Can the shelf life be extrapolated beyond the real-time stability data?

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Accepted Answer

SFDA: “However, a provisional shelf-life of 24 months may be established provided the following conditions are satisfied:” (GCC v3.3 (archived) · 3.2.8 Evaluation) “The API is known to be stable (not easily degradable).” (GCC v3.3 (archived) · 3.2.8 Evaluation) “Supporting data indicate that similar formulations have been assigned a shelf-life of 24 months or more.” (GCC v3.3 (archived) · 3.2.8 Evaluation) “Stability studies, as outlined above in section 3.1.11, have been performed and no significant changes have been observed.” (GCC v3.3 (archived) · 3.2.8 Evaluation) “The manufacturer will continue to conduct long-term studies until the proposed shelf-life has been covered, and the results obtained will be submitted to the national regulatory authority.” (GCC v3.3 (archived) · 3.2.8 Evaluation) EU: “Extrapolation to extend the retest period or shelf life beyond the period covered by long-term data can be proposed in the application, particularly if no significant change is observed at the accelerated condition.” (ICH Q1E · 2.3 Extrapolation) “Extrapolation of the retest period or shelf life beyond the period covered by long-term data can be proposed. The proposed retest period or shelf life can be up to twice, but should not be more than 12 months beyond, the period covered by long-term data.” (ICH Q1E · 2.4.1.1) “Where significant change occurs at the intermediate condition, the proposed retest period or shelf life should not exceed the period covered by long-term data.” (ICH Q1E · 2.4.2.2) US FDA: “Extrapolation of the retest period or shelf life beyond the period covered by long-term data can be proposed.  The proposed retest period or shelf life can be up to twice as long as, but should not be more than 12 months beyond, the period covered by long-term data.” (FDA Q1E · 2.4.1.1) “Limited extrapolation of the real time data from the long-term storage condition beyond the observed range to extend the shelf life can be undertaken at approval time if justified.” (FDA Q1A(R2) · 2.2.9) “FDA will grant a shelf life period of two times the available long-term data at the time of approval (up to 24 months) following the recommendation of the ICH Q1E Evaluation of Stability Data (ICH Q1E) guidance,7 provided the submitted data are satisfactory, and data evaluation and appropriate commitments are provided in accordance with ICH Q1E.” (FDA ANDA stability Q&A 2014 · II.A, A5(i,ii)) WHO: “Limited extrapolation of the long-term data from the long-term storage condition beyond the observed range to extend the shelf life can be undertaken, if justified. This justification should be based on what is known about the mechanisms of degradation, the results of testing under accelerated conditions, the goodness of fit of any mathematical model, batch size and the existence of supporting stability data. However, this extrapolation assumes that the same degradation relationship will continue to apply beyond the observed data (refer to ICH Q1E).” (WHO TRS 1010 Annex 10 · 2.2.9 Evaluation)

Can the shelf life be extrapolated beyond the real-time stability data?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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