Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 6 November 1996, this guideline is recommended for adoption to the three regulatory parties to ICH.

The ICH Harmonised Tripartite Guideline covering the Stability Testing of New Drug Substances and Products (hereafter referred to as the Parent Guideline) notes that light testing should be an integral part of stress testing. This document is an annex to the Parent Guideline and addresses the recommendations for photostability testing.

1.1 Preamble

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 selected as described under Selection of Batches in the Parent Guideline. 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.

a. By kind permission of ICH (ICH Secretariat c/o IFPMA, 30, r . de Saint-Jean, P. O. Box 9, 1211 Genève 18, Switzerland.

Decision Flow Chart for Photostability Testing of Drug Products

Photostability Chart
Figure 1. Decision flow chart for photostability testing of drugs products.

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 (Fig. 1). Acceptable change is change within limits justified by the applicant.

The formal labelling requirements for photolabile drug substances and drug products are established by national/regional requirements.

1.2 Light Sources

The light sources described below may be used for photostability testing. The applicant should either maintain an appropriate control of temperature to minimise the effect of localised 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.

1.2.1 Option 1. Any light source that is designed to produce an output similar to the D65/ED65 emission standard such as an artificial daylight fluorescent lamp combining visible and ultraviolet (UV) outputs, xenon, or metal halide lamp. D65 is the internationally recognised 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 ran, an appropriate filter(s) may be fitted to eliminate such radiation.

1.2.2 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.

1.3 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.

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