Volume 14, Issue 1/2012 - Pharma Special

Safe Handling of Hazardous Drugs


Jill Davis, 

Interview by Lee Campbell


 Firstly What are Cytotoxic Drugs and What  do We Use Them For?  

Cytotoxic drugs are drugs that kill cells. They  are mainly used to treat cancer but can be  used for other therapeutic indications e.g.  rheumatoid arthritis, multiple sclerosis. Cytotoxic  drugs mainly kill cells through their action  on cell reproduction, affecting cell DNA  division. They are indiscriminate in their effect  and will kill any type cell that commences cell  division to reproduce. Most cancers, especially  in the early stages of the disease, are dividing  rapidly and thus are the main target for cell kill.  However, some cells within the human body  also divide more often than others and it is  these cells that are also affected by cytotoxic  cells e.g. blood cells, the entire lining of the  gastro-intestinal tract and skin and hair cells.  Thus the most common toxicities we see in patients  being treated with cytotoxic drugs are  due to the death of non cancer cells. Low white  blood counts leading to increased susceptibility  to develop infections and less ability to  fight infections, low platelets leading to less  ability for blood to clot and an increased risk  of bleeding and low red blood cells leading to  anaemia and a need for blood transfusions.  

What Sort of Danger do They Pose for Staff  and Patients?  

As well as the general toxicities noted above,  cytotoxic drugs have unique toxicities of their  own. They may be carcinogenic, mutagenic  and/or teratogenic. Thus patients receiving  cytotoxic drug therapy have developed second  cancers from their treatment (carcinogenic),  have changes to their genetic DNA  that increase their risk of developing cancer  (mutagenic) and have increased foetal deaths  and birth abnormalities (teratogenic). Second  cancers do not appear for many years  after treatment has ceased. These second  cancers are not secondary cancer or metastases  but totally new cancers. In the past, many  patients did not live long enough after treatment  to see the development of these second  cancers but this is not the case today.  

In addition to the direct toxicity of the drug,  the administration of the drug can also pose a  risk. Many cytotoxic drugs can damage/kill tissue  if they are mistakenly injected into the tissue  surrounding the vein instead of into the  vein. Today’s patients are advised of the possible  toxicities of their treatments but as they  expect to gain from the treatment (after all they  have cancer) and their treatment is limited to  a specific number of different drugs and to a  certain time frame, the possible benefits outweigh  the possible risks.  

For staff it is a different matter. They can expect  no benefit from being exposed to cytotoxic  drugs. They handle many more drugs than a  patient would receive and they do this over long  periods of time, not a set course of treatment.  So while a patient receives much higher doses,  staff handling cytotoxic drugs may be exposed  to low levels of many different drugs over a long  period of time. Exposure may be via skin contact,  inhalation of aerosols/drug particles or needle  stick injuries. Adverse effects seen from this  exposure include increase in mutagenicity, change  in blood counts, foetal loss, foetal malformation  and contact dermatitis. The main concern is the  possibility of development of a cancer. It is impossible  to quantify this risk, especially as there  is rarely an immediate effect seen, but it is essential  to minimise exposure. After all, employees  are entitled to a risk free environment in which  to work. Employers may have scoffed once at  the possible toxic effects of asbestos exposure,  again a problem with a long lag time and we do  not want this delayed adverse outcome to happen  with exposure to cytotoxic drugs.  Evidently the handling of these drugs is a  huge safety issue for both pharmaceutical  companies and also hospitals and healthcare  institutions.

Could You Tell Us About the  Main Safety Precautions?  

Pharmaceutical company employees have  the biggest risk as they deal in very large  volumes of drugs during the manufacturing  process. However, they also have the best  possible resources to ensure employees do  not come into contact with the drug and require  the use of ‘space-suits’ with external  respiratory devices. Staff manipulating the  drugs to create an individual dose are most  at risk. Due to the requirement to individualise  doses (based on patient parameters  on the day of treatment) and the short expiry  date of prepared doses, cytotoxic drug  doses must generally be prepared on the  day of treatment at the site of administration  of the treatment. Many are provided as  powders and must be reconstituted to be  given as injections and even those provided  as liquids must be handled to withdraw  the correct dose and place it into an appropriate  administrative format (e.g. into an  IV infusion bag or a syringe or an ambulatory  delivery device). Those administering  the dose are also at risk although this risk  is less as no actual manipulation of drug is  required and the drug is often well diluted.  Disposal of drug is also vital. All equipment  such as used/partially used drug vials, used  syringes, needles, empty IV infusion bags  and IV giving sets, dressings and bandages  must be appropriately segregated and  stored prior to disposal. Waste must be identified  as cytotoxic and transported and disposed  of in a way to protect the environment  from contamination. Incineration at  over 1000°C is recommended.  

