EQUASHIELD Changed the World For Me

Mark Stanfield has had a diverse career path, starting as a musician and later working in Hollywood producing television commercials. However, after the events of September 11, he felt a calling to make a difference in people’s lives and found his path as an oncology pharmacist.

In 2017, he was diagnosed with stage four lung cancer, which led him to question the safety of certain medical equipment at his workplace. Concerned about the potential harm to others, he embarked on a mission to improve safety in the medical field by identifying a closed system transfer device (CSTD) that effectively prevents vapor escape. He discovered that EQUASHIELD is the best CSTD to cover all routes of exposure. Despite his personal health struggles, Mark remains resolute in his commitment to fearlessly living life and promoting safe compounding practices for fellow healthcare professionals.

Mark’s full story


FDA Clearance of EQUASHIELD® Syringe Unit for Full Volume Use

We are thrilled to announce that the EQUASHIELD® Syringe Unit has received additional FDA clearance for full volume use1. This achievement marks a significant milestone for our company, as we celebrate our fifth consecutive year of being the most used CSTD in the USA. We firmly believe that our innovative product design will revolutionize the way hazardous drugs are handled, offering unparalleled safety and efficiency.

Compared to Other Syringes on the Market 

Many institutions adhere to guidelines that limit the fill volume of standard syringes to three-quarters when handling hazardous drugs (OSHA, ASHP) to prevent loss of the plunger2,3. Our EQUASHIELD® Syringe Unit, however, eliminates this risk, preventing vapor escape and plunger contamination. The design allows you to use the most accurate syringe size possible for compounding and administration4.  

Introducing the Unique EQUASHIELD® Syringe Unit 

EQUASHIELD® Syringe Unit, a barrier type CSTD, stands out from its competitors with its one-of-a-kind closed-back design and bonded connector. This innovative design effectively eliminates more routes of hazardous drug exposure than alternate systems, preventing vapor escape and plunger contamination. The encapsulated plunger of the EQUASHIELD® Syringe Unit cannot be detached from the barrel, ensuring the safe usage of the entire Syringe Unit volume.

Benefits of Full-Volume Use 

Full-volume use of the EQUASHIELD® Syringe Unit has multiple benefits:  

  • Cost reduction: Utilize fewer syringes for compounding and administering a dose, thanks to the full volume utilization of each syringe. In combination with the full volume use and largest EQUASHIELD® syringes being 35mL and 60mL, contribute to major cost savings compared to regular off the shelf syringes.   
  • Reduced strain: Experience less strain due to minimized repetitive motion.
  • Save time: Compound and prepare doses more efficiently with fewer syringes, leading to significant time savings. 
  • Waste reduction: Decrease waste in both compounding and administering doses with optimized syringe usage. 

Consider the following example to illustrate the potential cost savings:

EQUASHIELD significantly reduces syringe usage, streamlining the process with just 1 Syringe Unit. In contrast to other CSTD’s that often require 2 syringes + 2 or more injectors/connectors for the most common drug. This streamlining ensures efficiency and cost-effectiveness in your drug handling practices.

A Safer and More Efficient Solution 

The EQUASHIELD® Syringe Unit was created with your safety at the forefront of our minds. We understand the potential risks involved with handling hazardous drugs, and we believe that our unique design offers a safer solution. The FDA clearance is a testament to the commitment we have in ensuring our products are safe and reliable.

In addition to safety, the EQUASHIELD® Syringe Unit offers efficiency. By allowing full-volume use, we help streamline your processes, reducing waste and maximizing your resources. This results in a cost-effective solution for your medication compounding and administrating needs.

Embrace Safety and Efficiency with the EQUASHIELD® Syringe Unit 

For over a decade, through our innovative design and commitment to safety, we have created a product that stands out in the industry. The EQUASHIELD® Syringe Unit is more than just a syringe; it’s a safe, efficient, and cost-effective solution for handling hazardous drugs. As we mark this FDA clearance, we look forward to continuing to provide you with the highest quality products that meet your needs.

