1. Mike Riepl Director of Compounding Services Gateway HealthMart Pharmacy 3101 N 11 th St, Ste #2 Bismarck, ND 58503 701.224.9521 mike@gatewaypharmacy.com

3.  A new USP chapter dealing with hazardous drugs.  Applies to all healthcare settings, infusion centers, home health, etc., not just pharmacy.  Affects non-sterile and sterile compounders and all types of pharmacies. i.e. anyone who handles hazardous drugs  Official implementation date of July 1, 2018  USP is only available via purchase of USP ‐ NF or the USP Compounding Compendium

4.  Hazardous drugs are found on the NIOSH (National Institute of Safety and Health) list  Living document  Updated every 2 years. September, 2016  List is public domain  Three categories Antineoplastics Non-antineoplastics Drugs with adverse reproductive effects

5.  Anastrozole  Chloramphenicol  Estrogens (E1, E2, E3)  Progesterone  Testosterone  Methyltestosterone  Carbamazepine  Fluconazole  Misoprostol  Tretinoin  Oxytocin  Methotrexate

6.  Maintain a list of HD’s  Implement facility and engineering controls  Train personnel  Promote safe work practices  Provide and ensure proper use of PPE (personal protective equipment)  Create policies for HD waste segregation and disposal

7.  Go through NIOSH list and make a list of HD’s you use that are manipulated.  Manufactured, final dosage forms need not be on the list unless they are broken, crushed or manipulated into a compounded preparation.  Manufactured final dosage HD’s may not be placed into automated counting or packaging machine.

8.  Handling areas must be located away from breakrooms and public areas  Must setup designated areas for receipt and unpacking Must establish SOP’s All HD API’s must be unpacked in an area of neutral or negative pressure. However, this excludes finished drugs such as manufactured tablets and capsules unless crushed or broken.

9. Spill kits must be accessible in the receiving area Cannot be unpacked in the sterile compounding areas PPE must be worn when unpacking HD’s

10.  Must be stored in a manner to prevent spillage or breakage  Cannot be on the floor  HD API must be stored in a negative pressure room with minimum air changes per hour (ACPH). Refrigerator must be located in this room  All HD API and antineoplastic (ANP) HD requiring manipulation  Sterile and non-sterile HD’s may be stored together

11.  C ‐ PEC: Containment Primary Engineering Control Powder Containment Hood, Biologic Safety Cabinet, Negative Pressure Glove Box  C ‐ SEC: Containment Secondary Engineering Control – the negative pressure room  CSTD: Closed System Drug ‐ Transfer Device

12.  HDs must be compounded in a C ‐ PEC & the C ‐ PEC must be located in a C ‐ SEC (the room).  C ‐ SEC (the room) must: Must be vented to the outside. Need not be filtered. Must have 12 air changes per hour Negative pressure between 0.01 and 0.03 relative to all adjacent areas. Must be physically separated from other preparation areas. All surfaces must be smooth, impervious, free from cracks and crevices, and non-shedding.

13.  Sterile & non ‐ sterile compounding can occur in the same negative pressure room, IF: The non ‐ sterile C ‐ PEC can maintain the room at ISO 7 conditions while compounding is occurring AND The two C ‐ PECs (one for sterile, one for non ‐ sterile, are separated by one meter) AND “Particle generating activity” is suspended while sterile compounding is occurring  Equipment must be dedicated to HD compounding

14.  must be followed  C ‐ PEC must be vented outside OR have redundant HEPA filtration into the room  C ‐ SEC must have at least 12 ACPH  All surfaces must be “smooth, impervious, free from cracks and crevices & non ‐ shedding”

15.  must be followed  C ‐ PECs must be externally vented and meet ISO 5 classification  Non ‐ HDs are not allowed to be prepared in the same C ‐ PECs which are used for HDs  C ‐ SEC must have at least 30 ACPH

16.  Preferred configuration for C ‐ SEC: ISO 7 buffer room with ISO 7 anteroom Both must have 30 ACPH Sink must be located in anteroom at least one meter from entrance to the buffer room Considerations for entering the HD buffer room via the non ‐ HD buffer room  The C ‐ PEC may be located in a non ‐ ISO area, however, C ‐ SEC must be contained and final products have a limited BUD.

17.  Disposable PPE must not be reused. Reusable PPE must be decontaminated and cleaned after use.  All PPE is considered hazardous.  Gowns, head, hair, shoe coverings and two pairs of chemotherapy gloves are required for compounding sterile and non-sterile HD’s. Note that masks are optional  No manufacturer to date because they have to prove impermeability to HD’s

18.  Gowns must be disposable and “shown to resist permeability by HD’s.”  Must close in the back  Cannot have “seams or closures that could allow HD’s to pass.”  Must be changed according to manufacturer’s recommendations and not worn in non-HD areas.

19.  Must meet ASTM standard D6978.  Powder-free.  Hands must be washed after removing gloves.  For sterile compounding-only outer glove must be sterile.  Cannot use gloves for different compounds. i.e. can’t use one pair of gloves for many compounds. Must change at least the outer pair of gloves.

20.  A second pair of shoe covers must be placed over shoe covers when entering the HD C-SEC and removed when leaving.  Eye and face protection must be worn if there is a risk of spills or splashes  Goggles must be used when eye protection is needed  Masks should be worn and meet NIOSH N95 standards  All PPE must be disposed per local, state and federal regulations

21.  Must establish SOPs  Must be labeled at all times indicating handling precautions  Packaging must protect HDs from damage, leakage, contamination and degradation  Must be transported in a way to decrease risk of breakage or leakage

22.  Must establish SOPs  Deactivation: refer to labeling OR use EPA ‐ registered oxidizers such as peroxide formulations, sodium hypochlorite, etc.  Decontamination: validated materials or other materials such as alcohol, water, peroxide, sodium hypochlorite, etc.  Cleaning: germicidal detergent  Disinfection (sterile) : EPA ‐ registered disinfectant and/or sterile alcohol

23.  Frequency is to be established by the entity, with the following considerations: Decontamination of the C ‐ PEC must occur at least daily and:  Work surface – between compounding different HDs  Any time a spill occurs  Before & after certification  After voluntary interruption such as when C-PEC or C- SEC is shut down. i.e.-if air flow is stopped.  If the ventilation tool is moved

24.  Entity must appoint a person who will be responsible for oversight of compliance to  Environmental quality control – wipe sampling should be performed, but not required If done and a measurable contamination is found, it must be identified, documented and contained  Hazard communication program and related SOPs must be developed

25.  Personnel training for anyone handling HDs must be performed and reassessed every 12 months  HDs cannot be placed in automated counting or packaging machines  SOPs must be written for spill control  If you have refrigerated HD’s, the refrigerator must be stored in a different refrigerator separate from other non-HD’s. Refer must be in the C-SEC

26.  Think about transporting labware to a dishwasher  Consider a dishwasher in the C-SEC  Consider a dedicated EMP and ointment mill or may deactivate and decontaminate if sharing with non-HD lab  Must have dedicated beakers, spatulas, stirring rods, hot plate stirrers, EMP mixing blades, mortar and pestles, graduated cylinders, etc.  Labware must be washed separately from non- HD labware