Compounding Flashcards
Sterile vs. non-sterile compounds
-Give examples
Sterile: injections, eye drops, irrigations that go into body cavity, pulmonary inhalations, baths and soaks for live tissues/organs, implants
Compounded nonsterile preparations (CNSPs): PO, via tube (gastric tube), PR, PV, topically, nasally, or in the ear (unless the eardrum is perforated)
What is USP? What are the different USP chapters?
USP: standards for compounding that are consistered to be minimum acceptable standards by FDA, state boards of pharmacy, and the Joint Commission
USP Chapters:
-795: Nonsterile preparation
-797: Steile preparation
-800: Hazardous preparations
Nonsterile Compouding: Space Requirements
-Think about environment, equipment, cleanliness, etc.
- Specifically designated area away from dispensing area
- Can be performed in ambient air (room air)
- All equipment, ingredients, and containers must be stored off the floor
- Temperature should be monitored daily (or continuously)
- Spill kit available and personnel trained on use
- Adequate plumbing and clean, easily accessible skin with hot and cold water
- Purified water, distilled water, or reverse osmosis water needed for rinsing equipment and utensils
Nonsterile Compounding: Compounding Personnel: Training Requirements
-When must be completed
-What should the training include
-What personal hygiene must be done
When: initially and Q12 months
Personnel must have training with documentation and proficiency along with core competencies (hand hygiene, garbing, cleaning/sanitizing, use of equipment, measure/mixing, and documentation of compounding)
Personal Hygiene:
-Remove jewelry, hats, or headphones prior to compounding
-Notify designated person of any concerns for contamination (ex. URTI, rash, conjunctivitis)
-Proper hand hygiene: soap and water for at least 30 seconds rubbing hands, interlacing fingers, rubbing back of hands, and cleaning under fingernails
-Garb gloves and other PPE if needed
Weighing Equipment
1. Equipment must be ________ to confirm accuracy
- Equipment should be made out of material that does not __________.
- All measurements should be made in what measuring system?
- Calibrated
- React with compounding ingredients (ex. metal spatulas should NOT be used with compounds containing metal ions)
- Metric
Nonsterile compounding: what are the types of balances that can be used and how to use them?
Class III Torsion Balance (Class A balance)
-Less commonly used
-External weights used for weighing > 1 gram; internal weights used for
-Has sensitivity requirement (SR): most have 6mg (6mg can be added or removed before dial thrown off by 1)
-Has acceptable error rates usually of 0.05 (5%)
-Calculate minimum weighable quantity (MWQ) = SR / acceptable error rate
Electronic Balance (Analytical Balance):
-MOST common and simple to use
-Have higher sensitivity (MWQ does NOT need to be calculated)
-Tare or “zero out” balance prior to measuring
BOTH: Ingredients should never be placed directly on scale (place paper down first) –> helps avoid contamination and reduce moisture penetration into molecules
Measuring Volume:
1. Graduated cylinders are more accurate for measuring than ________ or ______ which would be used for stirring since they have wider mouths. In general, the wider the mouth, the ____(higher/lowering the accuracy.
- Measuring volumes that are smaller than ___% of the graduate’s capacity can cause measuring error.
- To read the volume in a graduate, place it on a flat surface and view the height at eye level, looking at the ______.
- Conical graduates; beakers; lower
- 20%
- Bottom of the meniscus (downward curve from both sides)
Measuring Volume:
1. When are syringes useful?
2 What should oral syringes be labeled with?
- What are pipettes? What is the difference between volumetric pipettes and Mohr pipettes?
- To most accurately measure small volumes, especially for viscous liquids (ex. glycerin, mineral oil)
- “For Oral Use Only” over the syringe cap
- Thin plastic or glass tubes to measure small volumes and release liquids in drops
-Volumetric pipette: draws up a set volume only
-Mohr pipette: graduated and can measure different volumes
Grinding, Mixing, Transferring, and Heating:
1. When to or not to use a steel vs. rubber spatula?
- When can ointment slabs be used?
- What is a homogenizer?
- When to use a water bath?
- Steel should NOT be used when making a mixture that contains metallic ions. Rubber should be used to handle corrosive materials.
- Mixing compounds into ointments, forming pills, or rolling out suppositories
-Can put paper down when mixtures don’t have too high of water content - Also called an electric mortar and pestle similar to a blender that mixes ointments, creams, or other semi-solid preparations
- When temperature needs to be carefully controlled - place ingredients into a container to place into larger container filled with water to avoid direct heat source and prevent burning
Explain when to use glass, wedgwood, and porclean mortars.
-Glass: glazed surface for liqiuds, compounds that are oily or stain/dye
-Wedgwood: rough surface for grinding dry crystals and hard powders
-Porcelain: smooth surface for blending powders and pulverizing gummy consistencies
Ingredients:
1. The medication is called the ______________ whereas the other ingredients that do NOT produce therapeutic effects are called _________.
- Ingredients should be high quality to ensure purity and safety. You can find these ingredients listed in ________ which come from a FDA-registered facility. They also provide _______.
- If an ingredient comes without an expiration date, the pharmacist will assign a conservative date that is no more than ________ from the date of receipt and _______ should be written on the package.
- Active pharmaceutical ingredients (APIs); excipients
- USP National Formulary (USP-NF); monographs
- One year (book says 3?); date received
What is the purpose of adding surfactants to a compound?
