definiens: means the equivalent of the work of one employee full time for one year ( consisting of at least a to tal of [ * * * ] hours per year ( excluding vacations and ho lidays ) of work on or directly related to the Colla boration ), carried out by an Isis employee or Third Party mutu ally agreed upon by the Parties . For the purposes o f Appendix 2.3.1, the FTE rate will be ( i ) [ * * * ] ( U.S . ) per FTE for any of the following activities : dru g substance manufacturing ; analytical chemistry ; process chemis try ; formulation ; raw material ordering and handlin g ; quality control ; or manufacturing technology transfer ; and ( ii ) [ * * * ] ( U.S. ) per FTE for any of the following activities : toxicology ; pharmacokinetics / metabolism ; regulatory ; clinical development ; or data management . These F TE rates will be adjusted upward on a Calendar Year ba sis commencing January 1, 2002 ( and on January 1 of each year thereafter during the Term of this Agreement ) by a factor which reflects changes in the Consumer Price Index for San Diego, California as reported on that date in each applicable year during the Term of th e Agreement when compared to the comparable statistic for that date in the preceding year