Drug Product

Normally, the studies on drug products 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 progress until the results demonstrate that the drug product is adequately protected from exposure to light. The drug product should be exposed to the light conditions described under the procedure in Section 1.3.

Normally, only one batch of drug product is tested during the development phase, and then the photostability characteristics should be confirmed on a single batch selected as described in the Parent Guideline if the product is clearly photostable or photolabile. If the results of the confirmatory study are equivocal, testing of up to two additional batches should be conducted.

For some products where it has been demonstrated that the immediate pack is completely impenetrable to light, such as aluminum tubes or cans, testing should normally only be conducted on directly exposed drug product.

It may be appropriate to test certain products such as infusion liquids, dermal creams, etc., to support their photostability in-use. The extent of this testing should depend on and relate to the directions for use, and is left to the applicant's discretion.

The analytical procedures used should be suitably validated.

3.1 Presentation of Samples

Care should be taken to ensure that the physical characteristics of the samples under test are taken into account and efforts, such as cooling and/or placing the samples in sealed containers, should be made to ensure that the effects of the changes in physical states are minimised, such as sublimation, evaporation, or melting. All such precautions should be chosen to provide a minimal interference with the irradiation of samples under test. 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.

Where practicable when testing samples of the drug product outside of the primary pack, these should be presented in a way similar to the conditions mentioned for the drug substance. The samples should be positioned to provide maximum area of exposure to the light source. For example, tablets, capsules, etc., should be spread in a single layer.

If direct exposure is not practical (e.g., due to oxidation of a product), the sample should be placed in a suitable protective inert transparent container (e.g., quartz).

If testing of the drug product in the immediate container or as marketed is needed, the samples should be placed horizontally or transversely with respect to the light source, whichever provides for the most uniform exposure of the samples. Some adjustment of testing conditions may have to be made when testing large volume containers (e.g., dispensing packs).

3.2 Analysis of Samples

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.

When powder samples are involved, sampling should ensure that a representative portion is used in individual tests. For solid oral dosage form products, testing should be conducted on an appropriately sized composite of, for example, 20 tablets or capsules. Similar sampling considerations, such as homogenisation or solubilisation of the entire sample, apply to other materials that may not be homogeneous after exposure (e.g., creams, ointments, suspensions, etc.). The analysis of the exposed sample should be performed concomitantly with that of any protected samples used as dark controls if these are used in the test.

3.3 Judgment of Results

Depending on the extent of the change, special labelling 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).

4 ANNEX 4.1 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).1 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).

4.1.1 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 A = AT - Ao. The length of exposure should be sufficient to ensure a change in absorbance of at least 0.9.

4.1.2 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 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)

Stem length: 80.0 ± 1.2 mm
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