AALLBBUURRTTYYLLAABB
Investigation into the Impact
Of Air Pressure Driven
Drug Dispensing Machines
On the Environment of
Pharmacy Workers
Results in Two U.S. Pharmacies
Personal Exposure Monitoring
- McKesson/Parata RDS
- McKesson/Parata Max
July 27, 2009
RELIABLE AEROSOL SCIENCE AND ENGINEERING
INVESTIGATION INTO THE IMPACT OF AIR PRESSURE DRIVEN DRUG DISPENSING
MACHINES ON THE ENVIRONMENT OF PHARMACY WORKERS: MCKESSON/PARATA
MAX AND MCKESSON/PARATA RDS, PERSONAL EXPOSURE MONITORING
Executive Summary
This report is an extension of two previous studies of the potential negative impact of air pressure driven
drug dispensing machines on the environment of pharmacy workers. This study extension addresses the
exposure of personnel to aerosolized pharmaceutical compounds while working in the vicinity of a
McKesson/Parata Max and a McKesson/Parata RDS robotic dispensing system using a direct sampling
method.
The original study (“Investigation into the Impact of Air Pressure Driven Drug Dispensing Machines on
the Environment of Pharmacy Workers, Results in 15 U.S. Pharmacies” published October 15, 2008,
www.alburtylab.com) included detailed observation, study, and analysis of the McKesson/Parata
Robotic Dispensing System (RDS), the ScriptPro Robotic Prescription Dispensing System (SP 200), and
the manual counting method, in fifteen pharmacies. The McKesson/Parata RDS is an air pressure driven
dispensing machine, while the ScriptPro SP 200 uses a gravity driven process. Manual counting is
performed using counting trays and spatulas. The original study determined that the McKesson/Parata
RDS was a substantial source of respirable particles, raising concerns of potential exposure of thousands
of pharmacy workers. The study further concluded that manual counting was a source of very limited
particle emissions and that the SP 200 did not cause any particle emissions.
The core objective of the first extension of the original study (“Investigation into the Impact of Air
Pressure Driven Drug Dispensing Machines on the Environment of Pharmacy Workers, Results in Two
U.S. Pharmacies, McKesson/Parata Max” published January 6, 2009, www.alburtylab.com), was to
evaluate the McKesson/Parata Max to see if it, like the McKesson/Parata RDS, is a source of significant
respirable particle emissions. Highly elevated aerosol concentrations of PM-2.5 particles were observed
in the vicinity of the operating McKesson/Parata Max machines.
The results of the initial studies, which were peer reviewed by Dennis D. Lane, PhD, N.T. Veatch
Distinguished Professor of Environmental Engineering, University of Kansas, and by Ralph Keller,
PhD, CIH, PE, suggested that there should be a further evaluation of the exposure of personnel working
in the vicinity of the McKesson/Parata Max and the McKesson/Parata RDS machines. This was
accomplished using a direct sampling method. Personal exposure monitoring (PEM) devices were worn
by four individuals working in the pharmacy area during one work shift. Analysis of the samples
showed that all personnel were exposed to airborne respirable particles containing active drug agents
dispensed by the machines.
As in the original studies, this investigation focused on airborne particles less than 2.5 microns in
diameter (PM-2.5). These particles penetrate the lungs deeply and rapidly enter the bloodstream.
PM-2.5 particles are believed to cause a number of health problems, including increased heart rate
variability and myocardial infarction (heart attacks). Table 1 summarizes the results.
According to Dr. Lane's peer review of the original studies, "It is clear that pill dispensing methods have
the potential to drastically increase the risk of exposure by pharmacists to potentially unhealthy
pharmaceuticals through respiration." Data from the PEM devices employed in the current study
provide strong evidence that personnel working in the area of the McKesson/Parata Max and
McKesson/Parata RDS machines are exposed to airborne drug agents.
1
Table 1. Compounds Identified Using Personal Exposure Monitoring Devices in
Pharmacies using McKesson/Parata Dispensing Machines
Compounds
Acetaminophen
Diclofenac
Amitriptyline
Hydrochlorothiazide
Amoxicillin
Metformin
Atenolol
Paroxetine
Carisoprodol
Prednisone
Citalopram
Sulfamethoxazole
Clonidine
Tamsulosin
Cyclobenzaprine
Warfarin
Recommendation
This study once again points out the need for federal review of serious issues relative to exposure risks
for workers in pharmacies using air pressure driven dispensing machines. Specifically, further studies
should be conducted by federal regulatory agencies to assess risk, set guidelines for these types of
machines, and establish procedures to monitor the health impact on pharmacy workers.
Mr. David S. Alburty and Mrs. Pam Murowchick of AlburtyLab, Inc. were the principal investigators
and authors of this report.
Approved for:
ALBURTYLAB, INC.
David S. Alburty
President
July 27, 2009
About AlburtyLab, Inc.
AlburtyLab is an independent laboratory located in Drexel, Missour,i that serves the aerosol research, development, and
instrumentation communities. AlburtyLab has conducted independent studies for a range of agencies and companies,
including Boeing/US Navy, Boston Scientific, Northrop Grumman, US Postal Service, US Department of Homeland Security,
and the US Army Research Laboratory.
Technical questions may be directed to Mr. Alburty at (816) 619-3374 or via email to [email protected].
This study was funded by one of the technologies reviewed in the original study, ScriptPro LLC of Mission, Kansas.
2
Table of Contents
________________________________________________________________________
Executive Summary ....................................................................................................................1 1. Introduction.............................................................................................................................4 1.1 Sampling Setup and Procedures ................................................................................4 1.2 Public Health Concerns Regarding Aerosol Particle Emissions ...............................5 1.3 Methods of Filling Prescriptions in Pharmacies........................................................5 1.4 Robotic Dispensing Machines Observed ..................................................................6 1.5 Background and Health Implications of Respirable Active Drug Particles in
Pharmacies.................................................................................................................7 1.6 PM-10 Number Concentration Observations in Pharmacies using
Parata Dispensing Machines .....................................................................................9 1.7 PM-2.5 Number Concentration Observations in Pharmacies using
Parata Dispensing Machines ...................................................................................10 1.8 PM-10 Mass Concentration Observations in Pharmacies using
Parata Dispensing Machines ...................................................................................11 1.9 PM-2.5 Mass Concentration Observations in Pharmacies using
Parata Dispensing Machines ...................................................................................12 2. Phase IV Pharmacy R 24-Hour Sampling, Parata RDS........................................................14 2.1 Personal Exposure Monitoring (PEM) Filters.........................................................15 2.2 APS Monitoring ......................................................................................................17 2.3 Comparison of PM-2.5 Levels ................................................................................31 3. Phase IV Pharmacy S 24-Hour Sampling, Parata Max.........................................................32 3.1 Personal Exposure Monitoring (PEM) Filters.........................................................33 3.2 Reference Filters......................................................................................................34 3.3 APS Monitoring ......................................................................................................35 3.4 Comparison of PM-2.5 Levels ................................................................................48 4. Quantitation Results for Acetaminophen..............................................................................49 5. Summary of Phase I through Phase IV Data ........................................................................50 5.1 Phase I—Survey of Dispensing Methods................................................................51 5.2 Phase II—24-Hour Sampling ..................................................................................51 5.3 Phase III—24-Hour Sampling at Pharmacies Using Parata Max Dispensing
Machines .................................................................................................................52 5.4 Phase IV—Personal Exposure Monitoring in Pharmacies Using
McKesson/Parata RDS and Max Dispensing Machines .........................................53 6. Conclusions...........................................................................................................................55 7. References.............................................................................................................................56 3
1.
Introduction
________________________________________________________________________
1.1
Sampling Setup and Procedures
This study focuses on the measurement of small diameter particle emissions from air pressure
driven dispensing machines in retail pharmacies. All people working in and visiting
pharmacies would potentially have an increase risk of exposure to this airborne,
(“aerosolized”) pill dust. However the pharmacy staff would have a much higher potential
exposure than customers due to their proximity to the emission source over an extended time
period.
Minor amounts of pill dust can often be observed on the surfaces in pharmacies. It is produced
in drug stock bottles by agitation during transport. It can also be generated by the handling of
pills, especially tablets and broken capsules, during the counting and manual filling process in
pharmacies.
In recent years, various robotic dispensing machines have been put into use to dispense
prescriptions in pharmacies. Some of these machines use compressed air in the dispensing
process. Pill dust can be readily observed on or about some of these machines and is likely
also to be in the air. General airborne particulate emissions warrant special attention. When
particulate emissions involve airborne drug agents, the need for special attention is at an even
greater level. No safe ambient exposure limits have been established to provide guidance for
limiting drug containing particle emissions from these machines.
