ICH Guidelines of Stability

Ich guidelines for Stability
CONTENTS

INTRODUCTION
STRUCTURAL FEATURES OF ICH GUIDELINES FOR STABILITY

PREDICTION
OF SHELF LIFE
PARAMETERS EVALUATED
ICH
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
ICH is a joint initiative involving both regulators and research-based industry representatives of the European Union, Japan and the USA in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines.
Objective of ICH
To increase international harmonisation of technical requirements to ensure the safe, effective, and high quality medicines
Developement and registration of these drugs in the most efficient and costeffective manner
Prevent unnecessary duplication of clinical trials in humans
To
promote public health
Minimize the use of animal testing without compromising safety and effectiveness
Make information available on ICH, ICH activities and ICH guidelines to any country or company that requests the information
Promote harmonisation processes related
to ICH guidelines regionally
and globally
To
strengthen the capacity of drug regulatory authorities and industry to utilise them.
STABILITY
The capacity of a drug substance or drug product to remain within the established specifications to maintain its identity, strength, quality and purity through out the retest or expiration dating period.
NEED OF STABILITY STUDIES

# To determine the shelf life # To determine quality, safety and efficacy of a drug product.
ZONES MEAN KINETIC AVERAGE (CONDITION) TEMPERATURE YEARLY % RH

ZONE I (Moderate) ZONE II (Mediterranian) ZONE III (Hot, Dry) (Very hot, Moist) 21 25 30 45 60 35
ZONE IV 30 70 GLOBAL CLIMATIC ZONES
SHELF LIFE :-
The time during which the dosage form is supposed to retain its original qualities.
STEPS INVOLVED IN PREDICTION OF SHELF LIFE :1.
Division of formulation and storage at different elevated temperatures like 400C, 500C, 600C and 700C to accelerate degradation. Withdrawal of samples at various intervals of time and measurement of remaining concentration of active ingredients Determination of order of reaction
2.
3.
PREDICTION OF SHELF LIFE
4. Calculation of reaction rate constant K for the degradation at each elevated temperature.
5. Determination of K at room temperature from linear plot of log K values at different elevated temperatures against the reciprocal of absolute temperature
6. Extrapolation of curve to 25 0C and obtain K value at 250C

7. Substitution of K value in appropriate rate equation and shelf life is estimated 8. Calculation for determination of overage
FEATURES OF ICH GUIDELINES FOR STABILITY

SELECTION
OF BATCHES CONTAINER AND CLOSURE SYSTEM TESTING FREQUENCY For long-term studies every 3 months over the first year every 6 months over the second year annually thereafter through the proposed re-test period.
for
accelerated storage condition minimum of three time points, including the initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study
intermediate storage condition four time points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-month study
for
STORAGE CONDITIONS:Study Storage condition Minimum time period covered by data at submission 12 months
Long term*
25C 2C/60% RH 5% RH or 30C 2C/65% RH 5% RH
Intermediate**
Accelerated
30C 2C/65% RH 5% RH
40C 2C/75% RH 5% RH
6 months
6 months
*studies are performed at 25 2C/60% RH 5% RH or 30C 2C/65% RH 5% RH. ** If 30C 2C/65% RH 5% RH is the long-term condition, there is no intermediate condition.
Drug substances intended for storage in a refrigerator

Study Storage condition Minimum time period covered by data at submission 12 months
6 months
Long term Accelerated Long term**
5C 3C 25C 2C/60% RH 5% RH - 20C 5C
12 months
*FOR STORAGE IN FREEZER
EVALUATION

PHYSICAL TEST CHEMICAL TEST BIOLOGICAL TEST MICROBIOLOGICAL TEST
GENERAL PARAMETERS EVALUATED

APPEARANCE PHYSICAL PARAMETERS CHEMICAL PARAMETERS
- MOISTURE CONTENT - OXYGEN CONSUMPTION

DRUG CONTENT pH
PARAMETERS EVALUATED FOR DIFFERENT DOSAGE FORMS

Tablets
:-
Dissolution (or disintegration, if justified) Water content Hardness/Friability Tests for texture and colour stability (For coated and coloured tablets)
Capsules
:-
Brittleness dissolution (or disintegration, if justified)
water content
level of microbial contamination
Emulsions
:-
Phase separation pH Viscosity
Level of microbial contamination

Mean size
Distribution of dispersed globules
Oral

solutions and suspensions :-
Formation of precipitate clarity for solutions pH Viscosity Extractables level of microbial contamination Redispersibility rheological properties mean size distribution of particles polymorphic conversion (if applicable)
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 extractable/leachable from plastic and elastomeric components of the container, closure and pump.
Powders
and granules for oral solution or suspension :-
Water content Reconstitution time

Suppositories
:-
Softening range Dissolution (at 37C).
Topical,
:Clarity Homogeneity pH resuspendability (for lotions) Consistency Viscosity particle size distribution (for suspensions when feasible) level of microbial contamination/sterility weight loss (when appropriate).
ophthalmic and otic preparations
Cutaneous
sprays :-
pressure weight loss net weight dispensed delivery rate level of microbial contamination spray pattern water content particle size distribution (for suspensions)..
Parenterals
:-
Colour clarity (for solutions) particulate matter pH Sterility Endotoxins Volume*
1.
Sinko patrick J, Martins Physical Pharmacy & Pharmaceutical Sciences, published by Waulters kluwer health (India) pvt ltd, New Delhi, 5th edition, 2006 www.ema.europa.eu /docs.
2.
REFERENCES
THANKS

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Ich guidelines for Stability

STRUCTURAL FEATURES OF ICH GUIDELINES FOR STABILITY

Prevent unnecessary duplication of clinical trials in humans

promote public health

to ICH guidelines regionally

NEED OF STABILITY STUDIES

ZONES MEAN KINETIC AVERAGE (CONDITION) TEMPERATURE YEARLY % RH

ZONE IV 30 70 GLOBAL CLIMATIC ZONES

PREDICTION OF SHELF LIFE

6. Extrapolation of curve to 25 0C and obtain K value at 250C

FEATURES OF ICH GUIDELINES FOR STABILITY

25C 2C/60% RH 5% RH or 30C 2C/65% RH 5% RH

Drug substances intended for storage in a refrigerator

Long term Accelerated Long term**

5C 3C 25C 2C/60% RH 5% RH - 20C 5C

*FOR STORAGE IN FREEZER

PHYSICAL TEST CHEMICAL TEST BIOLOGICAL TEST MICROBIOLOGICAL TEST

GENERAL PARAMETERS EVALUATED

APPEARANCE PHYSICAL PARAMETERS CHEMICAL PARAMETERS

- MOISTURE CONTENT - OXYGEN CONSUMPTION

PARAMETERS EVALUATED FOR DIFFERENT DOSAGE FORMS

Brittleness dissolution (or disintegration, if justified)

Phase separation pH Viscosity

Level of microbial contamination

Distribution of dispersed globules

solutions and suspensions :-

and granules for oral solution or suspension :-

Water content Reconstitution time

Softening range Dissolution (at 37C).

ophthalmic and otic preparations

Colour clarity (for solutions) particulate matter pH Sterility Endotoxins Volume*

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