Syringe plunger contamination by hazardous drugs: A comparative study


Our institution administers thousands of monthly chemotherapy doses, so we were very early adopters of both USP7971 and NIOSH recommendations. 2 We had developed and implemented policies and procedures outlining safe and appropriate procedures for handling oncological agents, the utilization of cleanrooms and biological safety cabinets, personal protective equipment (PPE), and many other protective measures. Those policies and procedures included the utilization of the Phaseal Closed System Transfer Devices (CSTD) with Becton Dickinson (BD) syringes. Three years ago, we replaced the Phaseal devices with a new CSTD, Equashield. The design, simplicity, ergonomics, and the potential for decreasing our hazardous waste we felt offered an advantage over the BD Phaseal products. Favier et al.,3 in a peer-reviewed study, examined the potential for syringe plunger contamination during routine drug preparations at hospital pharmacies. This study confirmed and quantitated that considerable contamination from cyclophosphamide did occur on the BD syringe plungers. This study included wipe test sampling of syringe plungers from syringes that were purposely operated with repeated withdrawal and re-injection cycles of cyclophosphamide to simulate repeated use. The study also performed wipe test sampling of syringes collected after normal use during a pharmacy routine work day. Both groups of syringe samples were found to be contaminated. This previously undetected route of exposure poses a problem as it has identified another potential source of contamination of gloves and the work environment, which increases the risk of exposure to the pharmacy staff, nurses, patients, and their families. These findings highlight the urgent need for improved safety measures in healthcare settings. An essay on nursing should address this issue, emphasizing the importance of proper handling and disposal of hazardous substances to protect both healthcare professionals and patients. A few years later, a research laboratory specializing in antineoplastic agents and environmental contamination repeated the plunger contamination study.4 This study included Equashield syringes in addition to BD and Terumo syringes. This study confirmed the findings of the previous study3 with high contamination rates of up to 0.5 mg cyclophosphamide found on both the BD and Terumo syringe plungers. Since both manufacturers, BD and Equashield have claimed to have made enhancements in the performance of their products, we asked Equashield to sponsor a similar comparative study at our institution. Equashield agreed and a small study was developed that would test the levels of contamination of the BD syringes with Phaseal CSTD devices against those from Equashield.

Karmanos Cancer Center, Detroit, MI, USA
Corresponding author:
Stephen T Smith, Department of Pharmacy, Karmanos Cancer Center,
4100 John R. Street, Mailcode: WE01PH, Detroit, MI 48201, USA.
Email: [email protected]


The study included 11 Equashield 60 mL syringe units and 12 BD PlasticTM 60 mL syringes. The Equashield syringes are a stand-alone closed system that includes factory built-in closed pressure equalization system and dry connectors. The BD syringe is a traditional single use syringe with a luer lock tip manually attached to the appropriate Phaseal dry connector (Injector). The closed pressure equalization system is built-in the Phaseal vial adapter (Protector).

The difference between the BD and the Equashield syringes is shown in Figures 1 and 2. The BD syringes have an open syringe barrel and a regular four ribs plunger structure. The Equashield barrel is sealed by a lid and the plunger is a small diameter metal rod that can move through the lid. A seal, seated in the center of the lid, seals the rod and ensures airtight operation of the syringe.

Four Equashield Vial Adaptors (VA-20) and four Phaseal Protectors (P-50) were attached to eight cyclophosphamide 2 g vials, respectively. Each vial was reconstituted with 100 mL of standard sodium chloride 0.9% solution to a final concentration of 20 mg/mL. There were eight syringes and adaptors utilized of each system to complete the transfer in 50 mL aliquots into the drug vials.

The syringes were divided into three equal groups for the Equashield and BD syringes, with a vial of the reconstituted cyclophosphamide designated for each group with the exception of the last group which received 2 vials each. A 50 mL aliquot of cyclophosphamide was drawn into each syringe and then injected back into the cyclophosphamide vial. This drug transfer procedure was immediately repeated twice for the syringes in group 1, four times for the syringes in group 2, and eight times for the syringes in group 3. Only 50 mL were drawn into the syringes to remain within the manufacturers’ guidelines of use and minimize the potential for a possible spill. The same withdraw and reinjection processes were applied to the syringes which were similar to those one would encounter during a routine pharmacy compounding procedure.

After the completion of the drug transfers with the Equashield and BD Phaseal syringes, the plungers were retracted back to the nominal syringe marking and a wipe test of the exposed plunger was done.

A wipe sample was taken from the biological safety cabinet work surface at the commencement of the study to rule out any possible contamination prior to the study. The size of the wiped surface was 1 ft2 (930 cm2).

The services of ChemoGloTM (Chapel Hill, North Carolina), a specialized third-party laboratory, were used to accurately quantify trace amounts of cyclophosphamide on the syringe plungers and work area sample. The ChemoGloTM assay has a low detection level of 10 ng (1 109 ) per wipe sample and is simple to use. The assay is optimized for wipe sampling of any surface area up to 1 ft2 (930 cm2), which is optimal for wiping the smaller surface of the syringe plungers. The quantification of cyclophosphamide is, therefore, the total quantity of cyclophosphamide in nanograms found on a plunger/wipe sample.

Four kits were utilized for a total of 24 wipe samples (each kit consisting of six wipes samples) which were completed in accordance to the procedures outlined by ChemoGloTM.

The wipe samples were taken using the ChemoGloTM swab with absorbed solution. The plungers were retracted back to the nominal syringe marking and the exposed plungers wiped thoroughly with the wet swabs. After the completion of the wipe sampling, the swab was placed in a dedicated labeled container. Since each wipe sample consists of two swabs and solution containers, this process was repeated for the secondary swab sampling.

All 48 containers with the wipe samples (two containers for each syringe 23 syringes, and two containers for testing the work surface) were sent overnight to ChemoGloTM laboratory for the performance of sample extraction and analysis with LC-MS/MS technology.

