USP Updates Informational Chapter on Pharmaceutical Water

For those who have an interest in pharmaceutical waters, the recently released USP 39 Supplement 2 includes an updated Informational Chapter <1231>. This new and improved chapter has been rewritten and reorganized including a new table of contents, added hyperlinks for contemporization and ease of use, clear and concise technical explanations, and additional material including examples. The revised text dispels a number of long held misconceptions and provides users with more definitive and useful information than the prior versions.

The improvements to the chapter can be summarized best by reviewing some of the topics addressed by those changes which include the following:

• The chapter overview clarifies that this is an informational chapter that is neither mandatory nor an all-encompassing water treatise. The information is correct and important, however it remains the obligation of the user to determine the grade of water and quality specifications required to ensure the safety and efficacy of their products or applications.
• The chapter text explores the issues related to source water and provides clarity regarding the user’s responsibility to ensure the source water meets the potable water attributes of the US EPA NPDWR, or alternate regulations from Japan, EU or WHO. The reasons for this requirement are explained and the testing and verifications applicable to both regulated and unregulated sources are discussed.
• Water Monographs are discussed relative to quality and user responsibility. The difference between bulk and packaged waters is explained and the possible quality issues related to packaged waters is reviewed. Alternate water types including non-monographed waters are discussed and their purposes and use are explained. The subject of added substances, and their exclusion, based on language in the monographs, is explained with clarity to eliminate misunderstandings historically associated with this topic.
• The purpose and overall requirements for validation are discussed in general terms to assure there is an understanding of the interaction of various tasks and requirements to ensure system suitability and functionality.
• System installation and operation is discussed with a focus on sanitation. Methods of sanitization are explained including the associated limitations of various methods. The benefit and need for excessive sanitization temperature is considered and dispelled.
• The topic of sampling has been significantly enhanced to discuss both the reasons for sampling and the associated requirements. Process Control sampling seeks to assure proper system operation using data derived Alert and Action Levels which help to minimize the potential for conditions that might disable the system or put product at risk. Quality Control sampling seeks to assure water used in manufacturing meets or exceeds the specified quality requirements. QC sampling must be from the actual points of use where water is delivered to manufacturing including any hoses, accessories, etc. Details of procedural issues related to sampling have been included and offer assistance to those planning for or defining sampling activities.
• Microbial control within a water system is often a significant challenge. This expanded chapter provides meaningful clarity regarding microorganism sources, colonization likelihood, biofilm development and destruction/removal, and test methodologies. The differences between chemical, endotoxin and microbial distribution homogeneity within the system is clarified along with the impact on design, operation and testing including how rapid micro methods might be utilized effectively.

The changes to Chapter <1231> are a must-read for anyone working with or around pharmaceutical water whether you’re a seasoned veteran or just getting your feet wet for the first time.

For additional information, please visit:

https://www.ispeboston.org/files/ispe_feb_16%2C_2017_manfredi_afternoon_handouts.pdf