Medical Device Sterile Packaging In China (三)
First you need to make a definition of this packaging system. This packaging system is a combination of all the external factors that constitute the protection of the target body - medical device products. A packaging system is mainly completed through the steps of packaging material selection, packaging structure (or form) design, packaging process execution and packaging experiment inspection.
For medical device sterilization packaging systems, based on their specificity on the performance requirements of the packaging (mainly requiring systemic inhibition and ability to withstand the various types of sterilization methods that will be used in advance), this system can be divided It consists of two parts, the Sterile Barrier System (SBS), which belongs to the category of the inner packaging system, and the Protective Packaging System (PPS), which belongs to the outer packaging system. Relatively reorganized, SBS is more critical because its failure means absolute failure of the entire packaging system; and if PPS does not achieve the intended design, it does not necessarily mean the failure of the entire or bulk packaging system, and found And the failure to find such a package is simple and cost-effective. In fact, it seems that medical device sterilization packaging systems and other packaging systems that are sensitive to barrier properties (such as special food packaging and pharmaceutical packaging) can be divided into inner packaging systems and outer packaging systems. Industrial packaging is different, and it is not the same as the packaging of household appliances and electronic products that are very focused on cushion packaging.
1. Requirements for completeness
For medical device sterilization packaging, it is necessary and necessary to form a sealing system to ensure the barrier to various harmful microorganisms. This kind of barrier property may be very common in the field of flexible packaging made of paper and plastic, but for the packaging of medical devices that need to be sterilized, Chinese printing companies are strong, and when combined with the expected sterilization methods, they often face conflicting choices because In the existing popular sterilization methods in China, ethylene oxide (EtO) gas sterilization is most popular because of its low cost and universal adaptability to materials, but this sterilization method has proposed packaging integrity. One challenge: it requires packaging to be permeable to carton cartons, as ethylene oxide also enters through this sealed packaging system to kill microbes inside the packaging system.
It can be seen that in order to meet the needs of the ventilating method in which the oxirane needs to be ventilated, the material of the selected inner packaging system must satisfy the function of venting but also hindering bacteria, so it is necessary to select a sufficiently small pore and have a certain A material of mechanical strength, a so-called porous material. Of course variable data printing, the pores are slightly smaller than the diameter of harmful microorganisms, in order to effectively prevent the entry of microorganisms. At present, the commonly used porous materials mainly include the non-woven grade material Tyvek from DuPont, as well as medical grade packaging paper which has strict requirements on hygienic cleanliness and pore size. This medical wrapping paper can be provided by many companies. What is worth noting is the label. These porous materials do not have good direct processing properties themselves to form a complete inner packaging barrier system. They need to be processed by surface processing such as gluing to obtain processed materials together with other materials. The performance of the packaging barrier system.On the other hand, the porous gas permeable material only forms part of the inner packaging system, and the other part can be combined printing of various types of polymer film, blister box, etc. depending on the package form, and they are usually passed through various types of heat sealing methods. It is processed into a complete inner packaging system to achieve the function of blocking microorganisms from entering the interior of the package.
Investigate whether the inner packaging system is complete. According to the existing standard specifications, generally refer to ASTM F1929-1998, which is the "methodamine blue dye solution penetration test method". Prior to this special printing, the rhodamine solution dyeing and permeation experiment based on EN868-1 was also popular in China (it is estimated that the domestic application is still very wide), but it was banned because the US FDA suspected it was a potential carcinogen. The formulation of the toluidine blue dyeing solution is given in ASTM F1929, but the specific experimental method is not given in this standard. It must be pointed out that this experimental method is still a very skillful book review and requires simple training. Can be mastered, but the overall difficulty of the experiment is not great.
For the internal packaging aseptic system designed to meet the high-energy sterilization methods such as gamma rays and electron beams, since there is no gas permeability requirement, there is no need to use porous packaging materials, but the integrity of the inner packaging system. The same color management is required. At this time, the leak detection method suitable for the sealed packaging system can be used to check. There are many non-designated standards at home and abroad for reference, and it is relatively easy to operate. Moreover, such a sealing material is generally a polymer plastic material, and each layer of material is melt-heated by Shanghai Guanghua, and the probability of leakage is much lower than that of the glue bonding method, which is also advantageous.
2. Relevant protective requirements
The protection requirements are easy to understand relative to the integrity requirements. The most primitive function of the package is to protect the product, and then evolve into an additional function that promotes sales and convenient use, so whether it is an inner packaging system or an outer packaging system. Dazu Guanhua, its protective requirements are essentially the same, but differ in the form of composition.