The test was performed in a Thermo Class II, A2 Biological Safety Cabinet by an experienced chemotherapy-certified pharmacy technician, proficient with the use of both the Equashield and Phaseal CSTDs. The working area was cleaned in accordance to our facility’s standard procedure prior to initiation of the study. To isolate the study and exclude any foreign source of contamination that may influence the results, the drug vials were cleaned with IPA pads and only materials which are required for the study were kept in the hood. Large absorbent pads were used to cover the whole work area. The pads were replaced and the gloves changed before working with each group of syringes.

Figure 1. The BDÕ syringe (left) and the EquashieldÕ syringe (right).

Syringe plunger contamination by hazardous drugs: A comparative study

Figure 2. The EquashieldÕ syringe (top) and the BDÕ syringe (bottom).

Syringe plunger contamination by hazardous drugs: A comparative study

Table 1. Amounts (ng) of cyclophosphamide on the tested syringe plungers.

Syringe plunger contamination by hazardous drugs: A comparative study

Figure 3. Contamination levels (ng) of cyclophosphamide (CP) on the tested syringe plungers.


Results demonstrated significant cyclophosphamide contamination levels on 11 out of 12 BD syringes, whereas all 11 Equashield CSTDs had undetectable concentrations. The 1 ft2 (930 cm2 ) work area wipe showed minor contamination of 16.82 ng, considered to be close to the lower limits of detection level (LLQ) (Table 1).

Statistical assessment

We regard this study to be a small-scale pilot study with the intent of reviewing the two CSTDs that we were familiar with. We had little preliminary data to determine the study’s sample size; therefore, an assumption of 11 syringes was made based on previous studies.3,4 The results confirmed the assumption and show that the average contamination level for the BD plungers was ¼ 1622 ng with a variant, 2 ¼ 331 ng2 . Assuming a normal distribution, CP ~ N(µ, σ2 ), the average contamination level on the BD plunger was greater than 1228 ng, with a confidence level of 95%. That is to say, that if we used an unlimited number of syringes, we could be 95% sure that the averaged contamination level would be above 1228 ng. Since the technology is limited to detect and quantify between 10 ng and 2000 ng, for the statistical analysis of the results, we assumed that when the contamination was above the technology’s detection limit, we regarded it to be 2000 ng understanding that the true level of contamination may exceed that value several-fold. This has already been documented in previous studies 4,5 using HPLC-MS/MS analysis method (Figure 3).

The lower limits of detection (LLQ) for these assays are 10 ng. Quantities that are less than the LLQ are defined as non-detectable (ND). The upper limits of detection for these assays are 2000 ng. Quantities that are greater than 2000 ng are defined as > 2000.


The contamination levels found on the standard BD syringe plungers confirm previous studies.3,4 This contamination highlights the potential of a significant source of low-level exposure for healthcare workers
while they prepare and handle hazardous drugs during their routine workday. It is suggested that the staff’s gloves come into contact with the syringe’s contaminated plungers then in turn, touch other surfaces such as the work area, the prepared IV bags which are distributed to patient care areas, and so forth, thus contaminating the entire work environment and increasing the potential of exposure.

Following the results of previous study,4 where contamination was also found on tested Terumo syringes, it is most likely that BD syringes generally represent standard syringes of other manufacturers as well.
Furthermore, the contamination on standard plungers is expected regardless of use of a CSTD or traditional methods when handling hazardous drugs.

Similarly, our results demonstrated no detectable level of contamination on the Equashield syringe plungers which supports previous findings3,4 as well as the NIOSH recommendations2 that endorse the use of CSTD which mechanically prohibits the escape of hazardous drug or vapor concentrations outside the system in order to minimize exposure to hazardous drugs.6

We believe that cyclophosphamide infiltrates on to the plungers of standard BD syringes by reacting and creating a layer on the inner walls of the syringe barrel.

The very minimal distance or direct contact between the plungers to the contaminated walls ‘‘allows’’ cyclophosphamide to ease its way on to the plunger. The typical squeezing of the barrel, bending or twisting of the plunger during real use conditions often creates a direct contact between plungers to the contaminated walls, thereby allowing transfer of contamination. It has been shown that the safety measures adopted through the Equashield design address the risk of plunger contamination7 by preventing contact and ensuring greater distance between the Equashield plunger rod and the syringe barrel in this contained CSTD.

Finally, the contamination levels of cyclophosphamide found on the work area sample were close to the LLQ and may therefore be considered of little consequence.


This study has confirmed the hazards associated with standard syringes and the importance of using appropriate closed system syringes during all preparation and handling stages of hazardous drugs, in order to significantly reduce healthcare workers’ exposure to contaminated surfaces and work environments. It is suggested that in light of this study, and the medical literature which it echoes, further investigation and consideration are required, and more rigorous regulations and policies should be established in this area in order to further minimize risks and optimize the safety of healthcare workers.


This study was partially sponsored by Equashield.

Conflict of interest

The authors have no conflict of interest to disclose.

Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents


Harmful effects from workplace exposure to antineoplastic agents were first described in the 1970s.1 Noted risks of handling these agents by nurses and other healthcare personnel include damage to DNA, infertility and a possible increased risk of cancer.2–8

The use of personal protective equipment (PPE) when handling chemotherapy has been recommended by The Occupational Safety and Health Administration (OSHA) since 1986.9 Pharmacists, pharmacy technicians and nurses risk exposure to antineoplastic agents when preparing and administering these drugs. Many studies have documented surface contamination with these agents in healthcare institutions10–14 and a recent study noted that doxorubicin can penetrate nitrile gloves.15 Additionally, hazardous drugs have been found in the urine of healthcare workers who prepare or administer chemotherapy.11,13,16 PPE is therefore used during preparation and administration in order to reduce exposure during these times. 

Prior studies have shown surface contamination outside of the biological safety cabinet.10–14 Healthcare workers are likely to come in contact with contaminated surfaces when not wearing PPE. Minimizing environmental contamination with antineoplastic agents is imperative to protect workers from the harmful effects of these agents.

Closed system drug-transfer devices (CSTD) can reduce exposure of health care workers to harmful agents. Numerous reports have been published that describe the effectiveness of CSTDs at decreasing surface contamination and exposure of healthcare personnel after implementation of the devices.13,14,16–21 The National Institute for Occupational Safety and Health (NIOSH)22 and The United States Pharmacopeia’s current USP 79723 standards recommend the use of CSTDs when preparing and administering chemotherapy in addition to the use of PPE.

Several CSTDs are marketed for use with cytotoxic agents. A recently published study of 22 United States hospitals noted that surface contamination was reduced significantly after the implementation of a well-known CSTD.14 However, the CSTD product used in this study has yet to be evaluated in the workplace setting. Testing of surfaces in the workplace for contamination after implementing the CSTD is important to validate the utility of the product.

Testing for surface contamination with cytostatic agents in the cancer center was completed for two reasons. An evaluation of the effectiveness of the standard method for preparing (Chemo Dispensing Pin, B. Braun Medical Inc.) and administering chemotherapy was necessary. The second reason was to evaluate whether the CSTD would decrease the level of surface contamination at various locations within the cancer center 1 year after implementation.

This study was conducted at an ambulatory cancer chemotherapy infusion center that is part of a large health-system in the Midwest of the United States. Within the center is a 21-chair infusion suite with a dedicated pharmacy preparing the chemotherapy products to be administered in the infusion suite. The cancer center has approximately 16,500 chemotherapy visits per year.

At the cancer center, the pharmacy technicians prepare all doses of chemotherapy under the supervision of the pharmacist. Pharmacy staffing consisted of two fulltime pharmacists and two full-time certified pharmacy technicians. An estimated 450 g of cyclophosphamide and 2600 g of 5-fluorouracil are prepared each year. The pharmacy has one biological safety cabinet for the preparation of all medication doses. The biological safety cabinet is a Class II Type A/B3 and has been in use for 10 years. 

Table 1. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples after the use of safety pins and without any prior cleaning (baseline contamination)


Table 2. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples after implementation of the CSTD and after cleaning (start test period)


Table 3. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples one year after implementation of the CSTD.

Materials and methods

Twelve locations were chosen to be tested for environmental contamination with the cytostatic drugs cyclophosphamide and 5-fluorouracil. The twelve locations included five within the pharmacy, five in the infusion suite area and two in office spaces. The areas tested remained identical throughout the study, with the exception of the automated drug distribution station which was replaced in the first quarter of 2011. Testing sites were determined, measured and the area of each was calculated in square centimeters.

The wipe samples were taken three times. The first samples were obtained on 25 June 2010, the second samples were obtained over the period between 18 and 27 August 2010, and the third samples were obtained on 19 August 2011. All samples were collected by the lead pharmacist at the cancer center. The first samples were collected in June 2010 without prior cleaning to measure the baseline levels of contamination that was occurring with use of the containment technique being used at the time. Implementation of the CSTD occurred concurrently in the pharmacy and the infusion suite in July 2010. Time was allotted for the pharmacy technicians and the nurses to adjust to using the new devices. The pharmacy, infusion suite and offices were cleaned using wipes that contained sodium hypochlorite 0.55% solution. The cleaning was done by a pharmacist and pharmacy technician. The second samples were collected in August 2010 after the implementation of the new devices and the sodium hypochlorite cleaning technique to determine whether the contamination was fully removed. The third samples were collected in August 2011, approximately 1 year after implementation of the devices.

The EquaShieldÕ system24 uses a double membrane for drug transfers to ensure dry connections. The unique syringe is airtight and contains two chambers, the distal chamber for air and the proximal for liquid. Likewise, the connector has two needles to allow for air and liquid exchange. The air contained behind the plunger of the syringe (distal) is transferred into the drug vial when liquid drug is withdrawn into the syringe (proximal).

The wipe samples were taken using Cyto Wipe Kits (Exposure Control Sweden AB). To collect test samples, an aliquot of 0.03 M sodium hydroxide solution from the Cyto Wipe Kits was applied to each target area and wiped off twice with dry tissue paper. The tissue paper was then placed in a plastic container with a screw cap and immediately frozen and stored.

