Article 52 of the Drug Administration Law of People's Republic of China (PRC) stipulates: "Packaging materials and containers that come into direct contact with drugs must meet medical requirements and safety standards." Article 44 of the Regulations for the Implementation of the Drug Administration Law of People's Republic of China (PRC) stipulates: "The management measures, product catalogues, medicinal requirements and standards for packaging materials and containers that are in direct contact with drugs shall be formulated and promulgated by the drug supervision and administration department of the State Council." According to the requirements of the above laws and regulations, since 2002, the State Administration of Pharmaceutical Products has issued 1 13 standards for pharmaceutical packaging containers (materials) (including the standards planned to be issued in 2004), including 43 standards for medical glass bottles (materials), accounting for 38% of the total standards of all pharmaceutical packaging villages, covering powder injection, water injection, infusion solution and so on. A relatively perfect and standardized medical glass bottle standardization system has been initially formed. The formulation, promulgation and implementation of these standards are of great significance and role in upgrading the quality of pharmaceutical glass bottles, improving product quality, ensuring drug quality, accelerating the integration with international standards and international markets, and promoting and standardizing the healthy, orderly and rapid development of China's pharmaceutical glass industry.

Medical glass bottles are packaging materials that directly contact with drugs, which occupy a large proportion in the field of medical packaging materials and have irreplaceable properties and advantages. Their standards have a vital impact on the quality of drug packaging and the development of the industry. Standardization system of medical glass bottles

According to the principle that one material (variety) is a standard according to the drug packaging material standard of the State Administration of Pharmaceutical Products, there are 43 published and to be published standards for medical glass bottles. According to the standard type, it is divided into three categories. There are 23 product standards in the first category, of which 18 has been published and 5 are planned to be published in 2004. The second type of test method standard is 17, of which 10 has been published, and 7 plans were published in 2004. There are 3 basic standards in the third category, of which 1 has been published and 2 will be published in 2004. There are 23 product standards in the first category, which are divided into 8 categories according to product types, including 3 injection molding bottles, 3 control injection bottles, 3 glass infusion bottles, 3 injection molding medicine bottles, 3 control medicine bottles, 3 control oral liquid bottles, 2 ampoules and 3 glass medicinal tubes (note:

Bonding materials are divided into three categories, including eight borosilicate glasses, including neutral glass with α = (4 ~ 5 )×10 (-6) k (-1) (20 ~ 300℃) and α = (3). 2 ~ 3.4 )× 650. This kind of glass adopts international neutral glass, which is usually called Class I glass or Class A material. 8 pieces of low borosilicate glass, with low borosilicate glass α = (6. 2 ~ 7.5)× 10(-6)K(- 1)(20 ~ 300℃)。 This kind of glass is unique to China and can't meet the international standard of quasi-neutral glass. Also known as grade b glass. There are 7 items of soda-lime glass, and the ratio of soda-lime glass is α = (7. 6 ~ 9.0)× 10(-6)K(- 1)(20 ~ 300℃)。 Generally, this kind of glass is vulcanized, and its surface water resistance reaches Grade 2.

The standard of the second inspection method is 17, which basically covers various inspection items such as the performance and indicators of various medical glass bottles. In particular, the chemical properties of glass are tested according to ISO standards, which provides more, more comprehensive and more scientific testing methods for various products of medical glass bottles to adapt to drugs with different properties and dosage forms and to identify chemical stability. These detection methods ensure the quality of medical glass bottles. In addition, the detection method of harmful element dissolution is added to ensure the safety of medical glass bottles. The inspection methods and standards of medical glass bottles need to be further supplemented and improved. For example, the inspection methods such as alkali peeling resistance, breaking force and freezing impact resistance of ampoules have important influence on the quality and application of medical glass bottles.

There are three basic standards in the third category. Among them, the Classification and Inspection Methods of Medical Glass Bottles are formulated with reference to ISO 12775- 1997 Inspection Methods of Glass by Composition and Normal Mass Production, with the purpose of clarifying the classification and inspection methods of medical glass bottles and distinguishing the classification of glass materials in other industries. The other two basic standards limit the harmful elements of glass materials such as lead, cadmium, arsenic and antimony to ensure the safety and effectiveness of various drugs. Characteristics of medical glass bottle standard

The standard of medical glass bottles is an important branch of the standard system of pharmaceutical packaging materials. The quality of medical glass bottles is directly related to the quality of drugs and personal health and safety, because they have to be in direct contact with drugs, and some have to be stored for a long time. Therefore, the standards of medical glass bottles have special and strict requirements, which can be summarized as follows:

It is more systematic and comprehensive, enhances the selectivity of product standards and overcomes the lag of standards to products.

