Ministry of Health
*The views stated in this article are the author’s personal opinions and do not necessarily reflect the official position of the Israeli Ministry
Some 25 years ago, working as a hospital pharmacist, I was asked to initiate a new service in Israel: cytotoxic reconstitution. My knowledge of the subject at the time was negligible, but after some research and visits to a number of hospitals in the UK I was ready to open the new unit – the first of its kind in the region. I quickly learned many new and impressive words – “cytotoxics”, “chemotherapy”, “mutagenic”, “carcinogenic”, “teratogenic” – without really understanding their meaning. On my visit to the UK I learned that
“J-suits”, sterile gloves, masks and so on were vital when preparing chemotherapy as well as luer lock syringes. Previous experience working under aseptic conditions meant I was used to working using a laminar-flow hood. However, for all intents and purposes I opened the unit with absolutely no training or further guidance.
On reflection, one wonders what causes intelligent people devoid of training or expertise to handle potentially dangerous substances. I postulate that the cause is rooted in a great change that overwhelmed hospital pharmacy. At pharmacy school in the early 1970s I was taught how to prepare glycerine suppositories (and test them by throwing them up to the ceiling to see if they stuck). I learned how to prepare powders in white paper sealed with sealing wax, and learned to memorise the structure of innumerable opioid alkaloids. Clinical pharmacy had not yet been invented. The world of pharmacy then changed dramatically. The traditional functions of hospital pharmacists, such as preparing galenic, sterile and nonsterile products, diminished substantially, as only licensed products were acceptable. There was a real fear that hospital pharmacists would become extinct, if they could not justify their presence as useful members of healthcare teams. In the USA a saviour was found in the form of the “clinical pharmacist”.
However, for many, clinical pharmacy was not an option. Many were unsure about this new role. They expressed doubts about their ability to advise doctors on the ward, fearing that a clinical pharmacist would be seen as nothing more than a third-rate junior doctor.
In 1979, researchers reported finding cytotoxic drugs in the urine of nurses handling these medicines. Further epidemiological studies suggested that the spontaneous abortions and foetal malformations suffered by nurses preparing and administering cytotoxics might be related to their exposure to these drugs. Other effects included compromised fertility, inferior quality and quantity of sperm, and menstrual-cycle irregularities. Mutagenic effects, including chromosomal aberrations and DNA damage, were observed in unprotected nurses handling cytotoxics. As the nursing fraternity became aware of these possible dangers they fought to eliminate this task from their work routine, and the pharmacy was suggested as the ideal place to handle this function.(1–5)
Here at last was the chance for pharmacists to show what they could do. Stabilities, sterile preparations, choosing the diluent, unit dosing – all of these were our specialities. True, cytotoxics were classified as “biohazardous”, but by working under the motto “just be careful not to be exposed” the problem was minimised, as pharmacists knew how to work prudently. It was difficult to appreciate the real danger, given that neither mutagenicity, teratogenicity nor carcinogenicity can be sensed.
Management was happy to provide certain basic equipment, such as laminar-flow hoods, airlocks, luer lock needles, gloves, gowns, and masks – these were items that were available and with which managers were already familiar. Doing all this allowed management to substitute one or two pharmacists for large numbers of nurses reconstituting cytotoxics. Safety was never a major issue.
After I became a pharmacist with the Israeli Ministry of Health, my regulatory activities took me to all the hospitals in the country. There were then no national guidelines for the safe handling of cytotoxics, with vast differences in standards observable from one facility to the next. Eventually, the Minister of Health set up a committee to produce comprehensive guidelines on safe handling of cytotoxic drugs.(6) Budgetary problems were claimed to be the reason why these recommendations only actualised well beyond the designated timeframe.