Monitoring methods used in exposure assessment can be categorized into direct and indirect
approaches. Testing in earlier phases of this work employed indirect methods, since the goal
was to determine if the dispensing methods qualified as emissions sources. In the indirect
approach to exposure monitoring, factors that affect exposure are measured rather that
exposure itself. For example, fixed-site monitors are widely used to measure the
concentrations of pollutants in air. (Covello, 1993) For this study, ambient particulate
concentrations were measured using an Aerodynamic Particle Sizer® spectrometer (APS 3321,
TSI, St. Paul, MN).
While concentrations are produced by emissions from sources, exposures only occur if an
individual is close enough for a sufficiently extended period to result in a significant exposure
level. Fixed-location monitors do not incorporate the element of proximity, nor do they
account for the period of time that the person is actually nearby. Since proximity changes as a
person moves, personal exposure assessment provides the most complete and integrated picture
of exposure. (Ruzer, 2004)
In the direct approach, individual exposures are measured directly by instruments that
accompany the individual, such as personal exposure monitors (PEMs). (Wallace, 1982)
PEMs are small, self-contained, battery powered sampling systems that can be carried by an
individual to mimic the proximity of the breathing zone to local sources or spatial
concentration gradients. These relatively unobtrusive samplers are used to assess the timeintegrated exposure of an individual to aerosols, which hopefully minimal influence on normal
activity patterns. (Baron, 2001) The PEMs employed during this study have inlets with a
specific cut point, i.e. 2.5 µm. These PEMs have been developed for indoor sampling and use
4
impaction on oil-soaked or greased, sintered metal surfaces to remove particles with
aerodynamic diameters greater than 2.5 µm. (Marple, 1983)
1.2
Public Health Concerns Regarding Aerosol Particle Emissions
The United States Environmental Protection Agency (USEPA) and other governmental
agencies around the world have regulated airborne particulate emissions for many years.
Regulations were initially based on studies of industrial emissions including events such as the
infamous Donora, PA, disaster of October 1948, during and immediately after which 70 people
died due to respiratory or cardiac arrest.(Davis, 2002) Concerns were elevated by the London
fog of December 1952, which caused thousands of deaths. In the U.S., regulatory efforts led to
the Clean Air Acts of 1955, 1963, 1970, and 1990.
There have been many other health-related aerosol studies, including studies on air pollution,
cardiovascular disease, and indoor environmental quality (IEQ studies). (Brook, 2004) Four
IEQ studies dealing with pharmacies that were performed by the National Institute of
Occupational Safety and Health (NIOSH), a part of the U.S. Centers for Disease Control and
Prevention (CDC), were reviewed during the background research for this project. None of
these studies involved aerosols from pharmaceutical drug dispensing robots. Eleven NIOSH
studies related to pharmaceutical production were reviewed, seven of which were quite
relevant. These included investigations of aerosolized penicillin during production, (Hanke)
aerosolized Pentamidine (Pentam), (Deitchman) (Seitz), exposure to Ribavarin causing
spontaneous abortion in nurses, (Lenhart, 1990) (Lenhart, 1993) (Decker, 1998) and exposure
to Chlorthalidone during production (combined with Atenolol as Tenoretic). (Wantanabe,
1981) In these cases, NIOSH found evidence of unacceptable exposure and recommended the
implementation of engineering controls and personal protective equipment to reduce or prevent
exposure.
1.3
Methods of Filling Prescriptions in Pharmacies
Approximately 80% of the prescriptions filled by U.S. community pharmacies are dispensed as
loose tablets or capsules. The pills are supplied by drug manufacturers in stock bottles and
transferred by the pharmacy into smaller bottles (prescription vials) to be labeled and
dispensed to patients as required by the physician’s prescription order. In pharmacies without
prescription dispensing robots, the pills are counted out manually into a slot on a filling tray
using a spatula, and then poured from the tray into the vial. Any excess pills are poured back
into the stock bottle. The vials are then labeled by the pharmacist or pharmacy technician in
accordance with the prescription order. In pharmacies using robotic dispensing machines,
these functions are performed by the robot, which dispenses pills from large storage cells or
bins into a vial and prints and applies the label. Robotic dispensing machines fill vials in
various ways depending on the design of the particular machine used. At all pharmacies, the
prescription is checked by a pharmacist and then given to the patient.
The amount of pill dust produced by operation of a robotic dispensing machine is dependent on
the drugs dispensed and the methods used by the machine to handle and dispense them.
5
1.4
Robotic Dispensing Machines Observed
In a previous study titled “Investigation into the Impact of Air Pressure Driven Drug
Dispensing Machines on the Environment of Pharmacy Workers, Results in 15 U.S.
Pharmacies,” published January 6, 2009, www.alburtylab.com, and “Investigation into the
Impact of Air Pressure Driven Drug Dispensing Machines on the Environment of Pharmacy
Workers, Parata-Max” published December 31, 2008, www.alburtylab.com, it was determined
that certain air-pressure driven dispensing machines (Parata RDS) are significant sources of
respirable particles. These studies led to further concern regarding the use of air pressure in
robotic dispensing systems, and the exposure of personnel to aerosolized pharmaceutical
compounds while working in the vicinity of a McKesson/Parata RDS and a McKesson/Parata
Max.
An aerosol source attribution study employing a direct sampling method was therefore
performed at two community pharmacies, the first uses the recently released McKesson/Parata
Max (subsequently referred to as the Parata Max) and the second uses the McKesson/Parata
RDS Robotic Dispensing System (subsequently referred to as Parata RDS). 1 Four PEM
samples were collected at each of the two pharmacies and the resulting filter samples were
analyzed for pharmaceutical compounds. In the first study, we observed the Parata RDS, and
the ScriptPro SP 200 Robotic Prescription Dispensing System, (subsequently referred to as the
ScriptPro SP 200) 2 in operation in a total of five retail pharmacies for each. These are now the
most commonly used machines in pharmacies with robotic dispensing. (“Is There a Robot in
Your Future?”, 2004) (“Technology Update,” 2005) The manufacturers of these machines
claim to have thousands of units installed in U.S. pharmacies. We also observed pharmacies
that dispense manually (i.e., do not use robots). These four methods of dispensing (Parata
Max, Parata RDS, ScriptPro SP 200, and manual) are now estimated to cover about 97% of all
retail pharmacies currently operating in the United States.
In the Parata RDS system, a low pressure source (negative pressure) is used to agitate the pills
inside the dispensing cell. While the pills are being agitated, compressed air jets are used to
force the pills through an outlet nozzle and into the vial. The high-pressure jets operate in
alternating directions to clear the outlet nozzle. The pills are counted by optical sensors as they
pass through the nozzle. (Williams, 2006) The system then delivers the filled and labeled vials
to a pickup area for the pharmacist’s verification prior to being given to the patient. The Parata
Max operates similarly, but it is not equipped with a vacuum source and only uses positive
pressure to agitate the pills within the dispensing cell and to direct the tablets into the
dispensing channel and into the prescription vial.
The ScriptPro SP 200 singulates the pills (tablets or capsules) using gravity and a rotating
platen inside each dispensing cell. The platen moves the pills to an outlet funnel where they
drop into the vial and are counted via an optical sensor. (Coughlin, 1999)
To date four phases of this study have been conducted. The following paragraphs briefly
summarize the logical progression of this work.
1
The Parata RDS and Parata Max are manufactured by Parata Systems, LLC, 2600 Meridian Parkway, Durham,
NC 27713, and marketed both directly and by the McKesson Corporation, or through their subsidiaries. Parata
RDS, Parata Max, and McKesson are trademarks or registered trademarks of Parata Systems, LLC and/or
McKesson Corporation in the U.S. and other countries.
2
The ScriptPro SP 200 is manufactured by ScriptPro LLC, 5828 Reeds Road, Mission, KS 66202, and marketed
by the company or through its subsidiaries. ScriptPro and SP 200 are trademarks or registered trademarks of
ScriptPro LLC in the U.S. and other countries.
6
The first published study was conducted in two Phases. In Phase I, a screening of the robotic
dispensing machines was performed to determine if there were observable emissions of pill
dust during the dispensing operation. In addition, a standard procedure for observing and
measuring any such emissions in pharmacies was established. One of each machine type was
observed in operation in a retail pharmacy. The Parata RDS, which uses compressed air in the
dispensing process, clearly exhibited emissions of pill dust correlated with drug dispensing.
The ScriptPro SP 200, which does not use compressed air in the dispensing process, did not
exhibit any observable emissions of pill dust correlated with drug dispensing.
