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STABILITY STUDIES FOR PHARMACEUTICAL
Products
What is Stability Study
• The capability of a particular formulation in a
specific container/closure system to remain
within its physical, chemical, microbiological,
toxicological, protective and informational
specifications.
• OR
• It is the extent to which a product retains, within
the specified limits, throughout its period of
storage and use, the same properties and
characteristics possessed at the time of its
packaging
• Stability testing thus evaluates the effect of environmental factors on
the quality of the a drug substance or a formulated product which is
utilized for prediction of its shelf life, determine proper storage
conditions and suggest labeling instructions.
• Stability testing is termed as a complex process because of
involvement of a variety of factors influencing the stability of a
pharmaceutical product. These factors include stability of the active
ingredient(s); interaction between active ingredients and excipients,
manufacturing process followed, type of dosage form,
container/closure system used for packaging and light, heat and
moisture conditions encountered during shipment, storage and
handling. In addition, degradation reactions like oxidation, reduction,
hydrolysis or racemization, which can play vital role in stability of a
pharmaceutical product, also depend on such conditions like
concentration of reactants, pH, radiation, catalysts etc., as well as the
raw materials used and the length of time between manufacture and
usage of the product.
A pharmaceutical product may undergo change in
appearance, consistency, content uniformity, clarity
(solution), moisture contents, particle size and shape,
pH, package integrity thereby affecting its stability.
The chemical reactions like oxidation, reduction,
racemization etc. that occur in the pharmaceutical
products may lead to the formation of degradation
product, loss of potency of active pharmaceutical
ingredient (API), loss of excipient activity like
antimicrobial preservative action and antioxidants.
Stability of a pharmaceutical product can also be affected
because of microbiological changes like growth of
microorganisms in non sterile products and changes in
preservative efficacy .
• 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
Who establish guidelines for stability
• ICH guidelines Q1A-Q1F. Stability testing of new APIs
and FPPs has been harmonized at global level.
• WHO “Guidelines for stability testing of pharmaceutical
products containing well established drug substances in
conventional dosage forms”
• USP (US Pharmacopeia)
• EMEA Note for Guidance on Stability Testing of existing
active substance and Related Finished products (Draft),
February 2002
• ASEAN Guideline on Stability of Drug Product
ICH
• ICH stands for International Conference on
Harmonization 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 Guidelines
Quality Guidelines “Q” (chemical and pharmaceutical QA)
– details see next slide
• Safety Guidelines “S” (in vitro and in vivo pre-clinical studies)
– covering Carcinogenicity Testing, Geno-toxicity Testing,
Toxico-kinetics and Pharmacokinetics ….. etc.
• Efficacy Guidelines “E” (clinical studies in human subject)
– Covering clinical safety, Dose Response Studies, Good
Clinical Practices, Clinical evaluation …. etc.
• Multidisciplinary Guidelines “M”
– Covering Medical Terminology, Electronic Standards for
Transmission of Regulatory Information …… etc.
ICH Guidelines
:Codesandtitles usedinICHGuidelines.
ICHCode Guidelinetitle
Q1A StabilitytestingofNewDrugSubstancesandProducts(Second
Revision)
Q1B Stabilitytesting:PhotostabilitytestingofNewDrug Substances
andProducts
Q1C StabilitytestingofNewDosageForms
Q1D BracketingandMatrixingDesignsforstabilitytestingofDrug
SubstancesandProducts
Q1E Evaluationofstabilitydata
Q1F StabilitydatapackageforRegistrationApplicationsinClimatic
ZonesIIIandIV
Q5C StabilitytestingofBiotechnological/BiologicalProducts
Climatic Zones for Stability
Testing
Stability Testing of New Drug Substances and Products
Q1A(R2)
Objectives:
• defines the stability data package for a new drug substance or drug product
that is sufficient for a registration application within the three regions of the
EC, Japan, and the United States.
Photo stability Testing
• Photo stability testing should be conducted on at least one primary batch of
the drug product if appropriate.
