Science of the Total Environment 599–600 (2017) 1939–1944

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Science of the Total Environment

journal homepage: www.elsevier.com/locate/scitotenv

Safety analysis of occupational exposure of healthcare workers to

residual contaminations of cytotoxic drugs using FMECA
security approach
Laetitia Minh Mai Le a,b,⁎, Delphine Reitter a, Sophie He a, Franck Té Bonle a, Amélie Launois a, Diane Martinez c,
Patrice Prognon a,b, Eric Caudron a,b
a
Pharmacy Department, European Georges Pompidou Hospital, Paris, France
b
Lip(Sys)2 Chimie analytique Pharmaceutique, Université Paris Sud, Univ. Paris Saclay, Chatenay-Malabry, France
c
Risk Management Department, European Georges Pompidou Hospital, Paris, France

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Innovative approach to explore occupa-

tional risk associated to cytotoxic han-
dling
• First study combining antineoplastic
contamination on workplace surfaces
and FMECA
• Tool to assess, develop and monitor risk
management plans in chemotherapy
unit

a r t i c l e i n f o a b s t r a c t

Article history: Handling cytotoxic drugs is associated with chemical contamination of workplace surfaces. The potential muta-
Received 13 March 2017 genic, teratogenic and oncogenic properties of those drugs create a risk of occupational exposure for healthcare
Received in revised form 6 May 2017 workers, from reception of starting materials to the preparation and administration of cytotoxic therapies. The
Accepted 7 May 2017
Security Failure Mode Effects and Criticality Analysis (FMECA) was used as a proactive method to assess the
Available online xxxx
risks involved in the chemotherapy compounding process.
FMECA was carried out by a multidisciplinary team from 2011 to 2016. Potential failure modes of the process
were identified based on the Risk Priority Number (RPN) that prioritizes corrective actions.
Twenty-five potential failure modes were identified. Based on RPN results, the corrective actions plan was revised
annually to reduce the risk of exposure and improve practices. Since 2011, 16 specific measures were implement-
ed successively. In six years, a cumulative RPN reduction of 626 was observed, with a decrease from 912 to 286
(−69%) despite an increase of cytotoxic compounding activity of around 23.2%.
In order to anticipate and prevent occupational exposure, FMECA is a valuable tool to identify, prioritize and elim-
inate potential failure modes for operators involved in the cytotoxic drug preparation process before the failures
occur.
© 2017 Elsevier B.V. All rights reserved.

⁎ Corresponding author at: 20 rue Leblanc, 75015 Paris, France.

E-mail address: laetitia.le@aphp.fr (L.M.M. Le).

