Katarzyna Kruk, Katarzyna Winnicka

„Drug expiration date” versus „expiration date for use” of medicinal products – practical advice
2024-06-26

Study subject. The subject of the study includes issues and regulations concerning the shelf life of medicinal products, the shelf life of multi-dose preparations after the first opening, and stability studies.

Research Objective. The purpose of this study is to introduce the issue of drug shelf life as well as the methodology and purpose of conducting “in-use” stability studies, and to analyze the legal requirements concerning the information on the expiration date of medicinal products and the expiration date after first opening. It is necessary to distinguish between the concepts “expiration date” and “expiration date for use” of medicinal products.

Material and methods. A review of literature (scientific articles, international standards, Polish legal regulations, characteristics of medicinal products, and patient leaflets) on the shelf life of medicinal products and expiration dates after the first opening of multi-dose or single-dose reservoirs upon drug reconstitution was performed.

Results. The drug form should provide appropriate release and activity of the drug, which is documented in the drug specification. The drug's manufacturer is obliged to guarantee the proper content of the medical substance in the product and to specify the expiration date. Medicinal substances and excipients might interact with each other and degrade, resulting in the formation of toxic products. They might also change or lose their pharmacological properties due to physical, chemical, and biological factors. The expiration date is required by Polish legislation to be stated on the drug packaging. In order to establish the date, a number of analytical tests for stability must be carried out. The expiration date for use refers to the time during which the product might be utlized after its first opening, repackaging, or reconstitution. It usually applies to multi-dose drug forms, mostly liquid or semi-solid preparations, both proprietary products and those prepared in pharmacies individually on the basis of a prescription. The use of such formulations involves multiple instances of taking a dose from the drug packaging, which entails the risk of contamination and, consequently, might significantly affect the quality of the drug. With regard to these types of preparations, “in-use” tests are required, namely tests simulating multiple dose withdrawals from a drug container by a patient. The research methodology related to drug stability testing is regulated by the International Conference for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The test results enable determining the shelf life of a multi-dose preparation.

Conclusions. The safety and effectiveness of drug therapy are key aspects of the treatment process. It is essential for a patient to cooperate with their doctor and pharmacist and to adhere to the treatment regiment, thus the quality of the drug utilized is also of the utmost importance. The expiration date for use after the first opening of a multi-dose preparation is crucial in the context of the shelf life of an opened product. Performing “in-use” stability studies which include multiple doses withdrawals from the drug container is required in the registration process of medicinal products, however, including the information about the expiration date for use in the product characteristics is not mandatory. The expiration date is a relevant issue especially in the case of preparations for internal use, however, it is not always indicated on the product packaging, in the product characteristics or patient leaflet. This is true for both over-the-counter (OTC) and prescription (Rp.) drugs. The lack of information on the shelf life of a drug in a multi-dose packaging after it has been opened for the first time might lead to patients unknowingly using the drug after the expiration date for use, when the stability of the product is no longer assured by the manufacturer. As a result, the safety and efficacy of the therapy might be significantly affected.

Keywords: expiration date, expiration date for use, “in-use” studies, stability.

© Farm Pol, 2024, 80(2): 121–132