The new standard establishes the principle that the same product has different standards according to different materials, greatly expands the coverage of the standard, enhances the applicability and selectivity of various new drugs and special drugs to different glass materials and products with different properties, and changes the relatively backward situation of product development standards in general product standards.

For example, among the eight medical glass bottles covered by the new standard, each product standard is divided into three categories according to the material and performance. The first kind is borosilicate glass, the second kind is low borosilicate glass, and the third kind is soda-lime glass. Although a certain product of a certain material has not yet been produced, the standard of this product has been issued, which has solved the lag problem of formulating standards after the product is produced. Drugs with different grades, different properties, different uses and different dosage forms have more flexibility and greater choice space for products and standards made of different materials.

The definitions of borosilicate glass and low borosilicate glass are defined. International standard ISO 4802. 1- 1988 "Water resistance of inner surfaces of glassware and glass containers Part 1: Titrimetric determination and classification" defines borosilicate glass (including neutral glass) as containing 5 ~ 65438 boron trioxide. However, ISO 12775 "Classification of Glass Components and Test Methods for Normal Mass Production" is published in 1997, which stipulates that borosilicate glass (including neutral glass) contains more than 8 %(m/ m) of boron trioxide. According to the classification principle of glass in the international standard 1997, the glass material of B-2O-3 6 %(m/ m) widely used in China's medical glass bottle industry for many years should not be called borosilicate glass or neutral glass. The experiment shows that the water resistance and inner surface water resistance of some glass particles of this kind of material can not reach 1 grade and HC 1 grade, or the edge is between 1 grade and grade 2. Practice has also proved that some of this kind of glass will be neutral and unqualified or peel off in use, but this kind of glass has been produced and used in China for many years. The new standard keeps this kind of glass, and stipulates that its B-2O-3 content should reach the requirement of 5-8 %(m/ m). It is clearly stipulated that this kind of glass cannot be called borosilicate glass (or neutral glass) and is named low borosilicate glass.

Actively adopt ISO standards to meet international standards. The new standard fully refers to ISO standards, industry standards and pharmacopoeia of advanced countries such as the United States, Germany and Japan, and is in line with international standards in terms of glass types and glass materials in combination with the reality of China's medical glass bottle industry.

Glass material type: There are four kinds of glasses in the new standard, including two borosilicate glasses and three kinds. 3 borosilicate glass [α = (3. 30.1) ×10 (-6) k (-1)] and 5. 0 neutral glass [low borosilicate glass [α = (6. 2 ~ 7.5) ×10 (-6) k (-1)]1species, soda-lime glass [α = (7. 6 ~ 9.0) × 10 (.

Because soda-lime glass contains a lot of neutralization surface treatment in actual production and application, it is divided into five types according to products. The above four types of glass and five types of glass products include international standards, USP and medical glass bottles unique to China. In addition, among the eight categories of products covered by the standards, only ampoules have formulated two standards, namely borosilicate glass ampoules and low borosilicate glass ampoules. However, there is only one kind of 5. In the borosilicate glass ampoule standard, α = (4 ~ 5 )×10 (-6) k (-1), but there is no α = (3). 3 0. 1 )× 10 (-). In fact, the international standard is only 5.0 borosilicate glass ampoules, but there is no 3. Borosilicate glass ampoules and soda-lime glass ampoules. As for China's unique low borosilicate glass ampoule, at present, due to various reasons, 5. 0 borosilicate glass ampoule has not formed large-scale stable production in China, and can only be used as a transitional product. Finally, it is necessary to limit the use of low borosilicate glass ampoules and develop 5. 0 borosilicate glass ampoule, in order to fully integrate with international standards and products as soon as possible.

Glass material characteristics: thermal expansion coefficient α, 3. 3 borosilicate glass and 5. The 0 borosilicate glass specified in the new standard is in full compliance with international standards. Low borosilicate glass is unique to China, and there is no such product in international standards. The ISO standard of soda-lime glass is α = (8 ~10 )×10 (-6) k (-1), and the new standard is α = (7. 6 ~ 9.0) ×10 (-6) K. In the new standard, the chemical property of water resistance is 3. Borosilicate glass, 5. 0 borosilicate glass and soda-lime glass meet the international standards by particle method at 12 1℃. In addition, the content of boron oxide (B-2O-3) in the above three kinds of glasses completely meets the international standards.

Performance of glass products: The water resistance, thermal shock resistance and internal pressure resistance of the inner surface specified in the new standard are consistent with international standards. Internal stress index ISO standard stipulates that ampoules are 50nm/ mm and other products are 40nm/ mm, while the new standard stipulates that ampoules are all 40nm/ mm, so the internal stress index of ampoules is slightly higher than ISO standard. The transformation of standard content to trade-oriented standard

The formulation of new standard formats and items refers to the compilation formats of People's Republic of China (PRC) Pharmacopoeia and China Pharmacopoeia, and the standard names are drawn up according to the sequential formats of materials, uses and shapes.

