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describes the history and body of ICH with special emphasis on guidelines to carry out stability testing.

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  • Since its inception in 1990, ICH has evolved, through its ICH Global Cooperation Group, to respond to the increasingly global face of drug development, so that the benefits of international harmonisation for better global health can be realised worldwide
  • The design assumes that the stability of an intermediate levels is represented by the stability of the extremes tested.
  • Bracketing can be applied to studies with multiple strengths of identical or closely related formulations. Examples include: Capsules, tablets and oral solutions of different strengths. In cases, where different excipients are used among strengths, bracketing generally should not be applied. Bracketing can be applied to studies of the same container closure system where either the container size or fill varies while the other remains constant.
  • Ich

    1. 1. Stability studies ofPharmaceuticals as Per ICH Guidelines P. Raja abhilash. M.Pharm. (Ph.D.) Assistant professor S.R. college of phramacy.
    2. 2. CONTENTS What is stability What is the need of stability in pharmaceuticals What is the requirements of physicals stability under Indian drug law Possible changes Factor affecting stability Stages of Drug and Product Development and Stability Testing Types of stability Physical stability of Pharmaceuticals Different Organization regulating stability guidelines ICH Guidelines ICH Q1AR2 Conclusion References
    3. 3. What is Stability? Drug Stability refers to the capacity of a drug substance orproduct to remain within established specifications ofidentity, strength, quality, and purity in a specified periodof time. Stability is officially defined as the time lapse during whichthe drug product retains the same properties andcharacteristics that it possessed at the time of manufacture. The stability of a product is expressed as the expiryperiod or technically as shelf life.
    4. 4. What is the Need of Stability in Pharmaceuticals KEY ASSURANCE OF QUALITY OF PHARMACEUTICALSTo gather information during Preformulation 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. Transport conditions. Provide an evidence on how the quality of a drugsubstance or drug product varies with the time under theinfluence of environmental factor
    5. 5. Requirement of Stability Testing under Indian Drug Law With reference to Schedule M serial No 16 Quality Control System 16.10: The quality control department shall conduct Stability Studies of the products to ensure and assign their shell life at the prescribed conditions of storage. All records of such studies shall be maintained
    6. 6. The Possible Changes{Visible & Invisible}  Loss of active ingredient Alteration in bioavailability Loss of content uniformity Decline of microbiological status Loss of pharmaceutical elegance and patient acceptability Formation of toxic degradation products Loss of package integrity Reduction of label quality Modification of any factor of functional relevance (dissolution, release, etc.)
    7. 7. Why so much emphasis on right practice in Stability The ideal production The non-ideal shipment and environment storage environment - Transport - Regulations and Controls - Wholesalers - GMP - Retailers - GLP - Patients The ideal formulation Mishandling
    8. 8. Factor Affecting Drug Stability 1- Environmental factors - Temperature - Light - Moisture 2- Drugs or excipients in the dosage form -Particle size of drug -pH of the vehicle 3- Microbial contamination 4- Trace metal Contamination 5- Leaching from containers
    9. 9. Types of Stability In Pharmaceuticals Stability of DrugPhysical Chemical Packaging Microbiological Physical Stability of Pharmaceuticals
    10. 10. Physical stability of Pharmaceuticals Physical stability implies that: -The formulation is totally unchanged (appearance, organoleptic properties, hardness, brittleness, particle size etc). -It is significant as it affects:  pharmaceutical elegance  drug content uniformity  drug release rate.
    11. 11. Physical stability of Pharmaceuticals { ORAL SOLUTION}
    12. 12. Physical stability of Pharmaceuticals { PARENTAL SOLUTION}
    13. 13. Physical stability of Pharmaceuticals { SUSPENSION}
    14. 14. Physical stability of Pharmaceuticals { EMULSION}
    15. 15. Physical stability of Pharmaceuticals {SEMI SOLIDS}
    16. 16. Physical stability of Pharmaceuticals {TABLETS}
    17. 17. Physical stability of Pharmaceuticals {CAPSULE}
    18. 18. Different regulatory Authorities which regulates guidelines for stabilityICH: international Conference on Harmonization of technical requirements for registration of pharmaceuticals for human useWHO : World Health OrganizationUSFDA: United state food drug AdministrationCPMP: Committee for Medicinal Products forHuman Use formerly known as Committee forProprietary Medicinal Products
    19. 19. What is ICH The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH is unique project that brings together the regulatory authorities of Europe, Japan & U.S. and experts from the pharmaceutical industries to discuss the scientific and technical aspects of the product registration. Mission of ICH ICH’s mission is to make recommendations towards achieving greater harmonisation, thereby reducing or obviating duplication of testing carried out during the research and development of new human medicines. Global Cooperation Group In 1999 ICH made five regions INDIA has joined ICH in 2007 in GCC Region
    20. 20. Body of ICH1. Founder members in steering committee of ICH European Union: represents 15 current EU member states European Federation of Pharmaceutical IndustriesAssociation (EFPIA): located in Brussels, mainly medicinesresearch based pharma companies from 15 countries. Ministry of Health and Welfare (MHW)- Japan. Japan Pharmaceutical Manufacturer’s Association (JPMA): itrepresents all the 90 major research based pharmaceuticalcompanies. US Food and Drug Administration (USFDA) Pharmaceutical Research and Manufacturers of America(PHRMA): it represents 67 research based companies and 25research affiliates.
