Stability of the pharmaceutical products is determined by storing the product under Accelerated and Long Term Conditions. The product is then analyzed at different time stations for any significant change in physical or chemical condition.
“Significant Change” is an important or remarkable change in any physical or chemical condition of the pharmaceutical product. These changes may occur in the product during the stability study of the drug product.
According to ICH “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;
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;
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 of 12 dosage units.
5% change in the assay is an absolute change in the initial result; it means direct 5% from the initial value. For example - if the initial assay of any product is 98% then the significant change will be 93%. It will not be 5% of 98%. But if the assay is analyzed by the biological method, results below the acceptance criteria will be considered as significant change because biological methods have less accuracy and may produce fluctuated results.
Failure to meet the specification for related substances, physical appearance, moisture content, hardness, friability, solubility, pH and other similar tests are considered as a significant change in pharmaceutical substances and products.
A significant change in dissolution test is when a product fails to meet the specification in S2 stage i.e. 12 dosage units are used in the analysis.
Also see: Shelf Life Estimation of Pharmaceutical Products
According to ICH “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;
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;
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 of 12 dosage units.
5% change in the assay is an absolute change in the initial result; it means direct 5% from the initial value. For example - if the initial assay of any product is 98% then the significant change will be 93%. It will not be 5% of 98%. But if the assay is analyzed by the biological method, results below the acceptance criteria will be considered as significant change because biological methods have less accuracy and may produce fluctuated results.
Failure to meet the specification for related substances, physical appearance, moisture content, hardness, friability, solubility, pH and other similar tests are considered as a significant change in pharmaceutical substances and products.
A significant change in dissolution test is when a product fails to meet the specification in S2 stage i.e. 12 dosage units are used in the analysis.
Also see: Shelf Life Estimation of Pharmaceutical Products
all these changes are for accelerated as well as long term?
ReplyDeleteIf I am doing accelerated test for a cream of tretinoin, and the pharmacopoeia monograph accept contains not less than 90 and no more that 120%. Are some change in the limit of 5% like a "significant change " in my study?
ReplyDeleteThanks
Very nice notes. Easily understandable. Thank you sir
ReplyDeleteSignificant change observed, than what is the immediate action for example in assay or description shall we go for oos or any other explanation please kindly explain sir,
ReplyDeleteThe significant change in the %assay from the time T0 to the current Time point need to evaluate while performing the ACC conditions for biological and immunological Assay test procedures.
ReplyDeleteIs the same criteria applicable for Solid oral dosage forms testing regular Assay by HPLC method?
Please send your comments on this.
What is the acceptance criteria for stability samples of dissolution tests
ReplyDeleteWhat we should do when significant change observed in long term
ReplyDelete