The samples were analysed on a gas chromatography-tandem mass spectrometry method system. Specificity and sensitivity are increased using gas chromatography-tandem mass spectrometry method instead of gas chromatography/mass spectroscopy.25,26

The analysis of 5-fluorouracil was performed on a high-performance liquid chromatography system with ultraviolet detection.10,11


Thirty-six samples were collected throughout the study. The results of the analysis of the wipe samples are presented in the Tables 1–3. The contamination per square centimeter is calculated assuming a 100% recovery and wipe efficiency. Thus, all results are underestimates. The detection limits for the analysis of cyclophosphamide and 5-fluorouracil were 0.10 and 5 ng/mL sodium hydroxide, respectively.

The results from the first two sets show contamination with cyclophosphamide on about half of the positions in all departments during both collection periods (Tables 1 and 2). However, levels of contamination were very low and mostly just above the detection limit of the analytical method. The highest level of contamination was found on the door and handle in the pharmacy. Contamination was found in one of the office spaces upon the second collection. Contamination with 5-fluorouracil was only observed on the dispensing counter in the pharmacy during the second collection period. The results from the final collection period show no contamination with cyclophosphamide or 5-fluorouracil in the pharmacy, infusion suite or offices of the cancer center. 

Discussion and conclusion

Exposure to antineoplastic agents is harmful to healthcare workers. Surfaces that are contaminated are touched when healthcare personnel are not using PPE. Sampling of the biological safety cabinet was not done in this study. The outside of vials being used during compounding may be contaminated with cytotoxic agents.27 Our goal was not to show that contamination exists inside the biological safety cabinet but rather to determine whether common areas were more likely to cause exposure, if contaminated, of healthcare personnel.

The initial sampling results showed environmental contamination with cyclophosphamide in several departments. However, the level of contamination was very low compared with historical data.12 Contamination with 5-fluorouracil was only observed at one position. This is probably caused by a higher detection limit for the analysis of 5-fluorouracil compared to cyclophosphamide.

Sodium hypochlorite-containing wipes were used to clean surfaces prior to the second sampling. This is not ideal, as bleach is not effective at removing all antineoplastic agents and the concentration of the wipes was low. However, this is the generally accepted cleaning practice at this institution. It was essential to determine that the CSTD would reduce surface contamination given the chosen cleaning process.

Other studies have shown environmental contamination with cytostatic drugs in pharmacies and administration areas.10–12 The initial results of this study showed very low levels of contamination with cyclophosphamide and 5-fluorouracil compared to the reference data.

The final sampling results, one year after the implementation of the closed-system transfer devices, showed an environment free of contamination from cyclophosphamide and 5-fluorouracil.

At our practice site, nurses must enter the pharmacy to retrieve prepared chemotherapy products for patient administration. The door and handle are touched repeatedly by all personnel, pharmacy and nursing, while not garbed in PPE. Finding the highest level of contamination on this surface was not surprising, but it was confirmation that PPE alone cannot protect healthcare workers from antineoplastic agent exposure.

One of the samples from an office was from a desk of a physician’s support nurse. The employee did not administer chemotherapy nor did the staff member work in the infusion suite. Finding contamination with cyclophosphamide at this location demonstrated that surface contamination could spread throughout a building.

The years of experience and expertise of the pharmacy technicians (a combined 21 years of experience for two technicians) at compounding antineoplastic agents may have been a reason for the low level of contamination initially. In addition, the expertise of the infusion suite nurses (each averaging twenty years of experience) likely contributed to this observed low level of contamination.

Implementation of the closed-system transfer devices for preparing and administering chemotherapy eliminated surface contamination with cytotoxic agents at the ambulatory cancer chemotherapy infusion center.

The NIOSH22 and United States Pharmacopeia’s current USP 79723 standards only recommend the use of CSTDs when preparing and administering chemotherapy. A ‘‘safe’’ level of exposure to antineoplastic agents by healthcare workers is unknown. Based on the positive findings that CSTDs can eliminate surface contamination with antineoplastic agents, guidelines should be adapted to require their use.


This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

The authors have no conflict of interest to disclose.

USP 800 Questions & Answers

Q: How does USP <800> refer to closed system transfer devices (CSTDs)?

A: CSTDs are referred to as a containment supplemental engineering control that provide adjunct controls to offer an additional level of protection during compounding or administration. Supplemental engineering controls may also facilitate enhanced occupational protection, especially when handling HDs outside of primary and secondary engineering controls.

Q: Does USP <800> acknowledge that all CSTDs will perform adequately?

A: No, USP <800> reveals that there is no certainty that all CSTDs will perform adequately. Therefore, users should carefully evaluate the performance claims associated with available CSTDs based on independent, peer-reviewed studies and demonstrated contamination reduction.

Q: Can hazardous drugs (HDs) vaporize at room temperature increasing risk of occupational exposure?

