Originally licensed in 1993 the Tritium Laboratory Karlsruhe (TLK) is a unique pilot scale isotope laboratory focused on tritium handling and processing to conduct a variety of scientific experiments and development tasks. In order to fulfil all requirements regarding the license, a framework of regulations is applied as a basis for the operation of TLK, as well as the setup of new experiments and the design of components. This paper will give an overview on the framework of operation in view of licensing issues, as well as administrative and technical regulations mandatory to legally and reliably operate an isotope laboratory of this scale.