industry stability testing technique health

industry stability testing technique

1. STABILITY OF FORMULATED PRODUCTS

2. Table of Contents. Introduction. Definition of stability. The five types of stability. Factors affecting product stability. Stability studies in manufacturing. Observing products for evidence of instability. Responsibility of the pharmacist. Reference.

3. Objectives of stability studies Ø Determine Shelf Life: Establish the length of time a product remains stable and effective under specified storage conditions. Ø Evaluate Product Quality: Assess the physical, chemical, and microbiological characteristics of a product over time. Ø Identify Degradation Pathways: Understand how a product degrades or breaks down over time. Ø Ensure Patient Safety: Verify that a product remains safe and effective for patient use throughout its shelf life Ø Support Labeling Claims: Provide data to support product labeling claims, including shelf life and storage conditions. Ø Support Product Development: Inform product development decisions, such as reformulation or new product development, with stability data.

4. WHY STABILITY… Provide a 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. Establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions. Because physical, chemical or microbiological changes might impact the efficiency and security of the final product. 6

5. Where and Why? Stability Studies are preformed on ... Drug Substances (DS)  The unformulated drug substance that may subsequently be formulated with excipients to produce the dosage form. Drug Products (DP)  The dosage form in the final immediate packaging intended for marketing……. controlled and documented determination of acceptable changes of the drug substance or drug product

6. Importance of stability study Assurance to patient that drug is safe. Legal requirement to provide data.to protect the reputation of the manufacturer To provide a database.to determine shelf life and storage conditions To verify that no changes have been introduced in the formulation or manufacturing process

7. Testing scope for Solid dosage form Physical-chemical properties – Appearance – Elasticity – Mean mass – Moisture – Hardness – Disintegration – Dissolution Chemical properties – Assay – Degradation Microbial properties Container closure system properties – Functionality tests (e.g. extraction from blister) 9 Physical-chemical properties​ – pH​ – Loss on weight​ – Color & clarity of solution​ - Sterility Tests​ Chemical properties​ – Assay​ – Degradation products​ – Degradation preservatives​ – Content antioxidants​ Microbial properties ​ - Pyrogen Testing ​ Container closure system properties​ – Functionality tests​ - Leakage test Testing scope for Liquid dosage form

8. Stages of Stability Studies Stability study is performed at various stages of the drug development process . There are 6 different stages: Stage 1: Early stage, i.e., stress and accelerated testing with drug substances. Stage 2: Stability on pre-formulation batches. Stage 3: stress test done on scale-up batches Stage 4 : Accelerated and long-term testing for registration purposes. Stage 5 : Enduring stability testing. Stage 6: follow up studies.

9. Types of stability Chemical Each active ingredient retains its chemical integrity and labeled potency within specified limits. Physical Microbiological Therapeutic Includes appearance, palatability, uniformity, dissolution and suspend ability are retained. Sterility or resistance to microbial growth is retained according to specific requirement. Activity remains unchanged . No significant increase in toxicity . Toxicologic

10. Real time stability testing Accelereted stability testing Retained sample stability testing Cyclic temperature stress testing Stability testing method

11. Performed for longer duration of the test period in order to allow significant product degradation under recommended storage conditions. Depends upon the stability of the product which should be long enough to indicate clearly that no measurable degradation occurs. Data collected at frequency Stability of reference material include the stability of reagent as well as consistency of performance To distinguish instability from day to to day Real time stability testing

12. A product is stressed at several high temp. & the amount of heat input required to cause product failure is determined. This is done to subject the product to a condition that accelerates degradation. This information is then projected to predict shelf life or used to compare the native stability of alternative formulations. Samples subjected to stress Refrigerated Assayed simultaneously 2. ACCELERATED STABILITY TESTING

13. Usual practice for every marketed product for which stability data are reuired. Only one batch a year are selected. If the number of batches marketed exceeds 50, stability samples from two batches are recommended to be taken. Stability testing by evaluation of market samples is a modified method which involves taking samples already in the market place and evaluating stability attributes. 3. RETAINED SAMPLE STABILITY TESTING

14. Is not a routine testing method for marketed products. In this method, cyclic temp. stress tests are designed on knowledge of the product so as to mimic likely conditions in market place storage. The period of cycle mostly considered is 24 hours. The min, and max. temp. for the cyclic stress testing is recommended to be selected on a product by-product basis and considering factors like recommended storage temp. for the product and specific chemical and physical degradation properties of the products. The test should normally have 20 cycles. 4. CYCLIC TEMPERATURE STRESS TESTING

15. ICH ICH stands for I nternational C onference on H armonization of Technical Requirements for Registration of Pharmaceuticals for Human use Objectives of ICH • Harmonization of registration applications within the three regions of the EU, Japan and the United States. • ICH is a joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines. Tripartite guideline on stability testing of new drug substances and products (Q1A) in 1993, has become standard for stability evaluation in Japan, US, Europe.