Amphiphilic molecules (hydrophilic and hydrophoic) that lower surface tension between two ingredients (or phases) to make them more miscible
Surfactant types when to add and examples: Wetting Agents/Levigating Agents
-Use: reduce surface tension between liquid and solid (livegation = to grind particles with small amount of liquid)
-Ex. mineral oil for lipophilic compunds; glycerin or propylene glycol for aqueous compounds
Surfactant types when to add and examples: Suspending Agents
-Use: add to suspensions to help solid particles from settling, but suspensions should still be shaken to redisperse since the agent does not last too long
-Ex. sorbitol for glycerin capsules, Ora-plus (gel-like suspension, but bland in taste), Ora-sweet (similar to simple syrup, flavor added to Ora-plus), Ora-Blend (combination of Ora-sweet and Ora-plus)
Surfactant types when to add and examples: Foaming Agents
-Use: helps foam form often in soaps and detergents to reduce surface tension between dirt and water during cleaning process
-In compounding, anti-foaming agents more common (ex. simethicone)
Surfactant types when to add and examples: Glycols/gels
-Use: serve as delivery vehicles
-Ex. polyethylene glycol (PEG), poloxamer
Surfactants: Emulsifiers:
-Purpose
-w/o vs. o/w emulsions
-What is HLB?
Emulsifiers (“Emulgents”): added to emulsion (mixture of two or more liquids that do not blend together) to prevent separation
w/o: water-in-oil emulsion - typically not palpitable in taste and often topical
o/w: oil in water - typically oral products
HLB: hydrophilic-lipophilic balance: number that determines the type of surfactant required to make emulsion
-Scale is from 0-20 with 10 as midpoint
-<10 HLB: surfactant should be used in w/o emulsion –> “Lower HBL makes it Like Lipids”
->10 HLB: surfactant should be used in o/w emulsion –> “Higher HBL makes it Hug H20”
For the excipient, explain its role and examples: Binders
-Use: help ingredients stick together while permitting contents to be released once ingested (provide stability and strength)
-Ex. starch paste
For the excipient, explain its role and examples: Diluents, fillers
-Use: help make something more dilute and fill up size in very small dosages (liquids: help dissolve/suspend drug)
-Ex (tablets, capsules): lactose, starches, calcium salts, cellulose power
-Ex (liquids): water, glycerin, alcohol
-Ex (topicals): petrolatum
For the excipient, explain its role and examples Lubricants
-Use: prevent ingredients from sticking to equipment (glidants: help improve powder flowability by reduceing interparticle friction)
-Ex. magnesium stearate
For the excipient, explain its role and examples Preservatives
-Use: prevent or slow microbial growth. required in most compounds sterile or not
-do NOT use for neonates
-Ex. chlorhexidine, povidone iodine, sodium benzoate/benzoic acid, benzalkonium chloride, sorbic acid/propyl parabens, methyl/ethyl/propyl parabens, EDTA, thimerosal, cetylpyridinium chloride
For the excipient, explain its role and examples: Disintegrants
-Use: help breakup solids into smaller particles after ingestion or adding to liquid and speeds up absorption (alginates, cellulose: absorb water, causing tablet to swell)
-Ex. alginic acid, cellulose products, starches
For the excipient, explain its role and examples: Flavorings and coloring agents
-Use: improve taste or look of product
-Ex sweeteners (non-caloric): aspartame, sucralose
-Ex. sweeteners: glycerin, dextrose, mannitol, sorbitol, xylitol, stevia
For the excipient, explain its role and examples: Coatings
-Use: mask unpalatable taste and protect product from moisture, light, and oxygen (enteric coatings: can be used to prevent destruction from stomach acid)
-Ex. shellac, gelatin, gluten, cellulose acetate phthalate
For the excipient, explain its role and examples: Binders
-Use: keep pH within certain range to improve stability and solubility and decrease irritation to sensitive tissues in body
-Ionized compounds are more polar which makes them more waer-soluble
-Ex to maintain acidic: hydrochloric acid, citric acid, acetic acid
-Ex to maintain alkaline: sodium hydroxide, boric acid/sodium borate
-Ex to maintain neutral: potassium phosphate, sodium bisphosphonate
For the excipient, explain its role and examples: Adsorbents
-Use: keep powders dry and prevent hydrolysis reactions
-Ex. magnesium oxide/carbonate, kaolin
For the excipient, explain its role and examples: Humectants
-Use: retain moisture to prevent product from becoming dry and brittle
-Ex. glycerin or glycerol, propylene glycol, PEG, hyaluronic acid
For the excipient, explain its role and examples: Gelling agents
-Use: make products more viscous
-Ex. gelatin, cellulose, bentonite (most common)
-Others: agar, alginates, various gums (guar, xanthan, acacia), startches, poloxamer (pluronic) gels
List examples of hydrophobic solvents and what they may be used for
Oils and fats derived from plants, animals, or petrolatum
-Ex, mineral oil
-Use: delivery vehicles for therapeutical or nutritional use, sometimes scents or flavorings
Hydrophilic solvents, explain what the following may be used for and examples: Water
-Use: delivery vehicle (PO, topical, emulsions, creams, lotions) and cleaning
-Ex. purified water (treated to remove chemicals and contaminants - distillation, deionization, reverse osmosis) –> distilled water for reconstitution, potable water (tap) for drinking and handwashing
Hydrophilic solvents, explain what the following may be used for and examples: Sterile Water
-Use: purified from microbials and bacterial endotoxins (pyrogens)
-Ex. sterile water for injection (has preservatives), for irrigation
Hydrophilic solvents, explain what the following may be used for and examples: Alcohols
-Use: high miscbility (mixes easily) with water and can be used to dissolve solutes that would be insoluble alone
-Ex. benzyl alcohol for perservative and solvent, isopropal alcohol 70% (IPA) for disinfectant for sterile compounding
Hydrophilic solvents, explain what the following may be used for and examples: Glycols
-Use: low freezing point and high boiling point and water-soluble
-Ex. polyethylene glycol (PEG) - surfactant, solvent, lubricant –> longer T/2 from being linked to protein (peglyated); number refers to weight (PEG 350 = Miralax, 450 - may be used for compounding)
-Ex. Polybase: PEG mixture used as a suppository base and good emulsifier
Emollients:
-Define
-Discuss the differences and provide examples of the different types: ointments, creams, lotions,
