Infusion bottle from raw materials to finished product safety attracts attention from the industry

The officials from the State Food and Drug Administration and the National Development and Reform Commission stated at the meeting that the drug administration department is exploring the reform of the drug packaging material registration management system; price management will eliminate price differences in some differences in the packaging of soft bag infusion products in order to promote the industry. Healthy development to ensure drug safety. Cai Hong, secretary-general of the China Pharmaceutical Packaging Association, said that at present, the amount of infusion products in China is very large, with about 7 billion bottles (bags) each year. The quality of the infusion products directly affects the safety of patients' medications and the lives of the people. It is also related to the infusion companies. Survival, development and the image of medical institutions. There are many factors affecting the quality of infusion drugs, among which the selection and application of packaging materials is one of the key factors. At present, the cost of medicine packaging in China has accounted for more than 60% of the cost of medicines. At the same time, with the rapid emergence of new infusion packaging materials, new styles, and new structures, the proportions of infusion soft bags, plastic bottles, and upright soft bags have been increasing year by year, and the requirements for infusion packaging materials have been continuously improved. This is also a forum that causes quality inspection agencies. The main reasons for the widespread concern of manufacturers of pharmaceuticals and pharmaceutical packaging materials, and domestic and overseas suppliers of pharmaceutical packaging materials and equipment.

Security goes hand in hand

Start with pellets

At the forum, experts at home and abroad explained the situation at home and abroad, from the control of raw and auxiliary materials for infusion packaging, registration requirements, product testing, and production process control to clinical use. In addition, the organizers also invited foreign authoritative experts for the first time to comprehensively introduce the safety assessment system and test methods for foreign transfusion medicines and packaging, the purpose of safety assessment, and analysis of safety issues. The content runs through the infusion packaging production chain and involves various aspects of safety assessment, including the production of pellets from the upstream chemical production, the production and quality control of packaging materials, the control (validation) and evaluation of the pharmaceutical production process, and the safety during clinical use. Factors and so on.

As chief scientist at Baxter, Dr. Dennis Jenke focuses on the compatibility between drugs and packaging. He said that packaging systems used with finished pharmaceutical products should be suitable for their intended application. Among several useability factors, security is an important factor that must be effectively discussed for the product to be registered or sold. To this end, the safety assessment of the packaging system for injection preparations includes extractables, leachables and toxicology. This assessment can be divided into four stages: selection and characterization of packaging raw materials, qualitative research on packaging systems, verification of qualitative research, and maintenance of listed products (safety assessment). Interactions between the drug formulation and the system may affect the composition of the drug formulation and/or system. However, the complexity of the safety assessment depends on many factors such as the route of administration, the possibility and strength of interaction, the design dose, and the sensitivity of the target patient population.

When talking about the development of pharmaceutical packaging, Luetke Michael from LyondellBasell believes that the medical and health needs have driven the continuous growth of plastics and other materials industries. In this process, risk management has become a key point, and the FDA has increased With the management of suppliers, producers of pellets have also shifted from focusing on quality to focusing on quality. The European Pharmacopoeia has a list of available additives that contains 22 available additives. Polyolefin resins used in pharmaceuticals need to be managed using medical procedures.

“Pelleting and packaging of Polypropylene (PP) is performed in a certain environment, but for medical grade PP, we use a Class 10000 clean room for granulation and packaging to reduce the entry of external impurities.” from LG Wang Zhuo of the Chemical Technology Center said that as a pharmaceutical packaging manufacturer, plastics provided for the medical field should focus on safety. Taking polypropylene pellets used for large infusion plastic bottles as an example, the United States Pharmacopoeia USP focuses on biological experiments, and the European Pharmacopoeia EP focuses on chemical detection. The USP conducts the most rigorous testing of medical plastics, while EP defines the type and amount of additives.

From the research and development, design and production of pellets to pharmaceutical packaging products, to the use of pharmaceutical plants, the requirements for safety have been throughout. "The potential quality risks of pharmaceutical packaging products cannot be accurately analyzed, evaluated and eliminated, and will inevitably be passed on to pharmaceutical companies." Zhang Wenfang, chief technology officer of Beijing Ao Xing Company, believes that pharmaceutical packaging products should be in the R&D design stage. Conduct risk management to minimize insecurity. In terms of the use of pharmaceutical companies, Li Jie, Shandong Qidu Pharmaceutical Quality Minister, introduced the subject of the “Polypropylene Infusion Bottle Cleaning Process Study” undertaken by the company. "According to the current standard operating procedures for ionized air cleaning, operators can guarantee the quality of cleaning and achieve the purpose of removing film and fiber, but they must strictly control the sterilization process parameters to prevent the occurrence of filming," said Li Jie.