16. ICH CODE GUIDELINE TITLE Q1A Stability testing of New Drug Substances and Products (Second Revision) Q1B Stability testing Photo stability testing of New Drug Substances and Products Q1C Stability testing of New Dosage Form Q1D Bracketing and Matrixing Designs for stability testing of Drug Substances and Products Q1E Evaluation of stability data Q1F Stability data package for Registration Applications in Climatic Zones III and IV Q5C Stability testing of Biotechnological/Biological Products

17. Zone 1 Zone II Zone III Zone IV ( TEMPERATURE ) ( SUBTROPICAL & MEDITERRANEAN) ( HOT & DRY ) (HOT & HUMID ) United kingdom, Northern Europe, Russia, United states. Long term testing conditions – 21ºC/45 % RH Japan Southern Europe. Long term testing conditions- 25ºC/60% RH Iraq, India Long term testing conditions- 30ºC/35 % RH Iran, Egypt. Long term testing conditions- 21ºC/45 % RH Climatic zones for stability testing

18. Drug substances/Product- intended for storage in Freezer Study Storage condition Minimum time period covered by data at submission Long term -20°C ± 5°C 12 months Drug products - General case Study Storage condition Minimum time period covered by data at submission Long term 25°C ± 2°C / 60% ± 5% r.h. or 30°C ± 2°C / 65% ± 5% r.h. 12 months Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months Accelerated 40°C ± 2°C / 75% ± 5% r.h. 6 months Climatic Zones / Storage conditions

19. Stability chamber room

20. Stability Studies in Manufacturing

21. STABILITY STUDIES FOR PHARMACEUTICAL PRODUCTS TABLET Stable tablets retain their original size ,shape , weight ,roughness ,colour variation , cracking under normal handling and storage conditions throughout their shelf life. FRIABILITY TEST : studies revel the physical instability if any in tablet. Maximum weight loss should not be more than 1%. HARDNESS TEST : shows resistance to crushing. COLOR STABILITY : by colorimeter , reflectometer with heat , sunlight and intense artificial light. Uniformity of weight , odor , texture , drug and moisture content , humidity effects are also Studied during a tablet test. 27

22. Tests Method SOP# Specification (Low/High) Time (Months) appearance 3 6 9 etc. Color Degradation Assay Dissolution Clarity Stability Raw Data format

23. After registration… Once the pharmaceutical product has been registered, additional stability studies are required whenever variations that may affect the stability of the active pharmaceutical substance or pharmaceutical product are made, such as major variations like the following: a. Change in the manufacturing process. b. Change in the composition of the pharmaceutical product. c. Change of the immediate packaging.

24. Responsibility of Pharmacists

25. Pharmacists help to ensure that the products under their supervision meet acceptable criteria of stability by :

26. Rotation of Stock and Observance of Expiration Dates: Proper rotation of stock is necessary to ensure the dispensing of suitable products A product that is dispensed infrequently should be closely monitored so that old stocks are given special attention, particularly with regard to expiration dates. The manufacturer can guarantee the quality of a product up to the time designated as its expiration date only if the product has been stored in the original container under recommended storage conditions.

27. Storage under recommended conditions. These conditions are stated on the label it is imperative to adhere to those conditions. They may include a specified temperature range or a designated storage place or condition. (e.g., “refrigerator,” or “controlled room temperature”) as defined in the General Notices. Supplemental instructions, such as a direction to protect the product from light, also should be followed carefully.

28. In the absence of specific instructions, the product should be stored at controlled room temperature. Where a product is required to be protected from light and is in a clear or translucent container enclosed in an opaque outer covering , such outer covering is not to be removed and discarded until the contents have been used. The product should be stored away from locations where excessive or variable heat , cold , or light prevails , such as those near heating pipes or fluorescent lighting.

29. Conclusion. Stability testing is an essential part of the process of ensuring that the patient receives a product that meets established standards of safety, efficacy and quality.

30. Reference. USP – United States Pharmacopeia, 2008. {1191} Stability consideration in dispensing practice/ General information, page 2414.

31. Thank you.