ICH Q1B Guideline for photostability testing of pharmaceutical products

Share this article :

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:

  1. Tests on the drug substance
  2. Tests on the exposed drug product outside of the immediate pack
  3. Tests on the drug product in the immediate pack
  4. 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)

colourless ampoule for photo stability testing
colourless ampoule for photo stability testing

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.

  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.

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).

Leave a comment