ICH Guidelines

Q1A – Q1F
ICH guideline Q1-A(stability
studies)
Objectives of the Guideline :-

The guideline 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.

Scope:-
Addresses the information to be submitted in registration
applications for new molecular entities and associated drug product

General Principles :-

To provide 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.
To establish a retest period for the drug substance or a shelf life for the
drug product and recommending storage conditions.
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 STRESS TESTING

⚫ To validate the stability indicating power of the analytical procedures.

⚫ To identify stability-affecting factors such as ambient temperature, humidity
and light and to select packing materials which protects the formulation
against such effects
⚫ To identify potential degradants of the API and assess if they can be formed
during manufacture or storage of the formulation
⚫ To select manufacturing process for particular drug substance

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 SELECTION OF BATCHES
Applicability Minimum number Size and type
of batches
New drug 3 Pilot Scale
substance

New Drug product 3 Two pilot scale,

one small scale

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 Storage condition
Long term testing should cover a minimum of 12 months duration on at least three
primary batches at time of submission and should be continued sufficient to cover
the proposed re-test period
Drug product- general case
study Storage condition Duration
Long term 25°C ± 2°C/60% ± 5% RH or 12 months
30°C ± 2°C/65% ± 5% RH
Intermediate 30°C ± 2°C/65% ± 5% RH 6 months

Accelerated 40°C ± 2°C/75% ± 5% RH 6 months

Note:-
 It is up to the applicant, to decide whether long term stability is performed at
25°C ± 2°C/60% ± 5% RH or 30°C ± 2°C/65% ± 5% RH.
 If 30°C ± 2°C/65% ± 5% is the long-term condition, there is no intermediate
condition.
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EVALUATION
⚫ Evaluation should include results from the physical, chemical,biological
and microbiological tests.
e.g. physical parameter to evaluated for tablet.
1) Appearance
2) Friability
3) Hardness
4) Colour,Odour
5) Dissolution
6) Moisture absorption

STATEMENT AND LABELING

⚫ Storage Statement:-

Storage statement established for labeling should be in accordance with

national/regional requirements.
⚫ Re-test date:-
1.Statement based on stability evaluation
2.The re-test date should be displayed on the container label.

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 Photo stability testing: Q1-B
A systematic approach to photo stability testing is recommended covering, as
appropriate, studies such as :
i) Tests on the active substance;
ii) Tests on the exposed product outside of the immediate pack, and if necessary ;
iii) Tests on the product in the immediate pack; and if necessary ;
iv) Tests on the product in the marketing pack.

Light sources:
1. D65/ID65 emission

2.standard such as an artificial daylight fluorescent lamp combining visible and

ultraviolet (UV) outputs, xenon, or metal halide lamp.

3. D65 is the internationally recognized standard for outdoor daylight as defined

in ISO 10977 (1993). ID65 is the equivalent indoor indirect daylight standard.
For a light source emitting significant radiation below 320 nm, an appropriate
filter(s) may be fitted to eliminate such radiation.
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 BRACKETING :-
 Bracketing is the design of a stability schedule such that only sample on the
extremes of certain design factor (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 intermediates level is
represented by the stability of the extremes tested.
Example of a bracketing design:-

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

Key:-T = sample tested

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