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1
BGW • Pappelallee 35/37 • 22089 Hamburg • www.bgw-online.de
Wipe Sample Monitoring on Workplace Contamination with Antineoplastic Drugs in Pharmacies
Heinemann A1, Eickmann U1, Kiffmeyer TK2, Tuerk J2, Stuetzer H3, Hahn M3, Hadtstein C4
(1)
(2)
(3)
(4)
Berufsgenossenschaft für Gesundheitsdienst und Wohlfahrtspflege, BGW, Cologne, Germany
Institute of Energy and Environmental Technology, IUTA e.V., Duisburg, Germany
Institute of Medical Statistics, Informatics & Epidemiology, IMSIE, Cologne, Germany
Institute of Applied Pharmacy, IfAP e.V., Cologne, Germany
Introduction and Aims:
Antineoplastic drug applications for the treatment of
cancer patients are prepared in some 800 German
pharmacies. These drugs have carcinogenic, mutagenic and/or adverse developmental or reproductive properties and effective safety measures are
therefore required to protect the employees.
The BGW therefore launched a large-scale study
(MEWIP*) in order to determine the contamination
level and to investigate the suitability and effects of
wipe sample monitoring at regular intervals. Further
aims were to investigate the causes of contamination, its spread and the development of strategies for
minimizing exposure. In terms of the study, the
BGW expected monitoring to promote readiness
for taking appropriate measures to improve working
conditions and occupational safety. The German
ordinance on the handling of hazardous substances (GefStoffV) also stipulates measurements of such
workplaces.
For the purpose of the study, wipe samples in 130
German pharmacies (hospitals and public pharmacies) were taken from three sampling locations from
early 2006 until the end of 2007.
Fig. 1: Preparation area
Fig. 2: Sampling areas (floor, work top, fridge door)
Fig. 3: Wiping directions
Substance load (ng/cm2)
10000
substance load MEWIP-396: 0.6509
ranking MEWIP-396: 88
LOQ: 0.0128
values ≥ LOQ: 57 / 100
minimum: < LOQ
25th percentile: < LOQ
median: 0.0169
75th percentile: 0.122
maximum: 11791
calculated values in (ng/cm2)
1000
100
50
20
10
5
Methods:
Three selected sampling areas (floor in front of the
safety cabinet, most intensively used work top,
fridge door including handle) were repeatedly
monitored by wipe sampling. The samples were
analysed for their amount of 5-Fluorouracil (5-FU),
Cyclophosphamide (CP), Gemcitabine (Gem), Me* Monitoring-Effect-Study of Wipe Sampling in Pharmacies
2
1
0.5
0.2
0.1
0.05
0.02
0.0128
0
100
90
80
70
Ranking
Fig. 4: Report for participants
60
50
2
BGW • Pappelallee 35/37 • 22089 Hamburg • www.bgw-online.de
thotrexate (MTX), Etoposide (Eto), Ifosfamide (IF),
Docetaxel (Doc) and Paclitaxel (Pac). In addition,
the working conditions were recorded by a detailed
questionnaire on working procedures (e.g. type and
amounts handled, hazards and spillage, cleaning
procedures, waste management, protective equipment, education of personnel, training).
The participating pharmacies were split into two
study groups: 55 pharmacies performed quarterly
wipe sampling and were informed about the analytical results throughout the study (group A), while in
the remaining 75 sites, samples were taken only at
the start and end of the study and the analyses values were not reported until the project had finished
(group B). Samples were taken under strict, standardised conditions and the results were made anonymous (Fig. 4). Each sampling surface was wiped
clean with three cloths which had been soaked in
a solvent especially adapted for this purpose (Fig.
2, 3). Once the samples had been processed, they
were analysed by means of tandem mass spectrometry (LC-MS/MS). A total of 1,272 wipe samples
were taken resulting in 10,176 individual values.
Project phases
Period
2005
Year
II
Quarter
III
Partner(s)
2006
IV
I
II
III
2007
IV
I
II
III
IV
Phase 1:
Contact pharmacies, 1st questionnaire
IUTA (BGW, IMSIE,
IfAP)
Phase 2:
Evaluation 1st questionnaire
IUTA, IfAP
(BGW, IMSIE)
Phase 3:
Prepare and develop the study design
BGW, IUTA, IMSIE
Phase 4:
Kick-off events
BGW (IUTA, IMSIE,
IfAP)
Phase 5:
2nd questionnaire, interview, monitoring
IUTA, IfAP
(BGW, IMSIE)
Phase 6:
Evaluation, feedback to the pharmacies
IUTA, IMSIE (BGW)
Phase 7:
Develop handling instructions
BGW, IUTA
Phase 8:
Final report, closing event, publications (to 7/08)
BGW, IUTA, IMSIE,
IfAP
Fig. 5: Project work plan and time schedule
5-Fluorouracil
Cyclophosphamide
Etoposide
Cisplatin
Gemcitabine
Carboplatin
Cytarabine
Irinotecan
Oxaliplatin
Doxorubicin
Epirubicin
Docetaxel
Paclitaxel
Vinorelbine
Vincristine
Methotrexate
Trastuzumab
Ifosfamide
Fludarabine
Rituximab
0
20.000
40.000
60.000
80.000
100.000
120.000
140.000
160.000
180.000
Fig. 6: Number of preparations by substance per 100 pharmacies in 2005
Percentage
40
Results:
Sixteen percent, i.e. 1,699 readings, are positive.
