current Good Analytical Laboratory Practices (cGALP)

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Stability study
 
The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions. Stability testing is a routine procedure performed on drug substances and products. It is involved at various stages of product development.
 
In early stages, accelerated stability testing (at relatively high temperatures and/or humidities) can be used as a “worst case” evaluation to determine what types of degradation products may be found after long-term storage.
 
Testing under more gentle conditions (those recommended for long-term shelf storage), and slightly elevated temperatures, can be used to determine a product’s shelf life and expiration dates.

In these types of studies, the product is analyzed at regular  intervals for various parameters, which may include assay of the active ingredient, measurement of known degradation products, dissolution time, appearance, etc.


 

Stability Guidelines
 
ICH

Quality Guidelines : (Stability)

Q1A(R2): Stability Testing of New Drug Substances and Products 

Q1B: Photostability Testing of New Drug Substances and Products

Q1C: Stability Testing for New Dosage Forms

Q1D: Bracketing & Matrixing Designs for Stability Testing of Drug Substances & Drug Products

Q1E: Evaluation of Stability Data


WHO

Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms Annex 5, WHO Technical Report Series 863, 1996
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Item 10.1 TRS 937:
Item 10.1, WHO Technical Report Series 937, 2006
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Update, Item 11.1 TRS 908
Item 11.1, WHO Technical Report Series 908, 2003
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Stability testing of active pharmaceuticals ingredients and finished pharmaceuticals products - Annex 2
WHO Technical Report Series 953, 2009
 
Consultation of Stability studies in a global environment
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USFDA
 

EMEA
 
Stability testing of new drug substances and products

TGA
 
Australian Regulatory Guidelines for Complementary Medicines(ARGCM)
 
TGA : Questions & answers on the stability testing of Listed complementary medicines

ASEAN
 
Stability study of drug product

GCC
 
Stability testing of drug substances and pharmaceutical products

Decision Tree for Data Evaluation for Retest Period or Shelf Life Estimation for Drug Substances or Products (excluding Frozen Products)

Case 1 : No significant change in accelerated
 
   a) No or little change in long term and accelerated 
 
       Extrapolation (Y) = up to 2X, but not exceeding X + 12 months;
 
      or if refrigerated, Y = up to 1.5X, but not exceeding X + 6 months
 
   b) Change in in long term & acclerated       
        
        i)If backed by statistical analysis and relevant supporting data;
 
          Extrapolation (Y) = up to 2X, but not exceeding X + 12 months;
 
        or if refrigerated, Y = up to 1.5X, but not exceeding X + 6 months
 
        ii)If backed by relevant supporting data;
 
           Extrapolation (Y) = up to 1.5X, but not exceeding X + 6 months;
 
         or if refrigerated, Y = up to X + 3 months
 
       
Case 2 : Significant change within 6 month accelerated
 
   a) if refrigerated, and significant change within 3 months - No extrapolation
 
   b) if refrigerated, and no significant change within 3 months- No extrapolation
 
   c) if not refrigerated and significant change at intermediate - No extrapolation
 
   d) if not refrigerated and no significant change at intermediate condition
 
        i) If backed by relevant supporting data:Y = up to X + 3 months
 
        ii) If backed by statistical analysis and relevant supporting data
 
            Y = up to 1.5X,    but not exceeding X + 6 months

 
Note:
 
"Significant change" for a drug substance is defined as failure to meet its specification
 
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;
 
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 for 12 dosage units.

 
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