Preparation of Cytotoxics

Transcription

1 Chapter 19 Preparation of Cytotoxics By the end of this chapter, you will be able to: l Explain what Cytotoxics are and why they are prepared l Understand the preparation techniques required when working with cytotoxics l Explain the risks to operators when working with cytotoxics l Identify the types of waste disposal containers used for cytotoxics l List ways to reduce risks to staff handling cytotoxics Introduction This chapter examines the preparation of Cytotoxic products. We will look at examples of their uses (indications). Specific risks are associated with the handling and preparation of cytotoxics. These include risks to patients from product contamination, incorrect dose, calculation and administration. Risks to products include incorrect preparation and storage, and specific risks to operators from cytotoxic contamination and injury. The chapter also looks at steps taken to reduce those risks. Many of the techniques you will use are covered in the Aseptic Technique chapter and the Preparation of Central Intravenous Additive chapter. This chapter will provide information on the special techniques and equipment used in the preparation of cytotoxic products. Chapter 19: Preparation of Cytotoxics 1

2 Aseptic Processing What are Cytotoxics? Cytotoxic drugs kill tumour cells or inhibit their growth. They work in various ways but many are toxic to ordinary tissue too. They are extensively used to treat cancer, and some have other medical applications. Cytotoxic drugs, sometimes known as cytostatins, antineoplastic, anti-cancer or cancer chemotherapy includes a wide range of chemical compounds. Their actions are not specific to tumour cells and normal cells may also be damaged. This means that they can produce significant side effects in patients and others exposed to them. With the possibility of side effects from regular handling of cytotoxic drugs and the increasing use and complexity of chemotherapy, there are concerns about the risk to workers involved in the handling and preparation of cytotoxics. These risks may be associated with exposure to the cytotoxics agent through inhalation, ingestion, skin absorption or needlestick. We will look at these aspects in more detail later in this chapter. All staff should take steps to minimise the risk to themselves and others by increasing awareness of what they are handling and adopting safe working practices. This should be done whilst maintaining a high standard of product preparation. Indications for Cytotoxics Cytotoxic drugs are used in a number of conditions both orally and intravenously to treat cancers such as breast, lung, bowel, testicular, lymphatic and skin. They are also used in non-oncological/ haematological conditions e.g. rheumatoid arthritis, and in dermatology and ophthalmology. Cytotoxic drugs can be given alone or in combination with other drugs. For many cancers chemotherapy drugs are given together to maximise the effectiveness of the treatment because different types of cytotoxic drug act at a different sites on the tumour cell. The cytotoxic drug names used in combination chemotherapy regimens are used to refer to regimen names. Here are some standard regimen examples below: CMF Cyclophosphamide, Methotrexate, Fluorouracil VAD Vincristine, Doxorubicin (Adriamycin), Dexamethasone CHOP Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone BEP Bleomycin, Etoposide, Cisplatin 2 Chapter 19: Preparation of Cytotoxics

3 Chapter 19 Preparation of Cytotoxics How are Cytotoxics Administered? Chemotherapy can be used in a number of ways, on its own to potentially cure a cancer, in palliative care to reduce the pain and discomfort associated with non-treatable cancers, or in conjunction with surgery and /or radiotherapy. Cytotoxics drugs are commonly administered by intravenous injection of single doses or by continuous infusion. Other alternative routes are subcutaneous, intramuscular, intraocular, by perfusion, instillation (primarily bladder) intrapleural, and intrathecal. How do we prepare Cytotoxics for patients? On receipt of a chemotherapy prescription a number of checks need to be made. When standard (approved) regimens are used they have already been checked with regards to dose, route and frequency, but other checks should be made, for example doses based on body surface area calculations. Sometimes it is necessary to use unapproved (non-standard) regimens in certain patients for certain conditions. In these cases calculations, route of administration, frequency, diluents and administration routes with the relevant data sheet(s) need to be confirmed, checked and approved. Once all prescription checks have been made and worksheets and labels have been generated, we can follow the procedures for assembly and preparation and handling of cytotoxic drugs. We will look at the main facts when working with cytotoxic substances in the following section. Chapter 19: Preparation of Cytotoxics 3

