1. Total organic carbon TOC concept

English Total Organic Carbon, Chinese total organic carbon

The microbiological over-correction standard means that the microbial contamination reaches a certain value, indicating that the water for injection system has deviated from the normal operating conditions, and corrective measures should be taken to return the system to normal operation. "Pseogens" are usually produced by bacteria and are metabolites of microorganisms that are pyrogenic, expressed as "bacterial endomycin" indicators. Most bacteria and many molds produce heat, and the most heat-producing is the product of Gram-negative bacilli. Endotoxin in microbial metabolites is the most important cause of pyrogen reaction. Bacterial endotoxin has strong heat resistance and its size is about 1 - 50μm. Therefore, it can enter the filtrate through a general filter, but it can be adsorbed by activated carbon, diatomaceous earth filter or the like. The pyrogen itself does not volatilize, but water droplets that are vaporized during distillation are carried into the distilled water. Total organic carbon TOC=TC (total carbon) - IC (inorganic carbon).

The indicator of total organic carbon in a certain sense is the monitoring of water pollution. Various organic pollutants, microbial and bacterial endotoxins are converted into carbon dioxide by catalytic oxidation, which in turn changes the conductance of water, and the conductivity data is converted into total organic carbon. If the total organic carbon is controlled at a lower level, it means that the pollution of organic matter, microorganisms and bacterial endotoxin in the water is in a better controlled state. This is also an important reason for the verification of total organic carbon as a verification project.

2. Source of total organic carbon TOC

There are several ways in which total organic carbon enters the water system. The most common is brought in from the raw water. The main source of TOC is biological substances, such as: decay of animals and plants, bacterial activity, animal excrement. These biomasses enter the municipal tap water source by penetrating into wells or overflowing into lakes and rivers. These TOC-containing products have molecular weights ranging from low to high, low molecular weight methanol, and high molecular weight polycyclic materials. Another source of organic matter is industrial wastewater, pesticides, herbicides, chemicals. The power of these compounds is quite high and can cause serious health problems. Under the guidance of the local Environmental Protection Agency and the Health Bureau, most of the TOC can be removed from the raw water by purification. The standard for drinking water is the standard for pharmaceutical influent. All pharmacopoeia require high-volume pharmaceutical water purification to start with drinking water standards. In general, the TOC limit for drinking water is 10 to 20 times higher than that for pharmaceutical water.

Other TOCs are produced by the pharmaceutical factory itself. Unexpected TOC entry occurs through operator error or degradation of the water system. The operator's mistakes are unforeseen accidents, such as opening the wrong valve, etc. The entry of the TOC may also be caused by a design or process defect, such as the residue after wiping the drip with a disinfectant. The degradation of the water system may be due to the breakdown of plastic containers and resin materials in the water purification system. In addition, system failures can also increase TOC; for example, holes in RO and CDI membranes have problems. Endotoxin, another entity defined by USP/EP for independent mandatory testing, is also organic. Be sure to remove endotoxin because it causes an exothermic reaction. Endotoxins are usually caused by bacterial contamination by hygienic treatment and killing of water systems. Bacterial contamination, to some extent, is present in all water systems, and bacterial inhibition causes the TOC to become larger. Regardless of the source of the TOC, it is necessary to properly measure, monitor and control the TOC in the pharmaceutical water system.

3. Total organic carbon TOC removal

Reducing the TOC concentration in water can be carried out by means of a pretreatment bed, filtration or TOC degradation unit. Some effective filtration methods include carbon bed, solvent filtration, and reverse osmosis membrane filtration. When using a carbon bed for filtration, the TOC may react with carbon molecules or may penetrate into the carbon bed. Since most TOCs are non-ionic. When the TOC is removed by the ion exchange resin, the TOC is first ionized. When the TOC is oxidized to other forms, it becomes an ionic form. These ions can be removed by electronic or fixed ion exchange resins. There are currently two main TOC degradation devices in use: UV and ozone oxidation. In the TOC degradation process, the TOC is converted to CO2 by oxidation and then evolved from the system via an exhaust filter or degassing. In the new millennium, most installed pharmaceutical water systems typically achieve TOCs below 100 ppb and are mostly below 30 ppb.

4. What are the consequences of not detecting TOC?

a. I don’t know if the drug is contaminated, and I don’t know why and when it is contaminated.

b. The system's filter unit needs to be replaced without knowing

c. There are dead pixels in the pipeline design and do not know

d. Introducing new impurities cannot be verified

 USP, EP and ChP specifications and requirements for TOC and conductivity testing of pharmaceutical water

Comparison table of current pharmacopoeia regulations for purified water in Europe, America and China