TOC Analyzers and Real-Time Microbial Detection

Ensuring that water used in your production and processes meets both your production standards and legal regulations is critical to your operations. The right on-line and at-line equipment can replace time-consuming, costly and error-prone manual sampling. Two critical measurements related to organic contamination are bioburden and total organic carbon. METTLER TOLEDO offers a range of continuous, on-line sensors, including total organic carbon analyzers for on-line TOC analysis and at-line bioburden analyzers for microbial detection.

What is total organic carbon?

Total organic carbon, or TOC, is a measurement of all of the organic contaminants in a water system. TOC analysis is one indicator of water quality in pharmaceutical manufacturing, semiconductor manufacturing and power generation.

Why measure total organic carbon of water?

TOC measurement in water is important because high rates of TOC in water can degrade water purification systems, contaminate batches, reduce production yields and damage equipment.

I already measure conductivity; why do I need a TOC analyzer?

Conductivity measurements are great for identifying ionic contamination, but generally organic contaminants are non-ionic. Therefore, they cannot be detected with standard conductivity measurements and require a TOC analyzer to provide an adequate measurement of organic contamination.

How does a Total organic carbon analyzer (TOC analyzer) work?

Typically, TOC measurement is conducted off-line in a lab for high concentrations (>1 ppm), and on-line for concentrations lower than 1 ppm. With a TOC analyzer, in-line detection is quicker than lab methods; therefore, you can more quickly make a change to your process when there is an unexpected increase to the TOC of water.

METTLER TOLEDO TOC analyzers use UV oxidation and differential conductivity measurement. High performance digital conductivity sensors take a conductivity measurement before and after a sample of the water is exposed to 185 nanometer UV light. The UV exposure breaks down the bonds in the non-ionic, organic compounds (oxidation) which creates carbon dioxide and water. This further forms carbonic acid, which dissociates into ionic conductive species. The increase in conductivity after oxidation is directly proportional to TOC measurement.

Where should I take a TOC measurement in my water system?

TOC analyzers are typically used for measurement throughout the water purification process and at specific points in the water usage process. Key applications include where a TOC analyzer can provide benefit are:

• Monitoring membrane efficiency after reverse osmosis
• Monitoring resin life and efficiency after deionization
  
• Ensuring low organic levels are maintained after storage in pure water tanks after final polish
  
• Ensuring low organic levels prior to water return during recycle and reclaim processes
  
• Monitoring UV light efficiency after TOC destruction in water purification
  
• Ensuring final water quality before the point of use distribution lines

What is bioburden?

Bioburden is the number of bacteria living on a non-sterile surface. When talking about water, we generally discuss microbial contamination, which is a measurement of the bacteria in water. Microbial contamination regulations vary substantially by the use of the water that is being analyzed, for example, wastewater and pharmaceutical water have very different requirements for eliminating microbial contamination.

How do I measure microbial contamination of water?

There are now numerous ways to measure microbial contamination of water, and USP recommends specific ways of doing so for pharmaceutical waters. Traditionally plate count methods are widely used; however, they are prone to error and can take 5-7 days for results. Plate counting also requires the formation of a colony forming unit (CFU), which is an estimation of total bacteria present in the sample. Another way of measuring microbial contamination in water is through laser-induced fluorescence, with a microbial detection analyzer. This measures the total number of cells that are present in the sample. Systems that use this type of technology allow for at-line, real-time monitoring of microbial contamination in pharmaceutical waters by identifying auto fluorescent units (AFUs).

What are auto fluorescent units?

Auto fluorescent units are individual microorganisms and are reported in cells/mL. The 7000RMS illuminates the sample with a laser resulting in the fluoresce of metabolites (NADH and riboflavin) which are present in all bacteria. At the same time, Mie scattering measurements determine the size of the particle that is illuminated by the laser. With the use of algorithms and sample processing, the 7000RMS analyzes the fluorescence spectrum and the size of the particle to determine that a microorganism is or is not present. If present, it is reported as an AFU.

What are the different types of water used in pharmaceutical production?

There are several different types of water that are used in pharmaceutical production. Each is used at different steps in the process and has different specifications for purity. Some of the most common include:

• Purified Water (PW): water that has been processed to remove impurities to low levels
• Water for Injection (WFI): water used as an excipient in the production of parenteral medications
  
• Ultrapure Water (UPW): water that has been purified to extremely low levels of impurities that must meet very strict specifications. UPW conductivity is 0.055 µS/cm at 25ºC (18.2 MOhm)