In Phase II, using the established procedure, the same machines and manual counting processes
in operation in the same retail pharmacies were observed. The Parata RDS again clearly
exhibited emissions of pill dust correlated with drug dispensing. The ScriptPro SP 200 again
did not exhibit any observable emissions of pill dust correlated with drug dispensing, and
manual counting produced some minor emissions of pill dust.
In order to confirm these observations regarding the Parata RDS, Phase II observations were
expanded to four additional pharmacies using this machine, for a total of five pharmacies using
McKesson/Parata RDS dispensing machines. Each of the Parata RDS machines observed
clearly exhibited emissions of pill dust correlated with drug dispensing. Also, dust samples
collected from air filters placed at Parata RDS sites were analyzed using high-performance
liquid chromatography/diode array detection/mass spectroscopy (HPLC/DAD/MS) and were
determined to contain many peaks of interest, some of which were determined to be active
pharmaceutical compounds.
As reference points (experimental controls), in both Phases I and II, observations in
pharmacies not using a robot in the dispensing process were made. Observations were made in
a total of five such pharmacies dispensing manually. The observed pill dust emissions
correlated with the manual counting of certain drugs in the non-robotic pharmacies. The levels
observed were significantly lower than the emissions observed in the pharmacies using the
Parata RDS dispensing machines. As further reference points (experimental controls) in both
Phases I and II, observations in pharmacies using a robot that does not employ compressed air
in the dispensing process (ScriptPro SP 200) were made. Observations were made in five
pharmacies using ScriptPro SP 200 dispensing machines. It was observed that minor amounts
of pill dust emissions correlated with manual counting of certain drugs in these pharmacies.
Emissions of pill dust related to operation of the ScriptPro SP 200 were not observed.
In Phase III, the latest generation Parata Max robotic dispensing system which, like the RDS,
uses air pressure to dispense pills was observed. Substantial modifications to the Parata RDS
design have been implemented in the Parata Max. Notably, the HEPA filter used by the RDS
to remove some of the pill dust from the vacuum pressure side of the dispensing manifold has
been eliminated. Positive pressure only is used to dispense pills in the Parata Max.
The PEM conducted during this phase of testing was performed in two pharmacies, one
equipped with a Parata RDS and one equipped with a Parata Max.
1.5
Background and Health Implications of Respirable Active Drug Particles in Pharmacies
Respirable particles are generally considered to be those with aerodynamic diameter (AD) less
than 10 microns. In the past several years, recognition has grown that particulate matter of less
7
than 2.5 microns AD (PM-2.5 particles) is of special concern. This is because the small size of
PM-2.5 particles allows them to penetrate to the deepest parts of the lungs and to be quickly
absorbed into the bloodstream. (Lazaroff, 2007) Ambient PM-10 (particles less than 10
microns AD) is now regulated in the U.S. under the Clean Air Act National Ambient Air
Quality Standards (NAAQS) at a 24-hr average of less than 150 μg/m3. Ambient PM-2.5 is
regulated under the Clean Air Act NAAQS at 15 μg/m3 annual average and 35 μg/m3 24-hr
average concentration. (USEPA, 2007) Ambient PM-2.5 as considered under the Clean Air
Act is primarily made up of biologically inactive compounds, although bioaerosols and many
allergens can be and often are present. The composition of ambient PM-2.5 varies widely
based on season, location, and local sources of particles.
The presence in pharmacies of PM-2.5 particles arising from the dispensing of active drug
compounds adds another dimension of concern. First of all, our research indicates that there is
no defined safe level for these types of particles. Secondly, the active ingredients of most
drugs dispensed in pharmacies are designed for ingestion; the inhalation of the active
ingredients may have health impacts more severe than expected or unpredicted at this time.
Increases in urban PM-2.5 concentrations have been shown to cause adverse health effects,
including myocardial infarction (MI, or “heart attack”) and decreased heart rate variability
(HRV). (Gold, 2000) (Peters, 2001) (Chahine, 2007)
A study of six U.S. cities and another study of 20 U.S. cities indicated an association between
particulate air pollution and mortality, and showed that there was an increase in the relative
rates of deaths from cardiovascular and respiratory causes of 0.68% for each increase in the
average daily PM-10 level of 10 μg/m3. (Dockery, 1993) (Samet, 2000) These studies
corroborate the findings of other smaller studies which had determined increases in the relative
rates of death associated with increases in the average daily PM-10 level. (Maitre, 2006)
(Thurston, 1999) (Touloumi, 1997) Dr. Samet, author of the 20-city study, concluded that
“PM-10 levels are an imperfect surrogate for PM-2.5,” and also pointed out that his study “did
not address the extent to which life is shortened in association [with particulate matter and
other pollutants].”
Recent studies have determined that exposure to PM-2.5 aerosols is associated with adverse
cardiovascular events of several types. (Mills, 2007) (Mutlu, 2007) These studies looked into
the mechanisms behind the adverse events and determined that inflammation in the lungs
caused by breathing PM-2.5 aerosols increases the secretion of interleukin-6, which has been
shown to increase clotting.
The above studies have been primarily concerned with outside air. Particle mass
concentrations in pharmacies using McKesson/Parata dispensing machines frequently
exceeded NAAQS. While USEPA has not established general indoor air quality standards,
studies performed by Professor William W. Nazaroff of U.C. Berkeley and others indicated
that the likelihood of inhaling particles generated from an indoor source while working indoors
is increased by a factor of 100 to 1,000 as compared with inhalation of particles while
outdoors. For example, the quantity of PM-2.5 inhaled by exposed humans from a gram of
such particles released indoors is likely to be 100 to 1,000 times as large as what would be
inhaled from a gram of particles released outdoors. These studies indicate that pharmacy
personnel working in close proximity to machines generating airborne particles may be subject
to an increased risk of health effects as compared with NAAQS. The NAAQS regulate general
particulate matter and do not establish safe limits for exposure to airborne drug agents. (Lai,
2000) (Nazaroff, 2008) (Marshall, 2006) (Nazaroff, 2007) (Marshall J., 2005)
8
Because typical heating, ventilation, and air conditioning (HVAC) systems use loose-weave air
filters that are approximately 40% efficient for removal of particles with an AD of 0.2 microns,
very fine pill dust can be recirculated throughout the pharmacy, potentially impacting
personnel outside the dispensing area. All people working in and visiting pharmacies would
potentially be exposed to any aerosolized pill dust present there. However the pharmacy staff
would have a much higher potential exposure than customers due to their proximity to the
emission source over an extended time period.
1.6
PM-10 Number Concentration Observations in Pharmacies using Parata Dispensing
Machines
The following graphs are presented to provide direct comparisons to those presented in the
reports for the earlier testing phases. The results of particulate sampling using the APS are
shown below for the pharmacies using Parata dispensing machines. The PM-10 number data
for the entire sampling period at each pharmacy are shown in Figures 1-1 and 1-2.
1,000,000
100,000
10,000
1,000
100
10
1
6:00
7:00
8:00
9:00
10:00
11:00
12:00
13:00
14:00
15:00
16:00
17:00
18:00
19:00
20:00
21:00
22:00
23:00
0:00
1:00
2:00
3:00
4:00
5:00
6:00
7:00
8:00
9:00
10:00
Count Concentration (particles/L)
10,000,000
Time (hr:min)
Figure 1-1. Phase IV - Pharmacy R - PM-10 Count Concentration
Over Entire APS Sampling Time (Parata RDS)
9
Count Concentration (particles/L)
10,000,000
1,000,000
100,000
10,000
1,000
100
10
9:00
10:00
8:00
7:00
6:00
5:00
4:00
3:00
2:00
1:00
0:00
23:00
22:00
21:00
20:00
19:00
18:00
17:00
16:00
15:00
14:00
13:00
12:00
11:00
9:00
10:00
8:00
1
Time (hr:min)
Figure 1-2. Phase IV - Pharmacy S - PM-10 Count Concentration
Over Entire APS Sampling Time (Parata Max)
1.7
PM-2.5 Number Concentration Observations in Pharmacies using Parata Dispensing
Machines
The PM-2.5 number data for the entire sampling period at each pharmacy are shown in Figures
1-3 and 1-4.
