Part II: Forced Degradation Studies to Support Photostability
In Part One of this photostability blog series, a high level review on the background of photostability was presented. In this second part, work leading up to the execution of a photostability study on Active Pharmaceutical Ingredient (API) and pharmaceutical products will be discussed.
Prior to execution of a photostability study, the analytical test procedures (TP) must demonstrate the ability to detect degradants caused by photolysis (photodegradation). Not all compounds are susceptible to photolysis; a molecule must absorb the UV or visible light energy to be susceptible to this phenomenon. For example, if the absorption spectrum of a molecule has a maximum of ~254 nm and with minimal or no absorption above 300 nm, this molecule would not be susceptible to photodegradation during an ICH photostability study as the lowest wavelength of exposure is ~320 nm.
To ensure a TP has the ability to detect photodegradants, it is necessary to add photodegradation to the forced degradation study. Along with exposure to heat, heat/humidity, acid, base and oxidative conditions, the compound must be exposed to the same UV/visible light spectrum as described in the ICH guidance Q1B. At Alcami, the analytical method development/validation team routinely utilizes qualified and mapped photostability chambers to expose both API and pharmaceutical products. By using state-of-the-art chromatographic separation and detection techniques, the analytical team demonstrates that either the TP is able to separate and detect photo-degradants or photolysis does not occur. Alcami brings a full complement of separation technologies and detectors to bear on these projects including UV, photodiode array (PDA), charged aerosol detection (CAD), refractive index, triple quad LCMS and Q-TOF LCMS.
During forced degradation, just how much exposure is enough? As explained above, some compounds are photostable therefore photodegradation does not occur. In the ICH governed regions, the equivalent of 1 ICH exposure is sufficient. However, in 2015, ANVISA issued resolution RDC-53/2015, which lays out the expectations of forced degradation studies to a much greater detail than the respective ICH guidances. For photodegradation, RDC-53/2015 recommends >2 x ICH exposure of NLT 200 Watt·hrs/m2 of integrated near-ultraviolet energy and NLT 1.2 million lux·hours of visible light.
Occasionally, our clients may ask: “If the API in our product has been shown not to be susceptible to photodegradation, is it necessary to perform a photostability study on the product?” While direct photochemical reactions to the API in the product may be the first and most obvious consideration, there is still a possibility of indirect photochemical processes. An indirect photochemical process happens when light is absorbed by a compound in the formulation other than the API, which leads to a reaction with the API. To help ensure safety to the clinical volunteers, and eventual patients from photodegradants and to satisfy regulatory reviewers, a photostability study on the final drug product is a wise investment.
Stay tuned for the third and final post of this blog series: The protocol generation, execution of a photostability study, and report of a photostability study.