Selection of Batches:
• At least three primary batches of the drug substance. The batches should be
manufactured to a minimum of pilot scale by the same synthetic route as,
and using a method of manufacture and procedure that simulates the final
production batches.
Container Closure System:
• The stability studies should be conducted on the drug substance
packaged in a container closure system that is the same as or
simulates the packaging proposed for storage and distribution.
Testing Frequency
• long term studies - every 3 months over the first year, every 6
months over the second year, and annually thereafter through the
proposed shelf life
• accelerated studies - minimum of three time points, including the
initial and final time points.
Statements / Labelling :
• A storage statement should be established for the labelling in
accordance with relevant national/regional requirements. The
statement should be based on the stability evaluation of the drug
product.
General case – Storage Condition.
Study Storage condition Minimum time period covered by
data at submission
Long term* 25°C ± 2°C/60% RH ± 5% RH
or
30°C ± 2°C/65% RH ± 5% RH
12 months
Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months
Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months
*It is up to the applicant to decide whether long term stability studies are
performed at 25  2°C/60% RH  5% RH or 30°C  2°C/65% RH  5% RH.
**If 30°C  2°C/65% RH  5% RH is the long-term condition, there is no
intermediate condition.
Parameters for Stability Testing
1. Tablets
• Dissolution (or disintegration, if justified), water content and
hardness/friability. For coated and coloured tablets additional tests may
require for texture and colour stability.
2. Capsules
• Hard gelatin capsules: brittleness, dissolution (or disintegration, if
justified), water content, and level of microbial contamination.
3. Emulsions
• Phase separation, pH, viscosity, level of microbial contamination, and
mean size and distribution of dispersed globules.
4. Oral solutions and suspensions
• Formation of precipitate, clarity for solutions, pH, viscosity, extractables,
level of microbial contamination.
• Additionally for suspensions, redispersibility, rheological properties,
mean size and distribution of particles should be considered. Also,
polymorphic conversion may be examined, if applicable.
5. Powders and granules for oral solution or suspension
• Water content, and reconstitution time.
• Reconstituted products should be evaluated as described in “Oral
solutions and suspensions” above, after preparation according to the
recommended labeling, through the maximum intended use period.
6. Nasal sprays: solutions and suspensions
• Clarity (for solution), level of microbial contamination, pH, particulate
matter, unit spray medication content uniformity, number of actuations
meeting unit spray content uniformity per container, droplet and/or
particle size distribution, weight loss, pump delivery, microscopic
evaluation (for suspensions), foreign particulate matter and extractable/
leachable from plastic and elastomeric components of the container,
closure and pump.
7. Topical, ophthalmic and otic preparations
• Included in this broad category are ointments, creams, lotions, paste, gel,
solutions, eye drops, and cutaneous sprays.
• Topical preparations should be evaluated for clarity, homogeneity, pH,
resuspendability, consistency, viscosity, particle size distribution, level of
microbial contamination/sterility and weight loss.
8. Suppositories
• Softening range, dissolution (at 37°C).
9. Small volume parenterals (SVPs)
• Colour, clarity (for solutions), particulate matter, pH, sterility, endotoxins.
• Stability studies for powders for injection solution should include
monitoring for colour, reconstitution time and water content. Specific
parameters to be examined at appropriate intervals throughout the
maximum intended use period of the reconstituted drug product, stored
under condition(s) recommended in labeling, should include clarity,
colour, pH, sterility, pyrogen and particulate matter.
• The stability studies for Suspension for injection should include, in
addition, particle size, distribution, redispersibility and rheological
properties.
• The stability studies for Emulsion for injection should include, in addition,
phase separation, viscosity, mean size and distribution of dispersed
phase globules.
10. Large volume parenterals (LVPs)
• Colour, clarity, particulate matter, pH, sterility, pyrogen/endotoxin, and
volume.
PHOTO STABILITY TESTING OF NEW DRUG
SUBSTANCES AND PRODUCTS - Q1B
• Photo stability testing is carried out on a single batch of material
selected as described under Selection of Batches in the Parent
Guideline.
• The guideline primarily addresses the generation of photo stability
information for submission in Registration Applications for new
molecular entities and associated drug products.
