Although records of proper protection of subjects' rights date back over 100 years, the establishment of regulations to protect human subjects most notably focuses on the Nuremburg Code of 1947. The Nuremburg Code declared internationally the need for protection of subjects during clinical research trials. In 1964, the Helsinki Declaration expanded this protection of human research subjects and developed general principles and guidelines. But, do these and the many other ethical clinical research guidelines really cover cosmetic ingredient and formulation testing? Certainly, the answer is "YES".

All clinical research ethic guidelines, whether established by WHO, UNESCO, or others, require the basic need for evaluation of the safety of clinical studies at all stages, including the review of information and data obtained prior to the actual clinical study. Further, all guidelines reference the need for principles of precaution to minimize risk to the subjects. Commonly, these guidelines are applied in the review conducted by an Institutional Review Board (IRB), also known as an Ethics Review Board (ERB). However, some clinical testing laboratories do not require IRB approvals for cosmetic products and ingredients. Additionally, since most personal care companies do not publish their findings in medical journals which require the use of an IRB approval when using human subjects, the obligation of precaution and risk minimization falls on the study Sponsor and staff of the clinical research organization. According to Dr. Leslie Baumann, Board-certified dermatologist, clinical researcher and author, "Although going through an IRB can be a difficult and arduous process that many wish to avoid, the need to ensure the safety of your clinical subjects is paramount. You can only do this by making sure the Sponsor has done their homework prior to conducting a clinical study."

Traditionally, part of the "homework" was screening for adverse effects of a new materials in an animal model. However, in today's world where many personal care companies and ingredients suppliers have chosen to avoid animal testing, the use of non-animal Alternatives is key to the "homework" necessary to adequately review an ingredient or formulation. These Alternatives include the use of in silico and in vitro methods to generate data that can be used in risk assessment and product evaluation. Information on the potential for dermatitis (irritation and sensitization) and ocular irritation, the primary routes of adverse response for personal care products, provide the toxicologist and clinician valuable information to protect their subject panels while providing a greater potential for a "favorable clinical outcome" from a study. How can in vitro methods provide a greater potential for a "favorable clinical outcome"? Consider that many clinical studies can take weeks or months to complete and cost thousands to hundreds of thousands of dollars. The use of cheaper, quicker, and higher throughput in vitro methods allow the researcher to "weed out" lesser ingredients or formulations from those that are more mild and acceptable for human application. Additionally, a reduction in the potential for reactions may lessen the chance for an "adverse event" report, which may raise questions during a product or ingredient registration, and maintains the willingness of the subjects to comply with usage instructions, therefore, providing a higher likelihood of demonstrating the product benefit.

Toxicologists and clinicians alike need to have a reasonable understanding of the methodology used and the performance of non-animal tests in order to evaluate test results properly. For example, an in vitro study to assess dermal corrosion may come back as "negative", but this would likely not provide sufficient information to begin a patch test on humans for endpoints like cumulative irritation or a repeat insult patch test (RIPT). The product or ingredient may still be moderately irritating, even with a negative corrosion result. Such a material can cause a significant adverse response with your clinical subject and may "fail" in the clinical study. In addition to the loss of time and money, the lack of understanding of preclinical information may harm your subjects and damage both the Sponsor's and clinical laboratory's reputations.

Preclinical evaluation should be a routine and established process for any personal care product company, ingredient supplier or clinical research laboratory. For those companies and clinical research facilities that are looking for assistance in preclinical evaluation, IIVS staff has the experience to conduct preclinical assessment of dermal, ocular, phototoxicity and sensitization endpoints and to provide guidance in interpreting in vitro data for Sponsors and clinicians alike.