ICH Photosafety Guidance Aims to Bridge FDA, EU Differences

“The S10 draft guidance document clarifies some points in the current EMA and FDA guidance that are known weaknesses, based on accumulated information and experience since those documents were issued in the mid-2000s,” ​Doug Learn, director of photobiology at Charles River, told In-Pharmatechnologist.com.

The FDA guidance was quite broad and not very prescriptive, whereas the European guidance was quite prescriptive, said a phototoxicity expert who requested to remain anonymous because the guidance is still under consideration. One of the tests for phototoxicity is an in vitro cellular assay called 3T3 but one of the problems was industry was forced to use it and about 50% of the compounds tested were coming out positive, which could not be possible as most drugs aren’t phototoxic, the expert said.

And because this is an oversensitive assay, the new ICH guidance tries to add some perspective to the idea that if the 3T3 assay finds the compound is negative for phototoxicity, it’s very likely the compound won’t be toxic, but if it’s found to be positive, the compound will require further testing.  

Learn noted that relatively few drugs are phototoxic, though some tetracycline and fluoroquinolone antibiotics are examples of ones that are. But as long as “exposure to the sun can be controlled and the drug has good benefit, then the risk can be controlled​,” he added.

The basic criteria for photosafety testing are absorption between 29- and 700 nanometers, localization of the drug to the skin or eyes, or administration to the skin, and whether it generates a reactive molecule when exposed to light in this spectral region, Learn noted. 

He also said that photosafety evaluation is known to vary between performing laboratories, and “while there are some similar techniques, and the guidance provides suggestions on how to minimize these differences, this variability will continue under this draft guidance​.” 

However, as long as the study design is robust, contains the required controls, and the performing laboratory demonstrates experience in the assays and the scientific expertise to design, run and interpret the study, there should be little question of the validity of the study, he noted. 

The European Medicines Agency launched a consultation​ on the guideline in December, with comments due by the end of March.

The target is to get the ICH guidance document adopted  in November by the US Food and Drug Administration (FDA), European Medicines Agency and Japan’s Ministry of Health, Labour and Welfare, which is the only agency of the three that has not released previous guidelines on photosafety testing.