10,000,000
100,000
10,000
1,000
100
10
1
6:00
7:00
8:00
9:00
10:00
11:00
12:00
13:00
14:00
15:00
16:00
17:00
18:00
19:00
20:00
21:00
22:00
23:00
0:00
1:00
2:00
3:00
4:00
5:00
6:00
7:00
8:00
9:00
10:00
Count Concentration (particles/L)
1,000,000
Time (hr:min)
Figure 1-3. Phase IV - Pharmacy R - PM-2.5 Count Concentration
Over Entire APS Sampling Time (Parata RDS)
10
10,000,000
Count Concentration (particles/L)
1,000,000
100,000
10,000
1,000
100
10
9:00
10:00
7:00
8:00
6:00
5:00
4:00
3:00
2:00
1:00
23:00
0:00
22:00
21:00
20:00
19:00
18:00
17:00
16:00
14:00
15:00
13:00
12:00
11:00
10:00
9:00
8:00
1
Time (hr:min)
Figure 1-4. Phase IV - Pharmacy S - PM-2.5 Count Concentration
Over Entire APS Sampling Time (Parata Max)
1.8
PM-10 Mass Concentration Observations in Pharmacies using Parata Dispensing
Machines
The mass concentration was calculated from the number concentration as measured using the
APS by estimating a unit density for all particles. The PM-10 mass concentrations measured
during the daytime operating hours at each pharmacy are shown in Figures 1-5 and 1-6.
10000
100
10
1
0.1
20:00
19:00
18:00
17:00
16:00
15:00
14:00
13:00
12:00
11:00
10:00
9:00
8:00
0.01
7:00
Mass Concentration (µg/m3)
1000
Time (hr:min)
Figure 1-5. Phase IV - Pharmacy R - PM-10 Mass Concentration
During Operating Hours (Parata RDS)
11
10000
Mass Concentration (µg/m3)
1000
100
10
1
0.1
20:00
19:00
18:00
17:00
16:00
15:00
14:00
13:00
12:00
11:00
10:00
9:00
8:00
0.01
Time (hr:min)
Figure 1-6. Phase IV - Pharmacy S - PM-10 Mass Concentration
During Operating Hours (Parata Max)
1.9
PM-2.5 Mass Concentration Observations in Pharmacies using Parata Dispensing
Machines
The mass concentration was calculated from the number concentration as measured using the
APS by estimating a unit density for all particles. The mass concentration was calculated from
the number concentration as measured using the APS by estimating a unit density for all
particles. The PM-2.5 mass concentrations measured during the daytime operating hours at
each pharmacy are shown in Figures 1-7 and 1-8.
12
10000
Mass Concentration (µg/m3)
1000
100
10
1
0.1
20:00
19:00
18:00
17:00
16:00
15:00
14:00
13:00
12:00
11:00
10:00
9:00
8:00
7:00
0.01
Time (hr:min)
Figure 1-7. Phase IV - Pharmacy R - PM-2.5 Mass Concentration
During Operating Hours (Parata RDS)
10000
100
10
1
0.1
20:00
19:00
18:00
17:00
16:00
15:00
14:00
13:00
12:00
11:00
10:00
9:00
0.01
8:00
Mass Concentration (µg/m3)
1000
Time (hr:min)
Figure 1-8. Phase IV - Pharmacy S - PM-2.5 Mass Concentration
During Operating Hours (Parata Max)
13
2.
Phase IV Pharmacy R 24-Hour Sampling, Parata RDS
________________________________________________________________________
Pharmacy R uses a Parata RDS Robotic Dispensing System to fill approximately 100 to 500
prescriptions daily. This pharmacy was designated as Pharmacy A during Phase I and II of this
study. On the day that Phase IV testing was conducted, ninety-nine (99) prescriptions were
filled using the Parata RDS; 81 for tablets and 18 for capsules. Overall, 3,195 tablets and 765
capsules were dispensed during the sampling period, which covered one day. The number of
prescriptions filled on the day that testing was conducted (a Monday) was lower than usual.
This was because the pharmacist had come in the previous day (Sunday) and filled many
prescriptions in an effort to smooth workflow.
The layout of the pharmacy in the immediate vicinity of the Parata RDS is shown below. The
Parata RDS is located in the storage rack area in the rear of the pharmacy with the front of the
machine near a counter that is used to fill and transfer prescriptions to a front counter for
customer pickup. Pharmacy operations were generally the same as those described for
Pharmacy A during Phase I screening (See previous report, Section 3). For Phase IV, the
instrumentation was set up on the morning of Monday, February 2, and operated until the
morning of Tuesday, February 3. Three to six pharmacists and technicians worked in the area
around the machine at any one time during the workday during which 24-hr sampling was
performed. At this location, the weather on both days of testing was clear and cool, with light
winds from the northeast. It had rained overnight prior to the start of testing.
Pharmacy R Layout
14
2.1
Personal Exposure Monitoring (PEM) Filters
During one work shift, three Pharmacy R personnel working in the pharmacy area and one
AlburtyLab observer, who was recording manual counting and monitoring Parata RDS
operation near the machine’s prescription output chutes, were recruited to don PEMs. Each
subject wore a personal sampling pump (Leland Legacy, SKC Inc. Houston, TX) running at
10 Lpm with a Personal Environmental Monitoring impactor with a cut-point of 2.5 µm
located in the breathing zone, as shown in Photo 2-1. The PM-2.5 samples were collected on
37-mm Teflon filters (P/N 225-1709, SKC Inc., Houston, TX). The primary location of each
of these personnel within the pharmacy is indicated in the Pharmacy R layout with the letters
A, B, C, and D.
(a)
(b)
Photo 2-1. Sampling pump and PEM components (a) and as worn during testing (b)
The personal sampling pumps were identified with the labels A, B, C, and D, and the PEMs
were identified with the labels 1, 2, 3 and 4. In subsequent sections, the sampling systems will
be referred to as PEM-1A, PEM-2B, PEM-3C and PEM-4D. Prior to start of the aerosol
collection periods, the accumulated sampling time and sample volume were reset on each of
the personal sampling pumps. Due to the possibility of air flow loss through the PEM because
of kinks in the hose between the personal sampling pump and the PEM, the air sample volume
for each sampler was determined using the data logged by personal sampling pumps at the end
of the sampling period. PEM-1A was started at 8:20 a.m. and continued until 7:26 p.m., for a
total of 11 hr 6 min, resulting in a sampled air volume of 6.67 m3. PEM-2B was started at
8:26 a.m. and continued until 7:07 p.m. with sampling suspended from 1:13 p.m. to 2:09 p.m.
15
while the technician was at lunch, for a total of 9 hr 45 min, resulting in a sampled air volume
of 5.92 m3. PEM-3C was started at 8:28 a.m. and continued until 7:33 p.m., for a total of 11 hr
5 min, resulting in a sampled air volume of 6.64 m3. PEM-4D was started at 8:54 a.m. and
continued until 7:20 p.m. with sampling suspended from 12:02 p.m. to 1:43 p.m. while the
technician was at lunch, for a total of 8 hr 45 min, resulting in a sampled air volume of 3.40
m3. At 2:47 p.m. it was discovered that the PEM-4D personal sampling pump had stopped
sampling for an undetermined length of time due to a kink in the sampling hose connecting the
PEM to the personal sampling pump.
The PEM-3C sample was from the AlburtyLab employee who was not involved in any hand
counting of prescriptions and therefore serves as a control. All pharmacy personnel who were
wearing the other PEM sampling devices were involved in hand counting of prescriptions at
some time during the work day.
The four PEM filter samples and one blank filter were analyzed using high-performance liquid
chromatography combined with an ultraviolet diode array detection system (HPLC/DAD).
The results indicated several peaks in each sample except for the blank which were determined
to be pharmaceutical compounds.
The detection limit for the HPLC/DAD analysis method was estimated at 10 µg/filter, which
indicates that the average aerosol concentration for the peaks of interest exceeded the method
detection limit of approximately 1.5 μg/m3 for the PEM-1A sample, approximately 1.7 μg/m3
for the PEM-2B sample, approximately 1.5 μg/m3 for the PEM-3C sample, and approximately
2.9 μg/m3 for the PEM-4D sample. Confirmation analysis by mass spectroscopy is needed for
all peaks identified by HPLC/DAD. Additional compounds may have been collected on the
filters that were not apparent using HPLC/DAD alone.
The samples were analyzed further by mass spectrometric analysis (HPLC/DAD/MS). Several
analytes of interest were determined; these are summarized in Table 2-1. Also shown in this
table are the number of prescriptions filled during the PEM sampling period and the number of
Parata Max cells that contain the tentatively identified drug agent. There are numerous
instances where the drug identified was not dispensed during the PEM sampling period. This
could be attributed to emissions from manual counting or from recirculation of particulate drug
agents in the HVAC system previously dispensed manually or through the Parata device. The
column labeled “Corresponding PM-2.5 Responses” indicates the number of instances when
the PM-2.5 mass concentration, as measured by the APS, exceeded 20 µg/m3 within 2 minutes
of the Parata RDS dispensing a prescription.
