Best practices hierarchy of controls for carcinogens Level 4B Ingrid Vande Velde - Information provided subject to the 'Conditions for Sharing Materials and Advice' - - Information provided subject to the 'Conditions for Sharing Materials and Advice' -

Content Most important requirements Belgian legislation Carcinogens in pharmaceutical operations: secondary packaging cytotoxic compounds Carcinogens in pharmaceutical operations: quality control

Most important requirements Belgian legislation (1/2) Hierarchy of controls: Substitution by less potent compound (if not possible, make sure clear motivation is in place) Handle in closed system If not technically possible: handle in system as closed as possible In every case, make sure exposure is always lower than the acceptable limit

Most important requirements Belgian legislation (2/2) Risk assessment of activities with carcinogens Limit quantity of carcinogens handled Limit number of persons to zone where carcinogens are handled Clearly trace / indicate zone where carcinogens are handled All people need to be trained specifically to work with carcinogens People who work with carcinogens need to receive appropriate medical checks Document details of what persons handled what quantity of what carcinogen on what day during what kind of activity

Pharmaceutical operations: secondary packaging cytotoxic compounds (1/5) Pharmaceutical operations: almost no carcinogens in use (in Belgium) Belgian legislation: cytotoxic compounds as e.g. Velcade are also considered as carcinogens Following slides: pictures how secondary packaging cytotoxic compounds is performed Packaging area = limited access to employees (only employees who received specific training are allowed to enter)

Secondary packaging Velcade: visual inspection (2/5) Put box with vials with powder Velcade in cabinet and close cabinet Open box and inspect trays visually If OK: open cabinet at right side and take out trays Closed system

Secondary packaging Velcade: labeling on TB4 (3/5) In cabinet in underpressure In case of spill: stays in cabinet Underpressure

Secondary packaging Velcade: put vials in blisters (4/5) Vertical borders Strong vials Vertical borders

Secondary packaging Velcade: blistering with Multivac (5/5) Once vial blistered: minimal risk on spill Afterwards: packaging on AV65 Room: inwards flow pattern

Pharmaceutical operations: quality control (1/3) Substitution of carcinogens in quality control very often impossible because of fixed protocols If method internally developed: make sure no carcinogens are introduced Activities with carcinogens as closed as possible: - steps with dry powder in isolator or weighing cabinet - further steps in weighing cabinet or hood - never handling of carcinogens on bench! Zone always clearly traced and indicated

Pharmaceutical operations: quality control (2/3) 1. Isolator EnvAir

Pharmaceutical operations: quality control (3/3) 2. Weighing cabinet Hepa-filters don’t stop solvents!