Compounding Flashcards
USP Compounding chapters
USP 795: non-sterile compounding
USP 800: hazardous compounding
USP 797: Sterile compounding
Non-sterile compounding definition
Primarily used to prepare a dose or formulation that is not commercially available, avoid an excipient, or add flavor.
Administered only by mouth, tube, rectally, vaginally, topically, nasally, or ear.
USP 795 divides into complexity: Simple; requires following simple directions. Moderate; specialized calculations, or making something without stability data. Complex; specialized dosage forms such as transdermal.
Compounding space should be specific to non-sterile in a separate space from the dispensing part. There must be potable water and purified water.
Sterile compounding definition
Used to prepare injections (IV, IM, SQ), eye drops, irrigation, and inhalations.
Small volume is </=100mL, and large is >100mL.
Primary engineering control (PEC) should be ISO 5. Negative pressure must be used for chemo, and is generally class II or III biological safety cabinet.
Secondary engineering control is the buffer room and has an ISO of 7.
Segregated compounding area has ISO 5 hood in non-sterile area.
USP requirements for air in sterile compounding
In critical areas, ISO must be 5 or less. The buffer must be ISO 7, and the anteroom for garbing must be ISO 8 for positive pressure (non-HD), and ISO 7 for negative pressure (HD).
Room air is generally ISO 9.
HEPA, high-efficiency particulate air filters are 99.97% effective at removing 0.3 micron particles. Vertical hoods have the HEPA at the top, and in a laminar or horizontal hood it is in the back. Compounding is done in the first air in the direct compounding are of the hood. Must be certified every 6 months or after movement.
Use 70% IPA to decontaminate, leave 6 inches from the hood.
Positive pressure pushes air out of the area, and is used for non-hazardous compounding. Negative pushes air into the area, and is used for hazardous compounding.
Air changes per hour: non-sterile hazardous drugs must have 12 ACPH, sterile C-SEC must have 30, and in a C-SCA must have 12.
USP requirements for physical spaces in sterile compounding
Surfaces must be smooth, impervious, and free from cracks and crevices.
Cleanroom suites have one or more PEC inside a buffer room and is entered through an anteroom.
Primary engineering control is a device that provides ISO 5. A laminar airflow workbench can be used for non-hazardous and has an open front and air moves outwards. A compounding aseptic isolator has a closed front in a buffer room or segregated area.
Secondary engineering control is also called the buffer room and has ISO 7. The anteroom connects the buffer to the pharmacy and is ISO 8 used for garbing. The line of demarcation separates it into clean and dirty.
USP beyond use dates
Emergency use compounding has a BUD of 1 hour. The segregated area without a buffer or anteroom is used for low risk CSP and has max BUD of 12 hours.
Hazardous drugs from NIOSH
Antineoplastic drugs/chemotherapy
Non-antineoplastics:
Mifepristone, misoprostol, chloramphenicol, warfarin, fluconazole, voriconazole, abacavir, entecavir, zidovudine, cidofovir, ganciclovir, valganciclovir, isotretinoin, dronedarone, acitretin, azathioprine, leflunomide, fingolimod, terifluonomide, dutasteride, finasteride, pamidronate, zoledronic acid, dexrazoxane, paroxetine, exenatide, liraglutide, lomitapide, clobazam, clonazepam, carbamazepine, oxcarbamazepine, eslicarbazepine, divalproex, fosphenytoin, phenytoin, topiramate, vigabatrin, zonisamide, colchicine, ivabradine, spironolactone, ribavirin, androgens, estrogens, oxytocin, dinoprostone, progesterones, SERD/SERM, ullipristal, methimazole, propylthiouracil, temazepam, triazolam, defepirone, dihydroergotamine, apomorphine, rasagiline, ambrisentan, bosentan, macitentan, riociguat, ziprasidone, cyclosporine, mycophenolate, tacrolimus, sirolimus.
Compounding staff requirements
Standards include hand hygiene, garbing and gloving, cleaning and disinfectants, and sterile preparation.
Gloved fingertip test: Initially, then annually or semi-annually for high-risk CSP. A gloved sample is collected on a TSA tryptic soy agar plate. Passing requires 3 consecutive samples with zero colonies, and ongoing must have <3 colonies.
Media fill test: Determines aseptic technique. Turbidity or cloudiness determines contamination. Passing happens after 14 days of no turbidity.
Refrigeration requirements
SEC should be checked once daily and maintain <68F/20C.
The regular fridge should be checked once daily and maintained at 2-8C/36-46F.
A vaccine fridge should be checked twice daily and maintained at 2-8C/36-46F.
A regular freezer should be checked once daily and maintained at -25–10C.
A vaccine freezer should be checked twice daily and maintained at -50–15C/-58–5F.
Air and surface testing requirements
Air sampling for contaminants every 6 months.
Frequently touched surfaces tested at the end of every workday.
Air pressure testing once daily, or every work shift.
Humidity testing once daily to maintain <60%.
Cleaning requirements
PECs should be running continuously. If they stop, then they must be cleaned with a germicidal agent and then with IPA (70% isopropyl alcohol), and must remain on for 30 minutes prior to compounding.
Daily cleaning should be done on the PEC first at the end of the day with a germicidal agent and IPA. Cleaning is top to bottom, back to front.
Example order: Clean ceiling from back to front, then grill over HEPA top to bottom, the side was back to front, IV bar and hooks, clean equipment, and lastly the bottom surface back to front.
Hazardous cleaning
Sanitation is done in a specific order:
Deactivation and decontamination: 2% Na hypochlorite or bleach, or peroxide to reduce HD toxicity. Can neutralize afterward using Na thiosulfate, alcohol or water.
Cleaning: germicidal agent; Quat5, Ammonium, Phenolics to remove dirt and microbes.
Disinfection: 70% IPA to destroy and inhibit microbes.
Perform wipe sampling every 6 months.
Disposals of hazardous material
Yellow: trace bin; outer chemo gloves, gown, and shoe coverings.
Black: bulk; remaining drug, IV bags, any visible amount of drug.
Red: Non HD infectious material; used syringes.
Garbing for sterile compounding
Remove watches, rings, bracelets, makeup, and artificial nails.
Don headgear and masks, shoe covers over the line. Two shoe covers for HD.
Hand hygiene.
Don a gown, then enter buffer area, then disinfect hands with alcohol, chlorhexidine, or povidine iodine (Betadine).
Don gloves (two ASTM D6978 chemo-rated gloves for HD) and sanitize with IPA.
Instruments to measure volume
Cylindrical and conical graduates: has to be over 20% of the volume needing to be measured (5mL for 100mL graduated cylinder).
Syringes: good for small volumes and viscous fluids. In general, do not recap, use with safety features, and if it must be recapped use the scoop method. Do not confuse oral with parenteral, and use the closest size available.
Pipettes and droppers: volumetric has a specific volume help, Mohr pipette is graduated. Droppers measure 45-55mg water when held vertically.
Instruments to measure weight
Balances: class A or III have internal weights for 1 gram, and external weights for >1 gram. Torsion balances have a sensitivity of 6mg (6mg will move the dial one division). Minimal weighable quantity is based on the sensitivity and error rate of 5%: SR/error, or 6mg/5%=120mg. Electronic balances do not need to be calculated but must be tared.
