(Division of OBK Technology ltd.)

201 Spinnaker Way

Unit #3 Concord, Ontario

Canada L4K 4C6

Tel Fax [905] 761-1120 [905] 761-1122

Achieve USP H2O Success in Three Easy Steps.

Author – Geoff Sheffrin P. Eng., C. Eng.

Principal OBK Technology Ltd. A short summary of successful project delivery of USP PW &

WFI systems:

1

Achieve USP H2O Success in Three Easy Steps. Author – Geoff Sheffrin P. Eng., C. Eng. Principal OBK Technology Ltd. A short summary of successful project delivery of USP PW & WFI systems: In the previous article we introduced the concept that there is one foolproof approach that requires three easy steps and (if done right) to always ensures success: “Define it, Design it, Deliver it” ™©. This is the second of a three part review of all the key steps required for a successful USP water system delivery. In this review we will cover; completion of the “Define it” stage and review the design needs for the “Define it, Design it, Deliver it” ™© program. Included will be the development of the User Requirement Specification (URS), the context of a Design Specification (DS) or Functional Specification (FS), the Process and Instrumentation Diagram (P&ID), schematics and layout. Some further technical requirements for a successful design process leading to a full delivery program will also emerge. This second article is step 2. The initial most important document is the URS followed immediately by the P&ID. Let’s start with a little background: The previous article had covered items like the power of water as a solvent, the USP (United States Pharmacopeia) requirements and the various aspects of water systems design that are specific and essential to a successful PW (Purified Water) and WFI (Water for Injection) system. It is interesting to observe how many companies fail to complete the first essential steps of the definition process. The URS is the most critical starting document. It lays out in very clear and simple terms exactly what the user requires. What water is required for what purpose - what is the water supposed to be doing? Where is the water to go - to what users? When is the water required - is it constant flow, is it batch flow and at what frequency of use? Why is it needed - what is the rationale for the application - does it really need to be WFI or can it be PW that precedes the WFI in a rinse application with WFI as the final rinse? How will the water be used, in what quantities - at what temperature and at what flow rate? How many points of use will be in demand at any one

2

time? What about sanitization - how is that intended to be handled? Then - from a compliance perspective - there needs to be a Validation Plan and a large variety of supporting documentation. The URS needs to spell these expectations out in detail. As implied above in the URS - the detail of exactly how the water is to be used is critical. It can be useful if the users have included a Flow Schematic in the URS. Not essential but it does convey the users intent more graphically which then assists the design team. The system needs to be designed to maintain its biological and sanitary integrity. So temperatures, flow rates and usage rates are extremely important to specify correctly. An oversized system not only wastes water (in the constant flushing and self cleaning stages) but also is susceptible to variations that can lead to slow but progressive microbiological contamination developing. A PW or WFI system can never safely be left idle. The water must always be moving and moving at an optimal velocity to minimize the development of bio-film. So sizing is critical. to meet the needs of the users - it is quite common to have PW and WFI storage tanks which feed the process demand and are constantly replenished by the PW and the WFI supply system. Unfortunately the tanks actually make keeping sanitary conditions in tact more difficult. The tanks are slow moving and are therefore susceptible to the generation of bio-film. Some people ask - "why do I have a bio-film risk - where does it come from?" The answer is relatively simple - if you check the USP and the EU specification for purified water - they quote a maximum coli-form limit of less than or equal to 10 cfu/100 ml. That number is NOT zero. That means there are always a few coli-form units remaining. How do they grow? They regenerate themselves by feeding off the remaining dead cells that have been killed or inactivated by the technology being used. How do we get down to such low contamination numbers? The RO units can each deliver approaching a 2 x log reduction in bacteria count. A Ultra Violet unit can also deliver a similar reduction (though one is a highly discriminating filtration system whereas the other is a kill system (more accurately a de-activation) system). So the ability to reduce bio-burden in these systems is significant. But it is never at zero. So you have to design the system to keep the risk at an absolute minimum. That is always backed up by extensive monitoring and constant testing. The other factor that controls bio-film build up risk is the surface finishes of the tank and the product piping. The better the finish the less risk of bio-film being an issue (it is ALWAYS an issue but is controllable). The current norms are 25 Ra surface finish for the PW part of the system and 15 Ra for the WFI part. The surface finish- combined with the flow velocity in the pipe system is the best safeguard in minimizing the bio-film build up. Regular sanitization in any of the acceptable forms (heat or chemical) is a must.