Ointments: semisolds w/ 0-20% water
-Use: provide barrier to water loss from skin and vehicles for topical drug delivery
-Ex. petrolatum, Polybase, Aquaphor, Aquabase
-Hydrocarbon bases: “oleaginous” ointments that contain NO water (ex. white petrolatum or Vaseline petrolatum jelly)
Creams: 20-50% water that are often w/o or o/w emulsions
Ex. Lipoderm cream, Eucerin, Cetaphil
Lotions: contain more water than creams and may be aqueous or hydroalcoholic to help solubize ingredients
-Ex. Versabase lotion, calamine lotion
Discuss the differences in emollients and provide examples of the different types: gels, pastes, suppository bases
Gels: gelling agents are added to thicken product
-Use: works well for transdermal drug delivery (ex. application to dog’s ear)
-Poloxamer gels: aqueous solutions are liquid when refrigerated and form gel at room temp –> can be used for hydrophobic or hydrophilic drug delivery
Pastes: powder in an ointment base
-Ex. zinc oxide paste
Suppository bases: various fats and glycols, may melt easily
-Ex. Polybase, hydrogenated vegetable oils, PEG polymers, glycerinated gelatin
For the following excipients, list when to avoid use and alternatives: Alcohol
children (lack ability to breakdown; OTCs for children are required to contain no more than 0.5% alcohol - can cause alcohol intoxication or hypoglycemia)
-Alternative: water, sterile water
For the following excipients, list when to avoid use and alternatives: Aspartame
contains phenylalaine –> avoid in phenylketonuria that may not be able to metabolize (can cause CNS toxicity - impaired cognition, seizures, abnormal gait)
-Alternative: stevia, sucralose, dextrose, saccharin, sugar alcohols (mannitol, sorbitol, xylitol)
For the following excipients, list when to avoid use and alternatives: Gluten
found in wheat, barley, and rye – Celiac disease or anyone who wishes to avoid gluten (can cause diarrhea, gas, and stomach upset)
-Alternative: starch from non-gluten sources (ex. corn, potato, tapioca)
For the following excipients, list when to avoid use and alternatives: Gelatin
avoid in vegetarians or vegans or anyone who wishes to avoid animal products that
-Alternative: hypromellose capsule shells
For the following excipients, list when to avoid use and alternatives: Preservatives
neonates (cannot properly metabolize with immature liver - can cause metabolic acidosis, respiratory depression, or hypersensitivity)
-Alternative: preservative-free formulations
For the following excipients, list when to avoid use and alternatives: Sugar alcohols (sorbitol, mannitol, xylitol)
-Avoid all in IBS (can cause diarrhea and stomach upset)
-Sucrose: avoid in DM (can increase BG)
-Xylitol: avoid in dogs (toxicity can decrease BG and cause hepatotoxicity) or hx of GI upset from xylitol in humans
-Alternatives: dextrose, sucralose
For the following excipients, list when to avoid use and alternatives: Lactose
lactose intolerance or lactose allergy (can cause diarrhea, gas, and stomach upset)
-Alternative: depends on purpose (ex. choose a different sweetener or filler)
General Steps in Nonsterile Compounding:
1. Before accepting a prescription, what must be done?
- When compounding, make the product according to the ___________. Document all compounding steps and other details on the ____________.
- What should the quality check consider?
- Rx must not be commercial unless on shortage, know how to make preparation, review safety data sheets (SDS) for bulk ingredients to determine safety procedures
- Master formulation record; compounding record
3.
-Validate the weight
-Check product for mixing adequacy, color, clarity, odor, consistency, and pH
-Package product with container and any needed auxillary labels
. Define: Trituration, Levigation, Spatulation, and Pulverization by intervention
-Trituration: “mix thoroughly” to make homogenous –> ex. grinding into fine powder or triturating an emulsion via shaking
-Levigation: like trituration, but with levigating/wetting agent
-Spatulation: like levigation, but performed on a ointment slab with spatula
-Pulverization by intervention: crystals dissolved with solvent and mixed until evaporated (when recrystallized, particles are finer)
Preparing Powders:
1. _________ can be added as a glidant/lubricant to improve flowability of powder.
- _________ can be added as a surfactant to neutralize static charge and keep powder from floating away.
- What is comminution?
- After a powder has been grounded, place into a seive/sifter to ensure uniform particle size. A higher mesh size indicates what?
- Magnesium stearate
- Sodium lauryl sulfate
- Reducing particle size via grinding, crushing, milling, vibrating, or other processes
- More holes where only a fine powder can get through
Explain the ways to mix ingredients:
1. Geometric dilution
- Melting point order
- What is a eutectic mixture?
Geometric dilution: small amount of drug added into an equal amount of diluent and then repeated until all ingredients are mixed together
-Can be used with dry powders or pastes
-Ensures even distribution
Melting point order: melt ingredients with highest melting point before adding ingredients with lower melting point to prevent exposing substances to higher temperatures than necessary
Eutectic mixture: combination of ingedients will melt at lower temperature than either of the individual’s melting temperature
-Caution to avoid burning mixture
-Caution with solid powders at room temp to melt and become too sticky
Solutions:
-Define
-Explain the different types: syrups, elixirs, tinctures, and spirits
Solution: solute dissolved in solvent; homogenous (consistent, uniform throughout)
Syrups: oral solutions with sucrose or toher sugars/articifical sugars
Elixirs: sweet hydroalcoholic solutions for drugs that would be insoluble in purely aqueous formulation
Tinctures: plant or animal extracts dissolved in alcohol or hydroalcohol
Spirits: alcohols or hydroalcohols of volatile (evaporates easily), aromatic compounds such as camphor
How to prepare solutions
- Gather ingredients.
- Reduce particle size of solid drug to fine powder.
- Dissolve solute in solvent –> dissolution rate can be used to determine time for solute to dissolve (Fick’s First Law of Diffusion); a larger surface area (smaller particles), stirring, and heating increase dissolution rate
- Add any other excipients (buffer, preservative, flavorings, sweeteners, or coloring agents)
- Package and apply BUD.