    21. 21. 2. Observers: the following observers act as a link betweenICH countries and regions. i. WHO ii. Canada iii. IFPMA 3. ICH co- ordinator: nominated by each of the six co sponsors. 4. The ICH secretariat: its primary function is the organizationof steering committee and experts meeting and associateddocumentation. 5. ICH expert working group: carried by experts. 6.The harmonisation process: process development and theprogress of each guideline during harmonisation process.
    22. 22. ICH GUIDLINES GUIDELINES {QSEM} Quality guidelines Safety guidelines Efficacy guidelines Multi disciplinary guidelines
    23. 23. Quality Guidelines
    24. 24. The ICH Q1 series of guidelines are designed forstability programs which consists of 6 separateguidelines
    25. 25. ICH GUIDILINES Objectives Defines stability data package for drug substance and drug product for registration application, Within there region Exemplify the core stability package for new substance & products. General principle of Q1AR2  The purpose of stability testing is to provide evidence on how a drug substance or drug product varies with in time under the influence of environmental factor such as Temperature Humidity Light  To establish a re test period for the drug substance/shelf life  Recommended storage condition
    26. 26. ICH GUIDLINES Stress Testing : Studies undertaken to asses the effects of the sever conditions on the drug product. Carried out at 10 o c increment 50 o c….to 70 o c Humidity 75% RH Selection of Batches :at least three batches shall be studied for stability, out of which 2 batches shall be at least pilot batches and third one can be small if justified. Stability study can be performed on each individual strength and container size of the product.
    27. 27. ICH GUIDELINES Container Closure system Stability testing should be conducted on the dosage form packaged in the container closure system proposed for marketing Specification These guidelines states the list of test, reference to analytical procedure, and proposed acceptance criteria, include the concepts of different acceptance criteria for release and shelf life specification is addressed in ICH Q6A & Q6B.
    28. 28. ICH GUIDELINES Testing frequency For products with a proposed shelf life of at least 12 months the frequency of testing at the long term storage condition should normally be every 3 months over the first year, every 6 months over the second year, and annually thereafter through the proposed re-test period. First year------------------3 month Second --------------------6 month Thereafter------------------annually through out the proposed re-test period Testing frequency at accelerated storage condition min three point , at 0 , 3 , 6 month
    30. 30. ICH GUIDELINES
    32. 32. ICH GUIDELINES 2.Drug products packaged in semi permeable containers
    33. 33. ICH GUIDELINES 3.Drug products packaged in impermeable containers The stability studies for product stored in impermeable container can be conducted under any controlled or ambient humidity condition. 4.Drug products intended for storage in a refrigerator
    34. 34. ICH GUIDELINES 5.Drug products intended for storage in a freezerstability commitment submission includes data from stability studies on at least threeproduction batches, a commitment should be made to continuethese studies through the proposed re-test period.
    35. 35. Study design
    36. 36. In general significant change for drug product is definedas one or more of the following:1. A 5%change in assay from its initial value2. Any degradation product exceeding its acceptancecriteria3. Failure to meet the acceptance criteria for appearance,physical attributes and hard ness , dose delivery peractuation, etc.4. Failure to meet the acceptance criteria for pH.5. Failure to meet the acceptance criteria for dissolution for12 dosage units.
    37. 37. Evaluation A systematic approach should be adopted in the presentation and evaluation of the stability information. Where the data show so little degradation and so little variability that it is apparent from looking at the data that the requested shelf life will be granted, it is normally unnecessary to go through the formal statistical analysis; providing a justification for the omission should be sufficient. An approach for analysing data on a quantitative attribute that is expected to change with time is to determine the time at which the 95% one-sided confidence limit for the mean curve intersects the (lower) acceptance criterion (95% assay).
    38. 38. EVALUATION – BEST CASE 4. No significant change at accelerated conditions within six (6) months. 5. Long-term data show little or no variability and little or no change over time. 6. Accelerated data show little or no variability and little or no change over time. 7. Statistical analysis is normally unnecessary. 8. Proposed retest period or shelf life = double of period covered by long-tem data 9. A retest period or shelf life granted on the basis of extrapolation should always be verified by additional long- term stability data
    39. 39. CONCLUSION Stability studies should be planned on the basis of pharmaceutical R+D and regulatory requirements. Forced degradation studies reveal the intrinsic chemical properties of the API, while formal stability studies establish the retest date. The shelf life (expiry date) of FPPs is derived from formal stability studies. Variability and time trends of stability data must be evaluated by the manufacturer in order to propose a retest date or expiry date.
    40. 40. References Drug Stability: Principles and Practices, 3rd Edition, edited by Jens T. Carstensen and C. T. Rhodes www.pharmpedia.com www.ich.org www.fda.gov www.whoindia.org www.ema.europa.eu Remington the science and practice of pharmacy p1025
    41. 41. Questions
    42. 42. THANK YOU