For the protective requirements of the inner packaging system, it is required that the packaging material itself has a certain mechanical strength, and that the joint of different materials constituting the inner packaging system also has a certain strength, and usually the combination is through each Fuji Xerox, a kind of heat sealing method, commonly used heat sealing methods include ordinary heat sealing, high frequency heat sealing and ultrasonic heat sealing.
The mechanical strength of the material itself can be easily determined. Generally speaking, as long as the tensile strength, puncture strength, notch tear strength, and burst strength of the material are measured, conventional data can be obtained, and the commonly used materials, such as These various mechanical properties, Tyvek and medical wrappers are also easily identifiable.
The control of heat sealing strength at the joint of materials is more complicated and on-demand printing. Because the material's own mechanical properties, rubber composition and properties, heat sealing method and heat sealing equipment should be considered, it is very important to directly give a universally applicable heat sealing strength range. To be challenged, this must be combined with the packaged product and historical historical data.
Too much or too little heat sealing can cause problems. Excessive heat sealing strength causes two problems. First, it cannot be cleaned, because excessive heat sealing strength can easily cause the material to tear the packaging container in the heat sealing area, especially when the heat sealing strength is greater than the tensile strength of the material itself and the material When the elongation is not big enough, such as medical packaging paper materials, Tyvek materials rarely rupture due to their excellent mechanical strength; second, they cannot be easily opened, and the packaging is easy to open for potential customers of medical device products. CTF, which is a very stressful doctor during surgery or a very weak and unattended patient, is one of the key points that can attract them to buy. Excessive heat sealing strength will make opening a product package become It is very difficult or can't be opened in the right way. If the heat sealing strength is too small, it will obviously cause insufficient protection, and the product will fall from the inner packaging system and will not be adequately protected in actual circulation.
Summarizing years of experience and inkjet printing of packaging heat sealing strength data of many products, the author believes that the heat sealing strength is generally controlled at 0.80-8.00N/15mm, which is reasonable (except in extreme cases). Below this interval, it will cause insufficient protection; In this section, paper sheets will be published on the web of tearing and confetti problems, which will not meet the requirements of clean tearing. Although film and Tyvek materials will not have tearing problems, it takes a little effort to open them. It is not conducive to easy opening.
3. Requirements for convenience/clean opening
Convenience / clean opening requirements are a more subjective and difficult requirement, saying that it is subjective because there is no quantitative indicator at the time of judgment can refer to the screen, and the standard for opening the inner packaging system can not be qualitatively given until now. Out, so there will be different people who open the packaging of the same batch of products and come to different conclusions.
Convenience / clean opening requirements have high requirements on the material of the packaging system itself and the heat sealing between different materials, so the mechanical strength of the material should be qualified, and the heat sealing strength of the heat sealing place should not be too high, which is related in the previous Postpress equipment is mentioned in the description of the packaging protection requirements and will not be described here.
It must also be pointed out that the convenience/clean opening is a packaging performance requirement that is highly valued by the medical device sterilization packaging industry in developed countries, especially after the official publication of ISO11607-2006 in April 2006. However, this requirement has been neglected in the domestic medical device sterilization packaging industry. In domestic industry regulations, I have only heard of this requirement at some technical seminars hosted by DuPont.
DuPont's Tyvek materials are a good choice for solving the convenience/cleanness requirements, given the cost considerations. Of course, this assumption is not practical, because no manufacturing industry will consider material costs. The cost issue is particularly important in China, where packaging is printed in a country where low-end manufacturing costs are the main means of competition. However, it must be pointed out that the use of paper packaging is difficult to completely solve the problem of clean opening, especially when the length and width of the inner packaging system exceeds a certain limit. With the introduction of new standards, European and American customers are increasingly demanding in this regard, and domestic manufacturers should pay attention to this.
Functional requirements and experimental methods for packaging systems
Next, talk about the performance test requirements for the outer packaging system. The outer packaging system is a more typical protective packaging system manuscript, and more specifically, the cushioning transport packaging system, which protects the inner packaging system.
Among the components of the outer packaging system, the most important are corrugated boxes and various industrial cardboard boxes, or less common metal and wooden containers, such as metal and wooden containers, supplemented by various typical cushioning packaging materials, such as air cushion film, Various foam plastics and paper cushioning materials. In most cases, this outer packaging system is very simple. It is a single corrugated box of reasonable strength designed by reasonable calculation, or a little more complicated. In this outer packaging, a medium packaging and packaging machine, usually micro corrugated paper, is added. Box or ordinary cardboard box, etc. In disposable medical device products, it is not uncommon to use wooden boxes or metal boxes and add some necessary cushioning materials. This situation often occurs in the outer packaging of large electrical and electronic devices. At this point they usually do not require sterilization, that is, they are only scanned as a buffer transport package, which is a very different package from disposable medical device sterilization packaging.