4 Aseptic Processing Key Facts when handling and working with Cytotoxics In general, cytotoxic drugs are hazardous substances, as defined by the Control of Substances Hazardous to Health Regulations (COSHH). Under COSHH there is a legal duty by employers to assess the risks from handling cytotoxic drugs and to take suitable precautions to protect the health of workers dealing with these substances. You also have a duty to follow and comply with the precautions and guidance given. Listed below are some of the things you need to be aware of when handling and working with cytotoxic preparations. The subjects listed below are intended as a prompt to your overall learning. Separation from other products Protection for all staff Residues on stock Protection for operators involved in assembly The preparation of cytotoxic agents should be separated from other aseptic products. This can be managed ideally by a dedicated facility but if this is not practicable, then segregate them by time and use a validated cleaning regime. It is important to provide and use the most appropriate personal protective equipment (PPE) for staff involved in all aspects of a Cytotoxic service. Several scientific studies have shown that there may be high levels of cytotoxic residues on the outside of vials from manufacturers. Anyone who handles cytotoxic drugs e.g. stores staff, should therefore always wear suitable protection, such as disposable gloves, gown and a disposable plastic apron. Staff involved in the set-up/assembly of cytotoxic products should wear suitable protection such as, disposable gloves, gown, mask, armlets and a disposable plastic apron. Protection for operators involved in production Staff involved in the aseptic preparation of cytotoxic drugs should wear appropriate personal protective equipment including gloves and gown/apron in addition to their clean room clothing. 4 Chapter 19: Preparation of Cytotoxics

5 Chapter 19 Preparation of Cytotoxics Assembly When setting up or assembling cytotoxic products they should be kept separately from other product types Labelling Primary or supplementary labelling should always clearly identify the product as cytotoxic so that staff receiving the product are aware that they must use safe handling precautions Storage Refrigeration Cytotoxic Spillage Kits If prepared Cytotoxics are stored prior to distribution, they should be segregated from other products in the fridge and dispatch area. As starting materials, they should be stored in a clearly designated area preferably in trays which will contain an accidental spillage within the designated area. Products or starting materials requiring refrigeration should be stored in clearly designated areas within the fridge or cold room. A spillage kit should be available wherever cytotoxic products are handled and stored. Staff should be regularly trained to deal with spills Training Environmental Monitoring Staff should be given regular training on the safe handling of cytotoxic agents. There are environmental monitoring kits available to monitor the levels of cytotoxic contamination within preparation and support areas. A regular testing regime is advised. See local quality control procedures. Chapter 19: Preparation of Cytotoxics 5

6 Aseptic Processing Pregnancy Waste Disposal Identification Types of waste Disposing of waste Cytotoxic Workstations Equipment You must consider health and safety issues if you are pregnant or trying to conceive with regard to any aspect of handling cytotoxic agents. See MARCH Guidelines: Pregnancy in staff handling cytotoxics Disposal is in a purple-topped sharps bin or a yellow clinical waste bag with a purple stripe. All vials, ampoules or bags of cytotoxic drugs are classified as hazardous waste even if they are part used or empty. All consumables used during the preparation of cytotoxic drugs or in the cleaning of the cytotoxic isolator are potentially contaminated so must also be treated as hazardous waste. All vials, ampoules and consumables used in the preparation of cytotoxic drugs must be placed into a Cytotoxic Sharps Bin and sealed before the bin is removed from the isolator. The outer packaging removed from cytotoxic vials/ampoules should be disposed of in a yellow waste bag with a purple stripe. Any wipes used in the sanitisation process must be disposed of as cytotoxic waste. Any used wipes, consumable or disposable packaging from the preparation process should be disposed of as cytotoxic waste. It is preferable that this is done within the isolator and must be via either a purple-topped sharps bin or a yellow clinical waste bag with a purple stripe. Disposable gloves used by the operators during preparation and in the isolators should also be disposed of as cytotoxic waste. Chemotherapy should be preferably prepared in an externally ducted negative pressure isolator. Less widely used are Class II Biological Safety Cabinets and Vertical Laminar Flow cabinets (Horizontal Laminar Flow cabinets are not suitable for this work). Chemotherapy can be prepared in positive pressure isolators, but they offer less operator protection. Syringes and needles used must always be of the luer-lock type to prevent leaking or spillage. The use of venting filters and venting pins is considered best practice to prevent aerosols. 6 Chapter 19: Preparation of Cytotoxics

