Specialized services
Pharmacy aseptic compounding services and the range of medicines prepared in them
Equipment and procedures used in centralized cytotoxic reconstitution services
Occupational health risks of cytotoxic drugs and the effective management of these risks
Benefits of centralized, pharmacy-operated aseptic compounding services
Scope and operation of a centralized intravenous additive service (CIVAS)
Introduction
This chapter describes the specialized services provided by hospital pharmacy departments in the provision of various aseptic dosage forms. These services may include: chemotherapy reconstitution services, centralized intravenous additive services (CIVAS), radiopharmacy services (see Ch. 45) and home-care services. In each case, the service involves the provision of aseptically-prepared medicines which are often tailored to the specific needs of individual patients. This chapter introduces the scope, practice and pharmaceutical challenges of aseptic compounding services.
Cancer chemotherapy
The majority of chemotherapy doses are administered as injections or infusions. This offers the advantages of assured bioavailability, control over the rate and sequence of drug administration and also the ability to stop administration immediately in the event of adverse effects. However, the parenteral route may be associated with complications such as infection, extravasation and thromboembolism. The majority of these drugs are given in the hospital setting.
Cytotoxic drugs are available as sealed vials containing freeze-dried powders or sterile, concentrated solutions and are designed to provide an adequate shelf-life (usually>2 years). The freeze-dried powders require reconstitution with an appropriate diluent. Either may then require further dilution before being filled into syringes, infusion bags or infusion devices for administration.
Ambulatory infusion devices can be filled for use in the community by patients receiving home chemotherapy.
Occupational exposure risks
Cytotoxic drug exposure has been associated with various acute toxicities including headache, rash, nausea and dizziness. However, the more serious risks are related to the potential mutagenic, carcinogenic and teratogenic effects. Routes of exposure include ingestion, inhalation, needle-stick injury and skin contact – the most significant risk for occupational exposure.
In the UK, the requirements for safe handling of cytotoxic drugs are set out and enforced by the Health and Safety Executive. Pharmacy staff preparing cytotoxic agents must be fully trained in the necessary aseptic and safe handling techniques and must be fully aware of the potential health risks and the precautions that are required. Current opinion suggests that resources should be invested in appropriate equipment, staff training and competency assessment.
Published guidelines include the following areas of safe practice:
Useful guidelines on cytotoxic handling include The Cytotoxics Handbook and further references are available in Appendix 4.
Provision of a pharmacy-based chemotherapy preparation service
Protection of both the product and the staff involved in its preparation is technically demanding and requires carefully developed systems and procedures together with extensive validation, which must be integrated with the principles of good pharmaceutical manufacturing practice (GMP). Capacity plans should ensure that the service is capable of meeting current and future demand; for example, the rising demand for targeted therapies.
Despite the challenges outlined above, it is important that pharmacy staff ‘own’ chemotherapy preparation services and take a clear lead. In the UK, from NPSA Alert 20 on injectable medicines, it is clear that application of the risk assessment guidelines places all cytotoxic drugs in the high-risk category. It is therefore essential that these medicines are prepared by specialized hospital pharmacy aseptic units or by appropriate commercial providers. Pharmacy staff offer a unique combination of skills and expertise, including the practice of aseptic technique, a wide clinical knowledge of cancer chemotherapy, familiarity with formulation and drug stability issues, the application of GMP, quality assurance (QA) and quality control (QC) to aseptic preparation and considerable experience in working with SOPs, batch documentation and checking procedures. These are key attributes that help to ensure the provision of safe, effective chemotherapy and contribute towards minimizing the risks of occupational exposure to drugs used in the treatment of cancer.
Training required for staff preparing cytotoxics
All personnel involved in preparing and handling cytotoxics require training and competency assessment in the appropriate techniques. On a practical level, all staff must be aware of the following, over and above standard aseptic technique and the application of GMP to aseptic preparation:
Validation of operator techniques
Prior to commencing work on reconstitution of cytotoxics, an operator’s competence in this field must be assessed.
The operator is asked to carry out broth transfer simulations where solutions are transferred from one vial or container to another
The broth-filled vials can then be incubated and examined for microbiological growth
Operators must achieve negative results (no growth after incubation) on each occasion before they are deemed capable of preparing cytotoxic agents
Typically, each operator and each process would be re-validated at least every 3 months and training procedures should be reviewed on a regular basis
Operators routinely incorporate environmental monitoring tests such as settle plates and finger-dab plates into the production schedule as part of the QA process
Expert guidance on the validation and monitoring of aseptic compounding has been published by the NHS
Operator technique in the safe handling of cytotoxic drugs can be assessed by simulating aseptic transfer processes using a sterile solution containing a fluorescent dye as splashes or spillage can be visualized using a portable ultraviolet lamp
As with assessment of aseptic technique, safe handling should be evaluated using a combination of simulation and expert observation.
Documentation required for cytotoxics
On receipt of a prescription for a cytotoxic agent, a number of procedures must be undertaken. Figure 46.1 shows the areas of work in which a pharmacist may have involvement.
Figure 46.1 Documentation required for cytotoxic services. (From Allwood et al. 2002, reproduced with permission.)
When the prescription is received, it is clinically checked by an experienced oncology pharmacist. The prescription must be validated against an approved chemotherapy protocol. It is essential that patients receive the correct number of cycles of treatment at the correct intervals. The British Oncology Pharmacy Association Standards for Prescription Verification for Systemic Anti Cancer Therapy provides detailed guidance.
Information from the prescription is transferred to a worksheet or batch document and details of medicine(s) required, diluent and volume for reconstitution are recorded together with the number of drug vials required. Details of batch numbers and expiry date for each component used, all dose and dilution calculations, preparation methods, container(s) to be used, time and date of preparation, and expiry of the final product are also required. Additionally, a sample label is attached to the worksheet. Most chemotherapy preparation units use preprinted worksheets for each chemotherapy protocol, with a pharmacist-approved master document from which copies are made. Alternatively, some units use computer-based systems which contain a database of all approved chemotherapy protocols and produce batch documents and labels.
Labels should include the following information:
Patient’s name, hospital number and ward or clinic name
Drug name, total quantity and final volume of infusion
Vehicle in which the drug is prepared (e.g. 0.9% sodium chloride)
Batch number, expiry date and storage conditions required
Hospital pharmacy name and address
Route of administration and infusion rate
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