Guidelines for Stability Research of Plastic and Rubber Pharmaceutical Packaging Materials (1)

The purpose of the research on the stability of pharmaceutical packaging materials is to investigate the time-varying laws of packaging materials and containers (hereinafter referred to as pharmaceutical packaging materials) that are in direct contact with drugs under the specified temperature and humidity environment. The establishment of deadlines for use provides a scientific basis. The stability study of pharmaceutical packaging materials is generally carried out by pharmaceutical packaging material manufacturers to confirm the quality stability period of their products under specified storage conditions. Pharmaceutical manufacturers shall store, transport and use pharmaceutical packaging materials under specified conditions. The quality stability period of the pharmaceutical packaging material refers to the stable period of the pharmaceutical packaging material from the production date of the pharmaceutical packaging material to the validity period of the drug. The period is the time for which the quality characteristics of the pharmaceutical packaging are expected to be guaranteed under the specified environmental conditions or specified storage conditions.

This guideline is applicable to the research on the self-stability of pharmaceutical packaging materials made of plastic, rubber and other polymer materials. This guideline is formulated based on the quality standards and process of the drug packaging materials used in the approved drugs in my country. Other special materials and process products should consider the applicability of this guideline.

1. Stability study

Pharmaceutical packaging materials can be divided into various categories (general rules) according to the material and the degree of risk. In terms of materials, some products used for pharmaceutical packaging have problems of aging or stability due to the influence of environmental factors due to material reasons, and have received extensive attention at home and abroad, especially plastic and rubber products that are widely used in the field of pharmaceutical packaging. . And this type of polymer products are the main raw materials or components used in most high-risk pharmaceutical packaging materials. On the one hand, the stability of pharmaceutical packaging materials will cause the pharmaceutical packaging materials to lose their protection and functionality due to stability reasons, thus indirectly affecting the safety of drugs in clinical use. Risk of change in extractables and potential leachables. Therefore, the research on the stability of pharmaceutical packaging materials not only helps to provide a basis for pharmaceutical packaging material manufacturers to carry out reasonable formula, processing technology design, quality stability period verification and confirmation, but also provides a basis for pharmaceutical packaging material manufacturers to conduct drug packaging according to the characteristics of preparations. The selection and rational use of materials play an important guiding role.

1.1 Basic requirements

For the research on the stability of pharmaceutical packaging materials, we should first consult the literature related to the materials and processes of pharmaceutical packaging materials, and through literature research, we should understand the impact of environmental conditions such as temperature, humidity, light, and oxidation on the materials and finished products. In general, the basic requirements for the stability study of pharmaceutical packaging materials include the following aspects:

1.1.1 The stability study includes influence factor study, accelerated test and long-term test. If it is necessary to carry out the influence factor test, it should be carried out with at least one batch (including one batch) of samples. Accelerated test and long-term test should be carried out with at least 3 batches (including 3 batches) of samples.

1.1.2 Samples for stability studies should be representative. Stability studies should usually use samples from stable production lines and large-scale production. The product formulation, formulation amount, production process, product specifications and packaging should be consistent with those of commercial production. The quality standards of the samples should be the same as those used for mass production.

1.1.3 The data provided by the long-term test is the final basis for establishing the quality stability period of the drug packaging material. Long-term trials must be conducted at the end of shelf life of the drug product intended for packaging.

1.1.4 For the packaging container system, the stability period of the packaging container system shall be confirmed based on the comprehensive consideration of the stability period of each component. If there are differences in the stability period of each packaging component, usually, the one with the shortest stability period should be used as the stability period of the packaging container system.

1.2 Evaluation Considerations

1.2.1 Research on Influencing Factors

The main purpose of this research is to explore the factors affecting the stability of pharmaceutical packaging materials and possible degradation pathways, and to provide scientific basis for the processing, packaging and storage conditions of pharmaceutical packaging materials. The factors considered in the study of influencing factors generally include temperature, humidity, light, oxidation and so on. For plastics and rubber products, there have been a large number of domestic and foreign reports that affect their stability, especially the guideline standards for storage conditions of rubber or plastic products that have been published at home and abroad. Factors provide a useful basis for literature research. On the basis of literature research, if pharmaceutical packaging materials need to be tested for influencing factors, at least one batch of samples (including one batch) can be used, referring to the research models of influencing factors of plastic or rubber materials or products published at home and abroad or authoritative literature research models. experimenting.

1.2.2 Accelerated test

This test is carried out under accelerated conditions, the purpose is to evaluate the stability of the pharmaceutical packaging materials by accelerating the aging of the pharmaceutical packaging materials, and provide necessary conditions for the design, use, packaging, transportation, storage and establishment of the stability period of the pharmaceutical packaging materials. material. The test product requires 3 batches, packaged according to the market, and placed at the selected temperature and humidity for the required accelerated aging time. The equipment used in the accelerated aging test should be able to control the temperature ±2°C, relative humidity ±5%, and be able to monitor and automatically record the real temperature and humidity in real time.

The accelerated aging factor method is a simple and rigorous technique to study the long-term effects of pharmaceutical packaging materials. The accelerated test should be carried out at the same time as the long-term test. See Appendix 1 for details on accelerated aging principles and parameter determination.

1.2.3. Long-term test

The long-term test is carried out under the actual storage conditions close to the pharmaceutical packaging materials, and its purpose is to provide a real basis for the accelerated test research results and to provide support for the formulation of the quality stability period of the pharmaceutical packaging materials.

Three batches of the test product, commercially available packaging, are placed under the conditions of a temperature of 25 °C ± 2 ° C and a relative humidity of 60% ± 10% to the desired stable period (eg, not less than 3 years). Sampling is carried out every 6 months (including zero time), and the inspection items are mainly inspected according to the stability. The determination results are comprehensively evaluated using the proposed quality standards or guidelines, and the approved or proposed quality standards for pharmaceutical packaging materials to determine the quality stability period of pharmaceutical packaging materials.

For pharmaceutical packaging materials intended to be used for packaging refrigerated medicines, the long-term test conditions should be placed at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10% (for example, at least 1 year), and then at 5°C ± 2°C. 3°C for 2 years. Test according to the above time requirements to formulate the stability period for refrigerated pharmaceutical packaging materials.

For pharmaceutical packaging materials intended to be used for packaging frozen medicines, the long-term test conditions should be placed at a temperature of 25°C±2°C and a relative humidity of 60%±10% (for example, for at least 1 year), and then at -20°C. ±5℃ for 2 years. Test according to the above time requirements to formulate the stability period for frozen pharmaceutical packaging materials.

For pharmaceutical packaging materials that are expected to be packaged and stored at other temperatures, the long-term test conditions should be placed under the conditions of a temperature of 25 °C ± 2 ° C and a relative humidity of 60% ± 10% (for example, at least 1 year), and the corresponding drug should be subsequently stored. 2 years at storage temperature. Test according to the above time requirements to establish a stable period for drug packaging under other storage conditions.

Note: If the shelf life of the drug is more than 2 years in refrigeration, freezing or other temperature storage, it should be stored in refrigeration, freezing or other conditions for the required time.

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