In addition, standard solutions of acetaminophen were prepared at four levels and analyzed.
This allowed for the amount of acetaminophen present in each filter sample to be quantitated.
These results are presented in Section 4.
16
2.2
PEM-D
PEM-Ca
PEM-B
PEM-A
Table 2-1. Analytes of Interest Tentatively Identified in Pharmacy R PEM Filter Samples
Number of
Number of
Prescriptions
Tentative
Parata-RDS
Identifications
Filled
Corresponding
Cells
Reported by
Containing
PM-2.5
Containing
Inovatia
Drug
Responses
Drug
Acetaminophen
x
x
x
x
11
3
6
Acetylsalicylic
x
Acid
Amitriptyline
x
x
2
2
Amoxicillin
x
x
3
2
Atenolol
x
x
5
2
3
Carisoprodol
x
x
x
Citalopram
x
2
2
Clonidine
x
1
2
Colchicine
x
Desloratadine
x
Diclofenac
x
x
x
Enalapril
x
x
x
Hydromorphone
x
x
Meloxicam
x
Metformin
x
x
x
x
5
1
2
Methocarbamol
x
x
x
Niacin
x
Oxybutynin
x
x
x
Paroxetine
x
2
1
Penicillin
x
Phenobarbital
x
Phentermine
x
Prednisone
x
x
x
1
3
Propranolol
x
Sulfamethoxazole x
2
1
Warfarin
x
1
4
a
AlburtyLab employee.
APS Monitoring
As during the earlier Phases of this study, the APS was placed on top of the Parata RDS, so it
would be out of the pharmacist’s way. The APS samples were collected using a 118 cm length
of conductive silicone tubing to allow sampling at breathing height to be conducted.
The APS was used to measure particles present in the pharmacy at nose-height at the edge of
the dispensing area at the rear of the Parata RDS (see Photo 2-1). The sampling tube was
positioned on the left side of the machine for the entire sampling period.
17
Photo 2-1. APS Sampling Set-up for Phase IV 24-hr Sampling at Pharmacy R
(photo includes reference filter that was not employed at this pharmacy)
While observing the real-time particle size and concentration spectra during operation and
dispensing, a correlation appeared to be present between filling and delivery of prescriptions
and the emission of respirable particles from the machine. This correlation appears as
coincident peaks in PM-2.5 and PM-10 mass closely associated (within approximately 2 min)
with the dispensing of certain prescriptions.
Some unidentified peaks may be drug particles from manual counting or re-entrainment, and
some peaks could not be attributed to observed events. Also, note that the position of the
identifier text and notes with respect to peaks in the graphs seemed to vary slightly. This may
be partially dependent on airflow within the pharmacy, the position of the sampling tube with
respect to the dispensing cell in the robot, the number of pills dispensed, and the location to
which the prescription was delivered, as well as the ability of the observer to quickly notate
events in the log book.
The APS data were reduced using Microsoft Excel spreadsheets and matched with the Parata
RDS dispensing data and notes taken during sampling. The PM-2.5 data are also shown in
more detail in half hour increments in Figures 2-1 through 2-22 and 2-24. The PM-2.5
overnight mass concentration is shown in Figure 2-23. Please note carefully that the Y-axis is
adjusted somewhat from graph to graph based on the concentrations within the particular time
segment shown.
18
10
8
6
4
2
Time (hr:min)
Figure 2-2. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 9:00 to 9:30 AM - Parata RDS
19
9:04
9:02
9:00
8:58
8:56
8:54
8:52
8:50
8:48
8:46
8:44
8:42
8:40
8:38
8:36
8:34
8:32
8:30
Bisoprolol/HCTZ 5/6.25 mg
Started PEM 4 Pump D
Propo‐N/APAP 100/650 mg
Levothyroid 200 mcg
Levothyroid 25 mcg
12
Premarin 0.625 mg
Potassium Chloride 10 meq
Omeprazole 20 mg
Zolpidem 10 mg
Crestor 10 mg
Lisinopril 20 mg
Filling RDS cell L3
Furosemide 20 mg
Plavix 75 mg
Metformin 500 mg
Paroxetine 20 mg
Fexofenadine 180 mg
Levothyroxinee 50 mcg
Started PEM 3 Pump C
8:28
Started PEM 1 Pump A
Started PEM 2 Pump B
0
8:26
8:24
8:22
8:20
8:18
6
Metformin 1000 mg
Folic Acid 1 mg
8
8:16
8:14
2
Started APS
4
8:12
8:10
8:08
Mass Concentration (µg/m3)
10
Flomax 0.4 mg
Plavix 75 mg
Potassium Chloride 10 meq
Furosemide 20 mg
Plavix 75 mg
Aricept 10 mg
Cyclobenzaprine 10 mg
Lipitor 80 mg
Ranitidine 300 mg
Simvastatin 40 mg
Terazosin 10 mg
Bisoprolol/HCTZ 10/6.25 mg
Flomax 0.4 mg
12
8:58
8:59
9:00
9:01
9:02
9:03
9:04
9:05
9:06
9:07
9:08
9:09
9:10
9:11
9:12
9:13
9:14
9:15
9:16
9:17
9:18
9:19
9:20
9:21
9:22
9:23
9:24
9:25
9:26
9:27
9:28
9:29
9:30
9:31
9:32
Mass Concentration (µg/m3)
20
18
16
14
Time (hr:min)
Figure 2-1. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 8:12 to 9:00 AM - Parata RDS
20
18
16
14
0
8
6
4
14
12
Lisinopril 10 mg SMZ/TMP 800/160 mg
Canned air used to clean cell L3 sensor
Filled cell L3
HCTZ 12.5 mg
Singulair 10 mg
Furosemide 20 mg
Adjusting cell L3
150
Cephalexin 500 mg
Hand counting
50
Lisinopril 40 mg
Filling RDS w/ vials
100
Trazodone 50 mg
9:28
9:29
9:30
9:31
9:32
9:33
9:34
9:35
9:36
9:37
9:38
9:39
9:40
9:41
9:42
9:43
9:44
9:45
9:46
9:47
9:48
9:49
9:50
9:51
9:52
9:53
9:54
9:55
9:56
9:57
9:58
9:59
10:00
10:01
10:02
Mass Concentration (µg/m3)
200
Hydrocodone/APAP 5/500 mg
Amoxicillin 500 mg
Doxycycline 100 mg
Lipitor 40 mg
Lanoxin 0.125 mg
Zolpidem 10 mg
10
9:58
9:59
10:00
10:01
10:02
10:03
10:04
10:05
10:06
10:07
10:08
10:09
10:10
10:11
10:12
10:13
10:14
10:15
10:16
10:17
10:18
10:19
10:20
10:21
10:22
10:23
10:24
10:25
10:26
10:27
10:28
10:29
10:30
10:31
10:32
Mass Concentration (µg/m3)
250
0
Time (hr:min)
Figure 2-3. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 9:30 to 10:00 AM - Parata RDS
20
18
16
2
0
Time (hr:min)
Figure 2-4. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 10:00 to 10:30 AM - Parata RDS
20
10
8
6
4
2
12
14
Loading caps and vials in RDS
Prednisone 20 mg
Zolpidem 10 mg
Omeprazole 20 mg
Metformin 500 mg
Premarin 0.625 mg
Stopped APS Sampling
Premarin 0.625 mg
Tizanidine 4 mg
Alprazolam 1 mg
Hydrochlorothiazide 25 mg
Hand counting Cymbalta
Lexapro 10 mg
Drive up window open
Tramadol HCl 50 mg
Glipizide 5 mg
2
Ciprofloxacin HCl 500 mg
Lisinopril 10 mg
Plavix 75 mg
Metoprolol Tartate 50 mg
4
Celebrex 200 mg
Alprazolam 1 mg
Omeprazole 20 mg
12
Promethazine 25 mg
