IV Admixture Programs: Patient Safety

• IV Admixture Programs are vital for patient safety and rely on pharmacists
• Intravenous drug administration carries high risk and requires significant attention

Centralized Pharmacy IV Admixture Service

• Are essential for ensuring sterility through aseptic techniques.
• Vital for stability
• Accurate pharmaceutical calculations
• Avoiding incompatibility when preparing IV medications.

Advantages of IV Admixture Service

• Centralizes responsibility for preparing, dispensing, and controlling parenteral admixtures.
• Frees up nurses and physicians from preparing I.V. preparations.
• Increases the safety of parenteral medications.

Definitions

• Sterile products are pharmaceutical dosage forms that are sterile, including parenteral preparations, irrigating solutions, and ophthalmic preparations.
• Parenteral preparations are pharmaceutical dosage forms injected via intramuscular, subcutaneous, intravenous, or other routes
• Required to be sterile to bypass protective barriers
• Compounded Sterile Preparation (CSP) is a prescribed dose of medication for a specific patient that must be prepared sterilely for administration.
• Sterility is the absence of living microorganisms.
• Aseptic Technique involves methods used to manipulate sterile products to maintain their sterility.
• Ampule: A parenteral product container made entirely of glass, and intended for single use.
• Vial: A glass or plastic container closed with a rubber stopper and sealed with an aluminum crimp, which can be used for multiple doses if it contains a preservative, or used once if it does not contain a preservative.
• Prefilled Syringe: A ready-to-use prefilled medication syringe with a needle attached, as with epinephrine and some emergency drugs.
• Prefilled cartridges: Ready-to-use parenteral packages that offer improved sterility and accuracy; consist of a plastic cartridge holder and a prefilled medication cartridge, where the medication is premixed and premeasured, commonly available for narcotics
• Pumps and controllers are electronic devices used to administer parenteral infusions to avoid inaccurate dosing or risk patient safety compared to gravity flow alone
• Examples of use include: parenteral nutrition, chemotherapy, cardiac medications, and blood products.
• Small-Volume Parenterals (SVP): Infusion solutions with a volume less than 100 ml.
• Large-Volume Parenterals (LVPs): Infusion solutions with a volume of 100 ml or greater.

Design and Functions of Sterile Product Areas

• International Organization of Standardization (ISO) classifies particulate matter in room air, measuring particles 0.5 μm and larger per cubic meter.
• Key ISO Classes and their equivalents including Particle Count:
  • ISO Class 3/U.S. FS 209E Class 1: 35.2 particles/m³, 1 particle/ft³
  • ISO Class 4/U.S. FS 209E Class 10: 352 particles/m³, 10 particles/ft³
  • ISO Class 5/U.S. FS 209E Class 100: 3,520 particles/m³, 100 particles/ft³
  • ISO Class 6/U.S. FS 209E Class 1000: 35,200 particles/m³, 1,000 particles/ft³
  • ISO Class 7/U.S. FS 209E Class 10,000: 352,000 particles/m³, 10,000 particles/ft³
  • ISO Class 8/U.S. FS 209E Class 100,000: 3,520,000 particles/m³, 100,000 particles/ft³
• Laminar Flow Hoods are workbenches designed to create an aseptic environment for sterile product preparation.
• They use HEPA filters with higher efficiency than cleanrooms.
• Classified as ISO Class 5 (formerly Class 100).
• Contain no more than 100 particles 0.3 mm or larger per cubic foot of air and provide an efficiency of 99.99%.
• The underlying principle involves a constant flow of HEPA-filtered air at a velocity sufficient to sweep particles away which prevents contaminated air from entering and maintaining unidirectional airflow.
• Used to prevent contamination of compounded sterile products and parenteral preparations.
• HEPA-filtered unidirectional airflow principles must be understood for desired environmental conditions.
• Laminar flow hoods provide clean air, prevent room air entry, and remove contaminants, in three basic functions.
• Preparation of I.V. admixtures
• Preparation of ophthalmic solutions
• Reconstitution of sterile powdered drugs
• Filling unit dose syringes
• Preparation of miscellaneous sterile products
• Laminar flow units commonly used include bench and console models.
• Horizontal laminar flow hoods: -Were the first hoods used in pharmacies for sterile product preparation. -Airflow moves across the work area surface and through a prefilter and then through the HEPA filter -Their major disadvantage is that they offer no protection to the operator, especially when antineoplastic agents are prepared.
• Vertical laminar flow hoods have vertical airflow, flowing down onto the workspace protecting the operator against potential hazards.
• Aseptic manipulations should be performed at least SIX inches within the hood to prevent contamination from room air entering.
• Work should not be performed at the edge or outside the hood.
• Maintain a direct, open path between the filter and the manipulation area, or compounding area.
• Avoid placing large objects at the back of the work area to prevent contamination and airflow disruption.
• Leave laminar flow hoods operating continuously.
• If turned off, hoods must run for 30 minutes to reestablish laminar air flow before use.
• Clean hoods at the beginning of each shift and as needed throughout the shift.
• Before use, clean all interior working surfaces of the laminar flow hood from back to front and away from the HEPA filter.
• Laminar flow hoods are inspected and certified initially, every 6 months.
• Inspections are conducted by companies with trained personnel and sensitive equipment.
• The dioctyl phthalate (DOP) smoke test ensures that no particles larger than 0.3 mm pass through the HEPA filter.
• An anemometer is used to determine airflow velocity, and a particle counter is used to determine the particle count.
• High-efficiency particulate-air (HEPA) filters are used to cleanse the air entering the room or hood.
• These filters remove all airborne particles 0.3 mm or larger, with an efficiency of 99.97% in cleanrooms and 99.99% in laminar flow hoods.
• HEPA filters are typically constructed of paper-thin sheets of borosilicate medium, plated to increase surface area, and affixed to a frame.
• Aluminum separators are often added for stability.
• The HEPA filter is located behind the HEPA filter screen in horizontal laminar flow hoods.
• Nothing should contact the HEPA filter:
  • Cleaning solution
  • Aspirate from syringes
  • Glass from ampules
  • Fluids
  • Do not touch
• Anteroom is an ISO Class 8 or better area where personnel perform hand hygiene and garbing procedures, stage components, enter orders, label CSPs, and conduct other activities, also serving as a transition to maintain air pressure between clean and dirty areas.
• Provides assurance that pressure relationships are constantly maintained so that air flows from clean to dirty areas.
• Reduces the need for the heating, ventilating and air conditioning (HVAC) control system to respond to large disturbances .

