The ICH Guideline, Stability Testing Photostability Testing of New Drug Substances and Products-Q1B addresses the recommendations for photostability testing, an integral part of stress testing. This document is an annex to the Parent Guideline and focuses on evaluating the intrinsic photostability characteristics of new drug substances and products.

1. Stability Testing:
Photostability Testing of
New Drug Substances
and Products Q1B
The ICH Guideline addresses the recommendations for photostability
testing, an integral part of stress testing. This document is an annex to
the Parent Guideline and focuses on evaluating the intrinsic
photostability characteristics of new drug substances and products.
by Trishala Bhatt

2. General
1 Light Testing
Light testing is an integral part of stress testing, and photostability testing is
carried out on a single batch of material selected as described under
Selection of Batches in the Parent Guideline.
2 Repetition of Studies
Under certain circumstances, these studies should be repeated if variations
and changes are made to the product, depending on the photostability
characteristics determined at the time of initial filing.
3 Scope
The guideline primarily addresses the generation of photostability
information for submission in Registration Applications for new molecular
entities and associated drug products.

3. Light Sources
Option 1
Light sources like artificial daylight fluorescent
lamps, xenon, or metal halide lamps emit light
similar to D65/ID65 emission standards, with
D65 for outdoor daylight and ID65 for indoor
indirect daylight. Filters may be fitted for
radiation below 320 nm.
Option 2
Option 2 involves exposing the sample to both
cool white and near fluorescent lamps, with a
cool white lamp producing ISO 10977 output
and a near UV lamp distributing 320 to 400 nm
with maximum energy emission 350 nm and
370 nm.

4. Procedure
1 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 .
2 Actinometric Procedure
Samples can be tested using a validated chemical actinometric system or calibrated
radiometers/lux meters. Protected samples can be used as dark controls to evaluate
thermally induced change contribution to observed change. An example of an
actinometric procedure is provided in the Annex to monitor exposure to a near UV
fluorescent lamp.

6. Drug Substance
Forced Degradation Testing
Forced degradation testing studies are
undertaken to evaluate the overall
photosensitivity of the material for method
development purposes and/or degradation
pathway elucidation.
Samples should be in chemically inert and
transparent containers. Exposure conditions
may vary depending on the drug substance's
photosensitivity and light source intensity.
Decomposition products may be observed
under forcing conditions, useful for
developing analytical methods.
Confirmatory Testing
Confirmatory studies provide information
for handling, packaging, and labeling.
Typically, one batch of drug substance is
tested during the development phase,
followed by photostability characteristics
confirmation on a single batch if the drug is
photostable or photolabile. If the results of
the confirmatory study are equivocal,
testing of up to two additional batches
should be conducted.

7. Presentation of Samples
Transparent Containers
Samples should be in chemically inert and
transparent containers to minimize the effects of
changes in physical states.
For solid drug substances, place them in a glass
or plastic dish and cover with a transparent
cover. For liquid drugs, expose them in
chemically inert and transparent containers.
Sealed Containers
Efforts should be made to ensure that the effects
of changes in physical states are minimized,
such as sublimation, evaporation, or melting.
Possible interactions between the samples and
any material used for containers or for general
protection of the sample, should also be
considered and eliminated wherever not
relevant to the test being carried out.

8. Analysis of Samples
1
Physical Properties
Examine the samples for any changes in physical properties, such as
appearance, clarity, or color of solution.
2
Assay and Degradants
Assay and degradants should be analyzed by a method suitably validated
for products likely to arise from photochemical degradation processes.
Sample consideration
Solid drug substance samples should be representative in individual
tests, and homogenization of the entire sample is necessary. Analysis
should be performed alongside protected samples used as dark controls.

9. Judgement of Results
Forced Degradation Studies Designed to provide suitable information to
develop and validate test methods for the
confirmatory studies.
Identifying photolytic degradants.
Confirmatory Studies Identify precautionary measures needed in
manufacturing or formulation and whether
light resistant packaging and/or special
labeling is needed to mitigate exposure to
light.