Recently a debate has arisen over the position statement by NIOSH and the ASHP in the USA that all cytotoxic drugs should be reconstituted using “closed systems” wherever possible. In our case this position was the one adopted, and the appropriate recommendation was made.(7) Local hospital managers insisted quite categorically that they had no funding to purchase these devices. A further debate has arisen over devices claiming equivalence to closed systems.(8)
The question now is why the issue of safety for healthcare providers is not paramount in the priorities of hospital managers. To my mind the answer is simple: pharmacists claim to be scientists, yet they have never demonstrated in a clear-cut and scientific manner the exact dangers associated with handling cytotoxics. What are the ramifications for the health provider given that cyclophosphamide is mutagenic? Where are all the (retroactive) epidemiological studies comparing the long-term health effects on staff handling cytotoxics before and after introducing safety precautions? What is an “acceptable” level of contamination in pharmacies and for staff? All we got was the “ALARA” (“as low as reasonably achievable”) principle. For many people, minimal precautions are very reasonable.
From the very beginning, drug companies manufacturing chemotherapeutic agents should have been coerced into sponsoring this basic research – even if this reduced their massive profits somewhat. Definitive and clear-cut acceptable levels of contamination in the air, on work surfaces and in people should have been defined years ago. These safety standards would have then been mandated by law, as has happened in every other aspect of hospital life, industry and general living.
Imagine if the aviation or motor industries were to work on the ALARA principle. How many people would fly? Who would drive? It was these industries themselves which carried out the basic research to find ways to make their products in a safer way. But while everybody knows the danger of driving without a seat belt, we only buckle up because we do not want to get a ticket. Some 200 years ago Dr Joseph Lister was probably laughed out by his manager’s office when he asked for an extra penny on his budget to buy soap. Nothing has changed. Hospital management will never take the issue of safe handling seriously unless obliged to do so by law.
I fully agree with the comment of Dr Luci Power, of the University of California at San Francisco – one of the lead authors of the ASHP guidelines – on the NIOSH definition of a closed-system drug-transfer device. She says it is “unfortunate that NIOSH gave no performance standard or test system for such a device”.(9–11) However, I feel her position statement that “testing of these or similar devices should be conducted in clinical settings, over a comparable duration of time to provide valid comparisons between devices” has missed the point somewhat.
Without clearly defined levels of acceptable contamination from cytotoxic drugs on both objects and people, and without defining the means to measure these levels, how can we have “valid comparisons between devices”? Defining these levels is a priority. The true question then becomes: “which device can provide the as-yet-to-be-defined mandatory level of protection?” Devices conforming to this standard would then be permitted for use.
1. Falck K, Grohn P, Sorsa M, et al. Mutagenicity in urine of nurses handling injectable antineoplastic agents. Lancet 1979:1;1250-1.
2. Anderson RW, Puckett WH, Dana WJ, et al.
Risk of handling injectable antineoplastic agents.
Am J Hosp Pharm 1982:6;299-301.
3. US National Institutes of Health. Recommendations for the safe handling of parenteral antineoplastic drugs (NIH publication 82-2621). Washington DC: US Department of Health and Human Services; 1983.
4. Yodaiken R. Safe handling of cytotoxic drugs by healthcare personnel (Instructional Publication 8-1.1). Washington DC: Occupational Safety and Health Administration; January 1986.
5. US Occupational Safety and Health Administration. Controlling occupational exposure to hazardous drugs (OSHA Instruction TED 1.15). Washington DC: OSHA; 1995.
6. Israeli Ministry of Health. Ministry of Health guidelines: preparation and administration of cytotoxic drugs by hospital staff to patients. No 54/2000. Jerusalem: Israeli Ministry of Health; 5 Nov 2000.
7. Israeli Ministry of Health. Ministry of Health guidelines: preparation and administration of cytotoxic drugs by hospital staff to patients. No 68/2002. Jerusalem: Israeli Ministry of Health; 12 Dec 2000.
8. Cass Y, Seeton I. 25 years of safe handling of cytotoxics (antineoplastics) in Israel.
J Oncol Pharm Prac 2006;12:83-90.
9. US National Institute for Occupational Safety and Health. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. Washington DC: NIOSH; 2004.
10. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm 2006;63,1172-93.
11. Power LA. Position statement (quoted with permission), 2006.