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Stabilty study ppt
1. Drug stability testing involves conducting studies under various temperature, humidity and light conditions to determine a drug's shelf life and optimal storage requirements. 2. The ICH Q1A guideline provides the standard process for stability testing new drug substances and products to obtain registration. It defines testing stages, storage conditions and frequencies to evaluate how quality varies over time. 3. Stability testing helps establish expiration dates and provides evidence for appropriate packaging and labeling to ensure drug quality through a product's shelf life.
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Stabilty study ppt
- 1. Guided by: Presentedby: Dr. Arpana Patil Salim Mulla (M.Pharm, Phd) M.Pharm (SEM-I ) Alard College of Pharmacy 1
- 2. Drug stabilityrefers to the capacity of a drug substance or product to remain within established specifications of identity, strength, quality, and purity in a specified period of time. Stability is officially defined as the time during which the drug product retains the same properties and characteristics that it possessed at the time of manufacture. 2
- 3. STAGE 1-Early stage stress and accelerated testing with drug substances STAGE 2- Stability on pre-formulation batches STAGE 3- Stress testing on scale-up batches STAGE 4- Accelerated and long term testing for registeration purposes STAGE 5- On-going stability testing STAGE 6- Follow-up Stabilities 3
- 4. To gatherinformation during pre-formulation stage to produce a stable product To determine maximum expiration date. To get an idea of storage condition. To determine the packaging components. To establish retest period of pharmaceuticals. To establish transport condition. 4
- 5. Chemical degradationof active drug may reduce the quality of therapeutic indices like 5- flurouracil, carbamazepine etc have very small therapeutic range, sight degradation of drug may produce sub therapeutic concentration. After degradation a drug may produce more toxic product(s) which may be more toxic than the parent product. Instability of drug product reduce bioavailability. This may be caused by physical or chemical instability. Instability of a product may change the physical appearance of the product. 5
- 6. The ICH(International Conference on Harmonization) Guidelines Q1A(R2) “Stability testing of new drug substances and products” is the “gold standard” for conducting stability studies. This is valid for “new drug substances or drug products” that are sufficient for a registration application. 6
- 7. Q1A- Stabilitytesting of new Drug Substances and Products Q1B- Stability Testing : Photostability Testing of New Drug Substances and products Q1C- Stability Testing for new Dosage forms Q1D- Bracketing and Matrixing Designs for Stability Testing of New Drug Substsances and products Q1E- Evaluation of stability data Q1F- Stability data package for registration 7
- 8. OBJECTIVE OF THEGUIDELINE: It defines stability of drug substances and drug product for registration of application of associated drug, within three regions of ICH i.e. EU, Japan, USA. 8
- 9. 1. Purpose ofstability testing is to provide evidence how quality varies with time under influences of temperature humidity light 2. Establish re-test period for drug substances RE-TEST PERIOD: The period after which samples of the drug substances should be examined to ensure that the material is still in compliance with the specification, and thus suitable for use in manufacturing. A retest period should be proposed on the basis of stability results and may be extended to five years (e.g. Ethambutol 2HCI, or isoniazid) 9
- 10. 3. Establish shelflife for drug products: • SHELF LIFE (EXPIRY DATE/EXPIRATION DATING PERIOD): The period of time during which a pharmaceutical product, if stored correctly, is expected to comply with the specification as determined by stability studies on a number or batches of the product. The shelf life is used to establish the expiry date of DRUG PRODUCT. 4. Recommends storage conditions 5. Gives Test conditions based on analysis of effects of climatic conditions in the three regions of the EU, japan, USA. 10
- 11. Stress testing: Theseguidelines help to identify the likely degreadation products, to establish the degradation pathway of the molecule. Selection of batches: At least 3 primary batches of the drug substances should be selected. The quality should be representative to quality of material used for production scale. 11