http://dx.doi.org/10.1016/j.scitotenv.2017.05.066
0048-9697/© 2017 Elsevier B.V. All rights reserved.
1940 L.M.M. Le et al. / Science of the Total Environment 599–600 (2017) 1939–1944
1. Introduction
Cytotoxic drugs are used in chemotherapy to treat cancer. According
to the World Health Organization (WHO), 14.1 million new cancer cases
were diagnosed worldwide in 2012 and the number is still increasing
(WHO, 2013). Cytotoxic drugs contribute to reducing tumor growth
but most have adverse effects. Cytotoxic drugs may affect normal as
well as cancerous cells and may be responsible for serious adverse ef-
fects such as nausea, skin rashes, long-term adverse reproductive effects
or mutagenic effects (sub-chronic toxicity). In 2004, the National Insti-
tute of Occupational Safety and Health (NIOSH) published an alert to
warm health care workers about the risks of working with hazardous
drugs and recommends methods and equipments for protecting their
health (National Institute for Occupational Safety and Health, 2004). Ac-
cording to NIOSH, workers may be exposed to cytotoxic drug from
manufacturing to transport and distribution to use in health care or
home care settings, to waste disposal and in 2004, the number of
workers who may be exposed to hazardous drugs exceeded 5.5 millions.
In 2012, Lawson et al. suggested that the risk of spontaneous abor-
tion was related to occupational exposures of nurses (Lawson et al.,
2012). Handling cytotoxic agents (including drug compounding, ad-
ministration and waste management) may therefore present a major
risk for healthcare worker including nurses, pharmacy technicians,
pharmacists, and clinicians (American Society of Health-System Phar-
macists, 2006).
To prevent exposure, the American Society of Health System Phar-
macists (ASHP, 2006) and the International Society of Oncology Phar-
macy Practitioners (ISOPP, 2007) have published guidelines for safe
handling of cytotoxic drugs. They promote the use of collective protec-
tive equipment (preparation inside safety cabinets), individual protec-
tive equipment and specific practices such as standard labels for
identifying cytotoxic drug preparations or cytotoxic waste
(CAN/CSA-Z317.10-01, 2007; Easty et al., 2015). These guidelines have
made significant contributions to reducing exposure, particularly by
inhalation.
Despite those recommendations, a substantial danger for occupa-
tional exposure to cytotoxic drugs remains. Over the past few years, nu-
merous environmental contaminations by cytotoxic drugs have been
reported (CDC - Occupational Exposure to Antineoplastic Agents). Sev-
eral sources of exposure have been described since numerous chemical
contaminations were found on the external surfaces of cytotoxic vials,
workplace surfaces such as surfaces inside and outside safety cabinets
At the present time, the major route of exposure is cutaneous (ASHP,
2006). Cytotoxic contamination has been frequently found in biological
samples of workers currently handling these drugs, as well as of
workers who presumably are not in contact (Hon et al., 2015). Numer-
ous publications listed by the National Institute for Occupational Safety
and Health demonstrate this exposure and the associated risks for the
health of individuals exposed (CDC - Occupational Exposure to
Antineoplastic Agents). A recent study conducted by the French Nation-
al Research and Safety Institute for the Prevention of Accidents and Oc-
cupational Diseases (INRS) in 13 French hospitals showed that the urine
of N 50% of staff (almost 300 healthcare workers) were contaminated
with at least one of the three cytotoxic molecules screened (Ndaw
et al., 2013).
Despite risk, no recommended exposure limits have been
established for hazardous drugs. Only a workplace environmental expo-
sure level of 0.1 ng/cm for cyclophosphamide that is an alkylating agent
and nitrogen mustard, has been established by the United States Phar-
macopeia (USP b797N, 2015).
Consequently, provide tools for preventing represents a public
health challenge. Based on those considerations, we decided to explore
a reliability evaluation method called Failure Modes and Effects and
Critical Analysis (FMECA) for identifying failures of the chemotherapy
process before incidents occur. According FMECA, the risk is related to
the likelihood of failure occurring and the gravity of its consequences,
the potentiality of detection and interception before the failure occurs.
Since 1940's, this standardized approach that was initially developed
by the aerospace and automotive industries to analyze failures in de-
sign, manufacturing process or product or service is nowadays recom-
mended by the Food and Drug Administration (FDA). Despite FMECA
is usually conducted in process development stages, it may also have
yield benefits on existing process to anticipate risks. Considering indus-