• The guideline does not cover the photo stability of drugs after
administration (i.e. under conditions of use) and those applications
not covered by the Parent Guideline.
• A systematic approach to photo stability testing is recommended
covering, as appropriate, studies such as:
i) Tests on the drug substance;
ii) Tests on the exposed drug product outside of the immediate pack;
and if necessary ;
iii) Tests on the drug product in the immediate pack; and if necessary ;
iv) Tests on the drug product in the marketing pack.
Light Sources:
A cool white fluorescent lamp & A near UV fluorescent lamp.
• Procedure
For confirmatory studies, samples should be exposed to light providing an
overall illumination of not less than 1.2 million lux hours and an
integrated near ultraviolet energy of not less than 200 watt hours /
square meter to allow direct comparisons to be made between the drug
substance and drug product.
Objectives of the Guideline:
intended to address recommendations on the application of bracketing
and Matrixing to stability studies conducted in accordance with
principles outlined in the ICH Q1A
Reduced Designs :
Bracketing and matrixing are reduced designs based on different
principles. Therefore, careful consideration and scientific justification
should precede the use of bracketing and matrixing together in one
design.
BRACKETING AND MATRIXING DESIGNS FOR
STABILITY TESTING OF NEW DRUG
SUBSTANCES AND PRODUCTS - Q1D
Bracketing:
• Bracketing is the design of a stability schedule such that only
samples on the extremes of certain design factors.
• e.g., strength, container size and/or fill are tested at all time points as
in a full design.
• The design assumes that the stability of any intermediate levels is
represented by the stability of the extremes tested.
e.g.:
(1)Capsules of different strengths made with different fill plug sizes from
the same powder blend,
(2)Tablets of different strengths manufactured by compressing varying
amounts of the same granulation,
(3)Oral solutions of different strengths with formulations that differ only in
minor excipients (e.g., colourants, flavourings).
Strength 50 mg 75 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
Example of a Bracketing Design
Key: T = Sample tested
Product available in three strengths and three container sizes.
In this example, 15 ml and 500 ml container sizes & 50mg and 100mg
truly represent the extremes.
Matrixing:
Matrixing is the design of a stability schedule such that a selected
subset of the total number of possible samples would
be tested at a specified time point.
The design assumes that the stability of each subset of samples
tested represents the stability of all samples at a given time
point.
The differences in the samples for the same drug product should be
identified as, for example, covering different batches, different strengths,
different sizes of the same container closure system.
Examples of Matrixing Designs on Time Points
for a Product with Two Strengths
Time point (months) 0 3 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
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”
Key: T = Sample tested
Time point (months) 0 3 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-ThirdReduction”
Key: T = Sample tested
EVALUATION FOR STABILITY DATA - Q1E
Objectives:
• This guideline intended to provide recommendations on how to use
stability data generated in accordance with the principles detailed in
the ICH guideline “Q1A(R) Stability Testing of New Drug
Substances and Products”
• This guideline describes when and how extrapolation can be
considered when proposing a retest period for a drug substance or a
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”
• Data presentation:
• Data for all attributes should be presented in an appropriate format
(e.g., tabular, graphical, narrative) and an evaluation of such data
should be included in the application.
• The values of quantitative attributes at all time points should be
reported as measured (e.g., assay as percent of label claim).
• If a statistical analysis is performed, the procedure used and the
assumptions underlying the model should be stated and justified.
Extrapolation :
• Extrapolation is the practice of using a known data set to infer
information about future data.
• An extrapolation of stability data assumes that the same change
pattern will continue to apply beyond the period covered by long-
term data.
• When estimating a regression line or curve to fit the long-term
data, the data themselves provide a check on the correctness of the
assumed change pattern, and statistical methods can be applied to
test the goodness of fit of the data to the assumed line or curve.
