The document outlines the importance of stability studies in pharmaceuticals, summarizing definitions, requirements, and regulatory guidelines according to ICH standards. It discusses factors affecting drug stability, types of stability, and the need for comprehensive testing to ensure product quality and safety. Additionally, it emphasizes the structured approach to stability testing, including environmental impacts, formulation integrity, and the regulatory framework guiding these practices.

1. Stability studies of
Pharmaceuticals as Per
ICH Guidelines
P. Raja abhilash. M.Pharm.
(Ph.D.)
Assistant professor
S.R. college of phramacy.

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. What is Stability?
 Drug Stability refers 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 lapse during which
the drug product retains the same properties and
characteristics that it possessed at the time of manufacture.
 The stability of a product is expressed as the expiry
period or technically as shelf life.

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 drug
substance or drug product varies with the time under the
influence of environmental factor

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. 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. 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. 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. Types of Stability In Pharmaceuticals
Stability of Drug
Physical Chemical Packaging Microbiological
Physical Stability of
Pharmaceuticals

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. Physical stability of Pharmaceuticals { ORAL SOLUTION}

12. Physical stability of Pharmaceuticals { PARENTAL SOLUTION}

13. Physical stability of Pharmaceuticals { SUSPENSION}

14. Physical stability of Pharmaceuticals { EMULSION}

15. Physical stability of Pharmaceuticals {SEMI SOLIDS}

16. Physical stability of Pharmaceuticals {TABLETS}

17. Physical stability of Pharmaceuticals {CAPSULE}

18. Different regulatory Authorities which regulates guidelines for stability
ICH: international Conference on Harmonization of
technical requirements for registration of
pharmaceuticals for human use
WHO : World Health Organization
USFDA: United state food drug Administration
CPMP: Committee for Medicinal Products for
Human Use formerly known as Committee for
Proprietary Medicinal Products

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. Body of ICH
1. Founder members in steering committee of ICH
European Union: represents 15 current EU member states
European Federation of Pharmaceutical Industries
Association (EFPIA): located in Brussels, mainly medicines
research based pharma companies from 15 countries.
Ministry of Health and Welfare (MHW)- Japan.
Japan Pharmaceutical Manufacturer’s Association (JPMA): it
represents all the 90 major research based pharmaceutical
companies.
US Food and Drug Administration (USFDA)
Pharmaceutical Research and Manufacturers of America
(PHRMA): it represents 67 research based companies and 25
research affiliates.

21. 2. Observers: the following observers act as a link between
ICH 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 organization
of steering committee and experts meeting and associated
documentation.
5. ICH expert working group: carried by experts.
6.The harmonisation process: process development and the
progress of each guideline during harmonisation process.

22. ICH GUIDLINES
GUIDELINES {QSEM}
Quality guidelines Safety guidelines
Efficacy guidelines Multi disciplinary guidelines

23. Quality Guidelines

24. The ICH Q1 series of guidelines are designed for
stability programs which consists of 6 separate
guidelines

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. 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. 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. 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

29. ICH GUIDELINES
THE ZONE CONCEPT

30. ICH GUIDELINES

31. ICH GUIDELINES
1.STORAGE CONDITION {GENERAL CASE}

32. ICH GUIDELINES
2.Drug products packaged in semi permeable containers

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. ICH GUIDELINES
5.Drug products intended for storage in a freezer
stability commitment
submission includes data from stability studies on at least three
production batches, a commitment should be made to continue
these studies through the proposed re-test period.

35. Study design

39. In general significant change for drug product is defined
as one or more of the following:
1. A 5%change in assay from its initial value
2. Any degradation product exceeding its acceptance
criteria
3. Failure to meet the acceptance criteria for appearance,
physical attributes and hard ness , dose delivery per
actuation, etc.
4. Failure to meet the acceptance criteria for pH.
5. Failure to meet the acceptance criteria for dissolution for
12 dosage units.

40. 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).

41. 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

42. 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.

43. 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

44. Questions

45. THANK YOU