trial experiences and its simplicity, we decided to explore FMECA to
evaluate potential risk of occupational exposure of healthcare workers
to residual cytotoxic contamination in the chemotherapy preparation
process. Since 2011, Safety FMECA extended to FMECA (Berthe and
Vimeux, 1997) by including time of exposure and the possibility of
avoidance in order to chart the probability of failure modes against
the gravity of their consequences was annually conducted. Based on
Risk Priority Number (RPN) calculated for each failure mode, actions
to be taken were prioritized and the corrective actions plan was annual-
ly revised in order to reduce potential risk for operators and improve
practices.
This study is the first published experience of use FMECA to analyze
potential risk of exposure of healthcare workers in the chemotherapy
process at hospital.
2. Materials and method
The FMECA process involved the following five steps: defining the
scope of the study, constituting a multidisciplinary team, identifying
failures that may affect the process and collecting information on this
process, conducting the criticality analysis to rank the significance of po-
tential failure modes and finally, developing and implementing
correcting actions and outcomes measures to reduce risk.
2.1. Study period and scope
This study was conducted from 2011 to 2016 in a French teaching
hospital. The European Georges Pompidou Hospital is a part of the
Paris West Hospitals Group of AP-HP (Public Assistance-Paris Hospitals)
in which oncology activity is distributed among nine oncology units. In
2011, 28,588 antineoplastic preparations (1702 patients) were pro-
duced in the centralized compounding unit, compared to 35,220 prepa-
rations (2096 patients) in 2016 (+23.2%).
Drug therapy in oncology is a complex process. In the present study,
the system analyzed was the cytotoxic drug preparation process in the
oncology pharmacy unit. Five major steps were considered: starting
materials management, working in the controlled area, preparation in
safety cabinets, quality control of the final product and its transfer to
the treatment unit. In our hospital, 27 employees divided into five cate-
gory of healthcare workers are involved: i) pharmacists (n = 5) for
quality management, medical prescriptions analysis and quality control
activity, ii) pharmacy technicians (n = 14) for preparation
compounding, iii) laboratory technicians (n = 3) working in the analyt-
ical control area for quality control of cytotoxic drug preparations, iv)
pharmacy technician assistants (n = 3) for starting material storage
and transfer of preparations to treatment units and v) cleaning techni-
cians (n = 2) for cleaning work area surfaces.
2.2. Composition of the FMECA team and risk analysis
A team was formed that included three pharmacists (the head phar-
macist of the cytotoxic drug preparation unit, the pharmacist of the cy-
totoxic drug control unit and resident pharmacists) and a manager of
the risk management department of the hospital.
First, the team listed all potential failure modes that could cause ex-
posure of operators. Each failure mode was determined using assess-
ment parameters validated by the FMECA team: gravity (G),
occurrence (O), exposure (E) and possibility of avoidance (A). As de-
fined in (Table 1), a value range from 1 to 5 was attributed to each
 L.M.M. Le et al. / Science of the Total Environment 599–600 (2017) 1939–1944
Table 1
Rating scales used to assign values to the gravity (G), the occurrence (O), the exposure (E) and the possibility of avoidance (A) scores in the failure mode and effects analysis (LLOQ: low
limit of quantification, 0.06 ng/cm2 for platinum element).
Gravity (G) Occurrence (O)
Score Description of injury Score Description of injury
1 Very low: no detectable 1 Very low: b10% of
contamination (mean contamination contaminated samples
lower than the LLOQ)
2 Low: mean contamination lower than 2 Low: from 10% to 25% of
USP limit contaminated samples
3 Moderate: mean contamination lower 3 Moderate: from 25% to
than 10 time the USP limit 40% of contaminated
samples
4 High: mean contamination lower than 4 High: from 40% to 70%
100 times the USP limit of contaminated
samples
5 Very high: mean contamination 5 Very high: higher than
higher than 100 times the USP limit 70% of contaminated
samples
failure mode to quantify the gravity of the failure (G), its potential oc-
currence (O), the exposure of each worker to this failure mode
(E) and the possibility of avoidance before the failure occurs (A), accord-
ing to USP and ASHP recommendations. The risk priority number (RPN)
obtained by multiplying the four factors (G × O × E × A) was used as an
indicator to graduate the relevance of each failure mode and prioritized
remedial measures. The maximum RPN was 625 (5 × 5 × 5 × 5).
In order to evaluate the significant difference of RPNs, statistical
