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Chinese Pharmacopoeia (GMP) TOC pharmaceutical water requirements detailed

Time：2017-04-16 10:45:08

      For the injection water, the Chinese Pharmacopoeia requires the use of the method of distillation, usually using a multi effect distillation. This requirement is different from the requirements of FDA, UP and JP, in the selection of different treatment to pay attention to.　

      TOC requirements of the Chinese Pharmacopoeia (GMP) for pharmaceutical water use, especially for the TOC testing requirements for purified water and water for injection.

       One, the same pharmaceutical water use difference.

       1.1 purified water use：

       1、the preparation of water (pure steam) water injection。

       2、Equipment, appliances and packaging materials for the last washing of non sterile drugs directly in contact with drugs。

       3、The initial washing of the bottle of the injection and the sterile medicine。

       4、Non sterile pharmaceutical ingredients。

       5、Non sterile pharmaceutical raw materials refining。

       1.2 Use of water for injection 。

       1、The last washing water of the packaging material of the direct contact with the medicine 。

       1.2Use of water for injection。

       1、The last washing water of the packaging material of the direct contact with the medicine。

       2、Injection, sterile washing agent。

       3、Sterile APIs。

       4、The final washing water of the packaging material directly exposed to the sterile raw material。

       1.3Use of pure steam。

       1、Sterile drug materials, containers, equipment, sterile clothing or other items to be entered into the sterile operation area of the hot and humid aseptic processing。

       2、Moist heat sterilization of culture media。

       Two, 2015 edition of Chinese Pharmacopoeia (GMP) on the total organic carbon (TOC) of the new requirements for injection。

       2.1 why the need to detect total organic carbon (TOC)。

       Microbial standard is the standard of microbial pollution to a certain value, that the water system has deviated from the normal operation of the conditions, should take corrective measures, so that the system back to the normal operating conditions. "Pyrogen" is usually produced by the bacteria, microbes that can cause thermal metabolites, in terms of the bacterial neomycin indicator. Most bacteria and many molds are capable of producing heat, the strongest of which is the product of gram negative bacilli. Endotoxin microbial metabolites is the main factor causing pyrogen reaction. The heat resistance of bacterial endotoxin is strong, its size is between 1 and 50 m, so it can be passed through the filter, but it can be absorbed by activated carbon and diatomite filter. Pyrogen itself is not volatile, but can be vaporized in distilled water into 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. A variety of organic pollutants, microbial and bacterial endotoxin after catalytic oxidation to become carbon dioxide, and then change the water's conductivity, the conductivity of the data is converted into the total amount of organic carbon. If the total organic carbon is controlled at a lower level, it means that the contamination of organic matter, microbe and bacterial endotoxin in the water is in a better controlled state. This is also the main reason for the validation of the total organic carbon in some validation data。

       2.2No detection of TOC will have any consequences?

       1、Do not know the drugs have been contaminated, and do not know what and when to be contaminated。

       2、The filter of pure water system needs to be replaced and not known.

       3、There is a blind spot in the design of the pipeline, which is not known to the microorganism。

       4、The introduction of new impurities can not be verified。

       2.3Pharmacopoeia requirements

       The USP Committee establishes standards and guidelines for the compliance of Pharmaceutical (other) companies

       The United States FDA by examining the enforcement of these standards

       USP<645> requires pharmaceutical water to detect electrical conductivity

       USP<643> requires pharmaceutical water detection TOC

       China Pharmacopoeia 2010 will follow the requirements of the United States FDA, the requirements of the pharmaceutical water testing TOC

       According to the information currently available, the 2010 edition of the Chinese Pharmacopoeia will be for the injection water (WFI) mandatory requirements for measuring TOC, purified water proposed measurement TOC.

       2.4 Chinese Pharmacopoeia requirements for PAT (process analysis technology)

       Process analysis technology, PAT.

       FDA is being carried out in the United States PAT initiative, that is, all indicators are recommended to detect online testing, in order to determine the quality of the final product.

       2.5Main detection methods of total organic carbon (TOC) analyzer on the market。

       2.5.1TOC measurement is divided into two major categories: oxidation combustion infrared method and UV ultraviolet oxidation conductivity method

       2.5.2 oxidation combustion infrared method: usually applied to high TOC content occasions, such as running water, river water, sewage.

       2.5.3UV UV oxidation conductivity method: suitable for low TOC content occasions (ppb), such as purified water system, water injection system, cleaning certification.