7 Chapter 19 Preparation of Cytotoxics Dedicated Equipment Reconcilliation Any equipment used for cytotoxic preparations, e.g. automated pumps, should not be used for anything else but must be dedicated to that purpose. Where staffing allows, part used vials should be reconciled and disposed of in the isolator. If this is not possible they should be placed in a sealable plastic bag before being passed out for reconciliation checks. Cytotoxic Residues on finished products Packaging Transportation If part used vials/ampoules are passed out for reconciliation, it is preferred that they are not removed from the sealed plastic bags. It is good practice to wipe down syringes and bags before passing them out of the isolator to remove any cytotoxic residues. Cytotoxics should be over-wrapped using heavy gauge polythene tubing (minimum 400 gauge) and sealed completely using a heat seal. Procedures should be in place for the safe transport of cytotoxic preparations which avoid and would contain a spillage. All those involved in transporting these materials should be aware of the hazards and know how to deal with a spillage. MARCH Guidelines For detailed information on many of the subjects above please refer to Management and Awareness of Risks of Cytotoxic Handling Chapter 19: Preparation of Cytotoxics 7

8 Aseptic Processing Safe Handling Techniques for Aseptic Preparation of Cytotoxics Important: When preparing cytotoxic agents, safe-handling techniques must be used at all times. The basic techniques to minimise exposure should be demonstrated and practiced on the open bench using non-hazardous materials. We cover some of these techniques in this chapter, but they are included in the list below to provide a brief summary. Work over a sterile tray/absorbent mat to contain any spillage Use luer-lock syringes and connections whenever possible Use needles of the widest bore possible, depending on application for drawing up solutions from ampoules and vials to prevent pressure building up in the system whilst considering the increased risk of dripping from very large bore needles Use filters with great caution due to the risk of pressurising the system Filters with a pore size of not less than 5 microns can be used for particle removal preferably using negative pressure, i.e. when drawing up rather than pushing in. All liquid should be removed from ampoule necks before opening. They should be opened away from the body while keeping the sterile swab in place. When adding diluent to powder in an ampoule, it should be added slowly down the wall to allow wetting and thus prevent dust being generated. When adding to or removing doses from a vial, or rigid bottle, techniques should be used to equalise internal and external pressure using a vent needle or a chemo pin. When excess air is expelled from a syringe outside a closed system, it should be exhausted into a sterile swab and disposed of as cytotoxic waste. Remember to leave the luer connector part of the syringe dry and clear of liquid even though this will leave a small bubble in the syringe after capping. External surfaces of preparations should be wiped to remove any possible contamination prior to removal from the cabinet or isolator. All waste should be placed in the appropriate containers for disposal prior to removal from the cabinet or isolator. For more information on Cytotoxic Handling see the MARCH guidelines 8 Chapter 19: Preparation of Cytotoxics

9 Chapter 19 Preparation of Cytotoxics Prevention and control of exposure to Cytotoxics Facilities Preparation of cytotoxics should be centralised in the pharmacy or in a pharmacy controlled facility in a clinical area, undertaken by trained staff and using a negative pressure pharmaceutical isolator designed for the purpose. If a pharmaceutical isolator is not available, then a Class II microbiological safety cabinet may be used provided that it is suitably modified so that all surfaces that might become contaminated with cytotoxics are readily accessible for cleaning. Isolators and cabinets should be externally ducted, as studies have demonstrated that filters may not retain cytotoxic vapours resulting in contaminated air being recirculated back into the cleanroom. Monitoring Microbiological and physical monitoring should be carried out in accordance with 'Quality Assurance of Aseptic Preparation Services' and 'Pharmaceutical Isolators'. Both of these include a requirement for sessional leak tests of glove-sleeve systems and weekly pressure decay tests to check for isolator leaks. Isolators/cabinets should be examined for defects in function and performance at 6 monthly intervals, as part of a regular service programme. This is in addition to the daily/ weekly/monthly/quarterly microbiological and physical monitoring tests. Personal Protective Equipment (PPE) The aim of personal protective equipment is to maximise protection when handling, preparing and disposing of cytotoxic drugs and waste and to ensure that the equipment is suitable for its intended use. All staff should be trained in the use of personal protective equipment. Gowns and aprons can help prevent contamination of clothes and skin. The choice of material is important, as their absorptive properties may vary. Gowns should have a closed front, long sleeves, and tight fitted cuffs. Plastic disposable aprons prevent absorption onto skin and clothing from spills, splashes and sprays. Eye and face protection may be required where cytotoxic drugs are being handled outside an enclosed system. Eye protection should fully enclose the eyes. Surgical masks will only provide limited protection against the inhalation of fine dust or aerosols. Appropriate respiratory protection is required whenever total enclosure or local exhaust ventilation cannot control exposure, e.g. when clearing up a spill. Gloves must be worn when handling cytotoxics. They must be disposable and suitably impermeable to cytotoxic chemicals. A variety of gloves are available. Sometimes double gloving is used. Chapter 19: Preparation of Cytotoxics 9