Suspension:
-Define
-How to prepare
Suspension: solid dispersed into a liquid (two-phase heterogenous mixture); wedding agent/levigating agent typically aded to incorporate insoluble drug into liquid
Preparation:
1. Gather ingredients
2. Reduce particle size of drug of solid drug into fine powder.
3. Wet powder and levigate to form paste.
4. Continue to add liquid in proportions
5. Add surfactant to help keep dispersed.
6. Add any other excipients (preservatives, flavorings, sweeteners. or coloring agents).
7. Transfer mixutre into conical graduate or container to dispense and add quantity sufficient to final volume.
8. Package and apply a BUD.
9. Redisperse (shake) upon use.
*What is precipitation/sedimentation and how is it caused? *
Precipitation: when the dispersed phase settles (clumps) together
Sedimentation: settles on the bottom usually with suspensions and emulsions (less in solutions)
Shake or gently roll to redisperse
How to prepare an emulsion
4:2:1 ratio of 4 parts oil, 2 parts water, and 1 part gum
Continential (dry gum) method:
1. Levigate gum with oil
2. Add water ALL at once
3. Triturate by shaking in bottle or mixing in mortar until cracking sound is heard and mixture is creamy white
4. Add other ingredients by dissolving them first in solution and then QS with water.
5. Homogenize with homogenizer machine
English (wet gum) method:
1. Triturate gum with water to form mucilage (thick and sticky like mucus)
2. Add oil SLOWLY while shaking or mixing
3. Add other ingredients as in dry gum method
Capsules:
1. Shells are made of?
- _________ and ______ are used as plasticizers to make capsules less brittle and more flexible.
- How to prepare capsules via hand filling and manual capsule-filling machine method
- Gelatin or hypromellulose
- Glycerol or sorbitol
3.
-Hand filling: powder placed on paper or ointment slab, smoothed with spatula to height of about 1/3 of capsule length, and the open end of capsule is repeatedly “punched” into pule of powder until filled and then capped
-Manual capsule-filling machine: plates help sort capsule bodies and hold them in place to then put powder above capsules on to plastic sheet and spread to move into capsules. A comb or tamper and spreader and used repeatedly until all powder packed into capsules and the caps are then put over capsule bodies
Solid Dosage forms:
1. _________ tablets are the most common tablet type to make in compounding whereas ______ tablets are made in manufacturing.
- How to prepare these types of tablets?
- What are the types of lozenges/troches?
- How to prepare ointments?
- Molded; compressed
2.
-Triturate dry ingredients and mix via geometric dilution
-Add alcohol and/or water to moisten to have pasty consistency to mold
-Allow to dry and add coloring or coating if desired
3.
-Hard lozenges: sucrose or syrup
-Soft lozenges: polyethylene glycol (PEG)
-Chewable lozenges: glycerin or gelatin
4.
-Triturate powders using levigating agents that is miscible with base
-Mix powder into base via geometric dilution (may need heat –> fusion method; can use water bath and use lowest heat)
Suppositories:
1. Provide examples of oil-soluble and water-soluble bases
- Lubricants can be added to remove more easily, but what is the main consideration?
- Oil-soluble bases: cocoa butter, hydrogenated vegetable oils (palm, palm kernel, or coconut oils)
Water-soluble bases: PEG polymers and glycerinated gelatin
- Add a lubricant OPPOSITE of suppository base in terms of solubility to reduce friction (ex. glycerin or propylene glycol - both water soluble for oil-soluble bases; mineral oil or vegetable oil spray- both oil-soluble for water-soluble base)
Suppositories:
1. How to prepare suppositories using the hand rolling method
- In fusion molding, gently heat base and mix ingredients into base. Poor into room temperature mold. What can occur when pooring into a cold mold? What can be done if base does not harden?
- What must be known when doing compression molding?
- For when a few suppositories as being made; grate cocoa butter and mix with drug using mortar and pestle or pill tile w/ spatula then roll into cylinder to cut into pieces then form tip on one end to make easier insertion
- -Cold molds can cause suppository to crack and split
-Refrigerate if does NOT harden - Weight of each mold and drug’s density factor to caculate amount of base required to fill each mold
Beyond Use Dates (BUDs):
1. What is the BUD?
- BUD can be extended to a maximum of ______ days if stability data is obtained. This is similar to ___________ as well which is NOT compounding.
- How to assign BUD dating
- Date after which compounded product must NOT be used based on how susceptible compound is to microbial contamination and degradation
- 180; unit doses
3.
Aqueous dosage forms (Aw >/=0.6):
-Nonpreserved: 14 days, store in fridge
-Preserved: 35 days
Nonaqueous dosage forms (Aw < 0.6):
-Oral liquids: 90 days
-Other nonaqueous forms: 180 days
Exceptions to BUD:
-If any ingredients expire before BUD, then use earlier date
-If stability testing done, can extend to that date
Provide the maximum BUD for the following:
1. Cream (o/w emulsion, petrolatum free) with preservative, Aw 0.968
- Oral suspension (water-based) w/o preservative, Aw 0.992
- Ointment (in petrolatum), Aw 0.396
- Foam w/o preservative, Aw 0.983
- Lip balm, Aw 0.181
- 35 days
- 14 days, refrigerated
- 180 days
- 14 days, refrigerated
- 180 days
Provide the maximum BUD for the following:
1. Gelatin-based lozenge, Aw 0.332
- Suppostory (in oleaginous base), Aw 0.385
- Powder for inhalation, Aw 0.402
- Nasal spray, with preservative, Aw 0.991
- 180 days
- 180 days
- 180 days
- 35 days
What should the master formulation record (MFR) include?
