ICH Releases New Photosafety Testing Guideline for Comment

Posted 20 December 2012 | By Alexander Gaffney, RAC 

In an expected move, the International Conference on Harmonisation (ICH) has released to the public a new standard intended to improve the photosafety of pharmaceutical products, part of a bevy of documents coming out of a November 2012 meeting of ICH regulators.

The safety-oriented guideline, S10 Photosafety Evaluation of Pharmaceuticals, is meant to harmonize photosafety testing standards between the regulatory authorities of the US, EU and Japan.

Some pharmaceutical products can cause light-induced reactions, referred to generally as photosensitization-a term that includes both phototoxicity (tissue-based reactions) and photoallergies (immune system reactions).

"For a chemical to demonstrate phototoxicity and/or photoallergy, the following characteristics are critical," ICH writes. It must absorb natural sunlight or other light in the 290-700 nm range, and then generate a "reactive species," which must then be sufficiently distributed to tissues exposed by the light.

Unless all three conditions are met-absorption, generation and distribution-"a compound will not present a photosafety concern," ICH noted.

Should those three concerns be noted after an initial assessment, it should be studied in either Phase I or Phase II clinical safety testing-i.e. before Phase III efficacy testing.

Testing Considerations

S10 goes on to outline a number of testing considerations sponsors need to consider in the course of their photosafety testing. For example, products must be assessed for their photoreactive potential and wavelength absorption properties. The pharmacokinetic properties of a chemical must also be assessed to determine if a high enough concentration exists in surface tissue to cause a reaction.

For nonclinical testing, ICH explains that it is "most important that nonclinical photosafety assays show high sensitivity (i.e. produce a low frequency of false negatives)."

Why? Because false negatives in an assay test could lead to unexpected adverse events in clinical testing later on, ICH writes. "It is not essential that positive assay results always predict a clinically relevant phototoxic response … [but] the false positive rate for an assay should still be considered when deciding whether or not to use an assay."

Other aspects also represent difficulties during nonclinical testing. Seemingly simple factors-sunlight, for example-can be complicated by definition qualities such as the effects of latitude, altitude, season, time, skin type/color and weather on the properties of sunlight. Companies should conform to standards set by organizations, such as CIE-85-1989, for testing their products for potential phototoxicities, ICH wrote.

Chemical assays and in vitro assays should also be validated, the standard explains. To date, no in vivo phototoxicity assays have been validated for use, ICH noted, though it readily conceded that such tests are possible and, if successful, could be considered as a best practice.

Clinical phototoxicity testing is highly variable and should be determined on a case-by-case basis, ICH explained.

Regulatory Focus newsletters

All the biggest regulatory news and happenings.