• outlines the stability data package for a new
drug substance or drug product that is
considered sufficient for a registration
application in territories in Climatic Zones III
and IV
• The stability testing recommendations in
this guideline are based on the parent
guideline and the WHO guideline
STABILITY DATA PACKAGE FOR REGISTRATION
APPLICATIONS IN CLIMATIC ZONES III AND IV -
Q1F – WITHDRAWN ON 2006
• Storage Conditions
General Case
The recommended long-term and accelerated storage conditions for
Climatic Zones III and IV
Study Storage condition Minimum time period
covered by data at
submission
Long-term 30°C ± 2°C/65% RH ± 5% RH 12 months
Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months
Recommended labeling statements for finished
pharmaceutical products (FPPs)
Additional labeling statements for use where
the result of the stability testing demonstrates
limiting factors
THANKS YOU

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Stability study slideshare

  • 1. STABILITY STUDIES FOR PHARMACEUTICAL Products
  • 2. What is Stability Study • The capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, toxicological, protective and informational specifications. • OR • It is the extent to which a product retains, within the specified limits, throughout its period of storage and use, the same properties and characteristics possessed at the time of its packaging
  • 3. • Stability testing thus evaluates the effect of environmental factors on the quality of the a drug substance or a formulated product which is utilized for prediction of its shelf life, determine proper storage conditions and suggest labeling instructions. • Stability testing is termed as a complex process because of involvement of a variety of factors influencing the stability of a pharmaceutical product. These factors include stability of the active ingredient(s); interaction between active ingredients and excipients, manufacturing process followed, type of dosage form, container/closure system used for packaging and light, heat and moisture conditions encountered during shipment, storage and handling. In addition, degradation reactions like oxidation, reduction, hydrolysis or racemization, which can play vital role in stability of a pharmaceutical product, also depend on such conditions like concentration of reactants, pH, radiation, catalysts etc., as well as the raw materials used and the length of time between manufacture and usage of the product.
  • 4. A pharmaceutical product may undergo change in appearance, consistency, content uniformity, clarity (solution), moisture contents, particle size and shape, pH, package integrity thereby affecting its stability. The chemical reactions like oxidation, reduction, racemization etc. that occur in the pharmaceutical products may lead to the formation of degradation product, loss of potency of active pharmaceutical ingredient (API), loss of excipient activity like antimicrobial preservative action and antioxidants. Stability of a pharmaceutical product can also be affected because of microbiological changes like growth of microorganisms in non sterile products and changes in preservative efficacy .
  • 5. • 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
  • 6. Who establish guidelines for stability • ICH guidelines Q1A-Q1F. Stability testing of new APIs and FPPs has been harmonized at global level. • WHO “Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms” • USP (US Pharmacopeia) • EMEA Note for Guidance on Stability Testing of existing active substance and Related Finished products (Draft), February 2002 • ASEAN Guideline on Stability of Drug Product
  • 7. ICH • ICH stands for International Conference on Harmonization 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.
  • 8. ICH Guidelines Quality Guidelines “Q” (chemical and pharmaceutical QA) – details see next slide • Safety Guidelines “S” (in vitro and in vivo pre-clinical studies) – covering Carcinogenicity Testing, Geno-toxicity Testing, Toxico-kinetics and Pharmacokinetics ….. etc. • Efficacy Guidelines “E” (clinical studies in human subject) – Covering clinical safety, Dose Response Studies, Good Clinical Practices, Clinical evaluation …. etc. • Multidisciplinary Guidelines “M” – Covering Medical Terminology, Electronic Standards for Transmission of Regulatory Information …… etc.
  • 9. ICH Guidelines :Codesandtitles usedinICHGuidelines. ICHCode Guidelinetitle Q1A StabilitytestingofNewDrugSubstancesandProducts(Second Revision) Q1B Stabilitytesting:PhotostabilitytestingofNewDrug Substances andProducts Q1C StabilitytestingofNewDosageForms Q1D BracketingandMatrixingDesignsforstabilitytestingofDrug SubstancesandProducts Q1E Evaluationofstabilitydata Q1F StabilitydatapackageforRegistrationApplicationsinClimatic ZonesIIIandIV Q5C StabilitytestingofBiotechnological/BiologicalProducts
  • 10. Climatic Zones for Stability Testing
  • 11. Stability Testing of New Drug Substances and Products Q1A(R2) Objectives: • defines the stability data package for a new drug substance or drug product that is sufficient for a registration application within the three regions of the EC, Japan, and the United States. Photo stability Testing • Photo stability testing should be conducted on at least one primary batch of the drug product if appropriate. Selection of Batches: • At least three primary batches of the drug substance. The batches should be manufactured to a minimum of pilot scale by the same synthetic route as, and using a method of manufacture and procedure that simulates the final production batches.