In 61% of the 1,272 wipe samples, at least one of
the eight substances was established. In conformity
with the stated consumption quantities, 5-Fluorouracil, Cyclophosphamide und Gemcitabine were
found more frequently and in higher concentrations
than the other analysed cytostatics. The floors in
front of the workbench were the most contaminated
position, followed by the work surfaces and the
35
30
25
20
15
10
5
0
5-FU
Gem
MTX
CP
IF
Eto
Fig. 7: Percentage of positive wipe samples by substance
Doc
Pac
200.000
3
BGW • Pappelallee 35/37 • 22089 Hamburg • www.bgw-online.de
refrigerator doors. The measured concentrations
were similar to those found in other studies and
ranged from below the limit of quantification (LOQ)
through to a peak value of 1,888 ng/cm2 for Gemcitabine. It is notable, that the 9 highest values were
found in two pharmacies only (Fig. 8).
No correlation between the number of cytostatic
preparations, the amount of substances handled,
the day of the last cleaning and the substance load
on the surface concerned could be found (for instance Fig. 9). Neither was it possible to verify a
correlation with most of the other data describing
the work practices. There are no notable differences
between hospital pharmacies and dispensaries
(Fig. 10). The readings can be used to identify exemplary pharmacies. An explorative significant correlation between the degree of disinfection, type of
disinfection and substance load was established.
The type of ventilation (circulating air/outgoing air)
tends to have an influence, although this cannot be
statistically verified. The 90th percentile of the substance loads dropped during the course of the study
in group A (Fig. 11).
Phamacy
Position
Cycle of Wiping
Type of Pharmacy
Study group
Substance
Substance load
(ng/cm2)
1
„A“
Fridge
1
Hospital pharmacy
A
Gemcitabine
1,888
2
„A“
Work top
4
Hospital pharmacy
A
Gemcitabine
190
3
„A“
Fridge
2
Hospital pharmacy
A
Gemcitabine
109
4
„B“
Floor
2
Hospital pharmacy
A
Gemcitabine
105
5
„B“
Floor
3
Hospital pharmacy
A
Ifosphamide
89
6
„B“
Work top
1
Hospital pharmacy
A
Methotrexate
35
7
„B“
Work top
1
Hospital pharmacy
A
Ifosphamide
31
8
„B“
Floor
1
Hospital pharmacy
A
Ifosphamide
26
9
„B“
Work top
1
Hospital pharmacy
A
5-Fluorouracil
24
10
„C“
Work top
1
Dispensary
B
5-Fluorouracil
18
11
„D“
Fridge
5
Hospital pharmacy
B
Cyclophosphamide
17
12
„E“
Work top
2
Hospital pharmacy
A
Ifosphamide
17
13
„F“
Fridge
4
Dispensary
A
5-Fluorouracil
14
14
„G“
Work top
1
Hospital pharmacy
B
5-Fluorouracil
13
15
„H“
Work top
3
Dispensary
A
5-Fluorouracil
11
16
„I“
Work top
5
Dispensary
A
5-Fluorouracil
11
Fig. 8: Top values by substance load
Substance load (ng/cm2)
20
one pharmacy excluded
(substance load = 0.52873 ng/cm2,
preparation = 19700)
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
0.005
0.002
0
0
500
1000
Wipe samples are a proper method for a standardised ambient monitoring on workplace contamination with antineoplastic drugs. Values below 0.1
ng/cm2 are achievable and can be discussed as
“prior art”.
2000
2500
4000
4500
5000
5500
Substance load (ng/cm2)
Percentage
1
2
3
4
5
6
7
8
45
1
40
35
4
0.020
5-Flourouracil
Gemcitabine
Methotrexate
Cyclophosphamide
Ifosphamide
Etoposide
Docetaxel
Paclitaxel
Group A
Group B
0.015
4
2
2
30
5
1
25
0.010
20
15
0.005
5
10
6
3
5
7
8
6
7
8
0
Dispensaries
Contact: [email protected], +49 (0)221 377 25 07,
version 2008
3500
Fig. 9: Correlation between substance load and number of preparations for
5-FU during 2006 (group B)
3
The final MEWIP report will be available for download in German from autumn 2008 on the homepage of the BGW.
3000
Preparation 5-Fluorouracil
50
Conclusions:
1500
Hospital pharmacies
Fig. 10: Percentage of positive wipe
samples
0.000
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Cycle 5
Fig. 11: 90th Percentile over all substances
and surfaces
Berufsgenossenschaft
für Gesundheitsdienst
und Wohlfahrtspflege