10. Drug Product
Sequential Testing
Testing should be carried out in a sequential manner starting with
testing the fully exposed product then progressing as necessary to the
product in the immediate pack and then in the marketing pack.
Testing should ensure the product is adequately protected from light
exposure.
Batch Selection
Only one batch is tested during the development phase, and
photostability characteristics should be confirmed on a single batch
selected as described in the Parent Guideline.
If results are ambiguous, two additional batches may be conducted.
Exception
Testing for products impenetrable to light, like aluminium tubes or
cans, should be conducted on directly exposed drug products.
Infusion liquids and dermal creams may be tested for photostability,
with testing based on directions for use.

11. Presentation of Samples
Sealed Containers
Efforts should be made to
ensure that the effects of
changes in physical states
are minimized, such as
sublimation, evaporation, or
melting.
Possible interactions
between the samples and any
material used for containers
or for general protection of
the sample, should also be
considered and eliminated
wherever not relevant to the
test being carried out.
Transparent Containers
When testing drug product
samples outside the primary
pack, present them in a
similar condition and
position them for maximum
exposure to light as drug
substance. For example,
tablets, capsules, etc., should
be spread in a single layer.
If direct exposure isn't
possible (e.g., due to
oxidation of a product),
place them in a protective,
transparent container(e.g.,
quartz).
Immediate/marketed
container
Test drug product in
immediate container or
marketed form, placing
samples horizontally or
transversely for uniform
exposure. Adjust conditions
for large volume containers
(e.g., dispensing packs).

12. Analysis of Samples
1
Physical Properties
Examine the samples for any changes in physical properties, such as
appearance, clarity, or color of solution, dissolution/disintegration for
dosage forms such as capsules, etc.
2
Assay and Degradants
Assay and degradants should be analyzed by a method suitably
validated for products likely to arise from photochemical degradation
processes.
Sample consideration
To ensure accurate testing, use a representative portion of powder samples
in individual tests, and conduct testing on appropriate composites for solid
oral dosage form products (for example, 20 tablets or capsules).
Similar sampling considerations apply to materials like creams, ointments,
and suspensions that may not be homogeneous after exposure
Analyze exposed samples alongside protected samples as dark controls.
.

13. Judgement of Results
Depending on the extent of change special
labeling or packaging may be needed to
mitigate exposure to light
Photostability studies should consider
other stability studies to ensure product
meets shelf life specifications, as per ICH
Stability and Impurity Guidelines.

14. Quinine Chemical Actinometry
Option 1
To analyze a solution, place 10 ml solution in a 20 ml
colorless ampoule as a sample and 10 ml as a control.
seal it hermetically, wrap in aluminum foil to protect
completely from light, and use this as the control.
Expose the samples and control to a light source for hours,
then determine their absorbances at 400 nm using a 1 cm
path length. Calculate the change in absorbance.
Calculate the change in absorbance, ∆ A = AT - Ao. The
length of exposure should be sufficient to ensure a change
in absorbance of at least 0.9.
Option 2
Fill a quartz cell with a sample and a control, wrap in
aluminum foil to protect completely from light, and use
this as the control, then expose them to light for hours.
Determine absorbances at 400 nm and calculate the
change in absorbance. Use alternative packaging
configurations or validated chemical actinometers if
needed.
Calculate the change in absorbance, ∆ A = AT - Ao. The
length of exposure should be sufficient to ensure a
change in absorbance of at least 0.5.
The actinometric procedure for monitoring UV exposure to a near UV fluorescent lamp involves preparing a 2%
weight/volume aqueous solution of quinine monohydrochloride dihydrate, which should be calibrated for the light source
used.

15. Glossary
Immediate Pack
The constituent of the packaging that
is in direct contact with the drug
substance or drug product, and
includes any appropriate label.
Marketing Pack
The combination of immediate pack
and other secondary packaging such
as a carton.