Analysis of composite film for packaging of the ho

Analysis of composite film for drug packaging (III)

similarities and differences between GMP management and IS09000 quality system

as a quality management system, we are familiar with ISO9000 system. ISO9000 system originated from the quality assurance of military products by the U.S. Army in 1963, and has been applied to civilian products since 1987, becoming a worldwide popular quality management system. ISO9000, like GMP, emphasizes quality management based on prevention and comprehensive quality improvement. Although GMP management also introduces many new things from ISO9000 quality assurance system, GMP management is different from ISO9000 management. GMP management is the professional application of ISO9000 management in drug production management. GMP management is both technical management and management technology. Its goal is the same quality assurance as ISO9000, There is also a special mission to reduce human errors and prevent cross contamination and mixing. ISO9000 quality assurance system is valued at "all", while GMP management is valued at "strict". GMP management is a strict mandatory quality management system, which requires "all behaviors have standards, all procedures have verification, all operations have records, all processes can be monitored, and all errors can be traced"

at present, the international organization for standardization also recognizes the particularity and professionalism of the quality assurance system for drugs and drug packaging, and has set up a working group to study the quality system of drug packaging materials. In 2003, it issued the standard ISO/CD quality management system, special requirements for the application of ISO 9001:2000 for drug inner packaging materials (GMP). From the perspective of development, GMP management and ISO9000 quality assurance will interact and promote each other to jointly promote the management of drugs and drug packaging to a higher level

3 the current management of composite film for drug packaging

the national food and Drug Administration and the management of drug packaging material enterprises are becoming more and more strict, and its slogan is "drug packaging follows drugs". We can notice that the chapters and contents of the "good manufacturing practice for packaging materials and containers for direct contact with drugs" and the "good manufacturing practice for drugs" are basically the same, and some paragraphs are even identical. Some special medicine packaging materials, such as capsules, have been used as a kind of medicine with no curative effect, and they are completely managed according to drugs. The State Food and Drug Administration (SDA) has changed its name to the State Food and Drug Administration (SFDA). As a state food and Drug Administration accustomed to high standards and strict requirements, it will naturally put forward higher requirements for food, especially health products. Finally, like developed countries, food (especially some high value-added food) will also be included in the scope of GMP management. At that time, as a composite film for food packaging, it will not escape GMP management

China is a developing country, and price and cost are a big factor in real life. In order to compete at a low cost, some small pharmaceutical companies currently take part of the packaging materials for inspection in drug packaging enterprises with registration certificates, and at the same time, they buy some drug packaging materials at a low price from unlicensed packaging materials factories to reduce costs. For packaging material production enterprises, At present, some enterprises without drug packaging material registration certificate are still producing drug packaging materials. Because the printing, compounding and other processes of the composite film for drug packaging produce a lot of heat, and have a strong solvent smell, it requires a lot of air volume and refrigeration capacity to meet the requirements of 300000 cleanliness, which is undoubtedly a big burden on the cost of the enterprise (it is estimated that the cost per ton of product will increase by about yuan), so some drug packaging material enterprises, after obtaining the registration certificate, in order to reduce the cost of air conditioning, open the windows Ventilation production is implemented when the door is opened. In order to reduce energy consumption, some enterprises dismantle the high-efficiency filter (some even with primary and medium efficiency filters) after the superior inspection, close the refrigeration system, and use the high wind to meet the purpose of cooling and reducing odor. In order to reduce the finished products, some enterprises adopt the method of model engineering to establish a small clean model workshop for superior inspection and customer visits. In fact, large quantities of products are produced in other general environments

it has only been three or four years since the real implementation of GMP management in drug packaging materials and the clear requirements for the cleanliness of the production environment of drug packaging materials enterprises. At present, although some enterprises propose to implement GMP certification in drug packaging material enterprises, the State Food and drug administration still does not require drug packaging material enterprises to pass GMP certification. At present, less than 30% of the pharmaceutical packaging material enterprises produce strictly according to the clean requirements of GMP, but in the long run, just like the GMP transformation of pharmaceutical factories, the rope of GMP will bind the pharmaceutical packaging material enterprises more and more tightly, and it is inevitable to produce completely according to the requirements of GMP

II. Technical characteristics of composite film for drug packaging

drugs are a special commodity. As a packaging material for direct contact with drugs, composite film for drug packaging also has many differences in technical level in addition to special management requirements

1. Characteristics of composite film for drug packaging in product standards

the regulations for the implementation of the drug law of the people's Republic of China for three years promulgated in 2002 clearly stipulates that the standards of packaging materials and containers in direct contact with drugs shall be prepared and published by the state food and drug administration. Since then, the standard management right of drug packaging materials has been transferred from the State Administration of technology supervision to the State Food and drug administration. In more than a year since July, 2002, the State Food and drug administration has issued 49 product standards for drug packaging materials and 25 inspection method standards for drug packaging materials. Among them, the composite film standards for drug packaging include YBB general rules for composite film and bag for drug packaging, YBB composite film and bag for polyester/aluminum/polyethylene drug packaging, YBB composite film and bag for polyester low density polyethylene drug packaging, and YBB composite film for biaxially oriented polypropylene/low density polyethylene drug packaging. The standard of composite film for drug packaging is mainly drafted by Shanghai Pharmaceutical Packaging Materials Testing Institute, national drug packaging materials research and inspection center, Zhejiang drug packaging testing station and other units

