Ch. 16 Sterile Compounding

Stabinsky

sterile compounding is used to prepare:

injections, including IV, IM, and SC

eye drops

irrigations

inhalations

** standards are set by USP 797

CSPs

compounded sterile product

IV or other drugs that require sterile manipulation

SVP

small volume parenteral

IV bag or container with a volume of 100mL or less

LVP

large volume parenteral

IV bag or container with a volume >100mL

PPE

personal protective equipment

garb; "don" means to put on, "doff" means to take off

PEC

primary engineering control

sterile hood that provides ISO 5 air for sterile compounding

LAFW

laminar airflow workbench

a type of open-front sterile hood (PEC); air flow in one direction

SEC

secondary engineering control

the room containing ISO 7 air where the sterile hood is located; also called the buffer room

SCA

segregated compounding area

designated space that contains an ISO 5 hood but is not part of a cleanroom suite; air in the designated space is not ISO rated

CAI

compounding aseptic isolator

a type of closed-front ISO 5 sterile hood used for nonhazardous drug compounding; sometimes referred to as a glove box

RABS

restricted access barrier system

any closed-front ISO 5 sterile hood; sometimes referred to as a glovebox

physical space basics

surfaces must be smooth, impervious, and easy to clean and disinfect

stainless steel is often used

air quality - ISO ratings

ISO sets the standards for air quality, which is determined by the number and size of particles per volume of air

the lower the particle count, the cleaner the air

in critical areas (inside the sterile hood), air quality has to be at least ISO 5

the buffer area must be ISO 7

the anteroom (the room adjacent to the SEC where hand washing and garbing occurs) must be at least ISO 8 if it opens up into a positive-pressure buffer area

air changes

the air changes per hour (ACPH) is the number of time (per hour) that the air is replaced in the room

for a room with ISO 7 air, there must be at least 30 ACPH

air pressure

the air pressure inside the PEC and SEC are both positive

types of sterile compounding

cleanroom suite --> one or more ISO 5 PECs inside an ISO 7 buffer room that is entered through an adjacent anteroom

segregated compounding area (SCA) with an ISO 5 PEC --> a sterile hood, often an isolator (glovebox) with a closed front, located in a segregated space with unclassified air

primary engineering control

the PEC provides ISO 5 air --> achieve this by using a sterile hood

high-efficiency particulate air filters

the space in front of the HEPA filter is called the direct compounding area

the air coming directly out of the HEPA filter is called the first air

the HEPA filter must be recertified by a specialist every 6 months

types of PECs

a laminar airflow workbench (LAFW) --> horizontal laminar airflow

a compounding aseptic isolator (CAI) --> located in a segregated compounding area

air quality inside the PEC

the PEC provides ISO 5 air quality for sterile compounding

the air coming directly out of the HEPA filter is called the first air, which is cleaner than the rest of the air in the sterile hood

to prevent contamination of CSPs during compounding, the injection port of the container and the syringe needle must be kept in the first air

- do NOT obstruct first air, especially where the needle enters the vial or ampule

- do NOT block airflow from the HEPA filter with hands or supplies

- place items correctly inside the PEC to avoid creating turbulence, which can lead to contamination of the CSPs

secondary engineering control

SEC is commonly called the buffer area

ISO 7

anteroom

contains a sink, cabinet, and benches to facilitate garbing

running down the center of the anteroom is a large visible line called the line of demarcation, which separates the room into clean and dirty sections

shoe covers must be applies one at a time while stepping over the demarcation line

segregated compounding area

has unclassified air

there must be a visible, defined perimeter

personnel training and testing

must have a designated person

initial training

continuous training that must be completed every 12 months

aseptic procedures

hand hygiene

garbing

sterile drug prep

gloving

**gloved fingertip test

aseptic technique in sterile compounding is demonstrated by passing the media-fill test

both the gloved fingertip test and the media fill test must be completed by a compounder initially and every 6 months (if compounding only category 1 and 2 CSPs)

gloved fingertip test

collects a gloved sample from each hand of the compounder

the plates are incubated

spots that form are called colony-forming units (CFUs) and indicate contamination was present on the gloves

passing a gloved fingertip test

after garbing --> requires 3 consecutive gloved fingertip samples with zero CFUs

after media-fill testing --> at least one sample taken from each hand with 3 or less CFUs total