6
Metformin 1000 mg
Lipitor 20 mg
Zolpidem 10 mg
8
Restarted APS
Lorazepam 0.5 mg
10:28
10:29
10:30
10:31
10:32
10:33
10:34
10:35
10:36
10:37
10:38
10:39
10:40
10:41
10:42
10:43
10:44
10:45
10:46
10:47
10:48
10:49
10:50
10:51
10:52
10:53
10:54
10:55
10:56
10:57
10:58
10:59
11:00
11:01
11:02
Mass Concentration (µg/m3)
10
10:58
10:58
10:59
11:00
11:01
11:02
11:03
11:04
11:05
11:06
11:07
11:08
11:09
11:10
11:11
11:12
11:12
11:13
11:14
11:15
11:16
11:17
11:18
11:19
11:20
11:21
11:22
11:23
11:24
11:25
11:26
11:27
11:27
11:28
11:29
11:30
11:31
Mass Concentration (µg/m3)
20
18
16
14
0
Time (hr:min)
Figure 2-5. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 10:30 to 10:49 AM - Parata RDS
20
18
16
0
Time (hr:min)
Figure 2-6. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 11:15 to 11:30 PM - Parata RDS
21
8
6
4
2
6
4
2
Diovan HCT 160 /12.5
Lisinopril 10 mg
Benazepril HCl 10 mg
Dicyclomine 10 mg
Simvastatin 40 mg
Lanoxin 0.125 mg
Drive up window open
8
Drive up window open
11:28
11:29
11:30
11:31
11:32
11:33
11:34
11:35
11:36
11:37
11:38
11:39
11:40
11:41
11:42
11:43
11:44
11:45
11:46
11:47
11:48
11:49
11:50
11:51
11:52
11:53
11:54
11:55
11:56
11:57
11:58
11:59
12:00
12:01
12:02
Mass Concentration (µg/m3)
10
PEM 4D on break
Plavix 75 mg
Metoprolol 25 mg
10
11:58
11:59
12:00
12:01
12:02
12:03
12:04
12:05
12:06
12:07
12:08
12:09
12:10
12:11
12:12
12:13
12:14
12:15
12:16
12:17
12:18
12:19
12:20
12:21
12:22
12:23
12:24
12:25
12:26
12:27
12:28
12:29
12:30
12:31
Mass Concentration (µg/m3)
20
18
16
14
12
0
Time (hr:min)
Figure 2-7. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 11:30 AM to 12:00 PM - Parata RDS
20
18
16
14
12
0
Time (hr:min)
Figure 2-8. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 12:00 to 12:30 PM - Parata RDS
22
20
60
100
80
120
200
180
160
140
Hydrocodone APAP 5/500 mg
Lisinopril 40 mg
Diazepam 5 mg
Clonazepam 2 mg Canned air used to clean Q6 cell Singulair 10 mg
Canned air used to clean cell Lisinopril 2.5 mg
2
Drive up window open
Tramadol HCl 50 mg
Prednisone 20 mg
Cyclobenzaprine 10 mg
Drive up window open
Amoxicillin 500 mg
Singulair 10 mg
10
Levothyroxine Sod 50 mcg
HCTZ 50 mg
Prevacid 30 mg
Celebrex 200 mg
Glyburide 5 mg
4
Toprol XL 50 mg
6
Benazepril HCl 20 mg
Stopped PEM 2B Metformin 1000 mg
12:28
12:29
12:30
12:31
12:32
12:33
12:34
12:35
12:36
12:37
12:38
12:39
12:40
12:41
12:42
12:43
12:44
12:45
12:46
12:47
12:48
12:49
12:50
12:51
12:52
12:53
12:54
12:55
12:56
12:57
12:58
12:59
13:00
13:01
13:02
Mass Concentration (µg/m3)
8
Hydrochlorothiazide 25 mg
Atenolol 50 mg
Lisinopril 10 mg
Levothyroxinee 50 mcg
Hand counting
IBU 800 mg
40
12:58
12:59
13:00
13:01
13:02
13:03
13:04
13:05
13:06
13:07
13:08
13:09
13:10
13:11
13:12
13:13
13:14
13:15
13:16
13:17
13:18
13:19
13:20
13:21
13:22
13:23
13:24
13:25
13:26
13:27
13:28
13:29
13:30
13:31
13:32
Mass Concentration (µg/m3)
20
18
16
14
12
0
Time (hr:min)
Figure 2-9. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 12:30 to 1:00 PM - Parata RDS
0
Time (hr:min)
Figure 2-10. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 1:00 to 1:30 PM - Parata RDS
23
12
10
8
6
4
14
Hydrocodone/APAP 5/500 mg
Plavix 75 mg
Simvastatin 40 mg
Clonazepam 2 mg
Actos 30 mg
Hand counting
Verapamil 180 mg
6
Drive up window open
Alprazolam 0.5 mg
Benztropine mes 2 mg
Lorazepam 1 mg
Hydrocodone/APAP 7.5/750
Lorazepam 2 mg
Prevacid 30 mg
PEM 4D restarted
8
Fexofenadine 180 mg
Temazepam 30 mg
Loading vials in RDS
PEM 2B restarted
10
Clonazepam 2 mg
Amitriptyline 50 mg
12
Lisinopril 20 mg
14
Diovan HCT 160/12.5 mg
16
Zolpidem 10 mg
13:28
13:29
13:30
13:31
13:32
13:33
13:34
13:35
13:36
13:37
13:38
13:39
13:40
13:41
13:42
13:43
13:44
13:45
13:46
13:47
13:48
13:49
13:50
13:51
13:52
13:53
13:54
13:55
13:56
13:57
13:58
13:59
14:00
14:01
14:02
Mass Concentration (µg/m3)
18
13:57
13:58
13:59
14:00
14:01
14:02
14:03
14:04
14:05
14:06
14:07
14:08
14:09
14:10
14:11
14:12
14:13
14:14
14:15
14:16
14:17
14:18
14:19
14:20
14:21
14:22
14:23
14:24
14:25
14:26
14:27
14:28
14:29
14:30
14:31
Mass Concentration (µg/m3)
20
4
2
0
Time (hr:min)
Figure 2-11. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 1:30 to 2:00 PM - Parata RDS
20
18
16
2
0
Time (hr:min)
Figure 2-12. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 2:00 to 2:30 PM - Parata RDS
24
4
80
70
60
50
40
30
20
10
Warfarin Sodium 5 mg
6
Tramadol HCl 50 mg
Cyclobenzaprine 10 mg
Tramadol HCl 50 mg
14
Drive up window open
Trazodone HCL 100 mg
16
Crestor 10 mg
Simvastatin 40 mg
Zolpidem 10 mg
Prevacid 30 mg
Methadone 10 mg
Flomax 0.4 mg
Noticed PEM 4D hose was pinched
RDS cycling on and off w/o dispensing
18
Furosemide 80 mg
Lexapro 10 mg
Naproxen 500 mg
Canned air used to clean K5 or K6 cell Lexapro 10 mg
Alprazolam 2 mg
Hydrocodone/APAP 5/500 mg
Hydrocodone/APAP 7.5/750 mg
Crestor 10 mg
Atenolol 50 mg
Hydrocodone/APAP 5/500 mg
8
Fexofenadine 180 mg
Drive up window open
Furosemide 40 mg
10
Atenolol 25 mg
Avapro 150 mg
14:28
14:29
14:30
14:31
14:32
14:33
14:34
14:35
14:36
14:37
14:38
14:39
14:40
14:41
14:42
14:43
14:44
14:45
14:46
14:47
14:48
14:49
14:50
14:51
14:52
14:53
14:54
14:55
14:56
14:57
14:58
14:59
15:00
15:01
15:02
Mass Concentration (µg/m3)
12
14:57
14:58
14:59
15:00
15:01
15:02
15:03
15:04
15:05
15:06
15:07
15:08
15:09
15:10
15:11
15:12
15:13
15:14
15:15
15:16
15:17
15:18
15:19
15:20
15:21
15:22
15:23
15:24
15:25
15:26
15:27
15:28
15:29
15:30
15:31
Mass Concentration (µg/m3)
20
2
0
Time (hr:min)
Figure 2-13. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 2:30 to 3:00 PM - Parata RDS
100
90
0
Time (hr:min)
Figure 2-14. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 3:00 to 3:30 PM - Parata RDS
25
10
8
6
4
2
Amitriptyline 25 mg
Hydrocodone/APAP 5/500 mg
Hand counting
Drive up window open
Spironolactone 25 mg
Metoclopramide 5 mg
Lipitor 20 mg
Loading caps in RDS
Sertraline HCL 100 mg
Aricept 10 mg
Promethazine 25 mg
14
Sertraline HCL 100 mg
4
Alprazolam 1 mg
Lorazepam 0.5 mg
6
Clonazepam 1 mg
8
Propo‐N/APAP 100/650 mg
Lisinopril 10 mg
10
Alprazolam 0.5 mg 15:27
15:28
15:29