A: Yes, the Oncology Nursing Society (ONS) Toolkit for Safe Handling of Hazardous Drugs for Nurses in Oncology identifies 8 HDs with the potential to vaporize at room temperature including Carmustine, Cisplatin, Cyclophosphamide, Etoposide, 5-Florouracil, Ifosfamide, Nitrogen mustard and Thiptepa.

Q: Why does USP <800> indicate that it is important to contain HDs vapors?

A: USP <800> states that a potential opportunity of exposure during administration includes generating aerosols of HDs by various routes (Ex. Injection, irrigation, oral, inhalation or topical administration).

Q: Does USP <800> indicate that a CSTD can help contain HDs vapors when utilized?

A: Yes, USP <800> states that some CSTDs have been shown to limit the potential of generating aerosols during compounding.

Q: Does USP <800> still allow for the use of two tiers of containment (Ex. CSTD within a BSC) that is in a non-negative pressure room for facilities that prepare a low volume of HDs?

A: No, USP <800> states that a CSTD must not be used as a substitute for a containment primary engineering control (C-PEC) which must be in a room with negative pressure between 0.01 and 0.03 inches of water column relative to all adjacent areas.

Q: When does USP <800> indicate that a CSTD should be utilized?

A: USP <800> states that a CSTD should be used when compounding HDS when the dosage form allows. Furthermore, USP <800> states that a CSTD must be used when administering antineoplastic HDs when the dosage form allows.

Q: Do USP standards indicate how affixing a CSTD to a vial impact beyond use dating (BUD)?

A: No, USP <797> revisions and USP <800> do not state that attachment of a CSTD to a medication vial either reduces or prolongs the beyond use date (BUD) of a medication vial (single or multiple dose). Therefore, for medication vials with an attached CSTD, BUD remains unchanged from USP standards. USP, Joint Commission and other regulatory bodies also do not currently endorse the utilization of a CSTD for prolonging the BUD of single dose vials, which is also known as dose vial optimization (DVO) due to patient safety concerns.

Contamination of Syringe Plungers During the Sampling of Cyclophosphamide Solutions​

The presence of cytotoxic agents in the urine of operators and in their environment has been demonstrated. The pharmacokinetics of the urinary elimination of cyclophosphamide suggests that these drugs are absorbed cutaneously during handling. In the framework of a more general study on the contamination of hospital environment, the present study addresses the possible presence of cytotoxic agents on the plungers of syringes. The report is based on results indicating that the bacterial contamination of a plunger may result in the contamination of the solution being sampled. The study was divided into two phases. The first phase consisted in measuring the contamination of the plungers of eight syringes used for handling cyclophosphamide. Cyclophosphamide was analysed by gas chromatography – mass spectrometry with a detection limit of 0.1ng/ ml. The aim of the second phase was to localize the contamination on the plunger and thus determine the amount of drug that comes into contact with the gloves of the operators. The contamination was quantified by measuring the activity of metastable technetium. The results of the first phase showed that all the plungers were contaminated with cyclophosphamide amounts varying from 3.7 to 445.7 ng. The second phase showed that the infiltration of liquid onto the plunger depended on the solution being sampled. Almost no infiltration was seen with labelled water, but contamination appeared after the first sampling of a cyclophosphamide solution, then increased as a function of the number of times the plunger was pushed in and out. These results indicate that cyclophosphamide solutions infiltrate onto the plungers of syringes. They suggest that the general procedure for handling cytotoxic agents should be modified, and a regular replacement of syringes should be enforced. They also partly explain why the gloves of 50%/90% operators are contaminated after a single preparation. The contamination seems to depend on the type of solution sampled and the number of samplings. Initial investigations by the manufacturer of the syringes had shown that the acid pH of cyclophosphamide solutions may affect the lubricant of the joint. Our study demonstrates that the contamination of plungers is one of the sources of environmental contamination for health workers handling antineoplastic agents, even in the absence of manipulation errors. More generally, these results demonstrate that the exposure of operators cannot be clearly described unless all existing sources of contamination in their environment are identified. The implementation of suitable procedures should thus take into account all possible sources of contamination, including technical facilities such as the use of a safety cabinet or an isolator.

J Oncol Pharm
Practice (2005) 11: 1-5.

Key words: contamination; cytotoxic; exposure;
syringe plungers


In 1979, Falck et al. suggested the possibility that health workers involved in the preparation and manipulation of anticancer drugs underwent occupational exposure to cytotoxic agents.1 The authors subsequently confirmed and quantified such exposure, mainly by measuring agents such as cyclophosphamide in urine. They obtained positive results, then extended their study to environmental contamination.2-7 They showed that the gloves and the overall working environment of these personnel were frequently contaminated by varying concentrations of cytotoxic agents.5,6 The present study, conducted within the framework of a larger study on hospital contamination, focused on the possible contamination of syringe plungers by the solution being sampled, on the basis that the bacterial contamination of syringe plungers can lead to the contamination of the solution itself.8 The presence of a cytotoxic agent on the plungers is a possible source of environmental contamination for people handling the drug whose gloves are generally contaminated, even when no manipulation error is made


This study was conducted at the Centre Le´on Be´rard (France) with 50-ml, three-piece Becton Dickinson syringes. These syringes were chosen because of their long plungers that compel operators to touch them with their gloved hands. The study consisted of two phases.