media-fill test

used to determine if a compounder is preparing CSPs in an aseptic manner

turbidity (cloudiness) means that contamination is present

passing a media-fill test

if the liquid stays clear after 14 days

temperature and humidity monitoring

temperatures must be monitored and documented

the SEC should be checked once daily

temperature in the CSP storage areas (refrigerator, freezer) should be monitored at least daily

air and surface testing

have to ensure that the environment for compounding sterile products is acceptably free of contaminants

air sampling for contaminants should be performed at least every 6 months

surface sampling performed every 30 days --> areas touched most frequently should be tested at the end of the compounding shift

air pressure testing, using a continuous monitoring device, to confirm the correct differential between two spaces and ensure that the airflow is unidirectional

keep the PEC running

preferably kept running at all times

if there is a power outage, all compounding must stop, and the PECs will need to be cleaned and disinfected, then sterile 70% isopropyl alcohol (IPA) should be applied

the PEC must be on for at least 30 minutes before compounding can begin

cleaning the PEC

the PEC is cleaned daily and sterile 70% IPA is applied throughout the day

first, the PEC is cleaned with a detergent, then disinfected --> next, 70% IPA is applied

sterile, low-lint wipes are used to clean the PEC

PECs are cleaned from top to bottom, back to front --> this means that the cleanest areas will be cleaned first, and the dirtiest will be cleaned last

use slightly overlapping, unidirectional strokes

replace used wipes often

cleaning a horizontal laminar airflow PEC

1) clean the ceiling from back to front

2) clean the back of the hood from top to bottom

3) clean the IV bar

4) clean the side walls from back to front

5) clean anything kept in the hood

6) clean the bottom surface from back to front

cleaning frequency

daily cleaning and disinfecting -->

- PEC

- pass-through chambers

- work surfaces outside the PEC

- floors

monthly cleaning and disinfecting -->

- walls, doors

- ceiling

- storage shelves and bins

- equipment outside the PEC

** sporicidal disinfectant for everything MONTHLY

garbing for sterile compounding

don garbing --> should occur in anteroom

order is from dirtiest to cleanest

hand hygiene must be performed and sterile, powder-free gloves should be used

minimum garb attire includes head covers, facial hair covers, shoe covers, gowns, gloves, and face masks

steps for garbing

remove coats, rings, watches, and makeup before entering the anteroom. artificial or long nails are not permitted

don head and facial hair covers and face masks, then shoe covers while stepping over the line of demarcation

perform hand hygiene with soap and warm water --> clean under fingernails; working from the fingertips to the elbows, wash for 30 or more seconds

don a low-ling gown --> disposable preferred

enter the buffer area (SEC)

apply an alcohol-based surgical hand scrub --> chlorhexidine is used frequently. another option is povidone-iodine

don sterile, powder-free gloves

sanitize the gloves with sterile 70% IPA routinely

if the gown is not visibly soiled, it can be taken off and kept on the clean side of the anteroom in order to be re-worn for the current work shift

common products used in sterile compounding

syringes and needles

ampules and vials

IV bags

ready-to-use sterile medications

syringes and needles

syringes --> hypodermic (parenteral) syringes are used to transfer drugs; use the smallest syringe that can hold the desired amount of solution, but do not use a syringe of the exact size

needles --> recapping needles can lead to needle-stick injuries; do NOT recap needles; it is preferrable to use syringes with safety features

luer locks --> make secure, leak-free connections between syringes

ampules and vials

ampules --> a filter needle or filter straw is required when withdrawing liquid from the ampule to remove the glass

vials that contain liquids --> inject a volume of air equal to the volume of drug that is withdrawn to equalize the pressure

vials that contain lyophilized or freeze-dried powder --> the powder needs to be reconstituted by adding sterile water

IV bags

small volume parenteral --> IV bags or syringes that contain 100mL or less

large volume parenteral --> contain more than 100mL

ready-to-use sterile meds

ready-to-use meds (RTUs) --> prefilled; not compounded

ready-to-use vial/bag systems (ADD-vantage)

technology in sterile compounding

automated compounding devices (ACDs) that aseptically transfer ingredients --> ACDs should be interfaced with the electronic health record to prevent transcription errors

