1. 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' -

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

3. 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

4. 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

5. 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)

6. 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

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

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

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

10. 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

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

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