Storing, preparing and transporting cytotoxic medicines

Storing cytotoxic medicines

Any cytotoxic medicines must be clearly recognisable to all employees. They should be stored:

• in dedicated separate, clearly marked storage areas, including refrigerated areas where required
• in a manner that will protect the drug container from leakage if breakage occurs.

Storage in pharmacy departments, satellite pharmacies, wards and clinics should be as recommended on the Safety Data Sheet (SDS). Avoid overcrowding of storage areas. For example, do not stack prepared solutions on a refrigerator shelf.

Preparing cytotoxic medicines

Preparing includes:

• Handling cytotoxic medicines until they are ready to administer.
• Preparing a patient-specific single-dose unit. For example, drawing up cytotoxic medicines from a vial into a syringe and diluting ready for administration.

Dispensing is providing medicines that are ready to administer.

Employers must develop systems and procedures to ensure the safe preparation of cytotoxic medicines. This may include:

• cleanrooms
• suitable drug cabinet with air filtration, such as a:
  • cytotoxic drug safety cabinet (CDSC)
  • Compounding Aseptic Containment Isolator (CACI) with negative pressure ventilation
• closed system transfer devices
• secure storage facilities
• other specially designed equipment.

Use available controls

Available controls to eliminate or reduce the risks of exposure while preparing cytotoxic medicines for a workplace include:

• outsourcing the preparation of cytotoxic medicines to specialist companies
• buying cytotoxic medicines in a ready-to-use form, such as pre-filled syringes
• buying cytotoxic medicines in the safest form available
• using facilities and techniques that meet recommended technical and safety standards.

Where outsourcing is not possible, consider:

• reviewing health and safety information about cytotoxic medicines before deciding to buy them
• assessing if available controls will adequately manage the risks
• designing and laying out the work area according to recommended standards
• adopting closed-system operations.

For more information, see:

• Australasian Health Infrastructure Alliance, Australasian Health Facility Guidelines: Part B – Health Facility Briefing and Planning 0560 – Pharmacy Unit, 2021
• Pharmacy Board of Australia
• Society of Hospital Pharmacists of Australia (SHPA)
• Victorian Pharmacy Authority, Victorian Pharmacy Authority Guidelines, 2023.

Establish a cytotoxic preparation facility

Cytotoxic medicines should be prepared in purpose-designed facilities with:

• A cytotoxic cleanroom that houses either a CDSC or CACI. This provides a primary barrier for drug containment and aseptic handling.
• Access to the clean room only through an anteroom and pass-through hatch.
• A secondary barrier to prevent contamination of the outside environment. High efficiency particulate air (HEPA) filters should supply filtered air to the cleanroom that is at a lower pressure than that of the anteroom (outside of the clean room).

HEPA filters that supply filtered air to the cleanroom and the anteroom should be used in addition with other controls, not in isolation.

For more information, see 'Hierarchy of control for cytotoxic medicines' in Managing the risks from handling cytotoxic medicines.

The following technical standards describe available risk controls for cytotoxic preparation facilities and their installation:

• AS 2252.6-2011 Controlled environments, Part 6: Clean workstations - Design, installation and use
• AS 2252.5:2017 Controlled environments, Part 5: Cytotoxic drug safety cabinets (CDSC) - Design, construction, installation, testing and use
• AS/NZS ISO 14644.4:2002 Cleanrooms and associated controlled environments, Part 4: Design, construction and start-up
• AS ISO 14644.3:2021 Cleanrooms and associated controlled environments, Part 3: Test methods
• AS/NZS ISO 14644.5:2006 Cleanrooms and associated controlled environments, Part 5: Operations
• AS ISO 14644.1:2017 Cleanrooms and associated controlled environments, Part 1: Classification of air cleanliness by particle concentration
• AS 1807:2021 Separative devices - Biological and cytotoxic drug safety cabinets, clean workstations and pharmaceutical isolators - Methods of test
• AS 4273-1999 Design, installation and use of pharmaceutical isolators.

You can access these standards on the Standards Australia website.

Workplace layout and design

When organising workplace and equipment, and setting up work practices, employers should consider:

• comfort
• functionality
• safety.

This will make it:

• easier for employees to do their work safely
• less likely that they will make mistakes.

You must also consult with any Health and Safety Representatives (HSRs). 

Factors to consider in work layout and design include:

• the level of concentration and visual control required
• precision of movements needed
• the placement of accessible safety shower and eyewash stations
• design of equipment and availability of adjustable furniture such as chairs, stools and footrests
• storage requirements
• potential noise sources
• lighting.