IV workflow management systems --> automate the preparation, verification, tracking, and documentation of CSPs; includes technology to identify meds through barcode scanning, as well as photo capture

setting up items in the sterile hood

all components should be wiped off with 70% IPA to remove contaminants and dust prior to being brought into the PEC

all work must be performed at least 6 inches from the front

place all items side-by-side

nothings should be between the sterile objects and the HEPA filter in a horizontal airflow hood

equipment must be opened along the seal to avoid shedding (release of particles)

transferring solutions

swab the rubber top of the vial and port on the IV bag with 70% IPA

drug powders are reconstituted into a liquid such as SWFI

prior to withdrawing any liquid from a vial, inject a volume of air equal to the volume of fluid to be removed

puncture the rubber top of the vial with the needle, bevel up and at a 45 degree angle, then bring the syringe straight up; invert the vial with the attached syringe

coring occurs when a small piece of rubber from the stopper is aspirated into the needle. look for small cored pieces during visual inspection

if the medication is in a glass ampule, open the ampule by snapping the neck away from you. tilt the ampule, then withdraw the fluid using a filter straw or filter needle to remove any glass particles. the needle must be changed before injecting

visual inspection

supervising pharmacist should verify that the correct volume of product is in the syringe before compounding continues --> helps to see the actual volume in the syringe

the syringe pull back method is when the pharmacist verifies the volume in an empty syringe after the compounding is completed

finished CSPs are visually inspected for particulates, cored pieces, precipitates, and cloudiness --> the container should be lightly squeezed to check for leakage

sterility testing

can be performed to ensure the absence of contamination

testing for sterility is required for certain categories of CSPs

sterilization

terminal sterilization is required for CSPs that are compounded with any nonsterile ingredients

terminal sterilization methods include steam sterilization (with an autoclave), dry-heat sterilization, and filtration

do not use heat on heat-sensitive drugs (proteins)

CSPs that are heat-labile can be sterilized with filtration using a sterile 0.22 micron silter

if filtering is used, the manufacturer of the filter might require a test for filter integrity, such as the bubble-point test

pyrogen (bacterial endotoxin) testing

endotoxins are produced by bacteria and fungi

endotoxins from gram-negative bacteria are more potent

pyrogens can come from using equipment washed with tap water --> to avoid this issue, glassware and utensils should be rinsed with sterile water and depyrogenated using dry-heat (steam) sterilization with an autoclave

establishing beyond-use dates

USP categorizes CSPs by the risk of contamination

the risk levels are category 1, 2, and 3

these risk levels are then used to determine an appropriate BUD, which is the date or time after which the CSP should not be used

category 1 sterile compounding

prepared in an ISO 5 PEC that is placed in a segregated compounding area (SCA)

require shorter BUDs

BUD for a CSP made in an SCA is 12 hour or less at controlled temp; 24 hours or less if refrigerated

category 2 sterile compounding

made in a cleanroom suite

have longer BUDs than category 1

category 3 sterile compounding

made in accordance with specific requirements

longer BUDs, up to a max of 180 days

some of these requirements include sterility testing

sterile compounding for emergencies

emergency use (immediate use)

prepared in suboptimal conditions, so BUD is 4 hours

determining BUD based on CSP category

immediate-use --> uncontrolled (no PEC) --> 4 hours

category 1 --> ISO 5 PEC in SCA --> 12 hours room temp, 24 hours refrigerated

category 2 --> ISO 5 PEC in cleanroom --> 1-45 days room temp, 4-60 days refrigerated, 45-90 days frozen

category 3 --> ISO 5 PEC in cleanroom with additional requirements --> 60-90 days room temp , 90-120 days refrigerated, 120-180 days frozen

internal records

the master formulation record is needed for CSPs prepared for more than one patient or from nonsterile ingredients

the compounding record is needed for category 1, 2, and 3 CSPs, as well as for any immediate-use CSPs prepared for more than one patient

label requirements

must have the names and amounts or concentrations of ingredients, the BUD, ROA, and storage requirements

auxiliary labels on CSPs that require special handling

high-alert medications need appropriate warning labels

recalls

these actions include immediate notification of the prescriber, recall of any dispensed CSPs, quarantine of remaining stock and investigation of other lots that could be affected

physiochemical considerations

most CSPs should be isotonic to human blood and have a pH that is close to neutral

compounded preparations that require a narrow pH range will need a buffer system --> consists of an acid and its salt

henderson-hasselbalch equation is used to calculate the pH of a solution