The US Food and Drug Administration issued draft guidance for the development of drugs to treat the side effects of vaccination against smallpox with vaccinia virus. Smallpox is an infectious disease caused by the variola virus. Smallpox, which is incurable and often fatal, is regarded as a potential agent of terrorism, but can be prevented by vaccination with vaccinia virus.

The need for drugs to treat the side effects of this vaccine became acute after the terrorist attacks on September 11, 2001. Routine vaccination for smallpox in the United States had ended in the 1970s, when the disease stopped occurring naturally, but the potential threat that variola virus would be used as a weapon of terrorism has raised the possibility that a large-scale vaccination could be necessary in an emergency. Because the use of this vaccine may cause complications in some individuals, the FDA wants to help commercial and research sponsors plan and design appropriate studies for the development of drugs to treat such adverse events.

"Bioterrorism is one of the most profound new public health threats facing the U.S.," said FDA Commissioner Mark B. McClellan, M.D., Ph.D., "and our agency intends to identify all possible steps to help minimize or eliminate the potential risks of bioterrorism to Americans. Today's guidance should reduce the cost and uncertainty of developing medicines that will harden our defenses against one of the most dangerous bioterrorism agents."

According to experts, the currently available live vaccinia virus vaccine, when given before exposure to variola virus, substantially protects most people against smallpox for at least several years. In addition, if given within a few days after initial variola exposure, the vaccine may prevent or lessen the impact of smallpox infection.

The vaccinia virus vaccine, however, can potentially cause serious complications. Groups at increased risk of developing smallpox vaccine complications include immuno-suppressed people (such as persons with HIV/AIDs, organ transplant recipients, and patients on cancer chemotherapy), pregnant women, persons with a history of eczema and other chronic skin diseases, and possibly individuals with cardiac disease.

Important complications associated with the smallpox vaccine also include, but are not limited to: Spread of the vaccinia virus to other body sites or to close contacts; Generalized rash from vaccinia and other rashes; Vaccinia infection of the eye; Severe vaccinia infection at sites of eczema or of other skin diseases; Severe infection at the vaccinated site and subsequent spread to other areas of the body; Inflammation of the brain; Inflammation of the heart of surrounding tissues; and Vaccinia infection of the fetus.

The guidance first summarizes appropriate non-clinical studies recommended during early drug development. It includes sections on chemistry, manufacturing and controls; non-clinical toxicology; microbiology; and clinical pharmacology. The guidance also focuses on the acquisition of in vivo data through the use of animal models, an approach that may be necessary because of the low occurrence of serious vaccinia complications in the vaccinated population.

The guidance concludes with sections addressing the acquisition of human efficacy and safety data, issues surrounding the design of clinical trials, and sections detailing data collection requirements and recommendations, along with consideration of long-term patient follow-up and special population data collection. A sample case report form is provided as an example of a data collection format.

FDA continues to strengthen its ability to prepare for and respond to terrorism by fostering the development and availability of numerous drugs, vaccines, and other medical products to prevent, diagnose, and treat illnesses that could result from a terrorist attack. For example, in addition to advancing the development of the next generation of vaccines to prevent smallpox, FDA is preparing a guidance to speed the review and authorize the immediate use of effective newly developed medical products in the case of a biological, chemical, radiological, or nuclear attack.