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Q1 ppt by jahnavi bandi
- 1. Department of PharmaceuticalAnalysis and Quality Assurance Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Ananthapuramu, Andhra Pradesh (515721) PRESENTED BY B. JAHNAVI V.BHARATH NAIK B.MOHAN REDDY
- 2. • ICH • Stability •Q1A • Q1B • Q1C • Q1D • Q1E • Reference
- 4. • ICH initiallyinvolved EU, Japan and USA. • ICH was initiated in April 1990. ICH GUIDELINES
- 5. Stability studies DRUG SUBSTANCEDRUG PRODUCT Unformulated drug substance that may be formulated with excipients to produce the dosage form Dosage form in the final immediate packaging intended for marketing
- 7. • Stability datapackage for a new drug substance or drug product that is sufficient for a registration application with in three regions of the EC, Japan, and United States. Scope: • Information to be submitted in registration applications for new molecular entities and associated drug products. • The purpose of stability testing is to provide evidence on how quality of drug substance or drug product varies with time under influence of various environmental factors to establish retest period and shelf life . • This guideline addresses climatic zones I and II. Tripartite guidelines on stability testing of new drug substances and products (Q1A) in 1993 has become standard for quality evaluation in Japan, US and EU. Objective:
- 8. Stress Testing Container ClosureSystem Storage Conditions Evaluation
- 9. Photo stability Testing ContainerClosure System Evaluation Storage Conditions
- 10. DRUG SUBSTANCE DRUGPRODUCT General Systemic approach to stability evaluation Knowledge of behavior and properties of drug substance Stress testing(DS) /photostability testing(DP) To identify degraded products and to establish degradation pathways & intrinsic pathways Conducted on at least one primary batch of drug product Selection of batches Data from formal stability studies should be provided on at least 3 primary batches of drug substance Two of three batches should be at least pilot scale batches and third one is smaller Container Closure System Stability studies should be conducted on the drug substance packaged in a container closure system(storage and distribution) Conducted on dosage form packaged in CCS proposed for marketing Specification List of tests, reference to analytical procedures, proposed acceptance criteria Testing covers physical, chemical, microbiological attributes, preservative content, functionality tests.
- 11. DRUG SUBSTANCE DRUGPRODUCT Testing Frequency For long term studies, frequency of testing should be sufficient to establish stability profile. For long term studies, frequency of testing should be sufficient to establish stability profile. Storage Conditions Long term , Intermediate, Accelerated storage for general, refrigerator, freezer Drug products packaged in impermeable and semi permeable containers Stability Commitment Commitment should be made to continue stability studies on primary batch to establish a retest period. To establish shelf life for a drug product. Evaluation To establish retest period for future batches, based on testing of 3 batches. To establish shelf life for future batches, based on testing of 3 batches. Labeling Retest period should be derived from stability information, retest date should be displayed on container label. Specific instructions, expiration date ‘’ambient conditions "or ’’room temperature” are avoided on container label.
- 12. Study Storage conditionMinimum time period Long term* 25 ± 2°C, 60% RH ± 5% RH OR 30 ± 2°C, 60% RH ± 5%RH 12 months Intermediate ** 30 ± 2°C, 60% RH ± 5%RH 6 months Accelerated 40 ± 2°C, 75% RH ± 5%RH 6 months General case Study Storage condition Minimum time period Long term 5° ± 3°C 12 months Accelerated 25 ± 2°C, 60% RH ± 5% RH 6 months Storage in a refrigerator For storage in a freezer, long term- -20°C ± 5°C(12 months)
- 14. • Systemic approachto photostability testing covers studies, 1. Tests on the drug substance. 2. Tests on exposed drug product outside the immediate pack. 3. Tests on drug product in the immediate pack. 4. Tests on the drug product in the marketing pack. LIGHT SOURCE Option 1 Light source that is designed to produce output similar to D65/ID65 emission standard Option 2 1.Cool white fluorescent lamp. 2.Near UV fluorescent lamp.
