Stability Workshop Ich Q18

1. 2

ICH Q1B Guideline Photostability Testing of New Drug Substances and Products
Comments for its Application

ICH Q1B C

32

Preamble
The intrinsic photostability characteristics should be evaluated to demonstrate that light exposure does not result in unacceptable change. Photostability testing is carried out on a • single registration batch of drug substance and drug product Asystematic approach is recommended: • • • • Tests on the drug substance, Tests on the exposed drug product outside the immediate pack, Tests on the drug product in the immediate pack if unacceptable change outside immediate pack, Tests on the drug product in the marketing pack If unacceptable change in immediate pack.

Acceptable change is change within limits justified by the applicant. Actuallyit has to be differentiated between: • • Change in appearance which is justified by the applicant, decomposition the limits of which are described in the ICH Guidelines Impurities in New Drug Substances and New Drug Products.

B Light Sources
To distinguish between: • • 1 the effect of light and temperature the temperature should be appropriate controlled or a dark sample used as reference.Option I

Any light source that is designed to produce an output similar to the D 65/ID 65 emission standard such as an • artificial daylight fluorescent, • lamp combining visible and ultraviolet. (UV) outputs, • Xenon or metal halide lamp. D 65 internationally recognized standard for outdoor daylight (ISO 10977, 1993) (D 65 is applied for photographic material). ID 65 is the equivalent indoorindirect daylight standard.
ICH Q1B C 33

B Light Sources
1 Option 2

For option 2 the same sample should be exposed to both • • The cool white fluorescent lamp specified in ISO 10977(1993) and A near UV fluorescent lamp with spectral distribution from 320 nm to 400 nm

The spectral distribution of Xenon is still the best light source It has to be differentiated between illuminance andirradiance. Illuminance (how bright a light source Iooks) is measured in lux. 1 lux = 1 luman per square meter. Irradiance (how much energy a light source has) is measured in Watts per square meter. 1 Watt = 1 Joule per second.
(Illuuminace = Beleuchtungsstärke

Irradiance = Bestrahlung)

C Procedure I
For confirmatory studies, samples should be exposed to light providing an • • overallillumination of not less than 1.2 million lux hours and an integrated near ultraviolet energy of not less than 200 Watt hours/square meter.

Samples may be exposed side-by-side with a validated chemical actinometric system or calibrated radiometers/lux meter. These requirements are fulfilled by the application of the Suntest CPS (Atlas corp.). It is equipped with a Xenon lamp.

C Procedure
The requiredradiant exposure • 200 Wh/m² is given for a wavelength range from 320 nm to 400 nm (UV range) The cut-off in the UV at approx. 320 is achieved by a filter system consisting out of a coated quartz glass dish and a window glass filter.
ICH Q1B C 34

The second mentioned radiant exposure, • 1.2 million lux hours, is limited to the visible range from approx. 400 nm to 800 nm.

The irradiancelevel in the Suntest may be adjusted from min. 250 to max. 765 W/ m² between 320 nm and 800 nm. With the a.m. filter systems installed these limits correspond: • to approx. 22.5 W/m² to 68.9 W/m² in the UV range and • to approx. 55 k lux to 170 k lux in the visible range.

C Procedure
Confirmatory studies 320 - 400 nm 200 Wh/m² At min. irradiance level: 200Wh/m²:: 22.5 W/ m² = 8.9 hours At max.irradiance level: 200 Wh/m² : 68.9 W/m2 = 2.9 hours Confirmatory studies 1.2 million lux hours At min. irradiance level: 1.2 million lux hours : 55 klux = 21.8 hours At maximum irradiance level 1.2 million lux hours: 170 klux = 7.1 hours Higher irradiance levels shorten the test duration by the factor 3, but the temperature increases if the irradiance is raised. Therefore it is recommended to...