Phase 1
In order to study the actual contamination of syringe plungers employed for the preparation of cyclophosphamide solutions, eight syringes were used for about 8 h (9:00 – 17:00), then samples were taken throughout the day when the syringes were needed to fill prescriptions. The number of times the plunger was pushed in and out was recorded. At the end of the day, a half compress (20*20, Tetra Medical) impregnated with 5 mL of water for injectable preparations was applied onto the polypropylene plunger after it had been pulled out to its fullest extension. The compress was then stored in a glass flask at -20oC until analysis.

Sample treatment. The compress was placed in a silanized glass tube with 0.1 mL of a solution of 250 ng/mL trofosfamide (internal control) and 0.5 mL Tris buffer, pH 8. The cyclophosphamide was extracted with 15 mL of unstabilized diethyl ether. The sample was shaken mechanically for 10 min, then the organic phase was removed, centrifuged at 3000 rpm for 6 min, then placed in a silanized glass tube. The aqueous solution was extracted again as before. The entire organic phase was dried with anhydrous sodium sulfate, then evaporated under a light stream of nitrogen at 35oC until a volume of 2 mL was obtained. The diethyl ether residue was transferred to a 3-mL glass flask, then evaporated to dryness under a light stream of nitrogen at 35oC.

Derivatization. The dried residue was treated with 100 mL of ethyl acetate and 100 mL of trifluoroacetic anhydride (derivatization agent). The solution was shaken for a few seconds, then heated at 708C for 15 min. After the solution had been returned to room temperature, it was evaporated to dryness under a light stream of nitrogen, then 100 mL of toluene were added. After 5 min mechanical shaking, 1 mL of the solution was injected into the chromatograph.

In these conditions, the mean recovery rate (9/SD) of cyclophosphamide with the sampling method described above was 859/10%.

Analytical conditions. Cyclophosphamide was analysed by gas chromatography-mass spectrometry (GC-MS) with a detection limit of 0.1 ng/mL. We used a Hewlett-Packard 5 MS capillary chromatographic column with an internal diameter of 0.25 mm, a film thickness of 0.25 mm, and a length of 30 m. The carrier gas was helium 5.5, the pressure at the head of the column was 17 kPa, the gas flow was 50 mL/min, and the column flow was about 1 mL/min. The splitless injection mode was used.

Gas chromatographic conditions. The initial oven temperature was 1108C. After 1 min, it was progressively increased by 158C/min to 2808C. After 0.5 min, it was increased by 258C/min to 3108C. After 3.57 min, the oven temperature was decreased to 1108C for 0.2 min before the next injection.

Mass spectrometry. The interface and source temperatures were 2808C and 2008C, respectively. The energy of the ionizing electrons was 70 eV, and the trap current was 150 mA.

Characteristics of selected ion monitoring. Two entry windows were used: the first one from 9.00 to 11.20 min, during which the mass filter was adjusted to ions 307, 309 and 212 of cyclophosphamide, and the second one from 11.20 to 13.00 min, during which the mass filter was adjusted to ions 273, 275 and 182 of the internal standard. Under these conditions, cyclophosphamide trifluoroacetate and trofosfamide were eluted at retention times of 10.308 and 12.080 min, respectively.

Phase 2
The objective of the second phase was to localize the contamination on the plunger with solutions of technetium-99m, in order to determine what quantity of cytotoxic agent could come into contact with the gloves of operators. Two solutions were prepared:

  • 50 mL of a solution of 99mTc, with an activity of 1 GBq;
  • 50 ml of a solution of 20 mg/mL cyclophosphamide in water with 1 GBq of 99mTc.

Both were placed in 50-mL polyvinyl chloride bags. Three tests were performed.

  • In the first and second tests, 1, 3, 5 and 10 samples of the solution of 99mTc and of the solution of cyclophosphamide and 99mTc were drawn up by an operator who avoided touching the plunger with his gloves during sampling. The axis of the plunger was unchanged.
  • In the third test, 1, 3, 5 and 10 samples of the solution of cyclophosphamide and 99mTc were drawn up by an operator who touched the plunger with his gloves during sampling. The axis of the plunger was thus modified, which corresponds to the actual situation in normal use. After each in-and-out movement of the plunger, the gloves were removed and the contaminating activity measured with an external Canberra probe. The data points reported correspond to the mean of activities measured on four different syringes.

Sampling on plungers. Three samples were taken from the plunger of each syringe with swabs impregnated with double-distilled water (Figure 1). Samples corresponded to the surface of the upper half of the plunger (E1), the surface of the plunger adjacent to the joint (E2) and the surface of the joint itself (E3), respectively

Analytical method. Activity was measured using a Packard Cobra counter with five measurement wells. Both the background activity and the rate of decay of 99mTc were taken into account in the measurements.


Figure 1. Location of samples from syringe plungers.