- Compound’s name, strength or activity, and dosage form
- Ingredients with amounts
- Container closure system
- Instructions for preparation (including equipment/supplies)
- Physical description of final product
- BUD with reference
- Storage requirements
- Calculations if applicable
- Labeling requirements (including auxillary)
- Quality control procedures and expected results
*What should the compounding record (CR) include? *
- Compound’s name, strength or activity, and dosage form
- Date
- Assigned internal identification number
- Staff involved in compounding
- Ingredients w/ quantities/strengths (including manufacturers, sources, lot numbers, and expiration dates)
- Total quantity and physical description of final product
- BUD and storage requirements
- Calculations if applicable
- Quality control testing results
- MFR reference for product
Sterile Compounding Terminology:
-Small volume parenteral (SVP)
-Large volume parenteral (LVP)
-Primary engineering control (PEC)
-Laminar airflow workbench (LAFW)
SVP: IV bag or container with volume 100mL or less
LVP: IV bag or container with volume > 100mL
PEC: sterile hood that provides ISO 5 air for sterile compounding
LAFW: type of open-front sterile hood (PEC) where air flows in one direction
Sterile Compounding Terminology:
-Secondary engineering control (SEC)
-Seegregated compounding area (SCA)
-Compounding aseptic isolater (CAI)
-Restricted access barrier system (RABS)
SEC: room containing ISO 7 air where sterile hood (PEC) is located (“buffer room”)
SCA: designated space that contains ISO 5 sterile hood (PEC), but is NOT part of cleanroom suite; air in designated space NOT ISO-rated
-Alternative to SEC
CAI: type of closed-front ISO 5 sterile hood (PEC) used for nonhazardous drug compounding (“glovebox”)
RABS: any closed-front ISO-5 sterile hood (includes CAIs) (“glovebox”)
Air Quality in Sterile Compounding:
1. What is ISO?
- In critical areas such as closest to sterile drugs and containers (ex. inside a PEC), the air quality must be at least ISO ____ which contains no more than ______ amoutnt of particles/m3.
- The buffer area (or the SEC) must be at least ISO ___. The anteroom where handwashing and garbing occurs must be at least ISO ___ if it opens into a positive-pressure buffer area (ex. for non-hazardous sterile compounding). If its a negative-buffer area for hazardous drug compounding, it must be ISO _____.
- International Standards Organization that sets standards for air quality determined by number and size of particles per volume of air (lower partticle count, cleaner the air)
- ISO 5; 3520
- ISO 7; ISO 8; ISO 7
Air Quality in Sterile Compounding:
1. For a room with ISO 7 air, the ACPH (air replacements/hour) must be at least ____ and for ISO 8, the ACPH should be ___.
- Air pressure inside the PEC and SEC should be ______(positive/negative) for nohazardous compounding.
- 30; 20
- Positive (pushes pair out)
Types of Sterile Compounding Areas:
1. Cleanroom suite contains _____________.This room is entered through the adjacent ____________ where garbing is facilitated and the line of _______ seperates room into clean and dirty sections. ______ must be applied one at time while stepping over this line.
- Segregated compounding area (SCA) is within the _________, often an isolator “glovebox” with a closed front, located in a segregrated space with _________ air. The SCA is an option when __________ is not available, and there must be a visible ______.
- One or more sterile hood (ISO 5 PCAs) inside a buffer room (SEC); anteroom; demarcation; shoe covers
- ISO 5 PEC: unclassified; cleanroom; defined perimeter
Types of Sterile Compounding Areas:
1. Inside a PEC, the HEPA filter provides the clean ISO 5 air for compounding. The space in front of the filter is called __________ and the air coming directly out of the filter is called the _________ which is cleaner than rest of air in hood. The filter must be recertified by a specialist every __________ and anytime it has been moved. When compounding, the injection port and syringe needles should be kept in the ________.
- __________ is an open-front PEC that flows in a unidirectional line from filter, known as a horizontal laminar airflow. _________ is closed-front PEC often located in the SCA which keeps unclassified air from mixing with ISO 5 air.
- Direct compounding area (DCA); first air; 6 months; first air
- Laminar airflow workbench (LAFW); compounding aseptic isolater (CAI)
Sterile Compounding: Personnel Training and Testing
1. Each facility must have a designated person responsible for _______________.
- How often does training need to documented/done?
- What aseptic techniques must be demonstrated? Explain the two different tests to evaluate aseptic technique.
- Training and oversight of compounding personnel
- Initial training before performing any job functions independently and continuous training completed at least every 12 months (ex. knowledge of core skills)
- Hand hygiene, garbing/gowning, cleaning and disintefectnig space and equipment, sterile drug preparation
-Specific tests: gloved fingertip test (3 times) and media-fill test initially, Q6 months (if compounging category 1 and 2 CSPs) or Q3 months (if compouding category 3 CSP)
-Gloved fingertip test: glove sample collected from each hand over a microbial growth agar that contains tryptic soy agar (TSA) as a food source for microbials, plates are intubated and inspected after 7 days for colony-forming units (CFUs) –> must pass three consecutive gloved fingertip samples after garbing with zero CFUs
-Media-fill test: compounder prepares compound using a small IV bag or vial where tryptic soy broth (TSB) takes place of drug in preparation –> if liquid stays clear after 14 days of incubation, compounder has passed test; after media-fill testing, gloved fingertip test with at least one sample from each hand as well
Sterile Compounding: Environmental Monitoring
1. When must temperature and humidity be monitored and documented?
- Air sampling for contaminants should be peformed at least every _________. Air pressure testing using a continuous monitor should be used to confirm _________ and ensure airflow is _________.
- How often should surface sampling be done?
- Daily on compounding days or continuously with monitor
-SEC (buffer room), drug storage: check QD
-CSP storage areas (fridge, freeze): at least QD for temperature - 6 months; differential (difference between two pressure between two spaces; unidirectional
- Perform Q30 days for all classified areas and pass-through spaces
-Areas touched most frequently (ex. inside PEC, door handles): test at end of compounding shift
Sterile Compounding: Cleaning
1. To prevent contamination, the PEC should be run at all times. If the PEC is stopped, it should be cleaned and disinfected, and it must be on for at least ________ minutes before compouding begins. Regardless, the PEC should be cleaned everyday and throughout the day.
