Acknowledging the potential benefits of in vitro testing, the FDA wrote that it would consider in vitro alternatives if equivalency to the in vivo test could be proved.6 The agency has not published an official stance on in vitro SPF testing since those statements in 2007 and 2011. Of note, the FDA deems in vitro testing sufficient for making claims of broad-spectrum coverage.4
In contrast to the regulatory scenario in the United States, Europe regulates sunscreens as cosmetics, and the European Union (EU) has banned animal testing of cosmetics,7 which poses a problem for the development of new sunscreens. It is not surprising, therefore, that in 2006 the European Commission (the executive arm of the EU) published a mandate that in vitro SPF testing methods be actively developed due to ethical concerns associated with in vivo methods.8 In 2017, the International Organization for Standardization released specific validation criteria for proposed in vitro tests to facilitate the eventual approval of such methods.1
Progress of In Vitro Methods
In recent years, advances in in vitro SPF testing methods have addressed shortcomings noted previously by the FDA, which has led to notably improved reproducibility of results and correlation with in vivo values, in large part due to strict standardization of protocols,1 such as tight temperature control of samples, a multisubstrate approach, robotic product application to ensure even distribution, and pre-irradiation of sunscreen samples.
With these improvements, a 2018 study demonstrated an in vitro SPF testing methodology that exceeded published ISO validation criteria for emulsion-type products.1 This method was found to have low interlaboratory variability and high correlation with in vivo SPF values (Pearson r=0.88). Importantly, the authors noted that the consistency and reliability of in vitro SPF testing requires broad institution of a single unified method.1
The method described in the 2018 study1 has been accepted by the ISO Technical Committee and is undergoing further development3; it is expected to be approved by the European Committee for Standardization. After approval, adoption by member nations of the EU will require individual action, representing the next regulatory hurdle for in vitro SPF testing in Europe.
Final Thoughts and Future Steps
Recent data confirm the potential viability of in vitro testing as a primary method of determining SPF values.1 Although ISO has moved forward with development of this method, the FDA has been quiet on in vitro SPF testing since 2011.4 The agency has, however, acknowledged the disadvantages of in vivo broad-spectrum testing, including exposure of human participants to harmful UVR and poor interlaboratory reproducibility.6
Given the technical developments and substantial potential benefits of in vitro testing, we believe that it is time for the FDA to revisit this matter. We propose that the FDA take 2 steps toward in vitro testing. First, publish specific validation criteria that would be deemed necessary for approval of such a test, similar to what ISO published in 2017. Second, thoroughly assess new data supporting the viability of available in vitro testing to determine if the FDA’s stated position that in vitro testing is inadequate remains true.