Shelf Life Test (Medicines)

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The shelf life test (also: stability test) of a drug is used to experimentally determine its shelf life. It is checked whether the drug complies with the specified specifications in terms of microbiological , physical and chemical properties over the storage period. For example, the content of the medicinal substance (in the case of combination medicinal products: the medicinal substances) must not fall below a certain value (usually: 90%). Decomposition products may also only arise in very small quantities within defined limits. It is also particularly important that the release of the medicinal substance from the pharmaceutical form does not change adversely during storage. The expiry date , by which a drug must be used at the latest, is derived from the results of the shelf life tests.

For the storage of the drugs for stability testing, the storage conditions, i.e. H. Temperature and relative humidity , selected depending on the requirements specified by the climatic zone (s).

The procedure for carrying out shelf life tests is precisely specified for drug manufacturers by the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH).

execution

A prerequisite for performing and interpreting the shelf life tests is the establishment of a drug specification. It defines the quality characteristics of a drug in terms of quality and quantity. This includes a minimum value for the drug content as well as the naming of any decomposition products that may occur with upper limits. Physical characteristics that are relevant to stability, such as the release of the drug, and possibly other parameters such as pH value (in the case of solutions), water content (e.g. in the case of solid drug forms) or discoloration, are also limited.

The pharmaceutical manufacturer must prove that the analytical methods used are valid , i.e. specific and accurate.

With regard to storage, a distinction is made between long-term tests and accelerated shelf life tests.

Long-term tests

The finished medicinal products are stored in their final packaging under climatic conditions in climatic cabinets or climatic rooms, depending on the consumer region, and are regularly examined at prescribed intervals. The test lasts a maximum of 5 years.

climate zone description Storage condition
I. Moderate 21 ° C / 45% RH
II Subtropical and Mediterranean 25 ° C / 60% RH
III Hot and dry 30 ° C / 35% RH
IVa Hot and wet 30 ° C / 65% RH
IVb Hot and very humid 30 ° C / 75% rh

RH = relative humidity

Accelerated durability tests

These serve for the rapid, preliminary characterization of the stability through storage at higher temperatures.

The finished medicinal products are stored in their final packaging at 40 ° C and 75% relative humidity in climatic cabinets and are regularly examined at prescribed intervals, for a maximum of six months.

In the early pharmaceutical development, the performance of kinetic studies can already provide indications of the stability curve. One differentiates:

  • isothermal tests: storage of the drug at 40, 50, 60 and 70 ° C, for example. Determination of the respective reaction rate constant of the drug decomposition by analyzing the decrease in content. The measurement results are then converted to 21 ° C using the Arrhenius equation .
  • Allothermal test : linear or logarithmic heating of the drug, regular periodic analysis of the decrease in content due to the (partial) disintegration of the drug and calculation of the reaction kinetic data using complex mathematical equations.

Requirements of the drug authorities

In the application for approval, drug manufacturers must specify a shelf life from which the expiry date to be specified for the drug is determined. The shelf life indicates how long the drug specification is adhered to. The stability data must be collected in accordance with the ICH quality guidelines. Usually data from three batches over a storage period of at least twelve months under long-term conditions must be submitted, which can be supplemented by data from short-term tests (= accelerated stability test). Data from accelerated stability tests alone is not sufficient.

literature

Web links

  • Quality guidelines of the ICH , International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (English)

Individual evidence

  1. ^ WHO Technical Report Series, No. 953 (2009). Annex 2: Stability testing of active pharmaceutical ingredients and finished pharmaceutical products . Appendix 1: Long-term stability testing conditions, Table 2. ( PDF )
  2. ^ WHO Technical Report Series, No. 953 (2009). Annex 2: Stability testing of active pharmaceutical ingredients and finished pharmaceutical products . Appendix 1: Long-term stability testing conditions, Table 1