10 Aseptic Processing Equipment Here are some images of equipment used when preparing cytotoxic preparations. This is not an exhaustive list some units may use different equipment from different suppliers. Venting pin with 0.2 µm hydrophobic filter. Needle Vent 0.2 micron assembly Chemo pin Image supplied by Helapet Ltd Image supplied by Baxa Ltd Often referred to as a chemo pin it is used as part of the process of reconstituting and drawing up cytotoxics. It has a 0.2 micron filter which sterilises the air entering the vial. It also vents the vial to prevent any pressure build up within the system that could cause leaking or spillage. The filter in a venting pin must not get wet because this will stop the air passing through it. Vented filter needle assembly Chemo pin The 0.2 micron filter allows sterile venting as the air is sterilised as it passes through the filter. This type of device also protects the operator from aerosols caused by pressure build up within the vial. Several makes are available Containment trays and work mats Some aseptic services use disposable containment trays into which an absorbent mat is placed. This should contain and hold any spills during preparation. It is disposed of as cytotoxic waste. Images supplied by Baxa Ltd This type of device combines a needle through which fluid can be drawn and a venting filter which is separated in the design. Image supplied by Helapet Ltd Sterile work mats can also be used under the preparation areas to soak up any spills or leaks. They have a highly absorbent middle layer with a waterproof back. The absorbent surface must be uppermost! 10 Chapter 19: Preparation of Cytotoxics

11 Chapter 19 Preparation of Cytotoxics Waste Disposal Containers Suitable containers clearly labelled and reserved for the use of cytotoxic drug waste should be available. Heavy duty clear polythene bag with yellow cytotoxic notice and tamper evident seals can be used. Cytotoxic sharps waste should be disposed of in a yellow sharps bin with a purple top. Cytotoxic cleanroom waste should be disposed of in a yellow waste bag with a purple stripe. Information: Please refer to Chapter 14 Waste Disposal for further details. Labelling and Packaging l Over-wrapping of finished cytotoxic preparations is important and provides extra protection to the handlers. l Polythene of sufficient thickness (at least 400g gauge) is often used. It should be relatively impervious to the atmosphere, robust and tamperproof, provide adequate protection for the handler, contain any solution in the event of a leak and protect the product from light. l Packaging should be heat-sealed and checked to ensure security. The finished product could be labelled directly, placed inside the outer wrapper and a second label placed on the front panel. Follow local SOPs. All packaging must clearly identify that it contains cytotoxic material and be sufficiently robust to protect against leaks and spills. Chapter 19: Preparation of Cytotoxics 11

12 Aseptic Processing Transportation and Distribution All cytotoxic products waiting for transportation should be stored in a designated storage area separated from non-cytotoxic products and the outer containers should clearly state that the contents contain cytotoxic materials. Containers should have contact details of the supplying department and should carry brief spillage instructions. Standard operating procedures should be followed for the safe transport of cytotoxics. For more information on Handling and containment from goods received to clinical areas see MARCH guidelines There are two types of cytotoxic spillage: l Dry spillage l Liquid spillage In this section we will look at how to deal with both types of spillage. You should read and be familiar with your own local procedures and also read the information from MARCH. In the event of a cytotoxic spill you should: l Assess the spill according to the quantity, concentration, drug, type (dry or liquid), affected surface, location l Call for assistance DO NOT LEAVE SPILLAGE UNATTENDED l Warn others l Cordon off the spill to avoid spreading it l Put up a cytotoxic spill warning sign if available l Put on appropriate personal protection equipment (PPE) Cytotoxic Spillage How to deal with a Cytotoxic Spillage l A cytotoxic spillage can occur in any area where cytotoxics are handled l All staff should be regularly trained to deal with cytotoxic spillages l Cytotoxic spillage kits should be available in all areas where cytotoxics are handled l COSHH material safety data sheets (MSDS) for individual cytotoxics should be available l Check your local SOPs 12 Chapter 19: Preparation of Cytotoxics