The establishment of the project highlights the content of identification, and defines the material type of glass by thermal expansion coefficient and boron trioxide content. The content of the standard is clear and focused, and the restrictions on main performance indicators and harmful elements are written into the text as mandatory indicators. It is stipulated that there should be no obvious defects in the appearance index, and the specific appearance defects of products, such as bubbles, stones, stripes and various surface defects, can be determined by the supply and demand sides in the form of agreements, standards or contract annexes. The new standard also lists the specifications and dimensions in the appendix of the standard as recommended items to meet the needs of market diversification and new varieties and models. However, the author believes that the specification tolerance in the standard appendix should be mandatory to ensure the consistency of product specification tolerance accuracy and product performance. The testing items are comprehensive and the supporting testing standards are complete.

Compared with ISO related product standards and foreign related product standards, the testing items of the new standard are more comprehensive, mainly including the determination of thermal expansion coefficient and the determination of B-2O-3 content to identify glass materials. As arsenic trioxide (As-2O-3) or antimony trioxide (s b-2O-3)+ arsenic trioxide (As-2O-3) is still used as the fining agent for glass melting in most medical glass bottles in China, the limited control of the dissolved amount of the above harmful elements is added in the new standard to ensure the safety and effectiveness of packaged drugs.

In the new standard, the testing standards matched with the product standards are relatively complete, all indicators and items in the product standards have corresponding testing standards to choose from, and the testing methods and standards for important performance adopt ISO standards. Application of medical glass bottle standard

Various products and different materials form a vertical and horizontal interwoven standardization system, which provides sufficient basis and conditions for the selection of scientific, reasonable and applicable glass containers for various drugs. The selection and use of medical glass bottles with different dosage forms, properties and grades should follow the following principles: good chemical stability and suitability.

Glass containers used to hold various drugs should have good compatibility with drugs, that is, to ensure that the chemical properties of glass containers are unstable during the production, storage and use of drugs, and some substances react with each other to cause drug variation or failure. For example, high-grade drugs such as blood preparations and vaccines must use borosilicate glass containers, and all kinds of strong acids and alkalis, especially strong alkali water injections, should also use borosilicate glass containers. Low borosilicate glass ampoules widely used in China are not suitable for water injection. This glass material should be gradually transformed into 5. 0 glass material, in order to meet the international standards as soon as possible, to ensure that the drugs contained in it do not fall off, muddy or deteriorate during use.

For common drugs such as powder injection, oral preparation and infusion, the use of low borosilicate glass or neutralized soda-lime glass can still meet the chemical stability requirements. The corrosion degree of general drugs on glass is that liquid is greater than solid, and alkalinity is greater than acidity. Especially for strong alkali water injection, the chemical properties of medical glass bottles are higher. Good and appropriate resistance to sudden temperature changes.

In the production of different dosage forms of drugs, it is necessary to dry at high temperature, sterilize or freeze-dry at low temperature, which requires glass containers to have good and appropriate ability to resist sudden temperature changes without cracking. The resistance of glass to sudden temperature change is mainly related to its thermal expansion coefficient. The lower the thermal expansion coefficient, the stronger its resistance to temperature change. For example, many high-grade vaccine preparations, biological preparations and freeze-dried preparations generally use 3. 3 borosilicate glass or 5. 0 borosilicate glass. A large number of low borosilicate glasses produced in China are prone to cracking and bottle dropping when the temperature difference changes dramatically. China's 3. 3 borosilicate glass has made great progress, especially suitable for freeze-dried preparations, because its ability to resist temperature mutation is better than that of 5. 0 borosilicate glass. Good and suitable mechanical strength

Different dosage forms of drugs need to bear certain mechanical impact during production and transportation. The mechanical strength of medical glass bottles is not only related to bottle type, geometric size and heat treatment, but also influenced by glass materials. The mechanical strength of borosilicate glass is better than that of soda-lime glass.

The promulgation and implementation of the new standard for medical glass bottles will play a positive role in establishing a perfect and scientific standardization system, accelerating the pace of integration with international standards and the international market, improving the quality of packaging materials, ensuring the quality of drugs, and promoting industry development and international trade. Of course, just like the whole standard system of packaging materials, there are still many problems that need to be further improved, improved and perfected, especially to meet the requirements of the rapid development of pharmaceutical industry and the integration of international markets. The compilation, contents and indicators of standards, the adoption of international standards and the degree of integration with the international market all need to be adjusted and supplemented appropriately in the revision process.

Inspection standard for glass bottles and cans:

Stress detection method for glass bottles and glass bottle cans: ASTM C 148-2000(2006)