comparison were conducted online (https://marne.u707.jussieu.fr/
biostatgv) using paired t-test (α = 5%).
Gravity (G): at the present time, no limit value of exposure is avail-
able and so it is particularly difficult to rank the severity of conse-
quences when an operator is exposed to chemical contamination.
Indeed, the gravity was determined by the quantity of residual chemical
contamination observed by environmental monitoring; platinum was
used as a tracer of contamination. Samples were collected on workplace
surfaces using a representative and standardized sampling protocol and
were analyzed using a validated method (Chappuy et al., 2010). The low
limit of detection (LLOD) and the low limit of quantification (LLOQ)
were 0.02 and 0.06 ng/cm2 respectively. Gravity was described on a
5-point scale based on the limit of contamination of 0.1 ng/cm2 pub-
lished by United States Pharmacopeia (USP) (USP b797N, 2015) where
1 is no detectable contamination (b 0,02 ng/cm2) and 5 is very high con-
tamination (N 100 ng/cm2).
Occurrence (O): occurrence is described by the proportion of chem-
ical contaminations on a 5-point scale where 1 is the absence of detect-
able contamination and 5 is higher than 70% of contaminated samples.
Exposure (E): exposure takes the frequency and duration of exposure
into account and is described by a 5-point scale (1 for low and 5 for high
durations of exposure).
Possibility of avoidance (A): this component is also described by a
5-point scale where 1 is technical and human avoidance with the use
of closed collective protective equipment and 5 is the absence of avoid-
ance, i.e. no protection. According to the ASHP, only ventilated cabinets
designed to protect workers and adjacent personnel from exposure and
to provide an aseptic environment may be used to compound sterile
hazardous drugs. Moreover, double gloves have to be worn for all activ-
ities involving hazardous drugs as shipping cartons or drug vials,
compounding and administration of hazardous drugs, handling of haz-
ardous drug waste or waste from patients recently treated with hazard-
ous drugs, and cleanup of hazardous drug spills.
2.3. Corrective actions development and implementation
In order to reduce risk, all failure modes studied were classified into
three criticality classes (C1: acceptable, C2: tolerable under control and
1941
Exposure (E) Possibility of avoidance (A)
Score Description of injury Score Description of injury
1 Very low: very occasional 1 Very high: technical and human avoidance
exposure (only few minutes) with the use of closed collective protective
equipment
2 Low: occasional exposure (b1 2 High: use semi closed collective equipment
h a day)
3 Moderate: moderate exposure 3 Moderate: use individual protective
(b2 h per day) equipments recommended for cytotoxic
drug handling
4 High: frequent exposure (half 4 Low: use individual protective equipment
time activity, until 3 h per day) not specifically adapted to cytotoxic drug
5 Very high: very frequent 5 Very low: absence of avoidance, i.e. no
exposure (full time activity, N3 protection
h per day)
C3: unacceptable) defining the priority of actions that have to be imple-
mented. Thresholds of criticality were defined and validated by the
FMECA team after criticality analysis of all potential scenarios (n =
375). Therefore, no action was required for “acceptable” situations
(C1: RPN ≤ 74). For “tolerable under control situations” (C2: 74 b RPN
≤ 194), however corrective actions and monitoring on the short to me-
dium terms are required, and for “unacceptable” situations (C3: RPN
N 194) immediate actions are required to reduce exposure.
3. Results
3.1. Criticality analysis
For each category of workers, independent potential failure modes
were considered among steps of the compounding process. The
FMECA team identified 25 potential failure modes for the five major
steps previously described: starting materials management (n = 5),
working in the controlled area (n = 5), preparation in safety cabinet
(n = 5), quality control of final product (n = 5) and transfer of final
product to the treatment unit (n = 5).
The sum of RPNs was calculated for all potential failure modes
resulting from gravity, occurrence, exposure and possibility of avoid-
ance scores. This sum was calculated from 2011 to 2016 (Fig. 1) and is
a cumulative RPN reduction of 626 in six years, with a decrease from
912 to 286 (−69%) despite an increase of the cytotoxic compounding
activity by about 32% in 2012. Since 2011, various exposure situations
were observed but no unacceptable situation (RPN N 194) was found
(Table 2). Despite annual revision of the corrective action plan, no
Fig. 1. Changes of the total risk priority numbers (RPN) from 2011 to 2016.
1942 L.M.M. Le et al. / Science of the Total Environment 599–600 (2017) 1939–1944

