Non-sterile compounding

• The USP Chapters related to Compounding include USP 795 (Non-Sterile Compounding), USP 797 (Sterile Compounding), and USP 800 (Handling Hazardous Drugs) Non-Sterile compounding area must be separated from sterile compounding.
• USP 795 categorizes the risk based on the complexity of the preparation.
  • Simple: reconstitutes commercial produce with one or more ingredients, e.g: water or alcohol. E.g., adding water to amoxicillin powder.
  • Moderate: requires a calculation to determine the number of components to be added. E.g. Mixing 2 topical ingredients without stability data for either of them.
  • Complex: requires special training, environment, facility, and equipment. E.g. transdermal patches or ER capsules.
• For readings on compounding equipment and documentation, please refer to RxPrep 2020 or newer.
• Amphiphilic refers to both surfactants and other compounds that are both hydrophilic and hydrophobic.
• Surfactant: Reduce surface tension between a solid particle and a liquid. Also referred to as a wetting agent or levigating agent.
• Emulsifier: a surfactant that reduces the surface tension between oil and water.

 

Sterile compounding

• The sterile compounding space must include an anteroom, a buffer area, and a primary engineering control (PEC) or a segregated compounding area (SCA). PEC is the sterile hood. The Secondary Engineering Control (SEC) refers to the buffer room that houses most PECs.

• Vertical airflow: biological safety cabinet, the HEPA filter is at the top of the PEC. In a laminar airflow (horizontal) workbench, the HEPA filter is at the back of the PEC.
• The air pressure inside the PEC and inside a non-hazardous SEC can both be positive since the air will not cause toxicity. With hazardous compounding, the containment PEC (C-PEC) and the containment SEC (C-SEC) must have negative pressure to keep the toxic air contained in the space.

• Recommended action levels for viable microbial air sampling
• Air sampling identifies contaminants in the air. It should be performed at least every 6 months incubation, (CFU/m³ of air per plate, CFU: Colony-forming units)

Classification	Air sample
ISO Class 5       (PEC)	> 1
ISO Class 7 (buffer area)	> 10
ISO Class 8 or worse: (anteroom) handwash, garbing	> 100

 

 

Contamination Tests

• Gloved fingertip: sample is lightly pressed onto a separate petri dish that contains tryptic soy agar (TSA). The plates are incubated, spots that form are called colony-forming units (CFUs) and indicate contamination was present. Pass = 0 CFUs after 2-3 days incubation.
• There are three levels of risk: Low, medium, and high risk. Each level increases in the risk of contamination, therefore, the testing duration decreases in time (meaning tested more often).

• Low/Medium Risk: Annually; High Risk: Every 6 months
• The media-fill test is used to determine if a compounder is preparing CSPs in an aseptic manner (i.e., free from contamination). growth medium is tryptic soy broth (TSB). Turbidity indicates contamination.
• Pass = liquid stays clear after 14 days of incubation. Media fill test (assesses the quality of the aseptic skill of compounding personnel) → Annually (if no turbidity after 14 days, then you pass)

 

Sterile Beyond Use Dates (BUD’s)

Low-risk → Small volume, IV’s with < 3 Components

• Pretty much anything that’s small volume, or IV compounds with less than 3 components are in this category. (If compounded in a segregated area (e.g.: satellite pharmacy), all BUD’s are 12 hours (R.T. and fridge, and they are never frozen)).

Medium Risk → Batched, TPN, ophthalmic

• Think about compounds that batched in larger samples (25–50 at a time). Any TPN formulations.

High-Risk → Bulk drugs, non-sterile

• Substantial bulk batching (think 100s batched at a time) and anything that is not done in a sterile environment.
• Exceptions are for emergencies, which are high-risk compounding that have BUD’s of only 1 hour.

Beyond use date	Room expiration	Fridge	Freezer
Low Risk	48 Hours	14 days	45 days
Medium Risk	30 Hours	9 days	45 days
High Risk	24 Hours	3 days	45 days

 

Garb Order

You need to know the general steps to garb. The main concept is to clean the dirtiest first and the cleanest last.

