Analysis on Quality Standards and Supervision of Drug Packaging Materials

Foreword

Some industry insiders predict that the demand for international pharmaceutical packaging is growing at an average annual rate of 6.3%, which means that the total amount in 2009 may exceed 30 billion US dollars, which is a huge market easy. With the rapid development of social economy, the pharmaceutical packaging industry has become more and more mature. The diversification of drug types has also brought diversification into the form of pharmaceutical packaging and accelerated the development of the pharmaceutical packaging industry. Pharmaceutical packaging is the packaging of special commodities. Since the pharmaceuticals are processed and molded, they play an important role in protecting the safety and effectiveness of drugs and facilitating transportation, storage, sales, and use. The drug packaging material is used for packaging special commodities--drugs, so it belongs to the category of special packaging and has all the attributes and uniqueness of packaging.

However, compared with foreign countries, the production level of pharmaceutical packaging materials in China is apparently still in the primary stage: lack of accuracy in drug dosage, lack of children's packaging; drug packaging is rough and inconvenient to access; lack of packaging for toxic, hemp, and psychotropic drugs Safety; The minimum package size of the drug is too large to meet the needs of clinical use. Hospitals often need to open the inner packaging before the use of sub-zero problems and other common problems, making the overall value of drugs greatly reduced.

Some experts pointed out that currently 65% ​​of China's pharmaceutical packaging level still lags behind the world average level in the 1980s. The quality of packaging materials is very low, and its contribution to the pharmaceutical industry is also very weak. In developed countries, packaging accounts for 30% of the drug value, while in China, this value is 10% lower. In addition, there are still some outstanding problems, such as the urgent need to improve the compatibility test between new drug preparations and new packaging materials. The huge gap between the two makes the industry likely to become the growth potential of China's pharmaceutical economy in the next few years.

Classification of drug packaging

According to the use mode: The drug packaging material can be used directly according to the usage mode (such as solid pharmaceutical polyolefin plastic bottle, etc.), after cleaning (such as ampoules, etc.), indirectly or indirectly (such as medicinal glass tube) , antibiotic bottle aluminum cover, etc.) and so on.

According to the material composition:

(1) Plastics (thermoplastic, thermosetting polymeric substrates);

(2) Rubber (thermosetting polymer compound);

(3) Glass (usually silica);

(4) Metals (commonly used aluminum);

(5) Composite (aluminum-plastic composite cover, composite film for pharmaceutical packaging);

According to shape: drug packaging materials are divided into containers (plastic containers for eye drops, etc.), tablets/bags (pharmaceutical PVC hard films, pharmaceutical packaging composite bags, etc.), stoppers (butyl rubber infusion stoppers) Etc., cover (oral liquid bottle tearing aluminum cover, etc.).

Packaging material quality requirements

In order to confirm that pharmaceutical packaging materials can be used for packaging medicines, it is necessary to carry out quality control on these materials. According to the particularity of the use of packaging materials, these materials should have the following characteristics; they can protect the drugs from being stored and used in the environment. The impact of the drug, to maintain the original properties of the drug: drug packaging material itself in the storage and use of the nature of the process should have a certain degree of stability; drug packaging material in the packaging of drugs, can not pollute the drug production environment; drug packaging materials may not be carried during use The substances that have no effect on the packaged drugs cannot be eliminated; the drug packaging materials and the packaged drugs cannot react in a chemical or biological sense. Therefore, the quality standard of the drug packaging material needs to prove that the material has the above characteristics and is effectively controlled. At present, the quality standards for pharmaceutical packaging materials at home and abroad are similar to several systems.

(1) Pharmacopoeia system; The Pharmacopoeia appendix of each developed country lists the technical requirements (mainly materials) of drug packaging materials.

(2) ISO system; according to the shape of the standard (aluminum cover, glass infusion bottle).

(3) National industrial standards system; has gradually transformed into ISO standards.

(4) Domestic drug packaging material standard system; in the same form as IS0 standard, safety items are slightly less than those of the advanced national pharmacopoeia.

At present, the quality standard system for pharmaceutical packaging materials at home and abroad is as follows.

Foreign Pharmacopoeia: (1) safety items and; abnormal toxicity, hemolysis, cytotoxicity, chemical dissolution, arsenic in glass products, vinyl chloride in polyvinyl chloride, additives in plastics, etc.; (2) effectiveness items; Confirmation of material, amount of water vapor permeation (spillage), sealability, and torque.

ISO standard; basically covers all the characteristics of the drug packaging material, but lacks material confirmation items, and also lacks other substances (number of bacteria) that can not be eliminated during use and the quality level required for supervision and spot checks.

Domestic standards; The current major projects and formats are similar to the ISO standards, and some of the technical parameters are slightly inferior. There are also safety items such as "microbial count" and "abnormal toxicity".

Packaging material quality standards

According to the characteristics of the drug packaging materials, the standards for drug packaging materials should include the following items:

(1) Confirmation (differentiation) of the material; mainly confirms the characteristics of the material. This is because special inspection items need to be set according to different materials, such as polyvinyl chloride material should be checked for oxyethylene monomer, polyethylene terephthalate (PET) material should check the residual amount of acetaldehyde. The second is to prevent doping. In addition, the user must be able to confirm the consistency of the source of the material.