The importance of compatibility studies

In terms of drug safety, the compatibility of packaging containers with pharmaceutical preparations has been one of the key issues that the global pharmaceutical industry has focused on and continues to study. At the forum, relevant experts from Shanghai Food and Drug Packaging Materials Testing Institute introduced the study of additive migration in polypropylene infusion bottles. The expert said: "From the study of extracts to the interaction study, the two sides of migration and adsorption must be studied." The results show that the results of the antioxidant test of polypropylene infusion bottles are generally better, but there are also some Problems, such as the inaccurate information of additive formulas known or provided by some polypropylene infusion bottle manufacturers; detection of trace amounts of other phenolic antioxidants in non-formulations.

In 2002, China first proposed the compatibility of packaging materials and drugs, and formulated the corresponding guiding principles (YBB00142002 Guidelines for Drug Packaging Materials and Drug Compatibility Testing), but due to the lack of research experience in the use of the unit, the drug compatibility Insufficient understanding of the problem, resulting in compatibility studies often replaced by the Institute of Drug Stability, the results of the study are not sufficient to guide the rational use of drug packaging materials, selection. "Actually, the packaging structure of pharmaceutical packaging materials also has a lot to do with the safety of pharmaceuticals." Expert Jin Hong, an expert at Zhejiang Pharmaceutical Packaging Materials Quality Inspection Station, said that the purpose of drug packaging and drug compatibility testing is to examine the phase of packaging materials and drugs. In addition to capacitive, it is necessary to guide the selection of appropriate drug packaging materials (including structural forms) and to ensure that the drugs are safe and effective (including effective therapeutic doses into the human body).

At present, the commonly used packaging forms of infusion products (≥50ml) in China are broadly divided into: glass infusion bottles and their seals (butyl rubber stoppers and aluminum caps); infusion bags (three or five-layer coextruded films) and their seals ( Contains an interface or take over); plastic infusion bottle and its seal (combined cover) or (butyl rubber plug plus aluminum cover). Which kind of material is better? Manufacturers of glass bottles and plastic bottles are inconsistent. However, a common point is that the selection of pharmaceutical packaging materials must be based on the premise of ensuring the safety of drugs, and compatibility studies are the most important factors in the selection of packaging materials.

Dr. Michael Roü Bler, a consulting expert from Schott Glass GmbH in Germany, said that pharmaceutical companies in Europe and glass experts worked together to formulate the “Defective Evaluation Sheet for Glass Containers for Pharmaceutical Use”. This defines the final shipping control standard for the bottle-making factory, and also defines the purchase control standard for the pharmaceutical company. The testing plan and AQL value can be changed on the basis of consensus between the two parties to ensure that the package is suitable for drug safety. Sex.

SGD, the French company, is a pioneer in the field of global pharmaceutical molded glass bottles. Mr. Vincent LANGLADE from the company believes that soda-lime glass (category 3 glass) is not suitable for infusion bottles, but is treated with soda-lime glass on the inner surface ( Type 2 glass) is suitable for injections, but such bottles can only be filled and disinfected once. Due to the migration and adsorption of plastic containers, PVC (infusion) bags are rarely used in the German market. At the same time, the development of plastic medicine packaging containers is faced with many factors, such as the high cost of such containers for light-sensitive stability research; health authorities have stricter requirements for the follow-up of post-marketing plastic products than glass; high analysis and development costs and so on. "The stability and compatibility of glass are widely known, so general drugs are usually packaged in glass bottles." But European countries have different preferences for glass and plastic packaging, such as in Italy, glass packaging infusion products account for 68% of the total infusion products, while the French soft bag packaging infusion products in the country's market share reached 72%. In the European infusion market, the current market share of soft bag packaging infusion products has exceeded the glass packaging, soft bag packaging products, glass bag products and plastic bottle packaging products share respectively: 50%, 40%, 10%.