- First, the PEC is cleaned with ______ then disinfected (or a one-step disinfectant) then _________ is applied. _________ is required as well, but less frequently. _______ types of wipes should be used.
- Describe what should be cleaned first and then next in the PEC.
- 30 minutes
- Detergent; 70% isopropyl alcohol; sporicidal disinfectant; low-lint
- PECS are cleaned top to bottom, back to front (cleanest area cleaned first then dirtiest) –> use slightly overlappy, unidirectional stropes and replace wipes often
Ex. Cleaning horizontal laminar flow hood
1. Clean ceiling of hood from back to front
- Clean back of hood (grill over HEPA filter) from top to bottom
- Clean IV bar and hooks
- Clean side walls startinf from back to front
- Clean anything kept in hood (ex. automated compounding device)
- Clean bottom surface (work area) starting from back to front with side to side motion
Sterile Compounding: Explain how often each of the following should be cleaned (daily cleaning and disinfecting), disinfected (for category 1 and 2 CSPs), and sporicidal disinfectant (for category 1 and 2 CSPs)
1. PEC and equipment inside
2. Pass-through chambers
3. Work sufarces around PEC
4. Floors
5. Walls and doors
6. Ceiling
7. Storage shelves and bins
8. Equipment outside PEC
Sporicidal disinfectant: ALL monthly
1-4: cleaning and disinfecting daily
-PEC and equipment inside
-Pass-through chambers
-Work sufarces around PEC
-Floors
5-8: cleaning and disinfecting monthly
-Walls and doors
-Ceiling
-Storage shelves and bins
-Equipment outside PEC
Sterile Compounding: Garbing
1. What is minimum garb attire?
- What is process of garbing?
Minimum garb: hand hygiene the hand covers, facial hair covers, special shoes or shoe covers, gowns, powder-free gloves, and face masks ALL low-lint
Garbing:
1. Remove coats, rings, watches, braclets, and makeup before entering anteroom. Artificial or long nails are not permitted. Makeup not permitted due to shedding.
- Don head and facial hair covers and faces masks.
- Don shoe covers while stepping over line of demarcation.
- Perform hand hygiene w/ soap and warm water. Clean under fingernails and work with fingertips to elbows washing for >30 seconds.
- Dry hands and forearms with low-lint disposable towels.
- Don a low-lint gown. Disposable preferred.
- Enter buffer area (SEC). Apply alcohol-based surgical hand scrub (often chlorhexidine, alternatively: povidone-iodine).
- Don sterile, powder-free gloves. Sanitize gloves with 70% isopropyl alcohol.
Sterile Compounding: Garbing
1. All garb must be used when compounding with an _________ unless manufacturer provides documentation that garb is NOT required.
- When compounding is done, all garb goes into disposal container except __________ as long as not visibly soiled and re-worn for current work shift.
- When should a compounder re-garb?
- Isolator (“glovebox”)
- Gown
- Exiting anteroom or SCA
Sterile Compounding: Equipment
1. ______ syringes are commonly used to transfer drugs. What size syringes should be used for accuracy?
2, What is the use of a leur lock?
- ______ is required when withdrawing liquid from an ampule and why?
4, When drawing up liquid from a vial, what should be done first?
- When does a vial need to be reconstituted?
- Hypodermic
-Accuracy: use smallest syringe to hold desired amount, but do NOT use exact size since plunger can become dislodged - Make secure, leak-free connections between syringes, needles, catheters, and IV lines and in compounding, may be used for mixing or transferring fluids between drug delivery devices or IV sets
- Filter needle (“filter straw”) - when ampule broken, glass can be introduced into drug solution
- Inject a volume equal of air to the volume of drug withdrawn to equalize the pressure
- When the vial contains lypohilized or freeze-dried powder – reconstitute w/ sterile water for injection, bacteriostatic water for injection, or diluent provided by manufacturer
Sterile Compounding: Equipment
1. Define SVPs, provide examples, and how they are often used
- Define LVPs and provide examples.
- What are ready-to-use medications (RTUs)?
- What are examples of ready-to-use vial/bags?
- What are automated compounding devices (ACDs) and IV workflow management systems (IVWMS)?
- SVP = small volume parenteral: IV bag or syringe w/ 100mL or less
-Ex. NS or D5W, liquid drug w/ or w/o diluent
-Use: often “piggybacked” onto a LVP - LVP = large volume parenteral: IV bagwith more than 100mL
-Ex. NS, D5W, D5NS, LR - Prepared IV bags or prefilled syringes that do NOT need to be compounded
- ADD-Vantage, Minibag Plus
- -ACDs: devices that aseptically transfer ingredients into sterile final container –> should be interlaced with electronic health records to prevent transcription errors
-IVWMS: “IV room assisted workflow technology” that automate preparatoin, verification, tracking, and documentation of CSPs –> includes barcode scanning and photo capture
*Sterile Compounding: How should items be setup in sterile hood? *
- Only required items should be placed in hood. Wipe all components with 70% IPA prior to bringing into PEC.
- All work within PEC should be performed at least 6 inches from the front (less chance that ISO 5 air has mingled with buffer room)
- Place all items in hood side-by-side and NOT placed within six inches of back of hood
- Nothing should be placed between sterile objects and HEPA filter in horizontal airflow hood or above objects in vertical airflow hood
- Sterile syringes and other equipment should be individually wrapped and opened along seal (do NOT tear to avoid shedding)
- Move waste out of PEC shortly after created
How to draw up liquid from a vial
- Swab the rubber top of the vial with 70% IPA or alcohol pad
- Prior to withdrawing, draw up equal volume of air to equal volume being removed.