So how do you verify the effectiveness of this packaging system? That is to say, how to use the experimental method to judge the outer packaging design is in line with the predetermined goal, which can ensure that the inner packaging system of the product can withstand the test of various circulating storage environmental conditions until they are safely delivered to the final consumer. Considering the complexity of the circulation environment, engineers and technicians of small companies are unable to acquire and design simulation simulation circulation environment to test whether the product packaging system can withstand the test of circulation, so it is often referred to the relevant simulation circulation. Transporting the experimental protocol for dairy packaging, the two more authoritative experimental solutions to be mentioned here are the ISTA series and ASTM D4169.
The ISTA series of transport packaging protocols are written and made available to the industry by the ISTA organization (International Safe Transport Association). The ISTA members include companies that need to travel frequently to transport a variety of very challenging products, such as FedEx. Express logistics companies such as UPS and large consumer electronics companies such as HP use their accumulated transportation experience in various transportation environments for many years and accumulated information on various harmful factors such as shocks and vibrations in the transportation and circulation links. The compilation of these experimental protocols for the ISTA has accumulated a good amount of information. Fuji Xerox, and therefore these experimental programs are quite authoritative. Of course, if some large companies are very strong in the field of engineering technology, and their products are more special in circulation and transportation, they usually design their own simulation circulation schemes suitable for their own products.
At present, ISTA has a total of 7 series of standards. Each series of standards has a number of specific sub-programs under the dairy package. Therefore, ISTA has dozens of different experimental programs to deal with the transportation experiments of different product packaging systems. For the disposable medical device packaging system, because it is relatively simple, it is generally referred to the three series of 1, 2 and 3 in the ISTA, among which the 1 series generally simulates domestic transportation, and the 3 series simulates international transportation of other packaging, and The environment of the 3 series simulation is slightly more demanding, so the 2 series is the most frequently cited experimental solution in international transportation. Metal packaging
The simplest 2A experimental scheme is an example. The whole experimental procedure consists of the following specific steps: 1 normal temperature adjustment; 2 control environment adjustment; 3 full-box compression test; 4 fixed time and frequency vibration; 51 points 3 楞There are a total of 10 drop impacts on 6 sides, in which the drop height has a specific method to determine; 6 fixed time and frequency vibration. The specific experimental parameters for each step are not given here, because the experimental parameters need to be based on the characteristics of the packaging system of the specific product and the expected circulation environment, such as the vibration duration is calculated.
At present, there are not many laboratories that can carry out strict ISTA series experiments in China, and there are very few transportation experiments on medical device packaging systems. Of course, this transportation experiment is not indispensable because it is extinguished according to medical devices. A basic principle of bacterial packaging is that it can only be used for transportation experiments in the worst case (ie Worst Case State Book Review, which can be the heaviest, hardest, and most irregular size structure). If it passes, it can be inferred that the outer packaging system of those products that are better than it can pass this transport experiment, thus reducing the number of experiments and thus reducing the cost of the experiment and shortening the project cycle, thus accumulating historical experience and The experimental data will be very instructive for future project development. However, in the early stage of a new project development, it is necessary to conduct a complete packaging system transportation experiment on the worst-case products to determine whether the outer packaging system can be used in the worst circulation storage environment for the inner packaging system or the product itself. Provide adequate and necessary protection.
Exploring, accumulating, and advancing medical packaging
Humans have taken measures to prevent infection from the first surgical operation in ancient Babylon four thousand years ago. However, data from the European Union in the late 19th century also showed that 60% of cases of direct death due to postoperative infection. According to the Centers for Disease Control and Prevention (CDC), there are approximately two million patients affected by iatrogenic infections in acute medical institutions across the country, and the annual medical expenses for these patients are approximately $4.5 billion. Today, human beings have paid a huge price for this, and gradually understand the truth - the channels for possible infections should be eliminated and the chance of infection reduced. The study also showed that "one-third of iatrogenic infections can be prevented by the organization's infection control program." In fact, for the patients, the hospital is a "white sacred place" for giving health and regaining life. When the patient enters the hospital, he also entrusts health and life to the hospital, and the medical equipment, medicines, dressings and the whole environment used by the hospital. Responsibility should be shared by all relevant departments, so it is necessary to eliminate all possible infections and reduce the possibility of infection, but also by related enterprises, including raw material production, preformed packaging, components of equipment products, and end-use departments. Together, they will form a complete, safe and effective product to promote the advancement of the sterile medical device industry in the medical safety alert system.