When designing and setting up a cleanroom and anteroom, employers should also do the following:

• Provide access for cleaning.
• Use smooth and durable work surfaces and furniture.
• Install recessed lights.
• Limit the number of surfaces and shelves. This will minimise particle shedding or the accumulation of particulate matter.
• Install an accessible emergency shower outside the anteroom.
• Maintain an effective airlock between the cytotoxic suite and external environment.
• Ensure all equipment used is dedicated to the cytotoxic cleanroom.
• Ensure the anteroom provides: 
  • the only access to the cleanroom
  • access to only one cleanroom.
• Provide change room facilities for changing into personal protective equipment (PPE).
• Ensure the pass-through hatch has: 
  • no direct access to the external environment unless a HEPA filter is used to control emissions
  • interlocking doors and it is supplied with HEPA-filtered air.
• Provide a means of communication between the cleanroom and other areas.
• Install a manometer to: 
  • monitor the pressure differential within the cytotoxic suite
  • record daily differential pressure readings.
• Install a manometer alarm in case of inadequate pressure differentials.
• Install a system that reverses the airflow. In the event of a spill, this will minimise contamination to the external environment, with lower pressure environments in the cleanroom. 

Use appropriate equipment and techniques

Preparing cytotoxic medicines requires specific handling techniques and procedures. This should include equipment designed to reduce the risk of exposure.

Equipment used to prepare drugs needs to: 

• have a closed system transfer device where practicable
• reduce the potential for generating high pressure.

Specific controls to reduce the risk of exposure include using:

• Luer Lock syringes and fittings to keep connections together.
• Syringe-to-syringe connectors when transferring solutions from one syringe to another.
• Wide-bore needles to reconstitute and draw up cytotoxic medicines.
• Filter needles only when the cytotoxic medicine has been removed from a glass ampoule or if particulate matter is visible. For example, if coring of a vial rubber has occurred. Disc filters can be used when large volumes are involved.

Follow standard work procedures

Employers should ensure that standard work procedures for preparing cytotoxic medicines clearly detail:

• handling techniques
• instructions for using equipment.

This will help to minimise the risk of exposure for employees undertaking the tasks.

The standard work procedures should state how all employees must do all preparations. For example, in a CDSC or CACI. 

Standard work procedures for parenteral preparations should also include instructions on:

• Avoiding the use of cytotoxic medicines supplied in glass ampoules. If glass ampoules must be used, open with an ampoule breaker or a low-lint swab.
• Containing excess drug solutions and air when priming.
• Using techniques that avoid generating pressure differentials.

Specific additional information for non-parenteral preparations should include:

• using purpose-dedicated equipment
• making mixtures by dispersing tablets in water
• not crushing tablets in an open mortar
• not counting tablets or capsules by machine
• cleaning equipment immediately after use with a strong alkaline detergent with pH>10.

Packaging and transporting cytotoxic medicines

Cytotoxic medicines should always be packaged and transported in a way that:

• Provides adequate physical and chemical protection for the medicine.
• Protects handlers if a spill occurs. This includes risk control measures for the person transporting, such as PPE.
• Protects other equipment or medicines if a spill occurs.

Maintaining equipment

Employers should have a planned maintenance schedule for equipment used to prepare cytotoxic medicines. This includes air-handling facilities.

Performance-testing and equipment maintenance

A suitably qualified person should assess laminar-flow CDSC or CACI and suitable filters. In most cases, an external provider would be required.

Information about the basic requirements for the design, construction, installation, testing and use of CDSC is in:

• Australian Standard AS2252.5:2017 Controlled environments, Part 5: Cytotoxic drug safety cabinets (CDSC) - Design, construction, installation, testing and use.

An effective equipment maintenance schedule should involve:

• inspecting CDSC, CACI and HEPA filters 
  • at regular intervals 
  • after relocation or mechanical/electrical maintenance
• keeping test records and a summary of results in a place accessible to employees
• not using a cabinet that has failed, until the fault has been fixed and the cabinet recertified.

Cleaning cytotoxic medicine preparation facilities

The standard operating procedure should include cleaning instructions for cytotoxic medicine preparation facilities. This should cover:

• daily cleaning and record-keeping
• using a dedicated mop and bucket
• treating all equipment as potentially contaminated
• providing, wearing, removing and disposing of PPE.