ICH GUIDELINES FOR STABILITY Q1A powerpoint.ppt
- 1. ICH GUIDELINES FOR STABILITY Presented by, N.Jagannathan Senior scientist Lifecell international Pvt Ltd
- 2. What does ICH stand for ? The complete name of ICH is the “International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use”. What is ICH ? ICH is a joint initiative involving both regulators and research-based industry representatives of the EU, Japan and the US in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines.
- 3. When was ICH started ? The birth of ICH took place at a meeting in April 1990, hosted by the EFPIA in Brussels. What is the purpose of ICH ? The objective of ICH is to increase international harmonization of technical requirements to ensure that safe, effective, and high quality medicines are developed and registered in the most efficient and cost effective manner.
- 4. Who are the members ? ICH PARTIES JAPAN EUROPE USA • The Ministry of Health, Labour & Welfare (MHLW) • Japan Pharmaceutical Manufacturers Association (JPMA) • The European Commission (EC) • European Federation of Pharmaceutical Industries and Associations (EFPIA) • The Food & Drug Administration (FDA) • The Pharmaceutical Research and Manufacturers of America (PhRMA)
- 6. Worldwide zones and the temperature and humidity conditions Zone Mean kinetic temperature Yearly average humidity (%RH) Zone I ( Moderate) 21 ̊C 45 Zone II (Mediterranean) 25 ̊C 60 Zone III (Hot, dry) 30 ̊C 35 Zone IV (Very hot, moist) 30̊ C 70
- 7. Countries belonging to various zones Regions Zone I &II Zone III&IV EUROPE All countries AMERICA Argentina, Bolivia, Canada, Mexico, US Brazil, Columbia, Cuba, Jamaica ASIA Afghanistan, china, Iran, Nepal, turkey Bahrain , Hong Kong, India, Oman , Pakistan, Srilanka,UAE AFRICA Egypt, Algeria, south Africa, Libya Angola, Benin, Congo, Uganda, Sudan, Somalia, Senegal
- 8. ICH GUIDELINES FOR STABILITY
- 9. ICH GUIDELINES FOR STABILITY Q1A(R2) Stability Testing 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 Substances and Products Q1E Evaluation of Stability Data Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV
- 10. Stability Stability of a Pharmaceutical preparation can be defined as “the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic & toxicological specification throughout its shelf life”.
- 11. Purpose of stability testing To ensure the efficacy, safety and quality of active drug substance and dosage forms. To establish shelf life or expiration period and to support label claims.
- 12. Stability testing of new drug substances & products Q1 A(R2) – Principle To provide evidence how quality of drug substance or product varies To establish a retest period for drug substance or shelf life for drug product.
- 13. DRUG SUBSTANCE Stress testing • To identify degradation product • To evaluate its susceptibility to hydrolysis Carried out on a single drug substance Photostability is an integral part of this testing Selection of batches Studies carried on atleast 3 primary batches The primary batch should be of pilot scale Should be packed in same container closure system as proposed for storage and distribution
- 14. For long-term storage 12 month study – Testing frequency 0 3 6 9 12 For accelerated storage 6 month study – Testing frequency 0 3 6 (initial) (final) If significant change occur – Increase the testing by adding sample at final time point – Include 4th time point in study design For intermediate storage 12 month study - Testing frequency 0 6 12 If significant change occur - A 4th time point can be included Testing frequency To establish the stability profile of drug substance
- 15. Storage condition Drug substance is evaluated to test • Its thermal stability • Sensitivity to moisture Table 1: General case Study Storage condition Minimum time period for data submission LONG TERM 25ºC±2ºC/60%RH±5%RH Or 30ºC±2ºC/65%RH±5%RH 12 MONTH INTERMEDIATE 30°C±2°C/65%RH±5%RH 6 MONTH ACCELERATED 40°C±2°C/75%RH±5%RH 6 MONTH 0 6 12 Significant change 0 3 6 12 Additional testing at intermediate condition Long-term studies
- 16. Table 2: Drug substance intended for storage in a refrigerator Study Storage condition Minimum time period for data submission LONG TERM 5°C±3°C 12 MONTH ACCELERATED 25°C±2°C/60%RH±5%RH 6 MONTH 0 3 6 Significant change Retest period 12 month
- 17. DRUG PRODUCT Stability studies based on • Behavior & properties of drug substance • The stability study of drug substance Selection of batches Testing frequency Storage condition • General case • Drug product stored under refrigerator • Drug products packaged in impermeable containers act as a barrier to moisture or solvents conducted at controlled humidity condition • Drug products packaged in semi-permeable containers aqueous products should be evaluated for water loss conducted at low relative humidity
- 18. Statements & labeling • The statement should be based on the stability evaluation of drug substance. • Specific instruction should be provided for drug substance that cannot tolerate freezing. • Terms such as “ambient condition” or “room temperature” should be avoided. • Retest period derived from stability information. • Retest date should be displaced on container label.
- 19. References www.ich.org www.ijpsonline.com www.pubmed.com