Buffer Area

• Also known as Buffer or Core Room, Buffer or Cleanroom Areas, Buffer Room Area, or Buffer or Clean Area.

• An ISO Class 7 area where the primary engineering control area is located.

• Activities include preparation and staging of components and supplies to compound CSPs, and compounding sterile preparations.

• Cleanroom*

• Is a room in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class.

• Microorganisms in the environment are monitored so that a microbial level for air, surface, and personnel gear are not exceeded for a specified cleanliness class.

• Critical Area: An ISO Class 5 environment.

• Positive Pressure Room: Airflow is out of the room due to higher pressure.

• Negative Pressure Room: Net airflow is into the room due to lower pressure.

Primary and Secondary Engineering Controls

• Primary Engineering Controls: Devices or rooms providing an ISO Class 5 environment for critical sites during CSP compounding, including laminar airflow workbenches (LAFWs), biological safety cabinets (BSCs), and compounding aseptic isolators (CAIs).
• Secondary Engineering Controls: Cleanrooms and anterooms providing a buffer zone for the primary engineering control.
• Compounding Aseptic Isolator (CAI):* A form of barrier isolator designed for compounding pharmaceutical ingredients or preparations.
  • It is designed to maintain an aseptic compounding environment
  • Air exchange should only occur through a microbially retentive filter (HEPA minimum).
• Biological Safety Cabinet (BSC), Class II
  • This is a ventilated cabinet for personnel, product, and environmental protection having an open front with inward airflow for personnel protection
  • Includes downward HEPA filtered laminar airflow for product protection
  • HEPA filtered exhausted air for environmental protection Personnel Cleansing and Garbing Order

CSP Microbial Contamination Risk Levels

• Immediate-Use Category

  • For emergent use, or situations where low-risk compounding would add risk due to delays.
  • Requires no storage or batch compounding, a continuous compounding process lasting less than one hour, and aseptic technique.
  • Must be administered or discarded within 1 hour after preparation.
  • Includes simple transfer of sterile nonhazardous drugs or diagnostic radiopharmaceuticals

• Low-Risk Level

  • Includes simple admixtures compounded using closed system transfer methods, prepared in an ISO Class 5 LAFW located in an ISO Class 7 buffer area with ISO Class 8 ante area.
  • Examples include reconstitution of single-dose vials of antibiotics or other small-volume parenterals and preparation of hydration solutions.
  • For preparations with Less than 12 Hour Beyond Use Date, requires simple admixtures compounded using closed system transfer methods
  • Prepared in ISO Class 5 PEC, with a compounding area segregated from non-compounding areas, and administration must start no later than 12 hours after preparation

• Medium-Risk Level

  • Involves admixtures compounded using multiple additives and/or small volumes, batch preparations, complex manipulations, and preparation for use over several days, prepared in ISO Class 5
  • Located in ISO Class 7 buffer area with ISO Class 8 ante area.
  • Examples include pooled admixtures, parenteral nutrition solutions using automated compounders, and batch-compounded preparations lacking bacteriostatic components.

• High-Risk Level

  • Includes non-sterile ingredients, open system transfers, prepared in ISO Class 5 and located in ISO Class 7 buffer area with separate ISO Class 8 ante area
  • Examples include CSPs prepared from bulk, nonsterile components, or final containers that are nonsterile and must be terminally sterilized.

Cleaning And Disinfecting The Sterile Compounding Areas

• Minimum cleaning frequencies:
  • ISO Class 5 Primary Engineering Controls: Beginning of each shift.
  • Counters and easily cleanable work surfaces: Daily.
  • Floors: Daily.
  • Walls, ceilings, and storage shelving: Monthly.

Personnel Cleansing and Garbing Order

• Prior to entering buffer area or segregated compounding area:
  • Remove all personal outer garments and cosmetics.
  • Remove jewelry from hands, wrists, or any other visible body parts.
  • No artificial nails allowed and Don PPE in the following order: Dedicated shoes or shoe covers, head and facial hair covers, face masks/eye shields, hand cleansing procedures, and a non-shedding gown.
• Upon entering buffer area or segregated compounding area:
  • Antiseptic hand cleansing with surgical scrub and don sterile powder-free gloves.

Standard Operating Procedures (SOPs)

• Each pharmacy should have well written and approved SOPs.
• Should ensure the quality of the environment which the CSP is prepared in.