13 Chapter 19 Preparation of Cytotoxics Procedure for Powder Spills Work from the outside in Use water to moisten absorbent towels and place gently over the powder, then scoop powder up inside the towel Pick up sharp/broken material with tweezers Place all waste in a heavy duty hazardous waste bag including: l Sharps in sharps bin labelled cytotoxic waste l All packaging material l All cleaning materials and equipment l All personal protection equipment (PPE) Label and treat all waste from the spill as cytotoxic Ensure bags and bins are sealed and clearly marked as Cytotoxic Waste for incineration Clean spill site at least three times using mild detergent and water Wash hands thoroughly, even though you have worn gloves Complete relevant incident form Procedure for Liquid Spills Work from the outside in Use absorbent pads/granules/sheets and place gently over the liquid, avoid splashing. Repeat as necessary until the all the liquid is absorbed Pick up sharp/broken material with tweezers Place all waste in a heavy duty hazardous waste bag including: l Sharps in sharps bin labelled cytotoxic waste l All packaging material l All cleaning materials and equipment l All personal protection equipment (PPE) Label and treat all waste from the spill as cytotoxic Ensure bags and bins are sealed and clearly marked as Cytotoxic Waste for incineration Clean spill site at least three times using mild detergent and water Wash hands thoroughly, even though you have worn gloves Complete relevant incident form Chapter 19: Preparation of Cytotoxics 13

14 Aseptic Processing Cytotoxic Spillage Kits should contain the following: Absorbent granules/pads/sheets/paper towels Two pairs of powder free gloves (nitrile) Protective gown (Saranex/Tyvek laminated) Disposable shoe coverings FFP2 or FFP3 Filtered Face Piece Respirator; NOT surgical mask Safety Glasses BS EN 166 Clinical HAZARDOUS waste bag Cytotoxic label Plastic tweezers Sign to identify the spill Instructions For more information on Spillages: Management and Containment see the MARCH Guidelines 14 Chapter 19: Preparation of Cytotoxics

15 Chapter 19 Preparation of Cytotoxics Example Methods for the Preparation of Cytotoxic Products The following images show a variety of cytotoxic preparations being prepared in an isolator. These are not bench simulations. Cyclophosphamide powder for reconstitution Here the operator is checking the syringe for particle contamination before passing it out of the isolator. Cyclophosphamide is a white crystalline power for reconstitution, which takes time to dissolve completely. After the addition of water for injections, it requires vigorous shaking to dissolve the powder. Particles of un-dissolved powder can be seen clearly in this image. The syringe has been labelled and sealed in a heavy gauge polythene bag and the outer bag labelled with the addition of the yellow cytotoxic warning label. Once completely dissolved the solution can be drawn up into the syringe. Chapter 19: Preparation of Cytotoxics 15

16 Aseptic Processing Oxaliplatin powder for solution Etoposide Concentrated Solution for Infusion Here are the assembled components for the preparation of Oxaliplatin in Glucose solution for infusion. Etoposide is a concentrated viscous liquid which requires dilution before it can be administered to a patient. Due to the thickness of the concentrated solution it can be difficult to draw up and a wide bore needle is used. Once diluted Etoposide can precipitate and must always be checked for signs of precipitation during storage and administration. In the isolator the operator has drawn up the required amount of water for injections to dissolve the powder and has inserted a chemo pin ready to reconstitute one of the vials. The operator is slowly adding the required amount of water for injections to the vial of powder. The operator is drawing up the required amount of Etoposide into a syringe before adding to an infusion bag. It is necessary to check for particle contamination (pieces of rubber bung) in the syringe as the wide bore needle can break off some of the bung. Etoposide causes plastics to crack in its undiluted form. It also causes syringes and infusion bags to become slightly soft to the touch. In this image the syringe is empty and there is solution in the bottom of the vial. 16 Chapter 19: Preparation of Cytotoxics

17 Chapter 19 Preparation of Cytotoxics Doxorubicin solution for infusion In this example Doxorubicin is presented ready diluted and can be prepared in a syringe or added to infusion bags. The operator is drawing up the required amount of doxorubicin solution. These images show the doxorubicin solution being added to an infusion bag. Chapter 19: Preparation of Cytotoxics 17