1. Cover Hair + Face
2. Place Shoe Covers
3. Wash hands with soap
4. Put on gown
5. Place alcohol-based hand sanitizer on hands
6. Put on gloves

 

Monitoring frequency

• Laminar flow hood cleaning → Beginning, before & after, & every batch
• every shift to daily: HEPA filter, Air pressure, Temperature
• Surface → Periodically/Occasionally at random times.
• Air sampling + pharmacy environment → Q 6 months

 

BUD for single-dose Vs. multiple-dose containers

• Single-dose containers: Opened or needle-punctured containers, such as bags, bottles, syringes, and vials of sterile products and CSPs shall be used within 1 hour (worse than ISO Class 5 air quality) or up to 6 hours (ISO Class 5 or cleaner air) after the initial puncture.

• Multiple-dose containers (e.g., vials) contain antimicrobial preservatives and are formulated for multiple uses. BUD after initial entering or opening (e.g., needle-punctured) is 28 days unless otherwise specified by the manufacturer. 

 Hazardous drugs (HD)

• The National Institute for Occupational Safety and Health (NIOSH) determines which drugs are hazardous.
• Characteristics that Make a Drug Hazardous (> 1): Carcinogenic (cancer-causing), Teratogenic (causes birth defects)/reproductive toxicity, Causes organ toxicity at low doses, Genotoxic (damages the DNA)
• A closed-system transfer device (CSTD) reduces exposure to a HD.
• PECs (sterile hoods) used for HDs is called containment PECs, or C-PECs. Negative airflow in the PEC causes the air to flow into the hood (C-PECs) and away from the staff.
• There are nine drugs are currently listed by EPA as hazardous wastes: Arsenic trioxide, chlorambucil, cyclophosphamide, daunorubicin, diethylstilbestrol, melphalan, mitomycin, streptozocin, and uracil mustard.
• Lower risk HDs e.g., finasteride and methotrexate tablets.
• Appropriate PPE must be worn when administering HDs. Two pairs of chemotherapy gloves and a chemotherapy gown are required when administering IV drugs and are recommended when administering other HDs that are not in tablet or capsule form. Single chemotherapy gloves are acceptable when administering intact tablets or capsules.

 

Preparation of HD involving PPE (Personnel Protection Equipment)

• Two pairs of ASTM (chemotherapy)-rated gloves. Double ASTM-rated gloves are required when compounding or cleaning up spills. Single gloves for HD receiving and storage, or low-risk non-sterile HDs (intact tablets); Change gloves every 30 minutes or when torn, punctured, or contaminated. Discard immediately in a yellow chemotherapy waste bin.
• Consider latex-sensitive workers: a number of glove materials are suitable for protecting workers from antineoplastic drugs.
• Use chemo gloves for hazardous drugs that are not chemo drugs or for those that no information is available.
• Headcovers and (if applicable) beard covers; Two pairs of shoe covers.
• An impermeable gown: polyethylene-coated polypropylene or other laminate material. change Q 2-3 hours. Make sure gowns have closed fronts, long sleeves, and elastic or knit closed cuffs.
• Use disposable sleeve covers to protect the wrist area and remove the covers after the admixture is complete.
• A full-facepiece respirator or a face shield with goggles when there is a risk for spills or splashes
• Wash hands with soap and water before garbing and immediately after removal.

 

Chemotherapy wastes

 Trace wastes (Bin: Yellow)

• Residual amounts of chemo: empty drug bottles, dispensing devices (IV bags, tubing, etc.).
• Gloves, gowns, masks, goggles, and other disposable garbs are used when compounding or administering chemotherapy drugs (if they are not spilled, leaked, or dripped).

Bulk waste: any waste contaminated with more than residual amounts  

• Drug dispensing devices or IV bags that are not completely empty. black waste bin.
• Gloves, gowns, or other garbs that have chemo spilled/leaked on them; and spill cleanup materials.

 

Quiz

 

1. In ISO class 5, colony-forming unit (cfu) per 1000 liters of air per plate count of viable air sampling is found to be 2.  Shall this prompt a re-evaluation of the practices and procedures within the aseptic compounding area?

1. Yes
2. No

 

2. Opened or needle-punctured single-dose containers, and vials of sterile products and CSPs shall be used within 2 hours once opened in poorer than ISO Class 5 air quality.

1. True
2. False

 

3. Compounding diphenhydramine hydrochloride troches should be classified as:

1. Simple Compounding
2. Simple-Moderate Compounding
3. Moderate Compounding
4. Complex Compounding

Answers

1. Yes, any cfu count that exceeds its respective action level should prompt a re-evaluation.
2. (b) False. They shall be used within 1 hour if opened.
3. (c) Moderate Compounding is defined as making a preparation that requires certain calculations/procedures to determine quantities of each component; or making a preparation for which stability data for that specific formulation is unavailable. 

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