the preparation format of the standard of composite film for drug packaging is completely different from the national standard and industrial standard, but it adopts the format of Chinese Pharmacopoeia. Compared with ordinary composite membrane, its content has increased two health items: microbial limit and abnormal toxicity, and other health and safety indicators have been greatly improved compared with food packaging. The composite strength of the inner layer and the secondary inner layer shall be greater than 2.5n/15mm, which is significantly higher than that of the general composite film, but the standard does not give specific provisions for the appearance, size and other non safety indicators. The composite film standard for drug packaging also stipulates that the structure of the composite film for drug packaging must be identified, and the compatibility test of other packaged drugs should be carried out according to YBB "guiding principles for compatibility test between drug packaging materials and drugs", so as to ensure the safety and effectiveness of drug packaging

of course, since the drafting of the composite film standard for drug packaging did not carry out a large number of validation experiments, nor did it widely solicit opinions from all parties, it was found that there were many problems after its release, which need to be further improved

2. Barrier performance requirements of composite film for drug packaging

for composite film for food, high barrier packaging materials generally refer to high oxygen barrier materials (such as PA, EVOH, etc.), but for drug packaging, most drugs are sensitive to water vapor and insensitive to oxygen, so the barrier of drug packaging is usually moisture-proof

drugs are a special commodity with high added value and high requirements for safety and reliability. In addition to the packaging of traditional Chinese medicine slices and low-grade granules, the composite film of drug packaging is basically made of pure aluminum foil composite materials, while the food packaging is generally made of transparent or aluminized packaging

due to its high barrier property, the side penetration that could have been ignored can no longer be ignored, and the demand for material life is becoming larger and larger. For the packaging bag made of aluminum foil composite material, the cause of this failure is Electromechanical phase loss. In addition to the penetration through the packaging material, the penetration of the thermal sealing edge of the packaging bag should also be considered. The thermal sealing edge should have sufficient width, and the thermal sealing material used must have certain barrier performance. The author once took water and made the aluminum foil composite film into a bag with a vapor transmission rate of 0.25g/m224h (cup method 38 ℃ 90%rh), and sealed the fully dried anhydrous calcium chloride into the bag to measure the weight gain. It took one year. Under the condition of 50 ℃ 100%rh, the water vapor transmission rate of the aluminum foil composite film was 0.0014 g/m2.24h when the edge sealing width was 8mm, while the water vapor transmission rate of the aluminum foil composite film was only 0.0008 g/m224h when the edge sealing width was 20mm. This shows the influence of edge banding width on the barrier property of aluminum film composite bags. Further experimental results show that the thickness of aluminum foil is 15 μ M above, the barrier property of aluminum foil composite bag is completely determined by the edge banding width and edge banding quality

aluminum foil is a special material different from plastic. Aluminum foil composite film should also pay attention to the pressing through, breaking, folding and other problems of aluminum foil layer in the process of packaging, transportation and sales. After the high barrier aluminum foil layer is damaged, although there will be no air leakage, its barrier performance will be greatly discounted, seriously affecting the shelf life of products

3. Product form characteristics of composite film for drug packaging

the dosage of drugs is generally small, which is not convenient to make bags before packaging, and they are generally packaged by automatic packaging machines. In addition to the packaging of traditional Chinese medicine, a large number of composite films for drug packaging leave the factory with coiled materials. When they arrive at the pharmaceutical factory, automatic bag forming, filling and sealing packaging machines are used for drug packaging

the composite film used for drug packaging is delivered from the factory with coiled materials. Although the bag making process is saved, the requirements for the delivery of coiled materials are much stricter than that of packaging bags. First of all, there is usually a direction for coil coiling. The composite of unqualified products should be rolled twice, and the coiling tightness should be appropriate. There should be no loose film, let alone core wrinkles. Many pharmaceutical companies do not accept "live" wrinkles. The composite film used for drug packaging leaves the factory with coiled material. The thickness uniformity of the film is much higher than that of the bag. At the same time, the uneven distribution of the thickness should be uniform, otherwise the coiled film is easy to burst. Because the roll film is continuous, it can't be selected bag by bag like bag making products. As long as there is a unqualified point in dozens of meters, the whole roll will be scrapped, with a high risk. The paper core should not be too wet, otherwise the paper core will loosen after drying from the wet south to the dry north. Some pharmaceutical factories with strict requirements require plastic or aluminum tubes to be used as roll cores from the perspective of hygiene (paper products are easy to carry bacteria and may have peculiar smell)

4. Structural characteristics of composite film for drug packaging

the structure of composite film for drug packaging should not only consider the mechanical strength at room temperature, but also pay attention to the mechanical strength of packaging materials at heat sealing temperature. The vertical packaging machine commonly used in the automatic packaging of drugs, especially the roller heat sealing (also known as continuous) vertical packaging machine, the packaging materials are subjected to various forces in the packaging process. Generally, the products with BOPP/Al/PE, BOPP/Al/PP, BOPP/PE, BOPP/VM CPP, BOPP/PP and other structures have low strength of the whole material under the heat sealing temperature, and the opening sealing temperature of the inner layer (PP, PE) is very close to the heat-resistant temperature of the outer layer BOPP, In addition, the temperature control accuracy and reliability of domestic automatic packaging machine