hypochlorous and hypochlorite ions producing mono-, di-, and/or tri-chloramine depending upon the pH of the water. Removal of residual disinfecting agent is an important step in any pharmaceutical water system. Chloramine removal, unlike removal of chlorine related ions, results in release of ammonia. Further, if activated carbon is used for removal, the design, operating, and maintenance parameters must be significantly modified to insure complete removal of chloramines. Ammonia can be associated with increased reverse osmosis unit product water conductivity as well as increased product water conductivity in a distillation unit (and pure steam) product. It is imperative that the present and potential future use of chloramines in feed water be considered for pharmaceutical water systems.
3. Multimedia Filtration - Design, Vessel Diameter, Height, and Access
Multimedia filtration can be effectively used, as the initial water purification unit operation in a system, to remove particles with a size of 10 microns and larger. To achieve optimum performance, the diameter of the vessel containing the filtration media must be such that the face velocity through the bed is about 6 gpm per square foot of cross sectional bed area. Many multimedia units have diameters that result in a significantly higher face velocity. The vessel height must be adequate to allow full expansion of the filtration media, containing entrapped particles during the backwash process. Many standard manufacturer's vessels, including vessels constructed of lined steel, fiberglass reinforced material, or stainless steel, have inadequate height for the required expansion. As a result, entrapped particulate matter accumulates with operating time. Since routine measurement of multimedia feed and product water turbidity and total suspended solids is not performed, this situation is undetected until operation of downstream components is affected. Finally, many multimedia units are provided with limited interior access for replacement of media and/or repair/replacement/inspection of distributors. Obviously, access is critical to any pretreatment component vessel.
4. Multimedia Filtration - Backwash and Rinse Flow Rate and Backwash Frequency
Multimedia Unit backwash should be performed at a face velocity of about 2-2 ½ times the operating face velocity. For the recommended face velocity of about 6 gpm per square foot of cross sectional bed area, this results in a backwash face velocity of 12 -15 gpm per square foot of cross sectional bed area. The backwash operation should be followed by a brief "settling" step and subsequent final rinse-to-drain step at the operating flow rate. Multimedia units may not be supplied with feed water flow rate indication. It is impossible to achieve proper operation without feed water flow rate indication. The frequency of the backwash operation should allow time for "ripening" of the filtration bed. Ripening is a process that allows filtered material to accumulate, "tightening" the filter bed, improving unit performance. The ripening process is depicted in Figure 1. Unfortunately, "breakthrough" of filtered material may occur before full ripening is achieved as a result of distributor and column selection. Columns with inadequate height for expansion, operation at high face velocity, and top inlet/top distribution system all limit the ability to operate in a "ripened" mode.
5. Activated Carbon Units - Microbial Control
Activated carbon units are used to remove residual disinfecting agent and reduce the consideration of NOM. As residual disinfecting agent is removed, bacteria will proliferate within the carbonaceous activated carbon media. Effective bacteria control can be achieved by the following techniques:

• Periodic ambient backwash
• Periodic hot water sanitization
• Continuous recirculation with inline ultraviolet unit positioned directly downstream
• Semi-annual replacement of activated carbon media