18 Aseptic Processing Vincristine in 50 ml Sodium Chloride 0.9% for Intravenous Infusion Important: Vincristine is a vinca alkaloid and has been associated with incorrect administration in a number of cases worldwide, leading to the deaths of a number of patients. The components, worksheet and labels have been assembled and are ready for checking. Vincristine is presented as a solution in a vial and in this example will be diluted in sodium chloride 0.9 % 50 ml infusion bag (minibag). The NPSA has issued guidance (August 2008) on the administration of Vinka alkaloids in adults/adolescents. Vinca alkaloids should no longer be prepared in syringes. They should be supplied in 50 ml minibags. (Child doses will continue to be issued in syringes). A warning should be displayed on the label: For intravenous use only-fatal if administered by other routes. Further Reading Document Reference: NPSA/2008/RRR004 Rapid Response Report: Using Vinca alkaloid Minibags (adults/adolescent Units) Document Reference: Department of Heath HSC2008/001 Health Service Circular: Updated national guidance on the safe administration of intrathecal chemotherapy Check your local SOPs Vinca alkaloids require extra labelling and the above images show an example of the label and its wording. The label is applied to the infusion bag and the outer packaging, as well as the yellow cytotoxic label. Cytotoxic drugs may be fatal if administered by the incorrect route. Confusion over Intravenous/Intrathecal administration has lead to paralysis and death of a number of patients worldwide. Vinca alkaloids are only intended to be administered intravenously. 18 Chapter 19: Preparation of Cytotoxics

19 Chapter 19 Preparation of Cytotoxics Mitomycin in Instillagel Mitomycin can be used to treat cancers of the bladder and in this example another preparation called Instillagel is used to deliver the cytotoxic drug. Instillagel is a sterile gel containing other ingredients and is presented in disposable syringes. Here are the components, worksheet and labels assembled and waiting for a check. Mitomycin is a blue/purple crystalline powder for solution. The Mitomycin solution has been transferred into the Instillagel solution. It requires mixing as you can clearly see the Mitomycin solution suspended in the larger syringe. In this example Mitomycin powder is dissolved with the correct diluent and needs gentle agitation to dissolve the crystalline powder completely. Both solutions are now completely mixed together. The contents of the Instillagel syringe are drawn up into a syringe. Instillagel is not a cytotoxic preparation. The syringe is labelled and waiting to be checked and packaged. Using a fluid dispensing connector the syringe containing the Instillagel and the syringe containing Mitomycin are connected to allow the transfer of Mitomycin into the diluent syringe. An extra storage label has been added to the outer packaging as the final product requires storage at room temperature. Chapter 19: Preparation of Cytotoxics 19

20 Aseptic Processing Infusion Bag (bench simulation) The following bench simulation demonstrates a step-by-step preparation of a cytotoxic solution for infusion using a cytotoxic containment tray. l Swab the bung of the vial and allow to dry l Insert the Chemo pin, leaving the cap on l Vial with Chemo pin in position l Assemble the ingredients and equipment and place cytotoxic drug vial in cytotoxic containment tray (if used). l Remove cap from top of Chemo pin and attach luer lock syringe. l Draw up the contents of the solution into syringe with the Chemo pin in place l Swab the bung of the infusion bag and allow to dry. l Remove the required volume from the infusion bag to accommodate the volume to be added. l Swab additive port of infusion bag and allow to dry l Inject the required volume of solution into the infusion bag l Use a 0.2 micron filter with a 16g needle to regulate the pressure in the vial and prevent aerosols (Alternatively a Chemo pin could be used) l Add the solution to the infusion bag ensuring that the infusion port is positioned over the containment tray 20 Chapter 19: Preparation of Cytotoxics

21 Chapter 19 Preparation of Cytotoxics l Mix well after addition to prevent pooling (Note: If the solution is drawn from a vial that started as a powder the solution should be injected into the bag though a 5 micron filter needle (not to be mistaken for a chemo pin) l Swab additive port to remove any droplets of cytotoxic solution l Place the empty vial which contains cytotoxic solution in a polythene re-sealable bag and carefully seal it. l Pass the Infusion bag, worksheet and empty vial out of work zone for labelling and checking l Seal with a tamper proof seal. l Bag all waste, including containment tray separately in an appropriate polythene bag, seal and label as cytotoxic waste. l Wipe infusion bag to remove any potential cytotoxic residue before placing in polythene bag l Label the infusion bag and seal it in an appropriate polythene bag to contain any leaks. l Place product in re-sealable polythene bag with the worksheet and close seal carefully. l Place the infusion bag in the outer chemotherapy bag for transport and seal it using a tamper evident seal. Chapter 19: Preparation of Cytotoxics 21

