What is a significant change for the finished product in stability testing?

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Accepted Answer

SFDA: “In general “significant change” for an FPP is defined as: 1. A 5% or more change in assay from its initial content of API(s), or failure to meet the acceptance criteria for potency when using biological or immunological procedures.” (GCC v3.3 (archived) · 2. Glossary – Significant change) “2. Any degradation product exceeding its acceptance criterion. 3. Failure to meet the acceptance criteria for appearance, physical attributes and functionality test (e.g. color, phase separation, resuspendability, caking, hardness, dose delivery per actuation).” (GCC v3.3 (archived) · 2. Glossary – Significant change) “Also, as appropriate for the dosage form: 4. Failure to meet the acceptance criterion for pH; or 5. Failure to meet the acceptance criteria for dissolution for 12 dosage units.” (GCC v3.3 (archived) · 2. Glossary – Significant change) EU: “In general, “significant change” for a drug product is defined as: 1. A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures; 2. Any degradation product’s exceeding its acceptance criterion;” (ICH Q1A(R2) · 2.2.7.1 General case) “3. Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, resuspendibility, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions;” (ICH Q1A(R2) · 2.2.7.1 General case) “… and, as appropriate for the dosage form: 4. Failure to meet the acceptance criterion for pH; or 5. Failure to meet the acceptance criteria for dissolution for 12 dosage units.” (ICH Q1A(R2) · 2.2.7.1 General case) US FDA: “In general, significant change for a drug product is defined as one or more of the following (as appropriate for the dosage form): • A 5 percent change in assay from its initial value, or failure to meet the acceptance criteria for potency when using biological or immunological procedures • Any degradation product’s exceeding its acceptance criterion …” (FDA Q1A(R2) · 2.2.7.1) “Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, resuspendibility, caking, hardness, dose delivery per actuation).  However, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions. • Failure to meet the acceptance criterion for pH • Failure to meet the acceptance criteria for dissolution for 12 dosage units …” (FDA Q1A(R2) · 2.2.7.1) WHO: “In general, “significant change” for an FPP is defined as: –– a change from the initial content of API(s) of 5% or more detected by assay, or failure to meet the acceptance criteria for potency when using biological or immunological procedures; –– any degradation product exceeding its acceptance criterion;” (WHO TRS 1010 Annex 10 · 2.2.7.1 General case) “… failure to meet the acceptance criteria for appearance, physical attributes and functionality test (e.g. colour, phase separation, resuspendability, caking, hardness, dose delivery per actuation). However, some changes in physical attributes (e.g. softening of suppositories, melting of creams, partial loss of adhesion for transdermal products) may be expected under accelerated conditions.” (WHO TRS 1010 Annex 10 · 2.2.7.1 General case) “Also, as appropriate for the dosage form: –– failure to meet the acceptance criterion for pH; or –– failure to meet the acceptance criteria for dissolution for 12 dosage units.” (WHO TRS 1010 Annex 10 · 2.2.7.1 General case)

What is a significant change for the finished product in stability testing?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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