significant differences of RPNs were observed before 2015 (2011 versus
2015 and 2016, p b 0.05) (Table 2).
In order to prioritize the risk of exposure among the five categories
of workers, their RPNs in all steps involved to the cytotoxic
compounding process are listed in Table 2. In 2011, four of the five cat-
egories of workers (pharmacy technicians, cleaning technicians, labora-
tory technicians and pharmacy technician assistants) presented at least
a tolerable risk over all failure modes identified (RPNs from 80 to 128).
Only pharmacists had acceptable risk for all failures (mean RPN of 29).
From 2011 to 2015, RPNs have changed regularly in accordance with
corrective measures implemented with the aim of preventing exposure
and improving practices. Since 2014, all categories of workers have ac-
ceptable risks for all failures. The lowest risk was obtained for laboratory
technicians and pharmacy technician assistants (RPNs of 9) in 2016.
During this last year, a slightly higher RPN for the safety cabinet
(mean RPN of 8 in 2015 and 20 in 2016) was observed that increased
RPNs values for all categories of workers, albeit acceptable levels.
3.2. Corrective actions plan
Regarding cytotoxic contamination found in the working environ-
ment and the results of a previous study (Lê et al., 2013), cleaning prac-
tices were modified (cleaning products, frequency of cleaning and
operating methods). In 2011, the reception area and the control area
were associated with tolerable exposure (RPN 76 and 75 respectively).
Chemical decontamination was reinforced in these two areas. In 2012,
the same procedure was extended to the work area where the RPN of
91 may be explained by increased production and therefore residual
contaminations on workplace surfaces. In addition, the cleaning agent
was changed in the control area (RPN 78). A detergent solution was
used daily for chemical decontamination in order to remove residual
chemical contamination from work surfaces. Since 2013, this measure
has been extended to the entire area of the process where cytotoxic
drugs are handled.
In 2011, gloves for specifically testing cytotoxic drugs (ASTM D6978-
05, 2005) were referenced and used first in the control area by laborato-
ry technicians for the analytical control of final products before delivery
to patients and was then extended to all activities involved in the cyto-
toxic compounding process.