- Puncture rubber top of vial with need, bevel up, and at 45 degree angle
- Bring syringe straight up to 90 degree angle while need penetrates stopper
- Depress plunger of syringe, empyting air into vial
- Invert vial with attached syringe. Draw up amount of liquid required.
- Withdrawl needle from vial.
Sterile Compounding: Finalizing the Product
1. What is the “syringe pull back method”?
- What should the pharmacist verify?
- What is terminal sterilization?
- How is pyrogen contamination avoided?
- Pharmacist verifies the volume in an empty syringe after compounding is completed and technician “pulls-back” the plunger of syringe to volume of product that was added and places syringe next to vial –> method relies on memory and is NOT recommended
- Particulates, cored pieces, precipitation, and cloudiness –> can hold to light and dark background; lightly squeeze bag to check for leaks
- Sterilization used after compound with any non-sterile ingredients
-Steam sterilization with an autoclave
-Dry-heat sterilization (dehydrogenation): do NOT use on heat-sensitive drugs (ex. proteins such as hormones)
-Filtering w/ 0.22 micron –> manufacturer may require a test for filter integrity such as a bubble-point test - Pyrogens come from washing equipment with tap water –> wash glassware and utensils in sterile water and dehydrogenate using dry-heat sterilization with autoclave
Sterile Compounding: Beyond Use Dating (BUDs)
1. How does category 1, 2, and 3 CSPs impact BUD?
- How are immediate-use CSPs made?
- -Category 1: CSPs prepared in ISO 5 PEC placed in SCA which has unclassified air –> shorter BUD an no sterility test required
-Category 2: CSPs made in cleanroom suite (ISO 5 PEC located in ISO 7 SEC) –> longer BUD and sterility testing may be required
-Category 3: CSPs made with very specific requirements (ex. sterility testing, endotoxin testing if applicable, environmental monitoring) -> longer BUD, max 180 days
- Emergency use under suboptimal conditions (no PEC)
Sterile Compounding: Beyond Use Dating (BUDs):
1. BUDs for immediate-use and category 1, 2, and 3 CSPs under room temperature, refrigeration, and freezer
- BUDs for:
-Single dose container (vial, bag, bottle, syringe) inside ISO 5 environment
-Single dose container (ampule) inside or outside ISO 5 environment
-Multi-dose container inside or outside ISO 5 environment
- -Immediate use: 4 hour for any storage condition
-Category 1: 12 hours at room temp, 24 hours in refrigerator, N/A for freezer
-Category 2: 1-45 days at room temp, 4-60 days in refrigerator, 45-90 days in freezer
-Category 3: 60-90 days at room temp, 90-120 days in refrigerator, 120-180 days in freezer
2.
-SDC (vial, bag, bottle, syringe) inside ISO 5 environment: up to 12 hours from puncture or opening
-SDC (ampule) inside or outside ISO 5 environment: any unused contents must be discarded
-MDC inside or outside ISO 5 environment: up to 28 days from puncture or opening
Sterile Compounding: Miscellaneous
1. What are the different requirements with master formulation and compounding formulations records from nonsterile?
- Can CSPs be dispensed before receiving results of sterility tests?
- Compounded products that require a narrow pH range will need ____________.
- -Master formulations: required only when CSP prepared for more than one patient or from nonsterile ingredients
-Compounding formulations: for all category 1-3 CSPs and any immediate-use made for more than one patient
- Technically yes –> must have written procedure in place to take appropriate actions if did NOT meet specifications (ex. immediate notifications of prescribers, recalls, investigation)
- Buffer system consisting of acid and salt (ex. acetic acid to reduce pH and sodium acetate to increase pH)
Hazardous Drugs: Reasons to be classified as hazardous and key drugs that are hazardous
Reasons: carcinogenic, teratogenic, toxic to reproduction (causes infertility), genotoxic (damages DNA which can cause cancer), toxic to organs at low doses, simliar structure/toxicity profile to drug previously determined to be hazardous
NIOSH List:
-Antineoplastics
-Hormonal agents: androgens (testosterone), estrogens (estradiol), oxytocin, proestins (medroxprogesterone), SERD/SERMs (tamoixfen, raloxifene, fulvestrant), ulipristal
-Psychiatric medications: carbamazepine, oxcarbazepine, fosphenytoin, phenytoin, topiramate, valproate, clonazepam, temazepam, paroxetine
-CV meds: warfarin, lomitapide, spironolactone
-Anti-infectives: cidofovir, ganciclovir, valganciclovir, ribavirin
-Transplant meds: cyclosporine, mycophenolate, tacrolimus, sirolimus
-Autoimmune conditions: acitretin, azthioprine, fingolimod, leflunomide, teriflunomide
-PAH meds: ambrisentan, bosentan, macitentan, riociguat
-Abortifacients: mifepristone, misoprostol
-Miscellaneous: dustasteride, finasteride, tretinoin, methimazole, propylthiouracil
Hazardous Compounding: Basics
1. Safety data sheets (SDS) must be accesible to all employees per OSHA. What do they entail?
- Each facility must have a designated person responsible for ____________.
- Men and women with reproductive capability must confirm in writing what?
- What are some examples of lower risk activities with hazardous drugs (HDs)?
- What must be done if a pharmacy wishes to avoid having to follow all USP 800 requirements?
- PPE, first aid procedures, spill clean-up procedures
- Creating SOPs during all aspects of HD handling including a hazard communication program (written plan of safety procedures, training, assessments, and documentatoin) –> for low risk
- That they understand the risks associated with handling HDs
- Counting and packaging tablets
- Conduct and Assessment of Risk (AoR) to develop SOPs to limit staff exposure
Hazardous Compounding: Physical Space Basics
1. For compounding with HDs, the abbreviations have a “C” in front such as C-PEC, C-SEC, C-SCA, CACI which stands for __________, and they require _______(positive/negative) air pressure.
- C-PECs must be what ISO for sterile and nonsterile HDs?
