In 1997, the FDA adopted a new ICH guideline aimed at promoting international standards for regulatory requirements governing pharmaceuticals for human use. The new guideline describes the basic protocol for photostability testing of new drug substances and products (Federal Register 1997;62(95):27116).
In introducing this guideline the FDA states, "Light testing should be an integral part of stress testing," and that "the intrinsic photostability characteristics of new drug substances and products should be evaluated to demonstrate that light exposure does not result in unacceptable change."
Prior to the late 1990s, the FDA's emphasis in stability testing focused on evaluating the effects of temperature and humidity on product integrity and activity, according to Bob Dotterer, applications engineer at Caron Products (Marietta, OH).
The recent focus on light stability has had a significant impact on the selection of packaging and storage containers, in Dotterer's view. In the past, the extent of photostability testing was left up to individual companies, and the testing methods and criteria used varied greatly.
Unified standards among regulatory agencies in the U.S., Europe, and Japan give researchers a better opportunity to test the ingredients of a drug during the design phase and be able to evaluate various formulation strategies.
With regard to photostability testing, the issues and methods are basically the same regardless of whether the drug substance to be assessed is a biological or a small molecule. Because light has different kinetics than temperature, for example, photostability testing on a small scale has the advantage of being very predictive of what will occur with bulk storage.
Photostability is based on quantum yields and will vary with the spectrum of light used, the intensity of the light source, and the wavelengths absorbed by a particular molecule. In most cases, a three-day experiment using various light sources can predict what would be expected if a drug were exposed to light eight hours a day for a year.
The exception, which occurs infrequently, according to Allen Templeton, Ph.D., a research fellow at Merck & Co. (Whitehouse Station, NJ), is when dark reactions take place and exposure to light triggers a chain of events that continues to affect the drug substance even after the light source is turned off.
Photostability testing should take into account all phases of drug development, contends Templeton, from drug synthesis to manufacture, packaging, and use of the drug by the physician or patient. It is also important to focus on potential photo-degradation of excipients as this can greatly affect the physical nature of the overall product.
The FDA's photostability guideline includes a requirement to expose a product to both visual and near-UV light and allow for one of two scenarios: use of either a single light source that emits a combination of visible and ultraviolet outputs; or use of two different lighting sources, one being a cool white fluorescent lamp and one a near-UV fluorescent lamp.
"We have seen a big trend toward two light sources (option 2)," says Dotterer. Using two separate lamps allows researchers to evaluate these variables independently and to distinguish between degradation caused by different wavelengths of light. It also helps eliminate effects due to over-exposure.
Caron Products designs and manufactures test chambers that simulate various types of environmental conditions for use in forced degradation studies. The company offers standardized and customized test chambers capable of exposing a product to temperatures ranging from -20C to +80C, relative humidity of 2% to 98%, freeze-thaw cycling, freezer storage, and various light conditions.
In February, Caron introduced a new photostability chamber targeting the European pharmaceutical industry. The Model 6540 is a bench-top instrument designed to perform near-UV and visual light testing using fluorescent lamps that emit high intensity light with a uniform distribution. The instrument offers programmable light and temperature protocols and has an optional controlled humidity system.