What stability data is required for the active substance (API)?

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SFDA: “Data from stability studies on at least three primary batches of the API should normally be provided. The batches should be manufactured to a minimum of pilot scale by the same synthesis route as production batches, and using a method of manufacture and procedure that simulates the final process to be used for production batches.” (GCC v3.3 (archived) · 3.1.3 Selection of batches) “For existing active substances that are known to be stable, data from at least two primary batches should be provided.” (GCC v3.3 (archived) · 3.1.3 Selection of batches) “The long-term testing should normally take place over a minimum of 12 months for the number of batches specified in section 3.1.3 at the time of submission, and should be continued for a period of time sufficient to cover the proposed re-test period or shelf-life. For existing substances that are known to be stable, data covering a minimum of six months may be submitted.” (GCC v3.3 (archived) · 3.1.7 Storage conditions) EU: “… a) Stability information from accelerated and long term testing is to be provided on at least two production scale batches manufactured by the same manufacturing (synthetic) route and procedure described in part 3.2.S.2 of the application. The long term testing and accelerated testing should cover a minimum of 6 months duration at the time of submission …” (EMA existing actives · 2.1.3 Selection of Batches) “… b) Stability information from accelerated and long term testing is to be provided on at least three pilot scale batches manufactured by the same manufacturing (synthetic) route and procedure described in part 3.2.S.2 of the application. The long term testing and accelerated testing should cover a minimum of 6 months duration at the time of submission.” (EMA existing actives · 2.1.3 Selection of Batches) “The applicant should specify that the active substance complies with the pharmacopoeial monograph immediately prior to manufacture of the finished product. In this case no stability studies are required on condition that the suitability of the pharmacopoeial monograph has been demonstrated for the particular named source …” (EMA existing actives · 2.1.1 General (option a)) US FDA: “Data from formal stability studies should be provided on at least three primary batches of the drug substance.  The batches should be manufactured to a minimum of pilot scale by the same synthetic route as production batches and using a method of manufacture and procedure that simulates the final process to be used for production batches.” (FDA Q1A(R2) · 2.1.3) “The long-term testing should cover a minimum of 12 months’ duration on at least three primary batches at the time of submission and should be continued for a period of time sufficient to cover the proposed retest period.” (FDA Q1A(R2) · 2.1.7) “Study Storage condition Minimum time period covered by data at submission Long-term* 25°C ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH 12 months Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months” (FDA Q1A(R2) · 2.1.7.1 (table)) WHO: “Data from stability studies on at least three primary batches of the API should normally be provided. The batches should be manufactured at a minimum of pilot scale by the same synthesis route as production batches, and using a method of manufacture and a procedure that simulates the final process to be used for production batches.” (WHO TRS 1010 Annex 10 · 2.1.3 Selection of batches) “For new APIs, the long-term testing should normally have taken place over a minimum of 12 months for the number of batches specified in section 2.1.3 at the time of submission, and should be continued for a period of time sufficient to cover the proposed retest period or shelf life. For existing APIs, data covering a minimum of six months may be submitted.” (WHO TRS 1010 Annex 10 · 2.1.7 Storage conditions) “Study Storage condition Minimum time period covered by data at submission Accelerated 40 °C ± 2 °C/75

What stability data is required for the active substance (API)?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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