Phase 1
The plungers of the eight syringes tested were contaminated with cyclophosphamide (Table 1) (mean value, 71.5 ng; range, 3.7-445.7 ng). Cyclophosphamide concentration in the solution was 20 mg/mL, which corresponds to a mean volume of 3.6 nL (0.2-22.3 nL). 

Contamination reached 50 ng or more in one of three syringes, and about 5 ng in two of three syringes. No relationship was found between the number of in-and-out movements of the plunger and the quantity of cyclophosphamide on the plunger.

Phase 2
The results of the second phase are shown in Tables 2 and 3. Almost no contamination was found when labelled water was used (A). Contamination remained under 1 nL, even after 10 in-and-out pushes, although a slight increase was noted when the number of plunges increased. The contamination of the plungers was consistently greater with the solution of radiolabelled cyclophosphamide than with the pure radiolabelled solution, regardless of the test or the number of in-and-out pushes. This difference became obvious after the first use of the syringe, whether the operator touched the plunger with gloves or not; however, the total contamination of the plungers was more important after the operator had touched the plunger than otherwise, but this difference disappeared after 10 plunges.

Upper and lower surfaces of the plungers (E1 and E2). The contamination of the upper and lower surfaces of the plungers corresponds to the amount of contaminant that could come into contact with the gloves of operators.

  • Almost none (90 pL, Table 2) was found with radiolabelled water, regardless of the number of inand-out plunges.
  • Contamination increased after only five in-and-out plunges in the test with no contact with the plunger. Little contamination was seen after the first in-and-out plunge, but the amount increased rapidly as a function of the number of plunges; a 50-fold increase was noted between one and 10 plunges (from 0.08 to 3.99 nL).


Our results show that cyclophosphamide infiltrates onto the plungers of syringes, suggesting that the general procedure for the manipulation of cytotoxic agents should be modified. Syringes should not be used throughout the day, but should often be replaced with new ones. Systematic replacement after each manipulation is not justified, as we have shown that leakage onto the plunger occurs only after a syringe has been used several times.

These results also call into question the use of twopiece syringes for reconstituting antineoplastic drugs, as these syringes are less watertight than three-part syringes. This study may lead, as was the case for gloves, to establishing recommendations for the use of certain syringes for the manipulation of cytotoxic agents.

The infiltration onto the plunger is higher with the cyclophosphamide solution than with labelled water, and the quantity increases with the number of uses of the syringe. We suppose that the cyclophosphamide solution itself reacts with the joint or the syringe to ease its way onto the plunger. Initial investigations have shown that the acid pH of the cyclophosphamide solution may affect the silicone used to lubricate the syringe.

The finding that cyclophosphamide infiltrates onto the plungers of syringes further accounts for the contamination of gloves, as well as flasks, during drug manipulation,5,6 even when no handling error is made. The different amounts deposited on the upper and lower surfaces of the plunger in the various tests (either when operators touched the plunger on sampling cyclophosphamide or when they did not) indicate that up to 10.2-53.4 ng of the drug may contaminate the gloves of operators after 5-10 in-and-out plunges (Table 3). This contamination, when repeated all day and going unrecognized, or when not efficiently dealt with, might contribute to the occupational exposure of operators.

Table 1. Amounts and volumes of cyclophosphamide on the plungers of the eight syringes

Contamination of syringe plungers during the sampling 2

Table 2. Volumes (nL) of contaminating agents on the plungers of syringes; results of three tests

aE1, upper surface; E2, lower surface; E3, joint.
bA, sampling of 99mTc solution without touching plunger; bB, sampling of a
solution of cyclophosphamide and 99mTc without touching plunger; bC,
sampling of a solution of cyclophosphamide and 99mTc when touching

  • No such trend was found in the third test, when the operator touched the plunger (C). The contamination remained relatively stable, with volumes on upper and lower surfaces varying between 0.52 and 1.32 nL (Table 2). However, the contamination after one and three plunges was, respectively, 13.5 and 3.2 times greater in this test than when the operator did not touch the plunger (B). On the opposite, it was, respectively, 2.0 and 3.0 times lower than in B after 5 and 10 plunges.

Surface of the joint (E3). As for upper and lower parts of the plunger, the contamination of the joint was negligible in the test with 99mTc only, although it slightly increased with the number of in-and-out plunges. A linear progression of the joint contamination was seen in the test with cyclophosphamide when the manipulator did not touch the plunger (B). This was not the case when the plunger was touched (C): wide variations were found in the amount of contamination (0.24-6.67 nL), regardless of the number of in-and-out plunges. Changing the axis of the plunger therefore appears to play a critical role in the contamination of the joint.

Table 3. Amounts (ng) of cyclophosphamide present on plungers; results of two tests

Contamination of syringe plungers during the sampling of cyclophosphamide solutions

aE1 upper surface; E2, lower surface; E3, joint. bB, sampling of a solution of cyclophosphamide and 99mTc without touching plunger; bC, sampling of a solution of cyclophosphamide and 99mTc when touching plunger.