Since 2011, numerous measures were implemented successively

(Table 3). One of the major actions was consolidation of the training
program and a specific training program was implemented in 2011.
For each activity, staff are trained by a referent worker and specifically
authorized. Different working groups were constituted to improve prac-
tices, define needs and formalize instructions for different activities. Pe-
riodic training sessions were organized in order to sensitize workers to
the chemical risks of cytotoxic drugs. Procedures for the use of personal
protective equipment are clearly stated and posted on walls.
4. Discussion
According to ASHP, all workers involved in compounding cytotoxic
drugs are exposed to the potential of contact with uncontained drugs.
Due to the hazardous nature of these drugs, different monitoring proce-
dures are used to determine the exposure of healthcare workers, such as
medical monitoring to detect potential changes of the health status of
workers, e.g. tumor development or/and laboratory tests to measure

Table 2
Risk Priority Numbers (RPNs) and proportion of the cumulative RPN (%) for failure modes identified for the five categories of workers in the chemotherapy compounding process from
2011 to 2016.

2011 2012 2013 2014 2015 2016

Cleaning technicians
Preparation in safety cabinet 5 (3%) 10 (4%) 4 (2%) 3 (2%) 4 (7%) 10 (18%)
Quality control of final product 80 (41%) 100 (37%) 64 (32%) 48 (31%) 16 (28%) 8 (14%)
Working in the controlled area 10 (5%) 120 (44%) 72 (36%) 48 (31%) 16 (28%) 16 (29%)
Starting materials management 90 (46%) 30 (11%) 48 (24%) 48 (31%) 12 (21%) 12 (21%)
Transfer of final product 10 (5%) 10 (4%) 10 (5%) 10 (6%) 10 (17%) 10 (18%)
TOTAL 195 270 198 157 58 56

Pharmacy technician assistants

Preparation in safety cabinet 5 (3%) 10 (6%) 4 (3%) 3 (3%) 4 (9%) 10 22%)
Quality control of final product 40 (21%) 50 (31%) 40 (31%) 30 (27%) 10 (23%) 5 11%)
Working in the controlled area 4 (2%) 48 (30%) 27 (21%) 18 (16%) 6 (14%) 6 13%)
Starting materials management 120 (63%) 32 (20%) 48 (37%) 48 (43%) 12 (27%) 12 27%)
Transfer of final product 20 (11%) 20 (13%) 12 (9%) 12 (11%) 12 (27%) 12 27%)
TOTAL 189 160 131 111 44 45

Pharmacists
Preparation in safety cabinet 5 (3%) 10 (5%) 4 (3%) 3 (3%) 4 (8%) 10 (20%)
Quality control of final product 64 (44%) 60 (30%) 48 (33%) 36 (32%) 12 (24%) 6 (12%)
Working in the controlled area 8 (6%) 96 (48%) 54 (37%) 36 (32%) 12 (24%) 12 (24%)
Starting materials management 48 (33%) 16 (8%) 24 (17%) 24 (21%) 6 (12%) 6 (12%)
Transfer of final product 20 (14%) 20 (10%) 15 (10%) 15 (13%) 15 (31%) 15 (31%)
TOTAL 145 202 145 114 49 49

