Global pharmacopeia comparison of pharmaceutical water.

The 2020 edition of the Chinese Pharmacopoeia has been published, although the Pharmacopoeia contains 0261 pharmaceutical water general rules, but in the water production process, process control, operability and production facilities, there is still a lot of room for improvement.
recent years, the international pharmacopeia update and technological progress is very fast, pharmaceutical water involves all aspects of drug production, is an important factor to ensure drug safety.
in order to meet the needs of the current development of China's pharmaceutical industry, improve the pharmaceutical water technology and process control, revision and improvement of pharmaceutical water general rules is also the needs of the development of the industry.
China has been implementing the Code of Quality Management of Pharmaceutical Production (revised in 2010) for more than ten years, with reference to the current international pharmacopeia and relevant international organizations on the technical requirements of pharmaceutical water, combined with the principle of risk-based and the overall situation of China's pharmaceutical water and equipment, to further improve the current pharmacopeia contained in the 0261 pharmaceutical water general principles, strengthen the source and process control requirements of pharmaceutical water, promote advanced, energy-saving, environmentally friendly process facilities, improve the quality of pharmaceutical water to further safeguard the safety of drugs.
Pharmaceutical Water Introduction Pharmaceutical water usually refers to the various quality standards used in the pharmaceutical process of water.
pharmaceutical water is an important raw material in the pharmaceutical production process and is involved in the entire production process, including raw material production, separation purification, preparation of finished products, washing process, cleaning process and disinfection process.
therefore, pharmaceutical water systems are an essential component in the pharmaceutical production process.
pharmaceutical steam system is a medium for wet and thermal sterilization, which is mainly used in the sterilization of important equipment and systems such as injection water systems, wet thermal sterilization cabinets, bioreactive reactors, displument tanks, pipeline systems, filters, etc.
Common pharmaceutical steam systems are mainly pure steam systems, pure steam condensate directly contact with the surface of equipment or articles, or contact with materials used to analyze the properties of articles, pure steam condensation water quality needs to meet the quality standards of injection water, therefore, pharmaceutical steam system is also a very important part of the pharmaceutical industry aseptic production process.
The quality of pharmaceutical water and steam for pharmaceutical use is important from the point of view of the Pharmaceutical Manufacturing Quality Management Practice (GMP) and pharmacopeia, as well as from the point of view of good engineering management practices (GEPs) and economics, and pharmaceutical manufacturers must demonstrate that the pharmaceutical water systems and pharmaceutical steam systems used consistently provide pharmaceutical water and pharmaceutical vapors that meet quality standards.
, the pharmaceutical industry refers to pharmaceutical water systems and pharmaceutical steam systems collectively as pharmaceutical water systems, or water systems.
The nature of preparation of pharmaceutical water is to reduce or eliminate potential sources of pollution, the European Union and the WHO list impurities in pharmaceutical water as one of the potential sources of impurities, and based on this consideration, this book proposes how to design pharmaceutical water preparation, storage and distribution systems and ensure that pollution risks are controlled.
1.1 Classification of pharmaceutical water The definition and use of pharmaceutical water is usually based on the Pharmacopeia, which generally has different definitions and different uses for pharmaceutical water.
from the point of view of use, pharmaceutical water is mainly divided into bulk water and packaging water two categories.
Bulk water refers to pharmaceutical production enterprises in accordance with the relevant production process of home-made pharmaceutical water, for example, China Pharmacopeia approved bulk water including purified water and injection water;
Packaging water is also known as finished water, especially in accordance with the pharmaceutical process of the production of packaged finished water, for example, the Chinese Pharmacopeia includes sterilization injection water, the European Union Pharmacopeia includes packaging purified water and sterilization injection water, etc. , the United States Pharmacopeia includes antibacterial injection water, sterilization inhalation water, sterilization injection water, sterilization flushing water and sterilization purified water and other products water (Table 1).
1 Classification of pharmaceutical water Sterilization injection water for injection water prepared in accordance with the injection production process, mainly used for injection of sterilized powder solvents, injection thinners and detection solvents.
For example, during bacterial endotoxin testing, water is required for sterilization injections with endotoxin content less than 0.015EU/ml (for gel) or 0.005EU/ml (for photometrics) and no interference with endotoxin testing.
objectively speaking, the various quality standards used in the pharmaceutical process of water is not limited to pharmacopeia quality standards, pharmaceutical water can also be divided into pharmacopeia water and NONPD water two categories.
