Pharmaceutical Water System Microbiology Training

Presented by T. C. Soli, Ph.D. USP Pharmaceutical Water Expert Committee Member* and Vice Chair** *2000-2005 and **2005-2010

Course Description

This course is designed to provide a microbiology-focused education about all aspects of water systems and how biofilm manages to thrive there. Prior microbiological education or training, though a plus, is not necessary. The instructor can provide the background needed to understand this very important subject matter. This understanding is essential to the proper design, validation, operation, monitoring, and maintenance of a high purity water system. Without this understanding, water system design and control are merely managed by a set of rules that often don’t work and can cause very costly system downtime or even product recalls.

- See more at: http://www.aaps.ca/ws-pharmaceutical-water-system-microbiology.php#sthash.bkGeTDiX.dpuf

In order to understand the microbiology of a water system, one has to understand biofilms since that is the mode of microbial growth in a water system. There is much hype and fear about water system biofilms by users and regulators alike who do not understand how they grow, how to effectively control that growth, or even how to reasonably accurately monitor their presence. This course will help you understand how microorganisms respond to our efforts (or lack of effort) to control their numbers and even to how we try to count them.

One of two key resource for this course is the latest revision of the USP informational chapter on water <1231> “Water for Pharmaceutical Purposes”, first published in Supplement 2 to USP 28 and current through USP 35. The course instructor is the primary author of that revised chapter. The other resource is the ISPE Baseline Guide® for Water and Steam Systems, 2nd Ed, which contains a Microbiological Considerations chapter authored by the course instructor and designed for understanding by Engineers.

• The backstory for some common water system design and control myths

• Biofilm properties, resistances, susceptibilities and examples
• Water system sanitization approaches to control biofilm
• Water system microbial enumeration issues
  • USP’s view on sampling and microbial enumeration
  • Microbial enumeration options/advantages/disadvantages
  • How to choose the best microbial enumeration method and “validate” it

• Water System Validation and Change Control
• Improving outcomes and reducing the frequency of excursion investigations
• How to perform successful Water System excursion investigations
• What USP actually says about all this

• Understand the role of system design, maintenance and sanitization in controlling microbial levels in pharmaceutical water systems
• Successfully troubleshoot problems and discriminate between those resulting from poor design/maintenance versus sampling or testing problems
• Devise water system validation protocols that truly validate microbial control
• Validate your water microbial test method
• Develop sound Alert and Action Levels and Water Specifications as the key elements of a sound microbial program
• Defend your test method, in-process control levels and specifications to FDA

1-Controlling Water System Biofilm Through Design & Operation

• Microbial control – where and why it matters
• Biofilm basics and how it develops
• Biofilm impact on “active” surfaces
• Environmental resistances of biofilm
• Biofilm impact on purification unit operations and how to control it
• Good design practices to control biofilm
• Good maintenance practices to control biofilm

2-Successful Sanitization Approaches for Trouble-Free Water Quality

• Material and construction limitations
• Continuous vs intermittent sanitization
• The importance of biofilm removal
• How sanitants work (or don’t work)
• When to sanitize
• Common causes for sanitization failures and troubleshooting sanitization problems

3-Water System Validation by Logic Instead of Tradition

• Why validate a water system?
• Basic ground rules for water systems before you validate them
• Minimum validation expectations
• What happens after the honeymoon is over
• Making changes to a validated water system
• Special considerations for lab water systems
• Are packaged waters a viable option?

4-Understanding and Controlling Endotoxin

• Where does endotoxin come from?
• What are the properties of endotoxin ?
• How do you get rid of it?
• How do you detect it?
• What assay controls are used?
• What are the endotoxin specs for water?
• How do you control it?

5-Harmonizing vs Optimizing Water Microbial Testing for System Quality Control

• Water harmonization that has occurred
• Water Micro TM “Dis-Harmonization”
• Biofilm diversity in water systems
• The good and bad of Micro harmonization
• Where RMMs can fit in

6-Microbial Enumeration Issues with High Purity Water Systems

• Biofilm enumeration issues (planktonic vs surface)
• Purpose of sampling and testing (PC vs QC)
• Traditional cultivative approach issues
• Validation of your test method
• Alternative RMM choices (advantages/disadvantages)
• Significance of water isolates

7-Reducing Water Microbial Excursions & Improving Investigations

• What are excursions?
• Water system dilemma: process control or quality control (utility or raw material), or both
• Intended roles of Alert/Action Levels and Specifications
• Investigation, necessary and often fruitless
• Excursion responses and impact
• Criticality of valves, hoses, & outlet flushing
• Diagnosing the source of the problem
• Minimizing unnecessary excursion responses through best practices

8-Water System Investigation “How-To’s” and Example Case Studies

• Early information; user opinions
• Investigation approach elements
• Water system contamination case studies
  • The Beige Puddle
  • “TNTC”
  • High TOC
  • The Sloppy Lab
  • Flanged PolyPro System
  • The Stealthy Dead Leg
• Parting kernels of water system wisdom

9-Leadership in Manufacturing Contamination Control: The Microbiology Lab

• How contamination is controlled
• Why the microbiology lab should lead in contamination control
• Routine contamination evaluation activities
• Microbiological Training
• Root cause and impact investigations
• Impediments to leadership
• Doing the right thing

10-USP Chapter <1231>: What USP Says about PW, WFI, Pure Steam and Micro Issues

• PW, WFI, Pure Steam micro specifications?
• Starting water issues
• Misunderstood issues clarified
• Microbiological test issues clarified
• Suggested micro test method
• Micro Specifications
• Alert and Action Levels and max’s
• Recent/Upcoming USP water changes
• Discrepancies between pharmacopeia’s
• New USP water initiatives

Are you having persistent microbial problems with your water system – nothing you do seems to help for very long if at all? Are your water systems excursion investigations always inconclusive because you can never confirm the original out-of-limit result and the bad results come and go? Are you concerned that FDA or other regulators will not think your water system validation was adequate because of your current microbial problems? Are you afraid that biofilm has taken over and you can’t get rid of it? These are common concerns that primarily originate out of ignorance of appropriate design, maintenance, sanitization, sampling, and testing for your water system. Attending this 2-day course will open your eyes to what is really going on in your water system and how to “get it right”, finally! Can you afford to remain ignorant and repeat past problems or should you attend this course to replace that ignorance with the knowledge that allows you to get your water system under control and keep it that way?