Photostability Testing of New Drug Substances and Products:
The intrinsic photostability characteristics of new drug substances and products should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change.
Normally, photostability testing is carried out on a single batch of material. (Selection of Batches)
Under some circumstances, these studies should be repeated if certain variations and changes are made to the product (e.g., formulation, packaging).
Whether these studies should be repeated depends on the photostability characteristics determined at the time of initial filing and the type of variation and/or change made.
The guideline primarily addresses the generation of photostability information for submission in Registration Applications for new molecular entities and associated drug products.
The guideline does not cover the photostability of drugs after administration (i.e. under conditions of use) and those applications not covered by the Parent Guideline.
Alternative approaches may be used if they are scientifically sound and justification is provided.
A systematic approach to photostability testing is recommended covering, as appropriate, studies such as:
i) Tests on the drug substance;
ii) Tests on the exposed drug product outside of the immediate pack; and if necessary ;
iii) Tests on the drug product in the immediate pack; and if necessary ;
iv) Tests on the drug product in the marketing pack.
The extent of drug product testing should be established by assessing whether or not acceptable change has occurred at the end of the light exposure testing as described in the Decision Flow Chart for Photostability Testing of Drug Products.
Acceptable change is change within limits justified by the applicant.
The formal labeling requirements for photolabile drug substances and drug products are established by national/regional requirements.
Light Sources
The light sources described below may be used for photostability testing.
The applicant should either maintain 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/applicant 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.
1. A cool white fluorescent lamp designed to produce an output similar to that specified in ISO 10977(1993); and
2. 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.
Procedure
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.
An example of an actinometric procedure is provided in the Annex.
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.
Annex
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 percent 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)
Reference: ICH Guideline Q1B
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