2008 Proposed changes to USP General Chapter <643> Total Organic Carbon

In mid-2007, changes to the current general chapter USP <643> Total Organic Carbon were proposed. The reasoning behind the proposed changes stemmed from inquiries regarding:

• The relationship between microbiological activity and TOC levels.

• The need for guidance regarding having to choose between TOC methods.

• Providing emphasis for the allowance of on-line TOC measurement.

As always, interested parties were welcomed to respond with feedback to the proposed changes; initially with an October 2007 deadline. Due to a surge of communications late in October, the deadline to respond was extended to December. As some of the proposed changes are potentially significant, we took the time to review them for our customers.

Affected Sections and Proposed Changes to Read

1)      Introduction

a.       Added: A TOC measurement is not a replacement for endotoxin or microbiological control. While there can be a qualitative relationship between a food source (TOC) and microbiological activity, there is no direct correlation.

b.      Edited: “This chapter does not endorse, limit or prevent any technologies from being used, but…” <added “endorse”>

c.       Removed: Background on standard and system suitability solution purposes, explanation of different TOC measurement techniques (TOC = TC – IC and TOC = POC + NPOC).  Replaced with text stating that technologies essentially must be able to discriminate between different forms of CO₂ (organic and inorganic).

2)      Apparatus Requirements

a.      Added: Text stating that on-line measurements of TOC have advantages over laboratory results in that they are real-time and don’t suffer from sampling error.

b.      Added: Text stating that production scenarios and manufacturing usage should be considered when selecting a technology.

3)      Glassware Preparation

a.       Edited: Changed “glassware” to read “containers”

b.       Removed: “…glassware and sample” containers to leave only “containers”

4)      Standard Solution - Removed: “about” so that section would read: “to obtain a solution having a concentration of 1.2 mg of sucrose per L (0.50 mg of carbon per L).”

5)      Test Solution

a.       Removed: Note on general handling samples/solutions

b.      Added: Text stating specific concerns for off-line and on-line technologies.  Off-line: headspace, contamination, hold times.  On-line: installation, piping.

6)      System Suitability - Added: Text detailing r_s, r_ss and r_w definitions.

7)      Procedures - Edited: Changed to read: “This method can also be performed using on-line or off-line instrumentation that meets the apparatus requirements.” This is a change from instrumentation specifically needing to be “appropriately calibrated, standardized and …suitable (per system suitability test).”

With the increases focus on process analytical technologies in pharmaceutical water quality testing, the committee seems has moved to speak more directly to those forms of measurement.

For more information please contact the USP expert committee on pharmaceutical waters:

Pharmaceutical Waters (PW) Expert Committee

Chair: Anthony Bevilacqua, Ph.D.
Scientific Liaison: Gary Ritchie, M.Sc.
Executive Secretariat: Eugenia Macarthy

United States Pharmacopeia
12601 Twinbrook Parkway
Rockville, MD 20852-1790