(II) Material and sterilization compatibility In the introduction of ISO 11607-1; 2006, the importance of medical device packaging design is expressed as: “The process of designing and developing the final sterilization medical device packaging is a complicated and arduous process. jobs". And the complexity of the packaging design is described as: "The final medical device packaging design goal is that the material can be adapted to sterilization, sterilization can protect the product, should be kept sterile when used." It is thus stated that packaging that meets the requirements of sterility is an inevitable choice for medical equipment manufacturers. The concept of adapting to sterilization technology is the highest guarantee for medical equipment products. Otherwise the packaged product may become a deadly weapon. At present, the sterilization method basically adopts gas ethylene oxide and formalin, high temperature steam wet and dry, irradiated gamma rays, and low temperature plasma sterilization. The product itself is selective for sterilization and the expiration date of use, and the adaptation to sterilization methods, such as biological products can not be high temperature, PP plastics avoid irradiation, liquid product gas can not penetrate, plasma low temperature sterilization Can not use plant fiber, all kinds of ?., these require the design of packaging, at the same time, first determine the sterilization method, and the sterilization method should be based on the appropriate materials, while considering the preservation requirements, combined with the production process, Achieve the desired sterilization effect and the purpose of sterile preservation and barrier protection.
The selection of suitable materials for the final medical device packaging system is influenced by the interrelationship shown in the figure below. The relationship between the materials selected for the final sterilization medical device packaging system (3) The generation and application of the rubber coating process ensures that the requirement for aseptic opening is stripping and no fiber shedding. To solve this requirement, the initial intervention is the application of glue and glue. The main raw material is hot melt adhesive. When the hot melt adhesive is coated on the paper surface, the air permeability is affected. Therefore, the mesh coating process is used to solve the ventilation requirement. The hot-melt adhesive coating of the grid fully exploits its advantages due to the peeling of no paper dust, the processing temperature and the pressure of the bonding, and the compatibility with the bonding materials, and the requirements for opening the medical packaging: "hot and torn Open, no fiber, has a profound impact. Due to the continuous improvement of the requirements for sterilization packaging, the shortage of hot melt adhesive coating is manifested by:
1 . Hot melt adhesives are sensitive to temperature. At the temperature of ethylene oxide sterilization, the strength of the heat may be weakened by the temperature to cause breakage and sterilization failure.
2 . During transportation or storage, due to temperature, it may cause changes in the bonding strength, resulting in packet breakage and sterilization failure.
3 . Adhesion may occur with certain contents due to temperature.
4 . The hot melt adhesive coating process uses a non-alcoholic solvent to reduce the safety factor.
5 . With the multiple entry and exit of the sterilizing gas, the possibility that the residual collagen is carried into the bag is not excluded.
6 . The packaging of hot melt adhesives is not suitable for high temperature sterilization. The hot melt adhesive coating process opens up a channel for stripping paperless for aseptic packaging. As the requirements for sterilization packaging continue to increase, these deficiencies continue to be compensated and improved in the application. The appearance of the border coating process has made up for the shortcomings of the hot melt adhesive coating process to effectively ensure and solve the problems of air permeability, residue, breakage and adhesion.
However, due to the processing technology and cost, the frame coating process is limited to the conditions of mass production, and cannot be fully promoted, or more products cannot be satisfied. The water-soluble gel coat thus reveals a head angle. The solvent used in the water-based adhesive is alcohol or water, non-toxic, and does not reduce the peeling strength of the hot stamping due to temperature. It is safer for the product and makes up for the deficiency of the hot-melt adhesive coating. The crystallized state of the coating after curing does not significantly impede the gas permeability and can also be used for the border coating. It has been gradually adopted by the product manufacturer and accepted by the user. The processing technology of the water-soluble adhesive coating is very tolerant, and can be gravure, letterpress, Spray and anilox roll direct coating processing. The above two kinds of coating processes have relatively reasonable and dominate the position of sterilization packaging. At present, the intervention of peeling paperless medical paper without direct glueing can further exceed the performance of the above coating process. According to the description, the glue coating process is produced by the requirement of peeling off paperless, and thus, is not coated. The application of glue directly to the medical paper is to omit the coating process, reduce the production cost, ensure the safety of the product, and provide a wider space in the material selection of the sterilization package.
(4) Ensuring that the aseptic design concept is the subject of safety in the near-demanding design concept, effective sterilization establishment, successful post-sterilization protection and safe use are supported by the concept of ensuring aseptic design.
In the above report, we try our best to give a description and introduction. With a little knowledge and a little experience in learning, the topic we are discussing with you is based on our understanding of sterilization packaging. Because we started late, the foundation is weak. The purpose is to move forward together. In fact, whether in the United States, the European Union or Japan and other developed countries, there are strict management and requirements for the packaging of medical devices. In order to improve the quality of medical devices in China, the State Food and Drug Administration has proposed a management plan for the implementation of GMP for medical device production, which will certainly impose higher requirements on medical packaging to ensure the improvement of product quality of medical device manufacturers. Accelerate the process of integrating medical device manufacturing enterprises into the international market competition.