Engineering Controls and Aseptic Technique

Why should CSPs be verified (part 1)?

• Incompatibility and/or particulate matter is not present in the CSP

• All calculations involved in preparation of the CSP were performed correctly

• The right drug and diluent that were used, along w/ their respective volumes are correct

Why should CSPs be verified (part 2)?

• The expiration date of drug(s) and diluent(s) used are in-date

• Labeling accurately reflects contents.

• Auxiliary labels are included and are appropriate

• Instructions for administration are correct

• The correct Beyond-Use-Date (BUD) is assigned

What is the role of PEC?

• Primary engineering controls (PECs) are used for compounding

• Designed to maintain ISO Class 5 air quality in the work zone

• Work adjunct to secondary engineering controls to control air quality

Types of PEC

• Laminar airflow workbenches (LAFW)

  • Laminar airflow hoods/flow workbenches

  • Horizontal or vertical hoods

• “Laminar” describes airflow movement

  • Unidirectional, linear manner

What is “first air”

• Also referred to as “clean air”

• Exits the HEPA filter

  • Removes particles and microorganisms 0.3 micron or larger

• Positive velocity to prevent room air from entering clean zone

  • 90 feet per minute ± 20%

What role does “first air” plays?

• Important that manipulations are consistently exposed to first air to prevent contamination

• First air can easily be disrupted

  • Normal activities can create velocities that exceed the outward velocity of first air

    • Causes inward flow from room air or regurgitation of air into LAFW

  • Zones of turbulence created:

    • At front of workbench

    • Directly downstream from items placed in workbench

    • Directly downstream from items placed on side of workbench

Aspect of HLFW

• Must run at least 30 minutes prior to use if turned off

• Manipulations must be performed within central work zone

  • 6 inches from sides

  • 6 inches from front

  • 3 inches from back

Considerations when cleaning the HLFW?

• HEPA protective screen not part of routine cleaning

  • Remove every 6 months and clean well

• This is dependent on the manufacturer of the workbench, consult manufacturer’s guidance

What is the Vertical Laminar Flow Workbench (VLFW)

• Produces first air in vertical direction

• Requires altering of manipulations and technique

Aspects of Biologic Safety Cabinet (BSC)

• Vertical laminar airflow

• Provides product, environmental, and operator protection

• Inward flow of air through front opening

• Often exhausts air to outside

• Should run for at least 4 minutes if turned off

• Should be used when preparing hazardous agents

What should be used to clean the surface of these workbenches?

• Lint-free wipes

• Residue-free sterile 70% isopropyl alcohol (IPA)

  • Allow to dry for at least 30 seconds

When should these workbenches be cleaned?

• Beginning of each shift

• Prior to each batch preparation

• After spills

• When known or suspected to be contaminated

• Every 30 minutes for extended preparations

• Soiling can be first cleaned with sterile water then disinfected as usual

• A sporicidal agent must be used at least monthly (IPA is NOT sporicidal)

Aspects of Compounding Isolators

• Also known Restricted Access Barrier Systems (RABS)

  • Compounding aseptic isolator (CAI): Mostly used for nonhazardous preparations

  • Compounding aseptic containment isolator (CACI): Mostly used to prepare hazardous agents

• Improved protection of operator compared to BSC

• Decreased influence of room air on sterile preparation

• There are new isolators on the horizon with automated cleaning functions which can be used in an ISO 8 room

Considerations when cleaning isolators?

• Requires specialized cleaning tools

• Involves special cleaning steps such as rinsing

• If turned off > 24 hours, should be sanitized then run for at least 10 minutes then disinfected

• If turned off < 24 hours, should run for at least 2 minutes prior to using

consideration when prepping hazardous agents

• Must be performed in specific PEC that meets criteria

• Non-hazardous compounding must not be performed in PEC in which hazardous compounding occurs and vice versa

When should PECs be certified?

• Initial installation

• If device or room is moved

• Following a major repair

• Major service to facility

• Non-viable and viable air sampling

  • Conducted by a third party

• Surface sampling

  • Can be conducted “in house”

What is the role of secondary engineering controls (SEC)?