- 12. Container Closure system: ◦Should simulate packaging proposed for storage and distribution. Specification: ◦ List of tests, ◦ Reference to analytical procedure, ◦ Proposed acceptance criteria ◦ Test Attributes ◦ Attributes that are susceptible to changed storage, ◦ Influence quality, safety and/or efficacy ◦ Should cover physical, chemical, biological and microbiological attributes. 12
- 13. Testing frequency: Testing frequencyfor products proposed shelf life of at least 12 months. FIRST YEAR…. 3 month SECOND …… 6 month Thereafter…. Annually through out the proposed retest period . At accelerated storage condition: Minimum three time points (0,3 and 6 months)from a 6 month study At intermediate storage condition: Minimum of four time points (0,6,9 and 12 months) from a 12 month study. 13
- 14. Long termtesting should cover a minimum of 12 months duration on at least three primary bacterial batches at time of submission and should be continue sufficient to covered the proposed retest period. General Study Storage condition Duration Long term 25o C ± 2o C/60% ±5% Or 30oC ± 2oC/65% ± 5% 12 months Intermediat e 30oC ± 2oC/65% ± 5% 6 months Accelerated 40oC ± 2oC/75% ± 5% 6 months 14
- 15. Drugs packed insemi permeable membrane containers: Study Storage Condition Duration Long term 25oC ± 2oC/ 40% RH ± 5% Or 30oC ± 2oC/ 35% RH ± 5% 12 months Intermediate 30oC ± 2oC/ 65% RH ± 5% 6 months Accelerated 40oC ± 2oC/ 75% RH ± 5% 6 months 15
- 16. Drug substance intendedfor storage in a refrigerator If significant change between 3 and 6 month at accelerated testing propose re-test data based on real time data. (LONG TERM STUDY) If significant change within 3 month discussion should address excursion outside label storage. Single batch shorter than 3 months with more frequent testing Study Storage condition Duration Long term 5oC ± 3oC 12 months Accelerated 25oC ± 2oC/60%± 5% 6 months 16
- 17. Drug substance intendedfor storage in a freezer Re-test period based on real time data at long term storage condition. In absence of accelerated storage condition testing on a single batch at an elevated temperature e.g. 5oC 3oC address short term excursions Study Storage condition Duration Long term -20oC ± 5oC 12 month 17
- 18. Stability commitment: Whenretest period not covered or not mentioned. Long term stability data do not cover proposed retest period granted at time of approval to establish re test period. Not required for submission which includes data from 3 production batches commitment to continue through proposed retest period Fewer than three production batches commitment continue through proposed retest period and place additional production batches to a total of three on long term stability through proposed retest period. No production batches commitment to place first three production batches on long term stability studies through proposed retest period. 18
- 19. Evaluation: A systematicapproach should be adopted in the presentation and evaluation of the stability information which covers the physical, chemical & biological parameter. A minimum of 3 batches of drug product was tested. The analyst must found the batch to batch variability and if it is small than only it is accepted and it can be done by different statistical tests. Where the data shows so little degradation and so little variability that is apparent from looking the data that the requestedshelf life will be granted. It is normally unnecessary to go through the formal statistical analysis. 19
- 20. Significant change ofdrug substance or product: A 5% change in assay from its initial value. Any degradation product exceeding its acceptance criterion. Failure to meet the acceptance criteria for apperance, physical attributes and functionality test (e.g. colour, phase separation, hardness). As appropriate for the dosage form, e.g. failure to meet the acceptance criteria for dissolution for 12 dosage units. 20
- 21. Statements/Labelling: A storagestatement should be established based on the stability evaluation of the drug substances. Terms such as “ambient conditions” or “room temperature” should be avoided. Retest date should be displayed on the container label if appropriate. 21
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- 24. References: www.ich.org/product/guidelines/quality.html www.ema.europa.eu/pdfs/human/ich/273699en.pdf www.ich.org/fileadmin/.../ICH.../Guidelines/.../Q1BGuidel ine.pdf Apps.who.int/prequal/traninresources/pq…/stabilitystud ies.ppt Drug Stability: Principles and Practices. By Jens T. Carstensen. Marcel Dekker: New York, 1990, CRC press publication, Third edition, pg no. 54-110. 24
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