3

Tightly controlled bio-integrity of the tanks is critical. Sanitization is essential and frequent hot sanitization helps - particularly as the WFI is often from a hot source (the 'still). Alternatively - this is where there can be a benefit of using the two pass Reverse Osmosis (RO) technology at ambient temperature. Though not approved in Europe for the generation of WFI - the advantage is that they can be set up to provide variable flow rates and can often meet continuous demand volumes without the need for a storage tank. Also, subject to respecting the needs of an established patent, they can be engineered to be self-sanitizing. The next most critical document is usually prepared by the vendor of the system. With all user parameters understood from the URS - the vendors key guide is the Process and Instrumentation Diagram (P&ID). The P&ID is the detailed encapsulation of the URS into the item by item equipment needs which, when all linked together, spell out exactly which item of equipment follows what and exactly how each is controlled and monitored. It is not unusual for the P&ID to have several inputs from both the user team and the design team. The iterations' can take three or four weeks to fully complete. On more complex systems it is common to see the URS translated into a Functional Spec (FS) and for the P&ID to be translated into a Design Spec (DS). These are two detailed documents that assist in completing the full design requirements picture and they assist in specifying all the item detail which needs to be supplied and integrated into the finished water system. It is appropriate to establish early what the validation requirements will be. Generally - these systems are required to be GMP compliant. That means it will need to be validated. Validation of these systems is usually delivered in one of two contexts: either it is a standalone addition within an existing facility or it is part of a much bigger installation which covers numerous rooms, process and utility needs of which the water system is only one. In the first case, as a standalone, the system will have a simple document describing the validation needs for this unit in a manner that is consistent with other validation protocols and procedures at the location in question. If part of a much bigger installation, then the unit validation needs will be a section within a Master Validation Plan. This pre-cursor to the validation process is usually a user Quality / Compliance Assurance teams directive or initiative. In the text you will see two diagrams: One is a generic flow schematic which covers an array of detail needs for the system to function. Note - not all are required for all applications. The purpose in this text is to

4

remind the readers of what may be needed and therefore what should be included in the design. The other is a more detailed version of the same information but done as an actual document. This one still contains some of the many items required for the system to function but again only those items for the intended application need to be included. To clarify for both - the pre-treatment shown is an extensive array of front end options. It is unusual to have all of these features at the front end though we have had to create a system for a North American client where we have had to include some of all the items due to the fact that in late summer months - their water supply deteriorates to a very poor standard and needs a lot of pre-treatment attention. The purpose of this front end is to be sure that the PW system delivers "purification" and not "pre-cleaning". The reason for the split is loading. You do not want the PW system to be loaded with the contaminants that the pre-treatment should handle. While the PW system can do that pre-treatment you not only reduce PW capacity significantly but you also add to the cleaning and maintenance cost while reducing the operating life cycle of the system. For the PW portion - again you do not need all of the items - it is normal to pick two of the three of the RO, the EDI and the mixed bed polishing with the EDI or the mixed bed being the alternates. This is a capital cost versus maintenance choice. Similarly with the WFI - pick one of the three. Multi effect is usually the more common and vapor compression is usually reserved for large capacity systems.

5

Pre-treatment RO andpolishing (EDI)

PW StorageTank

Pump

POU’s

FeedWater

WFI StorageTank

Pump

DistillationPOU’s

Typical Components:

1. 316L SS storage Tank2. Ozone System3. Sanitary Pumps4. SS distribution loop5. UV6. Point’s of Use7. Heat exchangers8. Instrumentation

Typical Components:

1. 316L SS storage Tank2. Heat Exchangers3. Sanitary Pumps4. SS distribution loop5. Point’s of Use6. Instrumentation

Typical Equipment:

1. Multi-Media filtration2. Water softening3. Chemical injection4. particulate filtration5. UV sterilizing6. Instrumentation

Typical Equipment:

1. Reverse Osmosis2. Electro-deionization3. Mixed bed polishing4. Final filtration5. UV sterilizing6. Instrumentation

Equipment:

1. Single Effect2. Multi-Effect3. Vapor Compression

Figure 1: A broad view of the control elements that can be used to generate PW and WFI. In part 3 of this article we will complete the “Design it” stage and review the delivery needs of the “Define it, Design it, Deliver it” ™© program. This will include a review of the aspects needed to take all the front end definition stage and the design detail and translating that into a process delivery.

6

(Division of OBK Technology ltd.)

201 Spinnaker Way

Unit #3 Concord, Ontario

Canada L4K 4C6

Tel Fax [905] 761-1120 [905] 761-1122

About the Author

Geoff Sheffrin P. Eng. is a Principal Partner in OBK Technology Ltd.; Geoff has extensive and broad based experience in pharmaceutical, food industry and personal care products. The OBK Water Group traces its origins back for almost a decade serving industry needs for our various clients. Geoff can be reached at geoff.obk@netaxis.ca

About the Company:

OBK Technology Ltd. is a full-service consulting engineering firm providing service to the pharmaceutical, food and personal care industries. OBK is also a full-service and validated water turnkey water provider for high-end USP water purification systems and industrial utility water and waste water treatment systems. For a complete list of services check our website at www.obkltd.com, or we can be reached at phone 905-761-1120, fax 905-761-1122, or at obk@netaxis.ca

7