22 Aseptic Processing LV2 Infusion device l The cap is removed from the top of the infusion set l The 50 ml luer lock syringe is attached. l In this image you can see that the elastomeric balloon device inside the container is not inflated. l In this image the operator is priming the device before applying the cap. l Exert a constant but gentle pressure on the syringe barrel until the drug solution starts to fill the device and it passes through the flow restrictor and starts to fill the balloon. l Change syringes until the total quantity of drug solution has been added. l In this image you can see the top of the balloon is starting to expand. l Cap the tubing with the winged cap provided. l It is extremely important to ensure the cap is securely fastened to prevent leaking. l Remember that the solution in the luer connector should be below the end or lip to prevent fluid tracking into the screw thread when capped or connected. There are a number of infusion devices on the market. Each has special requirements for filling and use. Be sure you know how each type of device is handled in your local practice before attempting to prepare one of these. Follow local SOPs. l It is extremely important to ensure the cap is securely fastened to the top of the device to prevent leaking. 22 Chapter 19: Preparation of Cytotoxics

23 Chapter 19 Preparation of Cytotoxics Action Write down the different infusion devices used in your aseptic service and read the SOPs for handling each one (make notes on any differences). Chapter 19: Preparation of Cytotoxics 23

24 Aseptic Processing Risks to Products Risk Incorrect product reconstitution Use of Negative Pressure Isolators Leakage /damage or defects Particles Storage Transportation and Storage Information and Actions It s of paramount importance that the correct dosage is prepared and that the worksheet instructions are followed. All equipment must be suitable for purpose and available to staff. See local SOPs for receipt and checking of cytotoxic prescriptions. Negative pressure isolators operate with an internal pressure below that of the room. This protects the user from any aerosols of drug generated inside. However, if a leak occurs in the isolator body, or in the glove / sleeve system, air may enter the isolator from the room. The risk of producing a microbially contaminated product is therefore greater than with a positive pressure isolator. Skin and clothes are at risk of exposure from contact and spillage of cytotoxic drugs. Gloves and apron must be worn at all times during checking. Leaks or cracks can occur as a result of inappropriate storage or as a result of faulty equipment which has not been checked properly. Products should be inspected before and after preparation, and before issue to patient. Products should be inspected for particles before and after preparation. If particles are visible then container must be rejected by attaching label with reject written on and separating it from any other containers that are satisfactory. Many cytotoxic drugs need protection from light and refrigerated storage. Appropriate storage will prevent deterioration of a product. See Chapter 16 Completing Product Processing for more information on storage. The correct protocol for transportation and storage should be followed at all times. Staff involved in storage and transportation of chemotherapy should be aware of the risks and trained to handle an emergency situation e.g. spillage. 24 Chapter 19: Preparation of Cytotoxics

25 Chapter 19 Preparation of Cytotoxics Risks to Patients Risk Incorrect calculations Microbial contamination Incorrect Administration- Extravasation Information and Actions Dosage-All dosage calculations must be independently checked for errors i.e. by a second person. Body Surface Area (BSA)-Checks should be made on the prescriber s calculation and re-calculated if the patient has gained or lost weight. Creatinine Clearance-If this is needed to calculate the dose, this should be recorded and the calculation checked. Regimens-Checks must be made to confirm that the correct regimen has been selected and is followed. Cumulative doses- Some cytotoxics have a cumulative toxicity and the patient is only allowed a certain maximum permitted total lifetime dose. The presence of micro-organisms in an aseptic unit can have fatal consequences. Use of a Negative Pressure Isolator provides less protection for the product. Leaks occurring in the isolator body, or in the glove or sleeve system may cause microbial contamination of a product. Refer to Chapter 3 Basic Microbiology, for information on sources and control of contamination. Refer to Chapter 6 Work Zones, for more information on working in an isolator. Cytotoxic drugs can cause severe local tissue reactions if they are not administered correctly and leak into surrounding skin tissue. Some of the reactions reported are: burning, stinging, pain, swelling at injection site. For more information visit: Chapter 19: Preparation of Cytotoxics 25

26 Aseptic Processing Risks to Patients (continued) Risk Incorrect Administration Route Incorrect Labelling Exposure at home Information and Actions Cytotoxic drugs may be fatal if administered by the incorrect route. Confusion over Intravenous/Intrathecal administration has lead to paralysis and death of a number of patients worldwide. Vinca alkoloids are only intended to be administered intravenously. The National Patient Safety Agency (NPSA) has issued guidance (August 2008) on the administration of Vinka alkaloids in adults/adolescents Vinca alkaloids for adults should no longer be prepared for adults in syringes. They should be supplied in 50 ml minibags A warning label: For intravenous use only-fatal if administered by other routes must be applied Document Reference: NPSA/2008/RRR004 Document Reference: Department of Heath HSC2008/001 Check your local SOPs Risk of overdose due to mistakes in labelling, product strengths, route of administration and dilutions. Cytotoxic drugs and their metabolites are excreted in urine and faeces. Patients need to take adequate precautions to prevent exposure to cytotoxics to other individuals in their home environment. 26 Chapter 19: Preparation of Cytotoxics