  • 12. Container Closure System: • The stability studies should be conducted on the drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution. Testing Frequency • long term studies - every 3 months over the first year, every 6 months over the second year, and annually thereafter through the proposed shelf life • accelerated studies - minimum of three time points, including the initial and final time points. Statements / Labelling : • A storage statement should be established for the labelling in accordance with relevant national/regional requirements. The statement should be based on the stability evaluation of the drug product.
  • 13. General case – Storage Condition. Study Storage condition Minimum time period covered by data at submission Long term* 25°C ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH 12 months Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months *It is up to the applicant to decide whether long term stability studies are performed at 25  2°C/60% RH  5% RH or 30°C  2°C/65% RH  5% RH. **If 30°C  2°C/65% RH  5% RH is the long-term condition, there is no intermediate condition.
  • 14. Parameters for Stability Testing 1. Tablets • Dissolution (or disintegration, if justified), water content and hardness/friability. For coated and coloured tablets additional tests may require for texture and colour stability. 2. Capsules • Hard gelatin capsules: brittleness, dissolution (or disintegration, if justified), water content, and level of microbial contamination. 3. Emulsions • Phase separation, pH, viscosity, level of microbial contamination, and mean size and distribution of dispersed globules. 4. Oral solutions and suspensions • Formation of precipitate, clarity for solutions, pH, viscosity, extractables, level of microbial contamination. • Additionally for suspensions, redispersibility, rheological properties, mean size and distribution of particles should be considered. Also, polymorphic conversion may be examined, if applicable.
  • 15. 5. Powders and granules for oral solution or suspension • Water content, and reconstitution time. • Reconstituted products should be evaluated as described in “Oral solutions and suspensions” above, after preparation according to the recommended labeling, through the maximum intended use period. 6. Nasal sprays: solutions and suspensions • Clarity (for solution), level of microbial contamination, pH, particulate matter, unit spray medication content uniformity, number of actuations meeting unit spray content uniformity per container, droplet and/or particle size distribution, weight loss, pump delivery, microscopic evaluation (for suspensions), foreign particulate matter and extractable/ leachable from plastic and elastomeric components of the container, closure and pump. 7. Topical, ophthalmic and otic preparations • Included in this broad category are ointments, creams, lotions, paste, gel, solutions, eye drops, and cutaneous sprays. • Topical preparations should be evaluated for clarity, homogeneity, pH, resuspendability, consistency, viscosity, particle size distribution, level of microbial contamination/sterility and weight loss.
  • 16. 8. Suppositories • Softening range, dissolution (at 37°C). 9. Small volume parenterals (SVPs) • Colour, clarity (for solutions), particulate matter, pH, sterility, endotoxins. • Stability studies for powders for injection solution should include monitoring for colour, reconstitution time and water content. Specific parameters to be examined at appropriate intervals throughout the maximum intended use period of the reconstituted drug product, stored under condition(s) recommended in labeling, should include clarity, colour, pH, sterility, pyrogen and particulate matter. • The stability studies for Suspension for injection should include, in addition, particle size, distribution, redispersibility and rheological properties. • The stability studies for Emulsion for injection should include, in addition, phase separation, viscosity, mean size and distribution of dispersed phase globules. 10. Large volume parenterals (LVPs) • Colour, clarity, particulate matter, pH, sterility, pyrogen/endotoxin, and volume.
  • 17. PHOTO STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS - Q1B • Photo stability testing is carried out on a single batch of material selected as described under Selection of Batches in the Parent Guideline. • The guideline primarily addresses the generation of photo stability information for submission in Registration Applications for new molecular entities and associated drug products. • The guideline does not cover the photo stability of drugs after administration (i.e. under conditions of use) and those applications not covered by the Parent Guideline.
