ICH Q1B Guideline describe procedure photostability testing of pharmaceutical products. photostability testing is carried out on a single batch of material selected.
Procedure for photostability testing of pharmaceutical products
A systematic approach to photostability testing is recommended covering as appropriate studies such as:
- Tests on the drug substance
- Tests on the exposed drug product outside of the immediate pack
- Tests on the drug product in the immediate pack
- Tests on the drug product in the marketing pack
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.
Samples may be exposed side-by-side with a validated chemical actinometric system to ensure the specified light exposure is obtained, or for the appropriate duration of time when conditions have been monitored using calibrated radiometers/lux meters.
If protected samples (e.g., wrapped in aluminum foil) are used as dark controls to evaluate the contribution of thermally induced change to the total observed change, these should be placed alongside the authentic sample.
Quinine Chemical Actinometry
The following provides details of an actinometric procedure for monitoring exposure to a near UV fluorescent lamp (based on FDA/National Institute of Standards and Technology study). For other light sources/actinometric systems, the same approach may be used, but each actinometric system should be calibrated for the light source used.
Prepare a sufficient quantity of a 2 per cent weight/volume aqueous solution of quinine monohydrochloride dihydrate (if necessary, dissolve by heating).
Option 1
Put 10 milliliters (ml) of the solution into a 20 ml colorless ampoule seal it hermetically, and use this as the sample. Separately, put 10 ml of the solution into a 20 ml colourless ampoule (see note 1), seal it hermetically, wrap in aluminum foil to protect completely from light, and use this as the control. Expose the sample and control to the light source for an appropriate number of hours. After exposure determine the absorbances of the sample (AT) and the control (Ao) at 400 nm using a 1 centimeter (cm) path length. 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 1 cm quartz cell and use this as the sample. Separately fill a 1 cm quartz cell, wrap in aluminum foil to protect completely from light, and use this as the control. Expose the sample and control to the light source for an appropriate number of hours. After exposure determine the absorbances of the sample (AT) and the control (Ao) at 400 nm. 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.
Alternative packaging configurations may be used if appropriately validated. Alternative validated chemical actinometers may be used.
Note 1: Shape and Dimensions (See Japanese Industry Standard (JIS) R3512 (1974) for ampoule specifications)
Light Sources
The light sources described below may be used for photostability testing of pharmaceutical products with an appropriate control of temperature to minimize the effect of localized temperature changes or include a dark control in the same environment unless otherwise justified. For both options 1 and 2, a pharmaceutical manufacturer may rely on the spectral distribution specification of the light source manufacturer.
Option 1
Any light source that is designed to produce an output similar to the D65/ID65 emission standard such as an artificial daylight fluorescent lamp combining visible and ultraviolet (UV) outputs, xenon, or metal halide lamp. 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.
Option 2
For option 2 the same sample should be exposed to both the cool white fluorescent and near ultraviolet lamp.
- A cool white fluorescent lamp designed to produce an output similar to that specified in ISO 10977(1993) ; and
- A near UV fluorescent lamp having a spectral distribution from 320 nm to 400 nm with a maximum energy emission between 350 nm and 370 nm; a significant proportion of UV should be in both bands of 320 to 360 nm and 360 to 400 nm.
Evaluation
At the end of the exposure period, the samples should be examined for any changes in physical properties (e.g., appearance, clarity or color of solution, dissolution/disintegration for dosage forms such as capsules, etc.) and for assay and degradants by a method suitably validated for products likely to arise from photochemical degradation processes.
Depending on the extent of change special labeling or packaging may be needed to mitigate exposure to light. When evaluating the results of photostability studies to determine whether change due to exposure to light is acceptable, it is important to consider the results obtained from other formal stability studies in order to assure that the product will be within proposed specifications during the shelf life (see the relevant ICH Stability and Impurity Guidelines).