27 Chapter 19 Preparation of Cytotoxics Risks to Operators Risk Contamination Toxicity Equipment Information and Actions A study to investigate the cytotoxic contamination of preparation areas in simulated preparation scenarios has demonstrated significant contamination occurs within the isolator. Contamination has been shown in support rooms on door handles, telephone handsets and computer keyboards as well as in sluice rooms and beds on wards. Several scientific studies have shown that there may be high levels of cytotoxic residues on the outside of vials from manufacturers. Cytotoxics are: Mutagenic have ability to cause genetic mutation Carcinogenic have the ability to cause cancer Teratogenic have ability to cause physical defects in developing embryos Operators have the potential for occupational exposure to toxic substances, so safe handling and preparation techniques are required at all times. Studies have shown that good working practices such as those described in this manual significantly reduce the risk for operators. Regular staff training is essential. Appropriate personal protection equipment should be used at all times. Chapter 19: Preparation of Cytotoxics 27

28 Aseptic Processing Risks to Operators (continued) Risk Gloves Needlestick injury Upper limb disorders; ULDs (Repetitive strain injuries) Cuts Information and Actions Operators should make sure their gloves are intact at all times. This means that you must check your gloves regularly. Operators should always ensure they are wearing the correct gloves for the task and that they offer appropriate protection from cytotoxic chemicals. Nitrile and Neoprene gloves often offer more protection but users should always check supplier information. Double gloving is recommended when preparing chemotherapy i.e. operator is wearing gloves inside the isolator gloves. For further information on suitable glove material see local SOPs, MARCH guidelines on PPE Selection and Use at HSE Information Sheet MISC615 at This is any injury from a needle. Needlestick injuries can be harmful to the operator and also to patients as there is an increased risk of contamination. Correct operating procedures and practices should be followed at all times to avoid the incidence of needlestick injuries. See your local operating procedures for action to take in the event of a needlestick injury. This is particularly important when handling chemotherapy. Needlestick injuries should be reported and documented. When re-sheathing needle use drop on technique to apply needle cap. This is caused by continued repetitive movements. To reduce the risk of harm operators should take adequate short breaks and reduce resistance and force employed during manipulations. Rotation of activities can also help. For more information on ULDs visit Ref: HSG60 Upper Limb Disorders in the workplace Operators are at risk of cuts from glass shards or ampoule tops. This poses a risk not only to the operator, but also to the product as it increases the chances of contamination. 28 Chapter 19: Preparation of Cytotoxics

29 Chapter 19 Preparation of Cytotoxics Risk Cleaning Occupational Exposure Information and Actions Operators often work with highly toxic substances every day, so it s vital to have an appropriate cleaning schedule in place for both before and after preparation. It is important that appropriate Personal Protection Equipment (PPE) is worn for cleaning areas where cytotoxics are handled. Safe handling of cytotoxic drugs should not cause any problems with the health of staff. However in some hospitals additional steps are taken by the Pharmacy Department and the Occupational Health Department to monitor staff health. All members of staff are given a medical questionnaire and/ or routine medical on employment. This determines the basic level of health of all new staff members. Details of any needlestick injuries and any spillages should be documented both on a handling record form and on a Trust Incident Record. Read MARCH Guidelines for further information Chapter 19: Preparation of Cytotoxics 29

30 Aseptic Processing Questions Q1 Describe how you should dispose of cytotoxic waste, including half full ampoules Q2 When assembling cytotoxic drugs prior to preparation, what Personal Protection Equipment should you wear? 30 Chapter 19: Preparation of Cytotoxics

31 Chapter 19 Preparation of Cytotoxics Q3 What would you use to clean up each of the following: a) A liquid chemotherapy spill? b) A spill of dry powder chemotherapy? Q4 What type of syringes should be used for preparation of cytotoxics, and why? Q5 Explain why isolators used for preparing cytotoxics should be externally ducted. Chapter 19: Preparation of Cytotoxics 31

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