ICH Guidelines for stability testing

ICH Guidelines for stability testing (ICH Q Guidelines)

1. ICH GUIDELINES FOR STABILITY TESTING Presented by- Ankita Kawtikwar Roll no. 504 M.Pharm ( Sem -I) Seminar Department of Pharmaceutics Dr. D.Y.Patil Institute of Pharmaceutical and Sciences and Research, Pimpri , Pune,411018 1

2. WHAT IS ICH? International Council for Harmonisation of Technical Requirements for Pharmaceuticals for human use. brings together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. 2

3. NEED TO HARMONISE? Independent evaluation of medicinal product before they enter the market. Industry becoming Global Duplicate test procedures Time consuming Expensive Increasing R & D costs Meeting public demand 3

4. INITIATION OF ICH - 1980: European Community Discussions between Europe, Japan and the US - 1989: WHO conference of Drug Regulatory Authorities, Paris (ICDRA ) International Federation of Pharmaceutical Manufacturers and Association(IFPMA) - 1990: Birth of ICH at meeting hosted by European Federation of Pharmaceutical Industries (EFPIA) and Associations at Brussels Europe Japan US Topics of Harmonisation divided into : Safety, Efficacy and Quality 4

5. DRUG STABILITY A measure of how a pharmaceutical product maintains its quality attribute over a period of time. 5

6. TYPES OF DRUG STABILITY 6

7. STABILITY TESTING To provide evidence on how the quality of a drug substance or drug product varies with time. Establish shelf life for the drug product Determine recommended storage conditions Determine container closure system suitability 7

8. CLIMATIC ZONES 8

9. REGIONS AND ZONES 9

10. ICH GUIDELINES FOR STABILITY TESTING 10

11. Q1A(R2) STABILITY TESTING OF DRUG SUBSTANCE AND DRUG PRODUCT 11

12. STRESS TESTING Helps in Identification of degradants Identification of degradation pathways Determination of which type(s) of stress affect the molecule - Photo-stability - High Temperature - Low Temperature - Oxidation - pH extremes - Water 12

13. TYPICAL STRESS CONDITIONS 13

14. STRESS TESTING FOR NEVIRAPINE 14

15. Data from stability studies should be provided on at least three primary batches of the active substance. CONTAINER CLOSURE SYSTEM Studies should be conducted on the substance packaged in a container closure system that is the same or simulates the packaging proposed for storage and distribution. SELECTION OF BATCHES 15

16. TESTING FREQUENCY 16

17. STORAGE CONDITIONS *It is upto the applicant to decide whether long term stability studies are performed at 25±2°C/ 60%RH±5%RH or 30°C±2°C/65%±5%RH. **If 30°C±2°C/65%±5%RH is the long term condition, there is no intermediate condition. GENERAL CASE 17

18. If significant change occurs within the first 3 months testing at the accelerated storage condition, it is considered unnecessary to continue to test a drug substance through 6 months. DRUG SUBSTANCES INTENDED FOR STORAGE IN A REFRIGERATOR 18

19. In the absence of an accelerated storage condition for drug substances intended to be stored in a freezer, testing on a single batch at an elevated temperature (e.g., 5°C ± 3°C or 25°C ± 2°C) for an appropriate time period should be conducted to address the effect of short term excursions outside the proposed label storage condition, e.g., during shipping or handling. DRUG SUBSTANCES INTENDED FOR STORAGE IN A FREEZER 19

20. Testing of attributes that are susceptible to change during storage and likely to influence quality , safety and/or efficacy. E.g. Appearance, assay, degradation STABILITY COMMITMENT 1. If the submission includes data from stability studies on at least three production batches, a commitment should be made to continue these studies through the proposed re-test period. 2. Fewer than three production batches, a commitment should be made to continue these studies through the proposed retest period and to place additional production batches, to a total of at least three, on long term stability studies through the proposed re-test period. 3. If no data on production batches, a commitment to place the first three production batches on long term stability studies through the proposed re-test period. SPECIFICATION 20

21. EVALUATION Should include results from physical, chemical, biological and microbiological tests. STATEMENT AND LABELLING Storage statement Established for labelling should be in accordance with national/regional requirement. Re-test date -Statement based on stability evaluation -Should be displayed on the container label 21

22. FOR DRUG PRODUCT SELECTION OF BATCHES Data from stability studies should be provided on at least three primary batches of pharmaceutical product. Primary batches should be of same formulation and packaged in the same container closer system as proposed for marketing Two of three batches should be at least pilot scale batches and the third one can be smaller, if justified. TESTING FREQUENCY STORAGE CONDITIONS (general case- same as that of drug substance) 22

23. A 5% loss in water from its initial value is considered a significant change for a product packaged in a semi-permeable container after an equivalent of 3 months’ storage at 40°C/NMT 25%RH. Drug products intended for storage below -20 Stability commitment Evaluation Statements/Labelling DRUG PRODUCTS PACKAGED IN SEMI-PERMEABLE CONTAINERS 25%RH 23

24. If significant change occurs between 3 &6 months’ testing at the accelerated storage condition, the proposed shelf life should be based on the real time data available from the long term storage condition. DRUG PRODUCTS INTENDED FOR STORAGE IN A REFRIGERATOR 24

25. Q1B: Stability Testing: Photostability Testing of New Drug Substances and Products A systematic approach to stability testing is recommended covering as appropriate studies such as: Tests on the active substance On exposed product outside of the immediate pack and if necessary On the product in the immediate pack and if necessary On the product in the marketing Light sources D65/ID65, fluorescent lamp combining visible and UV outputs, Xenon or metal halide lamp 25

26. PROCEDURE 26

27. PHOTOSTABILITY TESTING OF DRUG SUBSTANCE FORCED DEGRADATION TEST CONFIRMATORY TEST To evaluate photosensitivity for method development and/or degradation pathway elucidation Sample should be in chemically inert and transparent containers Variety of exposure conditions may be used Provide information necessary for handling, packaging and labelling If clearly photo stable and photo labile then it should be confirmed in single batch. If results are equivocal two additional batches should be conducted 27

28. Q1C: STABILITY FOR NEW DOSAGE FORMS NEW DOSAGE FORM -Administration route - New specific functionality/delivery systems - Different dosage form STABILITY PROTOCOL Stability protocols should follow the guidance in the principle of parent stability guideline. However a reduced stability database at submission time (e.g. 6 months accelerated and 6 months long term data from ongoing studies) may be acceptable in certain justified cases. Same active substance 28

29. Q1D:BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS BRACKETING: The design of a stability schedule such that the samples on the extremes of certain factors (e.g. Strength, container size or fill) are tested at all time points as in a full design. 29

30. MATRIXING The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations would be tested at specified time point. 30

31. ONE THIRD REDUCTION 31

32. Q1E: EVALUATION OF STABILITY DATA Presentation Extrapolation No significant change at accelerated condition (For RT storage) Significant change at accelerated condition(RT) No significant change at intermediate condition (RT) Significant change at intermediate condition(RT) No significant change at accelerated condition(for storage in refrigerator) Drug substances or products intended for storage in a freezer Drug substances or products intended for storage below -20°C 32

33. THANK YOU 33