  • 18. • A systematic approach to photo stability testing is recommended covering, as appropriate, studies such as: i) Tests on the drug substance; ii) Tests on the exposed drug product outside of the immediate pack; and if necessary ; iii) Tests on the drug product in the immediate pack; and if necessary ; iv) Tests on the drug product in the marketing pack. Light Sources: A cool white fluorescent lamp & A near UV fluorescent lamp.
  • 19. • Procedure For confirmatory studies, samples should be exposed to light providing an overall illumination of not less than 1.2 million lux hours and an integrated near ultraviolet energy of not less than 200 watt hours / square meter to allow direct comparisons to be made between the drug substance and drug product.
  • 20. Objectives of the Guideline: intended to address recommendations on the application of bracketing and Matrixing to stability studies conducted in accordance with principles outlined in the ICH Q1A Reduced Designs : Bracketing and matrixing are reduced designs based on different principles. Therefore, careful consideration and scientific justification should precede the use of bracketing and matrixing together in one design. BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS - Q1D
  • 21. Bracketing: • Bracketing is the design of a stability schedule such that only samples on the extremes of certain design factors. • e.g., strength, container size and/or fill are tested at all time points as in a full design. • The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. e.g.: (1)Capsules of different strengths made with different fill plug sizes from the same powder blend, (2)Tablets of different strengths manufactured by compressing varying amounts of the same granulation, (3)Oral solutions of different strengths with formulations that differ only in minor excipients (e.g., colourants, flavourings).
  • 22. Strength 50 mg 75 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 Example of a Bracketing Design Key: T = Sample tested Product available in three strengths and three container sizes. In this example, 15 ml and 500 ml container sizes & 50mg and 100mg truly represent the extremes.
  • 23. Matrixing: Matrixing is the design of a stability schedule such that a selected subset of the total number of possible samples would be tested at a specified time point. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point. The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same container closure system.
  • 24. Examples of Matrixing Designs on Time Points for a Product with Two Strengths Time point (months) 0 3 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 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” Key: T = Sample tested
  • 25. Time point (months) 0 3 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-ThirdReduction” Key: T = Sample tested
  • 26. EVALUATION FOR STABILITY DATA - Q1E Objectives: • This guideline intended to provide recommendations on how to use stability data generated in accordance with the principles detailed in the ICH guideline “Q1A(R) Stability Testing of New Drug Substances and Products” • This guideline describes when and how extrapolation can be considered when proposing a retest period for a drug substance or a 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”
  • 27. • Data presentation: • Data for all attributes should be presented in an appropriate format (e.g., tabular, graphical, narrative) and an evaluation of such data should be included in the application. • The values of quantitative attributes at all time points should be reported as measured (e.g., assay as percent of label claim). • If a statistical analysis is performed, the procedure used and the assumptions underlying the model should be stated and justified. Extrapolation : • Extrapolation is the practice of using a known data set to infer information about future data. • An extrapolation of stability data assumes that the same change pattern will continue to apply beyond the period covered by long- term data. • When estimating a regression line or curve to fit the long-term data, the data themselves provide a check on the correctness of the assumed change pattern, and statistical methods can be applied to test the goodness of fit of the data to the assumed line or curve.
  • 28. • outlines the stability data package for a new drug substance or drug product that is considered sufficient for a registration application in territories in Climatic Zones III and IV • The stability testing recommendations in this guideline are based on the parent guideline and the WHO guideline STABILITY DATA PACKAGE FOR REGISTRATION APPLICATIONS IN CLIMATIC ZONES III AND IV - Q1F – WITHDRAWN ON 2006
  • 29. • Storage Conditions General Case The recommended long-term and accelerated storage conditions for Climatic Zones III and IV Study Storage condition Minimum time period covered by data at submission Long-term 30°C ± 2°C/65% RH ± 5% RH 12 months Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months
  • 30. Recommended labeling statements for finished pharmaceutical products (FPPs)
  • 31. Additional labeling statements for use where the result of the stability testing demonstrates limiting factors