Established in 1980 with a contract between the NC Department of Human Resources and the University of North Carolina at Chapel Hill, SPICE originally focused on tuberculosis management and the development of infection control programs at community hospitals. In 1988 long term care facilities, local health departments and other health care facilities became part of an expanded focus for SPICE. Since 2000 SPICE has provided regular training and daily consultation to thousands of health care personnel as the  administrator of the NC approved courses to meet the requirements of the North Carolina Infection Control Law: 10A NCAC 41A.0206.

10A North Carolina Administrative Code 41A.0206 and .0207 (formerly 15A NCAC 19A.0206 and .0207), approved by the North Carolina Commission for Health Services on August 5, 1992,  requires one health care personnel in each health care facility in which invasive procedures are performed to have completed an approved infection control course. The Communicable Diseases Section of the North Carolina Department of Health administered this law for several years and then transferred administration to the North Carolina Statewide Program for Infection Control and Epidemiology (SPICE) in 1999.

The original approved courses were designed by individual providers, submitted for review, and assigned a control number when approved. Approval for all those courses expired June 30, 2000. Since July 1, 2000, all approved Infection Control Courses must use the North Carolina Basic .0206 Infection Control Curriculum provided by the Statewide Program for Infection Control and Epidemiology (SPICE) to meet the requirements of 10A North Carolina Administrative Code 41A.0206. The curriculum was revised for individual settings in 2008 to be offered by providers approved by SPICE. (This infection control curriculum is not a substitute for the training required by the OSHA Bloodborne Pathogen Final Rule. Some elements of the Bloodborne Pathogen Final Rule are beyond the scope of the requirements of NCAC .0206.)