- Types of C-PECs: biological safety cabinets (BSCs) have __________ air flow and for sterile, must be Class ___. Containment ventilated enclosures (CVEs) are powder containment hoods for ________(sterile/nonsterile) compounding only. Compounding aseptic contaiment isolators (CACIs) are closed-front C-PECs located often in __________.
- Ideally, sterile and nonsterile compounding should be kept separate. What are the exceptions?
- Containment; negative - required to keep hazardous drugs and vapors within space due to toxicity risk
- ISO 5
- Unidirectional air flow (verticle laminar airflow); class II; nonsterile; C-SCA
- -C-SEC maintains ISO 7 air even when being used for nonsterile
-Seperate C-PECs for sterile and nonsterile at least 1 meter apart
Hazardous Compounding: Space Requirements
1. The anteroom should have ___________(positive/negative) air pressure and be maintained at ISO ___.
- Air changes per hous (ACPH) should be at least _____ in nonsterile HD space C-SEC, _____ in sterile C-SEC, and _______ in C-SCA.
- Air that had been contaminated with HDs must be externally exhausted and cannot be returned to room unless in nonsterile compounding only there is ___________.
- HDs must be stored away from non-HDs in a room with _______ (positive/negative) air pressure and at least _____ ACPH.
- Positive; ISO 7 (keeps roooms equal pressure between buffer and anteroom to prevent hazardous materials entering closer to pharmacy)
- 12; 30; 12
- Redundant HEPA filters where air is passed through two or more
- Negative; 12
*Hazardous Compounding: Garbing *
- Respirator: NIOSH-certified N95 for most activities that require respiratory protection (alterntiavely: surgical N95 respirator, powdered air-purifying respirato, full-facepiece chemical cartridge-type respiratory)
-Face mask for sterile if NOT using respirator
-Additional protection in direct HD exposure (ex. spills, undertray of C-PEC) - Head and hair covers
- Eye protection when risk for HD spills/splashes or when working outside of C-PEC (full-facepiece resipirator or face shield w/ goggles accepting)
- Chemotherapy gloves: must meet American Society for Testing and Materials (ASTM) standard D6978, be powder-free, must be changed Q30 minutes or when torn/punctured/contaminated, two pairs (one under cuff and one over cuff on gown)
- Chemotherapy gown: must be not be reused (disposable), must be impermeable, must close in back and be long and have closed cuffs, must be changed Q2-3 hours or immediately after spill/splash
- Shoe covers: two piars required
*What are scenarios with HD exposure that require some form of PPE? *
- Gloves for handling - even intact tablets/capsules
- Gown when administering HDs and recommended when administering others (ex. oral)
- Gloves when receving HDs and storage – pneumatic tube systems cannot be used to transport liquids or any antineoplastics (potential for breakage)
- Two pairs of gloves for administering injectable antineoplastics
Hazardous Compounding: Miscellaneous
1. What technique should be used when drawing up liquid from a vial
2, What are the labeling requirements for HDs?
- When disposing garb, outer chemotherapy gloves should be discarded in ________ inside the ____ or put in a sealable bag. The rest of the garb must be taken off before exiting ______ and thrown in _________. All trace hazardous waste (ex. empty vial, syringes) should be thrown away in _______. All bulk hazardous waste (ex. unused or partially used IV bags, syringes, vials) that contain a clearly visible amount of HD should be thrown away in _______.
- How often should surfaces be sampled?
- Unlike sterile compouding, avoid since positive pressure in vial can cause HD to spray out aroundt he needle
-Negative Pressure Technique: pull plunger back to fill the syringe with volume of air equal of volume of drug to be removed then insert needle intial vial, invert vial and pull on plunger –> creates vacuum that pulls drug out of vial into syringe (do in small increments)
-Closed-system transfer devlices (CSTDs): built in valve to equalize air pressure when fluid added or withdrawn from vial –> required in antineoplastics
- ALL preparations should have “Chemotherapy - dispose of properly” or something simila r
- Yellow trace chemotherapy waste bin; C-PEC; C-SEC or C-SCA; yellow trace chemotherapy waste bin; yellow bin; black bin
- Every 6 months
*Hazardous Compounding: Explain the different steps of cleaning. *
- Deactivation - make compound inert/inactivate
-Ex. peroxide or sodium hypochlorite (2% bleach) - Decontamination - remove HD residue
-Ex. alcohol, water, peroxide, or sodium hypochlorite (2% bleach) - Cleaning - remove dirt and microbial contamination
-Ex. germicidal detergent - FOR sterile compounding: disinfection - destroy microorganisms
-Ex. EPA-registered disinfectant or 70% isopropyl alcohol
Tips:
-Wetted wipes should be used since spraying onto surfaces can cause HD residue to aerosolize and spread
-Multipurpose agents (deactivation and decontamination): bleach or peroxide (neutralize bleach after with sodium thiosulfate, alcohol, or water to prevent corosion)
Hazardous Compounding: Spill kit contents and how to manage spills
Spill kit contents: gown, gloves, N95 respiraory mask, goggles w/ side shields, HD waste bag, scoop and scraper, chemo pads, HD spill report exposure form
First steps:
-Quickly limit access to the area and post warning signs around perimeter of spill
-Pregnant women should immediately leave the area
Cleaning the spill:
-Don ASTM D6978 chemotherapy-rated gloves on first then heavy-duty gloves on over (protection from glass)
-Clean up large amounts of spilled drug and broken glass –> never use brush and powder contaminated (airborne concern)
-Cover any liquid with absorbent spill pad
-Decontaminate surfaces on which HD has spilled moving from area of lesser concentration to greater concentration
-Discard in black waste bin
Explain how hazardous drug exposure should be handled
- Immediately remove garb with drug on it
- Immediately cleanse any affected skin with soap and water
- For eye exposure, flood affected eye at eyewash fountain or with water for at least 15 minutes
(depending on chemical, flush longer) - Obtain medical attention
- Document exposure in employee’s record
