NAPLEX: Compounding & Hazardous Products - Sterile Compounding

what is sterile compounding used to prepare

- injections (IV, IM, SC, intrathecal)

- eye drops

- irrigations (liquid washes that go into body cavities)

- pulmonary inhalations

- bath and soaks for live tissues/organs

- implants

CSP

compounded sterile product

IV or other drugs that require sterile manipulation

SVP

small volume parenteral

IV bag or container with a volume <100 mL

LVP

large volume parenteral

IV bag or container with a volume >100 mL

PPE

personal protective equipment

garb (gown, gloves, mask)

don = put on

doff = take off

PEC

primary engineering control

sterile hood that provides ISO 5 air for sterile compounding

LAFW

laminar airflow workbench

type of open front sterile hood (PEC)

air flow in one direction

SEC

secondary engineering control

room containing ISO7 air where sterile hood (PEC) is located

also called the buffer room

SCA

segregated compounding area

designated space that contains an ISO 5 sterile hood (PEC) but is not part of the cleanroom suite

air in designated space (room air) is not ISO-rated

CAI

compounding aseptic isolator

a type of closed front ISO 5 sterile hood (PEC) used for nonhazardous drug compounding

sometimes referred to as the glovebox

RABS

restricted access barrier system

any closed front ISO 5 sterile hood (includes CAIs)

sometimes referred to as glovebox

true or false

there are greater and stricter compounding space requirements for sterile compounding than non sterile compounding

true

surface requirements in sterile compounding

must be smooth, impervious, and free from cracks / crevices to make them easy to clean and disinfect

often stainless steel is used

who sets the standards for air quality

international standards organization (ISO)

what is air quality determined by

the # and size of particles per volume of air

lower the particle count, clearer the air

primary engineering control (PEC) air quality

ISO 5

3520 particles/m3

includes critical areas closest to exposed sterile drugs + containers

secondary engineering control (SEC) air quality

ISO 7

352000 particles/mm3

buffer area - further away from PEC, so air can be dirtier

anteroom air quality

ISO 7 or 8

3520000 particles/mm3

where handwashing + garbing occurs

must be at least ISO 8 if it opens into a positive pressure buffer area

air changes per hour (ACPH

# of times per hour that the air is replaced in a room

for a room with ISO 7 air, how much ACPH must there be

30 ACPH

for a room with ISO 8 air, how much ACPH must there be

20 ACPH

air pressure inside PEC and SEC must be ____ (positive/negative) for non hazardous drug compounding

positive

helps protect CSPs from contamination

types of sterile compounding areas

- cleanroom suite

- segregated compounding area (SCA)

clean room suite

one or more sterile hoods (ISO 5 PECs) inside an ISO 7 buffer room (SEC) that is entered through an adjacent anteroom

segregated compounding area (SCA) with an ISO 5 PEC

contains sterile hood, often an isolator w closed front located in a segregated space with unclassified air

HEPA filter

removes particles when air runs through the filter to provide clean ISO 5 air for compounding

direct compounding area (DCA)

space in front of HEPA filter

first air

air coming directly out of the HEPA filter

how often must a HEPA filter be recertified

every 6 mo and every time a PEC has been moved

laminar airflow workbench (LAFW)

open front PEC where air flows in unidirectional lines from HEPA filter typically from back of hood (horizontal laminar airflow)

positive pressure keeps the cleaner air in PEC from mixing w dirty air in room

compounding aseptic isolator (CAI)

closed front PEC that can be located in the buffer room (SEC) but is often located in segregated compounding area (SCA)

closed front keeps unclassified room air from mixing w clean ISO 5 air inside PEC

line of demarcation

line that separates the room into clean and dirty section

side closer to other areas of the pharmacy = dirty side of anteroom

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

handwashing and donning of the gown occur on the clean side of the anteroom

segregated compounding area (SCA)

option when cleanroom is not able to be installed

has unclassified air - no buffer area or anteroom

can only be used for certain CSPs

must be kept apart from other areas of the pharmacy + have a visible, defined perimeter around SCA

cannot be located adjacent to food preparation or windows/doors that connect to outdoors or areas of high traffic flow

useful for satellite pharmacies that are away from main pharmacy in a large hospital, infusion centers, clinics, small hospitals

training for sterile compounding

must have designated person responsible for training and oversight of compounding personnel

all people who compounds / has insight over compounders must have proper training including:

- initial training: knowledge + competency of compounding sterile products

- continuous training: every 12 mo

all staff must demonstrate they can follow aseptic procedures of what

- hand hygiene

- garbing and gloving technique

- cleaning and disinfecting procedures for sterile space and equipment

- sterile drug preparation

garbing competency evaluation

must be completed > 3 times and includes visual observation of procedures and gloved fingertip test

aseptic technique in sterile drug preparation is demonstrating by passing what

media fill test

surface sampling

how often must the gloved fingertip test and media fill test be completed

initially

then every 6 mo (if compounding category 1 & 2 CSP)

or every 3 mo (if compounding category 3 CSP)

gloved fingertip test

evaluator collects a gloved sample from each hand of compounder by rolling pads of fingers / thumb over surface that contains microbial growth (agar)

if microorganisms are present, will use agar as source of food + replicate

plates are incubated + inspected for growth after >7 days

to pass

- after garbing: must have 3 consecutive gloved fingertip samples after garbing w 0 CFU for both hands

- after media fill testing: requires at least 1 sample from each hand immediately after media fill test with <3 CFU total for both hands

media fill test

used to determine if compounder is preparing CSP in an aseptic manner

followed by gloved fingertip test and surface sampling

computer prepares a compound w aseptic technique using small IV bag or vial w TSB (growth medium) as drug in preparation. aseptic manipulations are completed then product is incubated and checked for microbial growth

cloudiness means contamination is present

to pass: liquid stays clear after 14 days of incubation

how often should SEC temperature + humidity be checked and what should be the results

check once daily

maintain at 20 C (68 F) or cooler, humidity at 60% or less

how often should temperature in CSP area be checked

monitored at least daily

if out of range take action + document

must calibrate temperature monitoring devices at least every 12 mo

air and surface testing

what does this entail + how often

- air sampling every 6 mo

- surface sampling every 30 days; areas touched most frequently (inside PEC, door handles) should be tested at the end of compounding shift

- air pressure (confirm correct differential between 2 spaces + ensure airflow is unidirectional)

true or false

PECs need to be shut off at the end of day

false

PECs are preferably kept running at all times to keep surfaces clean

PEC in a power outage

stop all compounding

PEC needs to be cleaned and disinfected, then sterile 70% isopropyl alcohol needs to be applied prior to re-initiation of compounding activities

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

how often should the PEC be cleaned

daily

anytime contamination is suspected

how often should sterile 70% IPA be applied to PEC work surface

throughout the day (every 30 min)

how to clean PEC

1. clean w detergent + disinfect w/ one step disinfectant cleaner

2. 70% IPA applied + sporicidal disinfectant

what types of wipes are used to clean PEC

sterile, low lint wipes

alternatively can use a spray bottle to wet a dry wipe

never spray inside PEC

what direction are PEC cleaned

from top to bottom, back to front

cleanest areas cleaned first then dirtiest areas cleaned last

use slightly overlapping, unidirectional strokes rather than circular motions

what areas of PEC need to be cleaned

1. ceiling from back to front

2. back of hood (grill over HEPA filter) from top to bottom

3. IV bar and hooks

4. side walls from back to front

5. anything kept in the hood

6. bottom surface starting from back to front

do not start compounding until surfaces have dried

surfaces that need to be cleaned daily

- PEC (and equipment inside)

- pass through chambers

- work surfaces outside PEC

- floors

surfaces that need to be cleaned monthly

- walls/doors

- ceiling

- storage shelves and bins

- equipment outside PEC

surfaces that need to be disinfected daily

- PEC (and equipment inside)

- pass through chambers

- work surfaces outside PEC

- floors

surfaces that need to be disinfected monthy

- walls/doors

- ceiling

- storage shelves and bins

- equipment outside PEC

how often should sporicidal disinfectant be used

monthly

what type of gloves must be used inside the CAI

sterile, powder free gloves

minimum garb attire

- head covers (bonnets)

- facial hair covers

- special shoes or shoe covers

- gowns

- powder free gloves

- face masks

garbing instructions

1. remove coats, rings, watches, bracelets, and makeup before entering anteroom. artificial or long nails are not allowed

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

3. perform hand hygiene with soap and warm water. clean under fingernails. working from fingertips to elbows wash for >30 seconds

4. dry hands and forearms w low lint disposable towels or wipers

5. don a low lint gown - disposable preferred

6. enter buffer area (SEC)

7. apply alcohol based surgical hand scrub

8. don sterile powder free gloves

9. sanitize the gloves w sterile 70% IPA routinely during compounding

when can a gown be reworn

if a gown is not visibly soiled it can be taken off and kept on the clean side of the anteroom to be reworn during teh current work shift

when to re garb

garb should not be worn outside of anteroom - if anteroom has been exited need to completely regarb

if working in SCA + left for any reason need to regarb

what size syringe should be used to draw up medications

use smallest syringe that can hold desired amount of solution but do not use a syringe of teh exact size

what is required when withdrawing liquid from ampules

filter needle or filter straw

how to equalize pressure in vials that contain liquids

inject a volume of air equal to the volume of the draw that is withdrawn to equalize pressure

how to reconstitute vials that contain lyophilized or freeze dried powder

add sterile water

automated compounding devices (ACDs)

device that aseptically transfers ingredients into a sterile final container which replaces need for manual transfer of ingredients