Pharmacopeia water refers to pharmaceutical water that is included by a state or organization, not pharmacopeia water, which is not included in the Pharmacopeia, but can be used for pharmaceutical production, such as drinking water, softened water, distilled water and reverse osmosis water.
Sodesic water must meet at least the drinking water requirements, usually require additional processing to meet the process requirements, AND THE water may contain some substances added to control microorganisms, so that all pharmacopeia requirements do not have to be met."
Sometimes, ADP water is named after the final operating unit or key purification process used, for example, reverse osmosis water;
it is worth noting that THEA water is not necessarily of a worse quality than pharmacopeia water, in fact, if the application requires, THE water quality may be higher than the quality of pharmacopeia water.
With reasonable instructions, Adage water can also be used throughout pharmaceutical operations, including cleaning of production equipment, laboratory applications, and raw materials for the production or synthesis of API, but it is important to note that pharmacopeia preparations must be made using Pharmacopeia water.
Whether it is pharmacopeia or NONPD, users should establish appropriate microbial limits, assess the importance of microorganisms in non-sterile formulations based on the use of the product, the nature of the product itself and potential hazards to the user, and expect producers to establish appropriate microbial alerts and operational limits based on process requirements and the history of the systems discussed.
1.2 The composition of the water system Pharmaceutical manufacturers are mainly concerned about raw water, that is, purified water, high purity water and injection water.
from a functional point of view, the pharmaceutical water system consists mainly of two parts: the preparation unit and the storage and distribution unit (Figure 1);
Figure 1 The composition of the preparation unit of the pharmaceutical water system mainly includes softened water, purified water machine, high purity water machine, distilled water machine and pure steam generator, whose main function is to continuously and steadily "purify" raw water into conformity with the internal control indicators of the enterprise or pharmacopeia requirements The storage and distribution unit mainly consists of storage unit, distribution unit and dot pipe network unit, whose main function is to carry the pharmaceutical water to the required process position with a certain buffer capacity, to meet the corresponding flow, pressure and temperature needs, and to maintain the quality of pharmaceutical water always in accordance with pharmacopeia requirements.
of microorganisms, which are one of the most important quality indicators, are highly likely to breed microorganisms.
measures need to be taken to inhibit the reproduction of microorganisms in the design, installation, verification, operation and maintenance of pharmaceutical water systems.
In view of the fact that pharmaceutical water is used as both a raw material and a cleaning agent in the pharmaceutical industry and is highly susceptible to microorganisms, national pharmacopeias have clear definitions and requirements for the quality standards and uses of pharmaceutical water.
Pharmaceutical water and product direct contact, which has a direct impact on the quality of drugs, countries and organizations of GMP pharmaceutical water preparation and storage distribution system as a key system for pharmaceutical production, its design, installation, verification, operation and maintenance of clear requirements.
1.3 Pharmacopeia Standard Pharmacopoeia is a national code for the documentation of drug standards and specifications, which is generally codified and promulgated and implemented under the auspices of the State Drug Administration, while the International Pharmacopeia is compiled by recognized international organizations or the relevant countries in consultation.
the early 1990s, at least 38 countries around the world had developed national pharmacopoeia, as well as three regional pharmacopeias and the International Pharmacopeia, compiled by the World Health Organization.
Drug standards are an important part of modern drug production and quality management, and a legal basis for drug production, supply, use and supervision and management departments to follow, and the formulation of drug standards plays a very important role in strengthening the supervision and management of drug quality, ensuring quality, ensuring the safety and effectiveness of drug use and safeguarding people's health. the connotation of
drug quality includes three aspects: authenticity, purity and quality, the concentrated performance of the three is the effectiveness and safety in use, therefore, drug standards generally include the following: legal name, source, character, identification, purity inspection, content (effective price or activity) determination, category, dose, specification, storage, preparation, etc.
purified water and injection water are important raw materials in the pharmaceutical production process, and the quality of them will directly determine the quality of the drugs to be produced, so each country or organization has clear regulations on them.
2 and 3 list the latest versions of the Chinese Pharmacopeia, the European Pharmacopeia and the United States Pharmacopeia on the different quality standards for bulk purified water and bulk injection water.
control table of bulk purified water on Table 2 Note: (1) See Appendix I of this chapter, GB 5749-2006 Standards for Sanitary Drinking Water.