Pharmacy technicians
Preparation in safety cabinet 25 (12%) 50 (17%) 20 (10%) 15 (10%) 20 (31%) 50 (56%)
Quality control of final product 64 (32%) 60 (21%) 48 (25%) 36 (24%) 12 (18%) 6 (7%)
Working in the controlled area 12 (6%) 144 (50%) 81 (42%) 54 (37%) 18 (28%) 18 (20%)
Starting materials management 90 (45%) 24 (8%) 36 (19%) 36 (24%) 9 (14%) 9 (10%)
Transfer of final product 10 (5%) 8 (3%) 6 (3%) 6 (4%) 6 (9%) 6 (7%)
TOTAL 201 286 191 147 65 89

Laboratory technicians
Preparation in safety cabinet 10 (5%) 20 (10%) 8 (5%) 6 (5%) 8 (17%) 20 (43%)
Quality control of final product 128 (70%) 120 (59%) 96 (64%) 72 (63%) 24 (51%) 12 (26%)
Working in the controlled area 4 (2%) 48 (24%) 27 (18%) 18 (16%) 6 (13%) 6 (13%)
Starting materials management 30 (16%) 8 (4%) 12 (8%) 12 (11%) 3 (6%) 3 (6%)
Transfer of final product 10 (5%) 8 (4%) 6 (4%) 6 (5%) 6 (13%) 6 (13%)
TOTAL 182 204 149 114 47 47
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Table 3
List of corrective actions implemented since 2011 to improve the safety of healthcare
workers involved in the cytotoxic compounding process.
Year Action
2011 Wearing a pair of gloves in the reception area
Wearing a pair of specific gloves (evaluation regarding ASTM D6978-05) in
the control area
Awareness of chemical risks (pharmacists and laboratory technicians)
Increasing the frequency of cleaning in reception and control areas
2012 Wearing a pair of specific gloves (ASTM D6978-05) for all activities
involving cytotoxic drugs
Increasing the frequency of cleaning in working and compounding areas
Using detergent solution in the compounding area in order to remove
residual contamination at the end of the activity
Awareness of chemical risks (pharmacy technicians and pharmacy
technician assistants)
2013 Revision and poster display of dressing procedures in the work area
Extend the use of detergent solution in other areas involving cytotoxic
drugs
2014 Revision of microbiological and particular cleaning procedure in the
working area
Training with Spill box
Establishment of a working group for health and safety (pharmacist,
pharmacy technician and laboratory technician)
Establishment of a working group for training (pharmacist and pharmacy
technician)
2015 Training for chemical risks associated with handling cytotoxic drugs
2016 Action plan for 2016: staff awareness regarding chemical risks and cleaning
procedures in the work area
contamination by cytotoxics in urine or blood samples (CDC -
Occupational Exposure to Antineoplastic Agents).
During the past several years, collective protective equipments such
as safety cabinets or isolators have been used to ensure aseptic condi-
tion and also to prevent exposure by inhalation. At the present time, cu-
taneous absorption and oral ingestion after contact with contaminated
hands are the main routes of exposure. In order to prevent exposure
and identify sources of contamination, other approaches such as envi-
ronmental monitoring have been explored. Some studies have
attempted to correlate occupational exposure to levels of cytotoxic con-
tamination on workplace surfaces. Based on contamination data of
workplace surfaces obtained from 102 German pharmacy units,
Schierl et al. (2009) described guideline values to classify environmen-
tal cytotoxic contamination. In Canada, Hon et al. (2011) proposed an
identification of job categories potentially exposed throughout the Hos-
pital Medical System in terms of exposure to contaminated surfaces.
Sessink (2011) were among the first authors to propose an exposure
prediction model that established a relationship between contamina-
tion of workplace surfaces and contamination in urine samples. Expo-
sure to drugs also affects a number of parameters such as individual,
organizational and environmental factors, which may determine differ-
ences in exposure levels among workers. Despite individual variabilities
and predispositions, the major parameters used to assess the risk of ex-
posure are the quantity of contaminants, the duration and frequency of
exposure. According Hon et al. (2015), the levels of experience and
training of workers for cytotoxic handling are also factors affecting
chemical risk and exposure levels.
In order to analyze the safety of healthcare process, FMECAs were
performed from 2011 to 2016 on the chemotherapy preparation pro-
cess to assess and anticipate risk of occupational exposure to residual
contamination of cytotoxic drugs. Risk management is a powerful key
component of the management system that identifies, assesses and de-
termines the means for reducing risks to acceptable levels across a wide
range of factors, in order to protect healthcare workers and the environ-
ment. Different methods are documented to analyze risk as the Hazard
Analysis and Critical Control Points (HACCP), particularly recommend-
ed for food safety analysis and recently explored to healthcare process
(Bonan et al., 2009), Preliminary Risk Analysis (PRA) (Bonnabry et al.,
2006; Niel-Lainé et al., 2011) or Global Risk Analysis (GRA) (Mazeron
1943
et al., 2014, 2015) that are used to evaluate risk on the conception stages
of a process and FMECA. Due to its inductive reasoning and simplicity,
FMECA application has particularly increased in the past several years
in the pharmaceutical industry and also in healthcare institutes for
health care management. FMECA is a qualitative technique used to iden-
tify and analyze all potential failure modes of the various parts of a sys-
tem, the effects that failures may have on the system and is intended to
avoid the failure or the effects of failures on the system. At the present
time, this method recommended by FDA for minimizing medication er-
rors is one of the first systematic methodologies for failure analysis in
healthcare institutes (Ford et al., 2009; Jiang et al., 2015; Lago et al.,
2012; Scorsetti et al., 2010).
Based on this approach, potential failures that have undesirable or
significant effects on process safety are identified. The results showed
considerable variations of potential exposure among categories of
workers and a decrease of potential exposure following the implemen-
tation of corrective measures. This method focuses on workers at risk,
essential for implementing customized preventive and protective mea-
sures to reduce the overall risk of exposure.
During the past five years, the corrective action plan was adapted
annually to sustainably anticipate risks and adverse events. Practices
of the process for compounding cytotoxic preparations have consider-
ably changed. All operators are now aware and informed of the risk of
exposure. They actively and consistently act to improve the process
for themselves and also for patients.
Despite the interest of FMECA to develop the correction action plan,
this study had nevertheless some limitations associated to the tracer of
the contamination, the limited number of workers included and scope
of the study. To evaluate environmental contamination, analytical
methods have to reliably quantify at least 0.1 ng/cm2 of cytotoxic tracer
per sample (USP b797N, 2015) with a tracer representative of produc-
tion. In this work, platinum was used as tracer. The lower limit of detec-
tion of 0.02 ng/cm2 (Chappuy et al., 2010) was compatible with
detection of residual contamination on workplace surfaces. The plati-
num, representative of three cytotoxic drugs (carboplatin, cisplatin
and oxaliplatin) and their metabolites, corresponds to 14.6% of the cyto-
toxic treatments in our hospital (the second after 5-fluorouracile prep-
arations and from approximately 50 cytotoxic molecules used for
chemotherapy). Despite platinum was a good tracer of our activity; it
is slightly used in pediatric unit. This approach should therefore be ex-
tended by the use of other tracers or multiple tracers in order to opti-
mize assessment of the residual chemical contamination.
Finally, this study was limited to the cytotoxic compounding pro-
cess. Occupational exposure, however, may occur at every step of the
process involving the use and administration of cytotoxic drugs when
control measures are absent or fail. Regarding chemical contamination
found in care units and biological samples of healthcare professionals,
the issue is not limited to the hospital pharmacy staff. It would be inter-
esting to extend this study to other activities potentially at risk, such as
drug administration, handling patient waste, transport and waste dis-
posal and spills, and to act to prevent exposure of all personal involved
in these activities including nurses, physicians, maintenance and waste
disposal staff.
5. Conclusion
Regarding its toxicity and the impossibility of substituting these
molecules by other less toxic substances, the risk of occupational expo-
sure to antineoplastic drugs (drugs used to treat cancer) but also other
hazardous drugs in health care settings have to be considered. This
study demonstrates the usefulness of FMECA as risk analysis method
for providing and maintaining a safe risk-free health working environ-
ment. Based on the concept that a risk is related not only to the occur-
rence but also on severity of the failure's consequences and the ability
to detect it before it occurs, FMECA approach represent an interesting
tool to prioritize failures and actions that have to be taken. This
1944 L.M.M. Le et al. / Science of the Total Environment 599–600 (2017) 1939–1944
approach will not substitute to biological monitoring to evaluate expo-
sure, but associated to annual environmental contamination evaluation,
represents with RPNs as indicator of the performance of the system, a
simple, standardized and pragmatic approach for preventing occupa-
tional exposure of healthcare workers in our units.
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