15:30
15:31
15:32
15:33
15:34
15:35
15:36
15:37
15:38
15:39
15:40
15:41
15:42
15:43
15:44
15:45
15:46
15:47
15:48
15:49
15:50
15:51
15:52
15:53
15:54
15:55
15:56
15:57
15:58
15:59
16:00
16:01
Mass Concentration (µg/m3)
12
Acetaminophen/COD #3
Paroxetine 20 mg
Levothyroxinee Sod 50 mcg
Zolpidem 10 mg
Omeprazole DR 20 mg
Drive up window open
2
Diazepam 10 mg
Lithium Carbonate 300 mg
Ambien CR 12.5 mg
12
15:57
15:58
15:59
16:00
16:01
16:02
16:03
16:04
16:05
16:06
16:06
16:07
16:08
16:09
16:10
16:11
16:12
16:13
16:14
16:15
16:16
16:17
16:18
16:19
16:20
16:21
16:21
16:22
16:23
16:24
16:25
16:26
16:27
16:28
16:29
16:30
16:31
16:32
Mass Concentration (µg/m3)
20
18
16
0
Time (hr:min)
Figure 2-15. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 3:30 to 4:00 PM - Parata RDS
20
18
16
14
0
Time (hr:min)
Figure 2-16. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 4:00 to 4:30 PM - Parata RDS
26
6
4
2
12
10
Aricept 10 mg
Zolpidem 10 mg
Sertraline HCL 100 mg
Effexor XR 150 mg
Heat sealing near RDS
Trazodone 100 mg
Amoxicillin 500 mg
Sertraline 100 mg
Sertraline 100 mg
Evista 60 mg
Alprazolam 1 mg
2
Drive up window open
4
Triam/HCTZ 37.5/25 mg
Technician sneezed near APS
Filling RDS cells
Filling RDS cells
6
Cephalexin 500 mg
8
Hand counting
Heat sealing in back room
Cheratussin AC
16:28
16:29
16:30
16:31
16:32
16:33
16:34
16:35
16:36
16:37
16:38
16:39
16:40
16:41
16:42
16:43
16:44
16:45
16:46
16:47
16:48
16:49
16:50
16:51
16:52
16:53
16:54
16:55
16:56
16:57
16:58
16:59
17:00
17:01
17:02
Mass Concentration (µg/m3)
10
Sertraline 100 mg
Tramadol HCl 50 mg
Drive up window open
Transderm Scop 1.5 mg/72 hr
Zolpidem 10 mg
Glipizide 5 mg
8
16:58
16:59
17:00
17:01
17:02
17:03
17:04
17:05
17:06
17:07
17:08
17:09
17:10
17:11
17:12
17:13
17:14
17:15
17:16
17:17
17:18
17:19
17:20
17:21
17:22
17:23
17:24
17:25
17:26
17:27
17:28
17:29
17:30
17:31
17:32
Mass Concentration (µg/m3)
20
18
16
14
12
0
Time (hr:min)
Figure 2-17. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 4:30 to 5:00 PM - Parata RDS
20
18
16
14
0
Time (hr:min)
Figure 2-18. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 5:00 to 5:30 PM - Parata RDS
27
300
200
100
RDS Warfarin cell cleaned
Cyclobenzaprine 10 mg
Clonazepam 2 mg
Ranitidine 300 mg
Tramadol 50 mg
Alprazolam 0.5 mg Dot matrix printer
Ciprofloxacin 500 mg
Filling RDS w/ vials
Prevacid 30 mg
Benztropine mes 2 mg
Tramadol HCl 50 mg
Zolpidem 10 mg
Alprazolam 1 mg
Atenolol 25 mg
Clonidine HCl 0.1 mg
Singulair 10 mg
Prevacid 30 mg
Drive up window open
Drive up window open
Drive up window open
2
Dumping trash
Hand counting Filling RDS w/ vials
4
Drive up window open
Peak Flow MTRPEDI/ Adult
12
Hand counting Depakote
6
Drive up window open
8
SMZ/TMP 800/160 mg
17:28
17:29
17:30
17:31
17:32
17:33
17:34
17:35
17:36
17:37
17:38
17:39
17:40
17:41
17:42
17:43
17:44
17:45
17:46
17:47
17:48
17:49
17:50
17:51
17:52
17:53
17:54
17:55
17:56
17:57
17:58
17:59
18:00
18:01
18:02
Mass Concentration (µg/m3)
10
17:58
17:59
18:00
18:01
18:02
18:03
18:04
18:05
18:06
18:07
18:08
18:09
18:10
18:11
18:12
18:13
18:14
18:15
18:16
18:17
18:18
18:19
18:20
18:21
18:22
18:23
18:24
18:25
18:26
18:27
18:28
18:29
18:30
18:31
18:32
Mass Concentration (µg/m3)
20
18
16
14
0
Time (hr:min)
Figure 2-19. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 5:30 to 6:00 PM - Parata RDS
600
500
400
0
Time (hr:min)
Figure 2-20. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 6:00 to 6:30 PM - Parata RDS
28
50
Stopped PEM 1A
10
50
40
RDS cell cleaned Naproxen
Refilling robot
Filling caps in RDS
Bagging scripts
Prevacid 30 mg
20
Stopped PEM 4D
18:28
18:29
18:30
18:31
18:32
18:33
18:34
18:35
18:36
18:37
18:38
18:39
18:40
18:41
18:42
18:43
18:44
18:45
18:46
18:47
18:48
18:49
18:50
18:51
18:52
18:53
18:54
18:55
18:56
18:57
18:58
18:59
19:00
19:01
19:02
Mass Concentration (µg/m3)
30
Stopped PEM 2B Cleaning Estradiol cell 100
18:57
18:58
18:59
19:00
19:01
19:02
19:03
19:04
19:05
19:06
19:07
19:08
19:09
19:10
19:11
19:12
19:13
19:14
19:15
19:16
19:17
19:18
19:19
19:20
19:21
19:22
19:23
19:24
19:25
19:26
19:27
19:28
19:29
19:30
19:31
Mass Concentration (µg/m3)
80
70
60
0
Time (hr:min)
Figure 2-21. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 6:30 to 7:00 PM - Parata RDS
250
200
150
0
Time (hr:min)
Figure 2-22. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 7:00 to 7:30 PM - Parata RDS
29
Time (hr:min)
Figure 2-24. Phase IV - Pharmacy R - PM-2.5 Concentration
2/3/09 - 7:30 to 8:15 AM - Parata RDS
30
8:18
2
Stopped APS
4
8:16
6
8:14
8:12
8:10
8:08
8:06
8:04
8:02
8:00
7:58
7:56
7:54
7:52
7:50
7:48
7:46
7:44
7:42
7:40
7:38
7:36
9:00
8:00
7:00
6:00
5:00
4:00
3:00
2:00
1:00
0:00
23:00
22:00
21:00
8
7:34
10
Stopped PEM 3C
12
20:00
19:00
18:00
Mass Concentration (µg/m3)
14
7:32
7:30
7:28
7:26
Mass Concentration (µg/m3)
20
18
16
6
4
2
0
Time (hr:min)
Figure 2-23. Phase IV - Pharmacy R - PM-2.5 Concentration
2/2/09 - 2/3/09 Overnight - Parata RDS
20
18
16
14
12
10
8
0
2.3
Comparison of PM-2.5 Levels
As stated previously, Pharmacy R was the same pharmacy designated as Pharmacy A during
Phases I and II. The average and maximum PM-2.5 concentrations as measured using the APS
during both phases are compared in Table 2.2. The average aerosol concentrations were lower
during this phase of testing. This could be attributed to the smaller number of prescriptions
filled by the Parata RDS during the 24 hour test period. During the previous Phase II testing
there were 310 prescriptions filled by the Parata RDS compared with the 99 filled during this
phase.
Table 2.2. Comparison of PM-2.5 Particle Concentration
Aerosol Particle
Aerosol Mass
Dispensing Method
Concentration
Concentration
PPLAvg
PPLMax
µg/m3Avg
µg/m3Max
Phase II-Pharmacy A-Parata RDS
72,916
487,368
4.46
854.3
Phase IV-Pharmacy R-Parata RDS
11,557
543,577
2.52
527.1
PPL = Particles per liter of air, used to measure the number of particles in a volume of air.
µg/m3 = Micrograms per cubic meter of air, used to measure the weight (mass) of the
particles in a volume of air.
31
3.