(2) purified water TOC detection method and easy oxide detection method can be selected as one.
(3) if the bulk purified hydropower conductivity does not meet the requirements for bulk injection water (0619), elemental impurities risk assessment is carried out in accordance with section 5.20.
3 Quality Control Table for Bulk Injection Water Note: (1) Bulk Injection Water for Commercial Use.
1.4 The latest version of the Chinese Pharmacopeia and Pharmaceutical Water Chinese Pharmacopeia (CP) is the 2020 edition of the Chinese Pharmacopeia, which will be officially implemented on December 30, 2020.
Like the 2015 edition of the Chinese Pharmacopoeia, the 2020 edition of the Chinese Pharmacopoeia consists of four parts, one for Chinese medicine, two for chemicals, three for biological products, and four for general rules and accessories standards.
2020 edition of the Chinese Pharmacopoeia added 319 species, revised 3177 species, no longer contains 10 species, variety adjustment combined with 4 species, a total of 5911 varieties.
chinese medicine contains 2711 kinds, of which 117 have been added and 452 have been revised.
contained 2,712 chemicals, of which 117 were added and 2,387 were revised.
153 new biological products were collected, of which 20 were added and 126 were revised;
Four contained 361 general technical requirements, of which 38 (revised 35), 281 testing methods and other general rules (35 new, 51 revised), 42 guiding principles (12 new, revised 12);
The pharmaceutical water collected in the Chinese Pharmacopeia includes purified water, injection water and sterilized water, and compared with the 2015 edition of the Chinese Pharmacopeia, the 2020 edition of the Chinese Pharmacopoeia has no change in the regulations related to pharmaceutical water.
2020 edition of the Chinese Pharmacopoeia purified water quality should comply with the relevant provisions of Part II on purified water, purified water can be used as a solvent or experimental water for the preparation of common pharmaceutical preparations; Extraction solvents for medicinal materials used in sterilization preparations, solvents or thinners for preparation of oral and external preparations, water for the fine washing of non-sterilization preparations, and extraction solvents for medicinal materials used as non-sterilization preparations.
water shall not be used for the preparation and dilution of injections.
, purified water has a variety of preparation methods, should strictly monitor the production links, prevent microbial pollution, to ensure the use of water quality.
2020 edition of the Chinese Pharmacopoeia on the quality standards of purified water see the following: Purified water Chunhuashui Purified Water H2O 18.02 This product is drinking water by distillation, ion exchange, reverse osmosis or other appropriate methods of pharmaceutical water, without any additives.
is a colorless clarified liquid;
the : acidity and alkalinity take this product 10 ml, plus methyl red indicator liquid 2 drops, not to show red;
nitrate take this product 5 ml test tube, cooling in an ice bath, plus 10% potassium chloride solution 0.4 ml and 0.1% diphenyl sulfuric acid solution 0.1 ml, Shake well, slowly drop 5 ml of sulfuric acid, shake well, place the test tube in a 50c water bath for 15 minutes, the solution produces blue and standard nitrate solution (take potassium nitrate 0.163g) , water dissolved and diluted to 100 ml, shake well, precision to take 1 ml, water to dilute to 100ml, then precision to take 10ml, water diluted to 100ml, shake well, that is (each 1 ml is equivalent to 1 sgNO3) 0.3 ml, plus nitrate-free water 4.7 ml, with the same method after color comparison, not deeper (0.000 006%).
nitrite take this product 10 ml, in the tube, add the acetate solution of aminobenzene sulfonamide (1 to 100) 1 ml with acetate solution (0.1 to 100) 1 ml, produce pink, with standard nitrite solution (take potassium nitrite 0.750g (by drying products) Calculated), water dissolved, diluted to 100 ml, shake well, precision to take 1 ml, water diluted to 100 ml, then precision to take 1 ml, water diluted to 50 ml, shake well, that is (every 1 ml equivalent to 1 μgNO2) 0.2 ml, plus nitrite-free water 9.8 ml, with the same method after treatment of color comparison, not deeper (0. 000 002%).
50 ml of ammonia, alkaline iodide mercury potassium test liquid 2 ml, placed for 15 minutes; Dissolve and dilute to 1000 ml) 1.5 ml, add ammonia-free 48 ml and alkaline iodide mercury potassium test liquid 2 ml made of control liquid, not deeper (0.000 03%).
conductive.