CDER NEWS by FDA

Guidance for Industry: S9 Nonclinical Evaluation for Anticancer Pharmaceuticals (PDF - 170 KB)
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM085389.pdf


Office of Nonprescription Products Consumer Update: Hydroquinone Studies Under The
National Toxicology Program (NTP)
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm203112.htm

Hydroquinone Studies Under The National Toxicology Program (NTP)
Why are we issuing this Q&A?

We, the Food and Drug Administration (FDA), receive many inquiries from the public regarding the regulatory status of OTC skin bleaching drug products containing hydroquinone. Therefore, we are providing the following update which summarizes our past and current actions regarding the safety and efficacy of hydroquinone.

What is hydroquinone?

Hydroquinone is a skin bleaching ingredient used to lighten areas of darkened skin. In 1982, we published a rule1 to propose that OTC skin bleaching drug products containing 1.5 to 2 percent hydroquinone be generally recognized as safe and effective (GRASE). This rulemaking represented the recommendation of a panel of experts from outside the FDA that reviewed the available data and information regarding the efficacy and safety of hydroquinone at the time. Subsequently, we published a proposed rule1 in 2006 after considering new data and information on the safety of hydroquinone. The 2006 rule proposed to withdraw the 1982 rule that recommended hydroquinone be GRASE because of evidence indicating that hydroquinone may act as a cancer-causing agent (carcinogen) in rodents (rats and mice) after oral administration. Hydroquinone also has been linked with a medical condition in humans known as ochronosis (skin darkening and disfiguration) when it is applied topically. In the 2006 proposed rule, we recommended that additional studies should be conducted by the NTP and/or industry in order to determine if there is a risk to humans from the use of hydroquinone. In the interim, we believe that hydroquinone should remain available as an OTC drug product.

What is the NTP and why is hydroquinone being studied under the NTP?

The NTP consists of scientists who evaluate substances for a variety of health-related effects. The NTP provides the study results to Federal Regulatory Agencies such as the FDA so that we can use the results to make better informed regulatory decisions. We believe that additional animal studies, such as dermal toxicity and carcinogenicity, are needed to better understand if topically applied hydroquinone may be harmful to humans. After we published the 2006 proposed rule, we received many submissions from the public, but none of them included new study data. Therefore, we nominated hydroquinone for further study by the NTP. We believe that the NTP studies are necessary before we can determine whether hydroquinone is safe and effective (GRASE) when used in OTC skin bleaching drug products.

When will the NTP hydroquinone studies begin?

Our nomination of hydroquinone was reviewed at a public meeting of the NTP Board of Scientific Counselors on December 10, 2009, at which time the nomination was approved. The proposed studies are:

comparative metabolism studies in rats and mice by the oral and dermal routes
reproductive toxicity study by the oral route in rats and mice
dermal carcinogenicity studies of hydroquinone in mice and rats
There are several more steps to the nomination process before the NTP studies begins. We will update this announcement when more information becomes available. Interested parties can also visit the NTP Web site for further information: National Toxicology Program (NTP)


Rulemaking History for Nonprescription Products: Acne (updated)
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm069967.htm