• Direct compounding areas

• Areas surrounding PECs must be controlled to prevent contamination

• SECs work adjunct to PECs to maintain environmental quality

Aspects of clean room

• Room in which air quality is controlled to meet specific ISO class

• May include buffer area and ante-area

  • Both are considered SECs

Aspects of buffer area

• ISO Class 7 minimum

• Location for PECs

• Limited traffic flow

• No handwashing

• Items brought into buffer area should be limited

  • Items must be wiped down prior to entry

Aspects of Ante-Area

• ISO Class 8 minimum for non-hazardous compounding

• ISO Class 7 minimum for hazardous compounding

• Located just outside of buffer area

• Location for activities such as:

  • Hand washing

  • Garbing

  • Staging

  • Labeling

• All outer garments, cosmetics, and jewelry should be removed in ante-area before entering buffer area

Aspects of the line of demarcation

• Must be a visible line on the floor

• Used to separate “clean” and “dirty” side of Ante Room

• 2 separate ante rooms may be used instead of the line

• Garbing should take place on the dirty side

• Only fully garbed personnel would be allowed to cross the line to the clean side

When cleaning the SEC, what needs to be clean daily?

• Floors

• Work surfaces (carts, tables, sinks)

When cleaning the SEC, what needs to be clean Monthly?

• Ceiling

• Walls

• Storage shelving

What are some other considerations for cleaning the SEC

• Separate dedicated instruments should be used for
  Buffer room and Ante room

• Sporicidal agents should be used at least monthly

Aspects of Buffer/Ante-areas

• BSC or CACI must be located in ISO Class 7 negative-pressure buffer area

  • Pressure gradients monitored

• ISO Class 7 ante-area

• Must be separated from other preparation areas

• PEC vented to outside

What influences sterility?

• Environmental quality

• Proper hand washing

• Proper hand hygiene

• Use of personal protective equipmen

• Primary and secondary engineering controls

• Maintenance of equipment and environment

• Aseptic technique

Aspects of hand washing

• Essential and critical step in preventing contamination of CSP. Needs to be a full 30 seconds to the elbow

• Transient hand flora

  • 15% of all flora

  • Removed with hand washing

• Resident hand flora

  • 85% of all flora

  • Not removed by hand washing

• Spores

  • Requires physical removal with hand washin

  • Not removed with hand sanitizers or alcoho

What is consider PPE?

• Shoe covers

• Beard cover

• Hair cover

• Jacket/Gown

• Gloves

  • Sterile

  • Powder-free

Aspects of donning PPE

• Also referred to as “garbing”

• Used to:

  • Protect preparation from the operator and vice versa

What should u do before donning gloves?

Wash hands prior to donning gloves

Aspects of critical sites and airflow?

• Critical sites are at greatest risk of contamination

  • Touch

  • Moisture

  • Contact with unclean air

• ALL critical sites must be in contact with first air AT ALL TIMES during compounding

Aspects of gathering supplies

• Wipe down supplies prior to placing in sterile hood

• All supplies needed should be placed in sterile hood

Aspects of Disinfecting Vials, Ampules, and Injection Ports

• Swab vials with sterile, lint-free alcohol wipe toward operator

• Swab around neck of ampule with sterile, lint-free alcohol wipe several times

• Allow alcohol to dry

Aspects of preparing syringe and needle

• First remove syringe first from package followed by removing needle from package

  • Do NOT push either through outer wrapper

• Attach needle to syringe and remove cap of needle

  • Use push-pull technique

Aspect of Enter Vial

• Place vial firmly on workbench surface

• Enter with bevel up at a 45 degree angle

  • To prevent coring

• Apply downward pressure

Aspect of Withdrawing from Vial

• Invert vial while ensuring no critical sites are blocked during process

  • “See-saw”

• Use “milking” technique

• Use “one-handed technique” or “two-handed technique” with “C” transitions

aspect of removing air bubbles

• Tap syringe so that air rises to top of syringe

• Pull plunger out slightly

• Push air completely out

  • Observe tip of needle

• Adjust final volume

• Double check volume

Aspects of Injecting into Solution

• Contents often injected through the additive port of a bag of diluen

• Place bag with port toward HEPA filter or horizontally with port closest to HEPA filter

  • May hang bag from pole although this method provides less stability and increases risk of needle sticks

Aspect of mix and check

• Gently agitate after all components added

  • Do not shake

• Check against light and contrasting background for:

  • Incompatibilities

  • Particulate matter

  • Coring

Aspects of positive pressure

• If air added exceeds volume of solution withdrawn then positive pressure is created

  • Results in spraying or dripping of solution from vial

  • Should be avoided if at all possible

Aspects of negative pressure

• If amount of air removed exceeds volume of solution removed, negative pressure within the vial will result

  • Results in difficulty removing volume needed from vial