Periodic ambient backwash provides fair bacteria control. Excessive ambient backwash (greater than 2X per week) can result in premature breakthrough of organic material and residual disinfecting agent as denser carbon media (with adsorbed material) migrates to the bottom of the bed. Periodic hot water sanitization is highly effective. When performed every 1-2 weeks, product water total viable bacteria levels can be maintained < 500 cfu/ml. Unfortunately, column, piping and valve materials of construction used for most systems inhibit hot water sanitization. Continuous recirculation with a full flow rate inline ultraviolet unit can provide a factor of 10-100 X reduction in activated carbon units total viable bacteria levels. Finally, activated carbon media replacement every six months provides an excellent method of bacteria control, removing bacteria and bacterial endotoxins with the used media. Chemical sanitization of the vessel during this operation is beneficial, removing biofilm.
6. Activated Carbon Units - Design, Vessel Diameter, Height, and Access
Activated carbon units used for chlorine removal must have a diameter that allows operation with a face velocity < 3 gpm per square foot of cross sectional bed area. The volumetric should be < 1.0 gpm per cubic feet of media. For chloramine removal the volumetric flow rate should be < 0.5 gpm per cubic foot. The ideal activated carbon bed depth is about 4 feet with an additional 4 feet of empty space ("freeboard") above the top of the activated carbon media. Access, as discussed, is a critical part of unit design. In general, many operating activated carbon units for pharmaceutical applications do not meet the indicated parameters.
7. Activated Carbon Units - Backwash/Rinse Flow Rates and Duration.
Activated carbon unit backwash should be performed at a face velocity of about 1 1/2 times the operating face velocity. For the recommended face velocity of about 3 gpm per square foot of cross sectional bed area, resulting in a backwash face velocity of 4.5 gpm per square foot of cross sectional bed area. The backwash operation should be followed by a brief "settling" step and a subsequent rinse-to-drain step performed at the operating flow rate. Activated carbon units (or upstream multimedia filtration units) may not be supplied with feed water flow rate indication. It is impossible to provide proper operation without feed water flow rate indication particularly since most units do not contain adequate height. This could allow granular activated carbon to impinge on the dome of the vessel, producing undesirable activated carbon "fines". The duration of the backwash operation should be about 20-30 minutes, followed by a 5 minute settle step and 15-20 minute rinse-to-drain step. A method should be provided, such as a site glass in the waste piping line for the unit, to verify that the post backwash rinse time is adequate to remove activated carbon "fines.
8. Pretreatment Inline Ultraviolet Sanitization Units
As indicated earlier, inline ultraviolet units can provide excellent pretreatment system bacteria control when positioned directly downstream of an activated carbon unit. It is critical to understand that inline ultraviolet unit capacity selection is a function of the level of impurities in the water being treated. It is suggested that units used for pretreatment applications be selected for 2X the manufacturer's stated flow rate, since pretreatment system impurities can reduce the transmission of ultraviolet radiation. To insure maximum bacteria destruction, lamps, sleeves, and o-rings should be replaced every six months. The cost of the larger unit capacity and recommended preventative maintenance are more than offset by the reduction in pretreatment system bacteria levels.
9. Reducing Agent Injection for Removal of Residual Disinfecting Agent
Reducing agents such as sodium bisulfite can be used to remove residual disinfecting agents. Removal of chloramines will yield ammonia, detrimental to successful operations of downstream components as discussed earlier. In addition, reducing agents will not remove NOM. Finally, frequent preparation of the reducing agent is required to avoid bacteria proliferation within the pretreatment system.
10. Removal of Residual Disinfecting Agent by Inline Ultraviolet Systems
Residual disinfectant may also be removed by high intensity inline ultraviolet radiation at a wave length of 185 nanometers. The units are custom sized by the ultraviolet unit manufacturer. It is suggested, based on operating experience, that two "full capacity" units be poisoned in series for disinfection removal, particularly chloramines. Periodic product water "free" and "total" chlorine measurements should be performed to verify unit operation. In certain situations, post activated carbon unit treatment may be required for complete removal of residual disinfecting agent. Finally, lamps, sleeves, and o-rings should be replaced every six months.
11. Cartridge Filtration Systems
Cartridge filtration may be used to remove activated carbon and/or ion exchange resin "fines". However, particularly at a point in the system where residual disinfecting agent has been removed, the use of cartridge filtration should be limited since the filter surface area provides a location for bacteria to accumulate and replicate. Cartridge filter housings should contain a positive sealing mechanism such as an o-ring. The use of a "knife edge - type" or flat gasket seal is discouraged. Finally, cartridge filter replacement should not necessarily be based on observed pressure drop. Bacteria control may be the factor determining replacement frequency.
12. Water Softening Units - General
Water softening units should have a diameter that allows operation with a face velocity ? 10 -12 gpm per square foot of cross sectional bed area. The volumetric flow rate should be less than about 1.5 - 2 gpm per cubic feet of media. A minimum bed depth of 3 feet is suggested with an additional 1.5 -2 feet of freeboard. Access is a critical part of water softening unit design for media replacement, inspection of distributors, and sanitization. In general, many operating water softening units for pharmaceutical applications do not meet the indicated parameters.
13. Water Softening Units - Series Operation
Most water systems are equipped with two water softening units to allow uninterrupted system operation during a 2-3 hour regeneration cycle. One unit is in an operating mode while the second is in a regeneration or standby mode. For pharmaceutical water systems, this situation is undesirable. The non operational unit is stagnant, allowing proliferation of bacteria. Series operation of units is suggested to minimize pretreatment system bacteria levels.
14. Water Softening Units - Iron Fouling
Dissolved and ionized iron will be removed by cation resin. The exchanged iron is not completely displaced by sodium during the regeneration process. There are two important items that should be noted regarding this situation. For pharmaceutical water systems, the use of regenerant salt containing "iron removal" additives is discouraged. The additives are "Foreign Substances or Impurities" as defined in the General Notices Section of the United States Pharmacopeia. Many pharmaceutical water systems operate with iron fouled water softening cation resin. The iron is eventually eluted in the product water, adversely effecting downstream components such as reverse osmosis. The cost of cation resin is reasonable. It is suggested that systems using water supplies containing iron consider water softening unit cation resin replacement as frequently as yearly.
15. Water Softening Units - Regeneration, Slow Rinse, and Fast Rinse
To provide effective removal of heavy molecular weight multivalent cations, the recommended salt dose is 15 pounds per cubic foot of cation resin. The regeneration process should consist of an initial backwash step (about 6 gpm per square foot of cross section bed area), followed by brine introduction, slow rinse and fast rinse. The recommended duration of each operation is presented as follows:

Backwash: 15-20 minutes
Settle: 5-10 minutes
Brine Introduction: 30-45 minutes
Slow (Displacement) Rinse: 30-45 minutes
Fast Rinse: 15-60 minutes

The effectiveness of the regeneration cycle and determination of regeneration frequency should be determined by product water total hardness measurement (grab or online).
16. Brine Storage Tanks - Salt Quality, Debris, and Microbial Concerns
The salt and storage system are important to successful operation of the water softening unit. The salt quality shall be such that chemical additives are not present. Debris in salt is undesirable since it can clog the eductors introducing brine solution into the water softening unit. Provisions should be included to sample the concentration of regenerant brine. Salt storage tanks are exposed to the atmosphere. While a cover is strongly suggested to minimize introduction of debris, atmospheric bacterial may be present. It is recommended that the salt storage tank be drained and cleaned with a 50-100 ppm sodium hypochlorite solution every 3 months.
17. Recirculation/Rinse
Bacteria control in the pretreatment system can be achieved by recirculation. The flow rate must be high enough to avoid channeling (flow through vessels per cross sectional bed area). However, mechanical heat input from the recirculation pump can be a concern when demand is low. A heat exchanger using chill water or cooling water may be used to reduce temperature and subsequently bacteria proliferation. A less attractive alternative is to divert pretreated water to waste for a time period prior to use.
18. Chemical, Microbial, and Physical Parameter Intra-Component Monitoring - Location and Frequency
Sample provisions should be included in the feed water and product water piping to, and from, each component in the pretreatment system. Chemical, microbial, and physical parameters should be monitored periodically to verify operation before the performance of downstream components is affected. As an example, activated carbon unit, feed water and product water should be monitored for residual disinfecting agent, total suspended solids, turbidity, TOC, and total viable bacteria.
19. Valves - Selection: Manual and Automatic
Manual valves should be of diaphragm or needle type. Ball valves, particularly of PVC or other plastic material construction, should be avoided. Automatic valves should be of diaphragm type. Multiport valves, while commonly used for smaller capacity systems, require periodic sanitization to minimize bacteria growth.
20. Monitoring Provisions
The following table provides a summary of representative monitoring devices that should be considered for pharmaceutical water pretreatment systems:

(Click image for larger version.)
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