(2) Inspection items for materials and containers

Check the chemical properties of the material: First check the amount of material extracted in various solvents, mainly check harmful substances, low molecular weight substances, unreacted substances, substances brought into production, additives, etc. The commonly used solvents are water, ethanol, n-hexane. Commonly tested items include reducing substances, heavy metals, evaporation residues, pH, UV absorbance and so on. Then check specific materials in the material, such as vinyl chloride monomer in the PVC hard sheet, the amount of the polypropylene infusion bottle catalyst, and the amount of the solvent in the composite family. Finally, the additive during the processing of the material was examined, such as the sulphide in the rubber, the plasticizer in the polyvinyl chloride film (dioctyl phthalate), and the amount of the antioxidant in the polypropylene infusion bottle.

Check the performance of materials and containers: The container should be inspected for tightness, water vapor transmission, anti-dropping capacity, and dripping volume (if the container has a quantitative function); the sheet must be checked for water vapor transmission, tensile strength, and elongation. If the material and container are to be used in combination, the heat seal strength, torsion, and the size of the combined part need to be checked.

(3) Biosafety inspection items for materials and containers

Number of microorganisms: The amount of each type of microorganism was measured based on the type of the material and the container used.

Safety: According to the dosage form of the material and the container, it is necessary to select the items such as abnormal toxicity, hemolytic cytotoxicity, eye irritation, and bacterial endotoxin.

The blind spot for pharmaceutical packaging supervision

Drug packs are packaging materials and containers that come into direct contact with the drug. The quality of the drug packaging material has a great influence on the quality of the drug. Because the drug packaging material may bring bacteria and other microorganisms, some harmful substances in the packaging material may be dissolved by the drug and cause drug pollution; at the same time, some components of the drug may be During the process of packaging and storing, it is absorbed by the packaging material or reacts with the packaging material, which directly affects the quality of the medicine or the dosage of the medicine.

At present, an important issue for pharmaceutical packaging that is currently well received by the United States is how to reduce accidents caused by children's exposure to drugs or misuse of drugs. According to statistics, 30% of the deaths of leopard children in multiple countries are due to misuse of drugs. Some governments have also enacted legislation to control all blister-packed medicines because the packaging of these medicines is similar to that of many candies. However, compared with pharmaceutical quality management in our country, the quality management of pharmaceutical packaging material has lagged behind, and even a regulatory “blind area” has emerged.

Existing problems: Mainly concentrated in the following aspects.

(1) The overall quality of the staff of pharmaceutical packaging materials companies is not high, especially the quality and capability of inspection personnel is not high;

(2) The hardware facilities are not perfect, and the detection equipment cannot keep up with the requirements;

(3) Production quality management is not standardized.

Regulatory countermeasures

(1) Improving laws and regulations concerning the supervision and management of pharmaceutical packaging materials: It is recommended that more rigorous supervision and management measures be formulated for the supervision of the production and use of pharmaceutical packaging materials, so that daily supervision will be scientific, standardized, and procedural, so as to promote the quality of the company. Improved management.

(2) As soon as possible, the GMP certification system for pharmaceutical packaging materials production enterprises is introduced: It is recommended that GMP certification be carried out on pharmaceutical packaging material production companies, and the quality of the pharmaceutical packaging materials must be guaranteed at the source. The implementation of GMP certification for drug packaging companies will play a catalytic role in the normal competition and healthy development of the drug packaging industry.

(3) Strengthen the construction of testing institutions and testing capabilities: It is recommended that the Shanghai Municipal Institute for Drug Control and Inspection should improve inspection items for drug packaging materials, such as physical testing of drug packaging materials. Not only meet regulatory requirements, but also can solve the problem that drug packaging materials cannot be fully examined in one region, and it can also achieve resource sharing in a region. Require companies to strengthen the general detection equipment, strengthen the detection capabilities, the limited conditions can not do the inspection such as infrared, abnormal toxicity test can be commissioned by the drug packaging material testing agencies. Units that use drug packaging materials must also specify the inspection items that must be done to get the quality of good drug packaging materials.

(4) Intensify training: For the current situation where the professional quality management personnel and inspectors of pharmaceutical packaging companies are weak in technical strength, the State Bureau and the Provincial Bureau of the People's Republic of China can compile books on drug packaging materials and organize training and study to strengthen the drug package. The training of materials standards, inspections, compatibility testing of drug packaging materials and drugs, etc. improves the quality awareness, standard awareness and testing level of pharmaceutical packaging materials companies. At the same time, it is required that the quality management and inspection personnel of pharmaceutical packaging materials must achieve the corresponding professional and technical capabilities and implement the job access system.

summary

In order to strengthen the management of pharmaceutical packaging materials and containers, the State Drug Administration passed and promulgated the "Measures for the Management of Packaging Materials and Containers Directly in Contact with Drugs" on June 18, 2004, and specified the types of packaging materials for registration management. , And carry out spot checks on the production and distribution of pharmaceutical packaging materials. However, compared with strict management of GMP for pharmaceutical production, packaging companies also appear to be more relaxed. The above proposal is only one of the words. If it can benefit domestic pharmaceutical packaging supervision, I believe that it will be a lot of progress for the entire industry.