What Methods can Hospitals Use to Reduce  Contamination as Much as Possible?

Institutions should review their need to create  doses on site. If the use of cytotoxic  drugs is limited, they should be purchased  pre-prepared from an external source  (such as a commercial company or a larger  institution). If doses are required to be  produced on site, their preparation should  be centralised and done only by trained  staff. Specific secure preparation areas are  needed with clean rooms containing laminar  flow cytotoxic drug safety cabinets or  pharmaceutical isolators. Use of closed  needleless systems further reduces possibility  of exposure. Personal protective  equipment is essential not only for those preparing the cytotoxic drug doses but  also for those administering the doses, for  staff unpacking purchased drug from suppliers  (drug contamination has been found  on the outside of newly purchased vials,  glass vials may have broken) or for staff  handling/moving waste. Other decisions  can reduce the risk of exposure. Where  there are choices always purchase vials  not ampoules, liquids not powders, drugs  packaged in plastic or plastic coated glass  rather than glass alone. Staff transporting  cytotoxic drugs must have training to  ensure correct procedures are carried out  should a spill occur. All of these require a  substantial financial investment and ongoing  financial commitment.


Risk Management for These Processes Must  be Key. In General What Protocols and  Processes are Put in Place by the Management?  

Yes risk management is the key issue. If  an institution is using cytotoxic drugs  within its premises, such use crosses  many departments and staff with different  knowledge. Education is the key to  risk minimisation. Written policies and  procedures need to be developed, promulgated,  implemented and evaluated  throughout the institution. Effective planning  and design of the workplace, ‘best  practice’ control measures and specialised  equipment, stringent safe handling  procedures, training and education  of employees (on commencement and  at regular intervals), provision of personal  protective equipment (and ensuring  its use), instituting a staff health monitoring  programme, ensuring specialised  laundry of non-disposable equipment  and arranging appropriate waste disposal  of contaminated items are all vital.  Clearly successful staff training is essential.  In general how are staff trained and is this  a continuous process?  In general staff are trained on-the-job by  experienced practitioners.

Many institutions  have developed their own in-house training  modules. At a minimum, staff preparing  cytotoxic drugs must be validated in aseptic  technique (using broth manipulations)  and in the specialist requirements for handling  cytotoxic drugs. Validation is recommended  to be performed yearly.  Prior to introducing any new techniques required  for specific manipulations, time to provide  full training to those handling the drugs  must be available. Since staff preparing the  cytotoxic doses are often ‘isolated’ in their  secure cleanrooms, it is imperative that these  training requirements are considered well in  advance of the patient arriving at the hospital  ready to receive their treatment. Communication  is a key issue.  

Many Healthcare Facilities are Introducing  Robotics into the Process. Can This Really  Help With Safety and Prevent Dosage Errors?  

The use of robots in drug dose preparation  does certainly reduce the opportunity for  exposure but does not eliminate it. The robot  still has to be loaded and the final products  handled and transported. Not all drugs  are able to be handled by a robot. Robots  are best used when large preparation runs  are planned rather than for individualised  doses. In addition, robots are very expensive.  Robots do not replace the need for  experienced staff but they can supplement  preparation activities. Robots can work  non-stop but they cannot operate unsupervised  and are best utilised in very large  operations such as a major institution supplying  surrounding smaller institutions or  in commercial operations. I am not familiar  enough with the use of robots to comment  on their ability to prevent dosage errors  – however, as humans have to  programme the robot, I do not see how human  error would be totally eliminated. 


In Your Opinion What Does the Future Hold  for the Safe Handling of Hazardous Drugs?  

It is really pleasing that the current breakthroughs  in cancer treatment are not reliant  on cytotoxic drugs. Most new treatments involve  targeted therapies, vaccines and monoclonal  antibodies. The risks handling these  drugs are much reduced compared to cytotoxic  drugs. Even new forms of cytotoxic drugs  such as liposomal forms are much less toxic  to handle and administer BUT much more expensive  to purchase and cannot be simply  substituted for the parent drug. So while I think  the percentage of patients requiring cytotoxic  drugs is reducing, unfortunately the numbers  of patients requiring treatment is increasing.  Cytotoxic drugs are also becoming  progressively cheaper compared to the newer  treatments and they still remain the treatment  of choice in many cancers.  In the foreseeable future I do not see an elimination  of the use of cytotoxic drugs and as  such it behoves us to create as risk-free as  possible an environment in which these drugs  can be prepared, administered and the contaminated  waste disposed.



References available online or upon request, [email protected]

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Author Jill Davis, Interview by Lee Campbell  Firstly What are Cytotoxic Drugs and What  do We Use Them For?  Cytotoxic drugs

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