IV workflow management systems (IVWMS)

technology that automates teh preparation, verification, tracking, and documentation of CSPs

includes technology to identify medications for compounding through barcode scanning + photocapture

workflow for csp preparation

- review order (pharmacist)

- gather + inspect materials

- clean hood + place only needed items in hood

- prepare CSP with aseptic technique

- dispose of any syringes, needles into sharps container

- visually inspect all finished CSP

- complete terminal sterilization and/or sterility testing

how to set up items in sterile hood

- all components should be wiped off with 70% IPA prior to being brought into PEC

- all work must be performed at least 6 in from the front

- place all items side by side

- nothing should be between sterile objects and HEPA filter in horizontal airflow hood

- sterile syringes must be opened along the seal inside PEC

- move waste out of PEC shortly after itis created

how to transfer solutions

- swab rubber top of vial and port of IV bag with 70% IPA and wait for it to air dry

- reconstitute drug powders w sterile water for injection

- prior to withdraw liquid from vial inject a volume of air equal to volume of fluid to be removed

- puncture top of vial w needle, bevel up, and at 45 degree angle. then bring syringe straight up to a 90 degree angle while needle penetrates the stopper. invert vial w attached syringe + draw up amount of liquid required then withdraw vial

- look for any small cored pieces floating near top of solution during visual inspection of CSP

- if medication is in glass ampule, open ampule but snapping neck away from u then use filter straw/needle to remove any glass particles that fell in + change needle before injecting syringe contents into IV bag

- inject solutions from syringe into IV bag via injection port

syringe pull back method

pharmacist verifies volume in an empty syringe after compounding is complete

technician pulls back plunger of syringe to volume of product that was added into IV admixture + places empty syringe next to vial

relies on memory - not recommended

what to check for when performing visual inspection

- particulates

- cored pieces

- precipitates

- cloudiness

lightly squeeze to check for leakage

terminal sterilization

steam sterilization (autoclave)

dry heat sterilization (depyrogenation)

filtration

what filter should be used for CSP that are heat labile

0.22 micron filter

bubble point test

used to check for filter integrity

determines pressure required to see bubbles out of a filter

pyrogens + how to avoid them

come from using equipment washed with tap water

to avoid glassware and utensils should be rinsed w sterile water + depyrogenated using dry heat (steam) sterilization w an autoclave

category 1 sterile compounding

- environment

- room temp BUD

- refrigerated BUD

- frozen BUD

ISO 5 PEC in SCA w unclassified air

- have higher risk of contamination > shorter BUD

BUD:

room temp: <12 hrs

refrigerated: <24 hrs

frozen: N/A

category 2 sterile compounding

- environment

- room temp BUD

- refrigerated BUD

- frozen BUD

ISO 5 pec in cleanroom suite

- can have longer BUD compared to category 1

sterility testing may be required based on BUD

BUD:

room temp: 1-45 days

refrigerated: 4-60 days

frozen: 45-90 days

category 3 sterile compounding

ISO 5 PEC in cleanroom + additional requirements

- longer BUD than category 2

- requirements = sterility testing, endotoxin testing, frequent environmental monitoring, personnel qualifications

BUD:

room temp: 60-90 days

refrigerated: 90-120 days

frozen: 120-180 days

sterile compounding for emergencies BUD

may be prepared under suboptimal conditions (no PEC)

BUD = 4 hrs for any storage condition

BUD for single dose containers (vial, bag, bottle, syringe) inside ISO 5 environment

up to 12 hrs from puncture or opening

BUD for single dose containers (ampule) inside or outside ISO 5 environment

any unused contents left in ampule cannot be stored and must be discarded

BUD for multi-dose containers inside or outside an ISO 5 environment

up to 28 days from puncture or opening

what are master formulation records required for

any CSP prepared for more than 1 patient or from non sterile ingredients

what are the compounding records required for

category 1, 2, 3 CSP + immediate use CSP prepared for more than 1 pt

need lot # and expiration date

CSP label requirements

- name

- amount or concentration of ingredients

- total volume

- BUD

- dosage form

- route of administration

- storage requirements

- auxiliary labels on CSP that require special handling

- warning labels on high alert medications

- telephone # of pharmacy

what should CSP quality assurance plans include

- adherence to procedures

- error prevention and detection

- evaluation of complaints

- investigation and corrective actions

what to do for recalls of CSP

- immediately notify prescriber

- recall any dispensed CSP

- quarantine remaining stock

- investigation of other lots that could be affected

CSP should be ___ to human blood

isotonic

common buffer system to decrease pH

acetic acid

common buffer system to increase pH

sodium acetate

immediate use BUD

4 hours

how long do sterile compounding certification records need to be kept

3 years

requalification for sterile training

category 1 & 2

every 6 mo

requalification for sterile training

category 3

every 3 mo

what kinds of preparations do not require pyrogen testing

topical, opthalmic, inhaled preparations