- 15. For drug substances,photostability testing should consists of 2 parts Forced Degradation Testing • To evaluate overall photosensitivity of material for method development purposes/degradation pathway elucidation. • This involves drug substance alone/sample solution/suspensions. • Samples- chemically inert , transparent containers. • Variety of exposure conditions may be used depends on photosensitivity of drug substance and intensity of light source. • Information may be useful in developing and validating suitable analytical methods.
- 16. Confirmatory Testing • Thisshould be undertaken to provide information necessary for handling, packaging and labeling. • Normally one batch of drug substance is tested during development phase and then photostability characteristics should be confirmed on a single batch as described in parent guideline. • Quinine chemical actinometry.
- 17. START DIRECTLY EXPOSED ACCEPTABLE CHANGE? IMMEDIATE PACK ACCEPTABLE CHANGE? MARKETINGPACK ACCEPTABLE CHANGE? REDESIGN PACKAGE OR REFORMULATION TEST END TEST END TEST END FORMULATION CHANGE? IMMEDIATE PACK CHANGE? MARKETING PACK CHANGE? NO NO NO YES YES YES YES NO NO For a drug product:
- 18. • New dosageform is a drug product which is a different pharmaceutical drug product but contains same active substance as in the already existing drug product approved by regulatory authority. • Such pharmaceutical product types include 1. Route of administration. 2. Delivery systems. 3. Same route of administration with different dosage forms.
- 19. • Full studydesign is one in which samples for every combination are tested at all time points. • Reduced design is one in which samples for every combination are not tested at all points. .
- 20. Strength 50 mg75 mg 100 mg Batch 1 2 3 1 2 3 1 2 3 Container Size 15 ml T T T T T T 100 ml 500 ml T T T T T T
- 21. Time point (months) 0 36 9 12 18 24 36 S t r e n g t h S1 Batch 1 T T T T T T Batch 2 T T T T T T Batch 3 T T T T T S2 Batch 1 T T T T T Batch 2 T T T T T T Batch 3 T T T T T One – Half Reduction
- 22. Time point ( months) 03 6 9 12 18 24 36 S t r e n g t h S1 Batch 1 T T T T T T Batch 2 T T T T T T Batch 3 T T T T T T T S2 Batch 1 T T T T T T T Batch 2 T T T T T T Batch 3 T T T T T T One – Third Reduction
- 23. • Intended onhow to use stability data generated in accordance with principles mentioned in the ICH guideline Q1A to propose a retest period or shelf life in registration application. • Describes when and how extrapolation can be considered when proposing a retest period or shelf life for a drug product that extends beyond the period covered by “available data from the stability study under the long term storage condition.” • This guideline addresses evaluation of stability data that should be submitted in registration applications for new molecular entities and associated drug products.
- 24. • Extrapolation isthe practice of using a known data set to infer information about future data. • Extrapolation to extend the retest period or shelf life beyond the period covered by long term data can be proposed in the application, particularly if no change is observe at accelerated condition. • Extrapolation of stability data assumes that the same change pattern will continue to apply beyond the period covered by long term data.
- 25. Statistical Approaches: • Appropriatestatistical method should be employed to analyze long term stability data . • The purpose of analysis is to provide high degree of confidence, retest period or shelf life during which quantitative attribute will remain within acceptance criteria for all future batches . • Regression analysis is considered to evaluate the stability data for quantitative attribute. Examples: 1.Data analysis of a single batch. 2. Data analysis for One-Factor, Full Design Studies. 3. Evaluating whether all batches support the proposed retest period or shelf life. 4. Testing for poolability of batches(Analysis of covariance)
- 26. 1. Chen, J.J.,Ahn, H., and Tsong, Y., “Shelf – life Estimation for Multifactor Stability Studies” Drug Inf. Journal, 31:573-587, 1997. 2. Carstensen, J.T., and Rhodes, C.T., “Drug Stability Principles & Practices”, Third Edition. 3. Yoshioka S. et al., Drug Development and Industrial Pharmacy,20 (13), 2049-2062 (1994). 4. Ruberg, S.J. and Hsu, J.C., “Multiple Comparison Procedures for Pooling Batches in Stability Studies” Technometrics, 34:465-472,1992
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