Phase IV Pharmacy S 24-Hour Sampling, Parata Max
________________________________________________________________________
Pharmacy S uses a Parata Max Robotic Dispensing System. This pharmacy was designated as
Pharmacy P during Phase III of this study. On the day that Phase IV testing was conducted,
one hundred twenty-one (121) prescriptions were filled using the Parata Max during the test
period; 108 for tablets and 13 for capsules. Overall, 5,330 tablets and 434 capsules were
dispensed during the sampling period, which covered overlapping parts of two days. The
layout of the pharmacy in the immediate vicinity of the Parata Max is shown below. The
Parata Max is located in the storage rack area in the rear of the pharmacy with the front of the
machine near a counter that is used to fill and transfer prescriptions to a front counter for
customer pickup, and a waiting area. The instrumentation was set up prior to the pharmacy
opening on Monday, February 23, 2009, and was operated until the following morning. Four
to six pharmacists and technicians worked in the area around the machine at any one time
during the workdays during which sampling was performed. At this location, the weather on
both days of testing was rainy and cool, with light winds.
Pharmacy S Layout
32
3.1
Personal Exposure Monitoring (PEM) Filters
During one work shift, three Pharmacy S personnel working in the pharmacy area and one
AlburtyLab observer, who was recording Parata Max dispensing data at the front of the
machine, were recruited to don PEMs. Each subject wore a personal sampling pump (Leland
Legacy, SKC Inc. Houston, TX) running at 10 Lpm with a Personal Environmental
Monitoring impactor with a cut-point of 2.5 µm located in the breathing zone, as shown
previously in Photo 2-1. The PM-2.5 samples were collected on 37-mm Teflon filters (P/N
225-1709, SKC Inc., Houston, TX). The primary location of each of these personnel within
the pharmacy is indicated in the Pharmacy S layout with the letters A, B, C, and D.
The personal sampling pumps were identified with the labels A, B, C, and D, and the PEMs
were identified with the labels 1, 2, 3 and 4. In subsequent text, the sampling systems will be
referred to as PEM-1A, PEM-2B, PEM-3C and PEM-4D. Prior to start of the aerosol
collection periods, the accumulated sampling time and sample volume were reset on each of
the personal sampling pumps. Due to the possibility of air flow loss through the PEM because
of kinks in the hose between the personal sampling pump and the PEM, the air sample volume
for each sampler was determined using the personal sampling pump’s LCD display at the end
of the sampling period. PEM-1A was started at 9:12 a.m. and continued until 5:30 p.m., for a
total of 8 hr 18 min, resulting in a sampled air volume of 4.98 m3. PEM-2B was started at
9:15 a.m. and continued until 5:34 p.m. with sampling suspended from 11:03 a.m. to 12:13
p.m. while the technician was at lunch, for a total of 7 hr 8 min, resulting in a sampled air
volume of 3.20 m3. At one point during the work shift, it was discovered that the PEM-2B
personal sampling pump had stopped sampling for an undetermined length of time due to a
kink in the sampling hose connecting the PEM to the personal sampling pump. PEM-3C was
started at 9:18 a.m. and continued until 5:36 p.m. with sampling suspended from 1:46 p.m. to
1:48 p.m. and from 2:56 p.m. to 4:09 p.m. while the technician was at lunch, for a total of 7 hr
2 min, resulting in a sampled air volume of 4.20 m3. PEM-4D was started at 9:24 a.m. and
continued until 5:39 p.m. with sampling suspended from 2:03 p.m. to 2:50 p.m. while the
technician was at lunch, for a total of 7 hr 28 min, resulting in a sampled air volume of 4.48
m3.
The PEM-1A sample was from the AlburtyLab employee who was not involved in any hand
counting of prescriptions and therefore serves as a control. All pharmacy personnel who were
wearing the PEM sampling devices were involved in hand counting of prescriptions at some
time during the work day.
The four PEM filter samples and one blank filter were analyzed using high-performance liquid
chromatography combined with an ultraviolet diode array detection system (HPLC/DAD).
The results indicated several peaks in each sample except for the blank which were determined
to be pharmaceutical compounds.
The detection limit for the HPLC/DAD analysis method was estimated at 10 µg/filter, which
indicates that the average aerosol concentration for the peaks of interest exceeded the method
detection limit of approximately 2.0 μg/m3 for the PEM-1A sample, approximately 3.1 μg/m3
for the PEM-2B sample, approximately 2.4 μg/m3 for the PEM-3C sample, and approximately
2.2 μg/m3 for the PEM-4D sample. Confirmation analysis by mass spectroscopy is needed for
all peaks identified by HPLC/DAD. Additional compounds may have been collected on the
filters that were not apparent using HPLC/DAD alone.
33
The samples were analyzed further by mass spectrometric analysis (HPLC/DAD/MS). Several
analytes of interest were determined; these are summarized in Table 3-1. Also shown in this
table are the number of prescriptions filled during the PEM sampling period and the number of
Parata-Max cells that contain the tentatively identified drug agent. There are several instances
where the drug identified was not dispensed during the PEM sampling period. This could be
attributed to emissions from manual counting or from recirculation of particulate drug agents
in the HVAC system previously dispensed manually or through the Parata device. The column
labeled “Corresponding PM-2.5 Responses” indicates the number of instances when the PM2.5 mass concentration, as measured by the APS, exceeded 20 µg/m3 within 2 minutes of the
Parata Max dispensing a prescription.
Amoxicillin
Atenolol
PEM-D
X
X
Carisoprodol
X
X
X
Diclofenac
X
Hydrochlorothiazide
X
X
Oxybutynin
Prednisone
X
2
2
2
1
2
1
1
2
2
7
2
2
X
X
Prochlorperazine
5
4
2
X
Propranolol
Tamsulosin
X
2
1
Cyclobenzaprine
Metformin
a
PEM-C
PEM-B
PEM-Aa
Table 3-1. Analytes of Interest Tentatively Identified in Pharmacy S PEM Filter Samples
Number of
Number of
Tentative
Prescriptions
Parata-Max
Identifications
Filled
Corresponding
Cells
Reported by
Containing
PM-2.5
Containing
Inovatia
Drug
Responses
Drug
Acetaminophen
X
X
7
5
6
X
X
1
AlburtyLab employee.
3.2
Reference Filters
Two 47-mm dry reference filters were placed on either side of the dispensing station at the rear
of the Parata Max for air sampling at approximate breathing height (Photo 3-1). Whatman
EPM 2000 filters, rated as 99.99% efficient in air for 0.3 µm particles, were used for the
reference filters. The samples were collected on the filters by pulling air through them at a
flow rate of 10.0 liters per minute (Lpm) using a vacuum pump (Leland Legacy, SKC, Inc.,
Houston, TX). Aerosol collection on the reference filters was started at 6:01 p.m. and
continued overnight until 5:37 p.m., for a total of 510 min, resulting in a sampled air volume of
5.1 m3 on the left-side filter, and 5.1 m3 on the right-side filter. Following sampling, the filters
were harvested into a labeled 50-mm Petri dish and packed for shipment to the laboratory.
34
The reference samples were analyzed using high-performance liquid chromatography
combined with an ultraviolet diode array detection system (HPLC/DAD). The results
indicated several peaks in each sample which were determined to be pharmaceutical
compounds.
The detection limit for the HPLC/DAD analysis method was estimated at 10 µg/filter, which
indicates that the average aerosol concentration for the peaks of interest exceeded the method
detection limit of approximately 1.1 μg/m3 for the samples taken during the overnight hours.
Confirmation analysis by mass spectroscopy is needed for all peaks identified by HPLC/DAD.
Additional compounds may have been collected on the reference filters that were not apparent
using HPLC/DAD alone.
The sample was analyzed further by mass spectrometric analysis (HPLC/DAD/MS). Analytes
of interest were determined to be benztropine, glimepiride, isosorbide, labetalol, lansoprazole,
loratadine, lovastatin, meloxicam, metoprolol, niacin, nitrofurantoin, pseudoephedrine and
tramadol.
3.3
APS Monitoring
As during the Phases II and III, the APS was placed on top of the Parata Max, so it would be
out of the pharmacist’s way. The APS samples were collected using a 118 cm length of
conductive silicone tubing to allow sampling at breathing height to be conducted.
The APS was used to measure particles present in the pharmacy at nose-height at the edge of
the dispensing area at the front side of the Parata Max (see Photo 3-1). The sampling tube was
positioned on the left side of the machine.
While observing the real-time particle size and concentration spectra during operation and
dispensing, a correlation appeared to be present between filling and delivery of certain
prescriptions, and the emission of respirable particles from the machine. This correlation
appears as coincident peaks in PM-2.5 and PM-10 mass closely associated (within
approximately 2 min) with the dispensing of certain prescriptions.
The APS data were reduced using Microsoft Excel spreadsheets and matched with the
observer’s dispensing data and other notes taken during sampling. The PM-2.5 mass
concentration data are shown in Figures 3-1 through 3-20 which are comprised of graphs
broken down into half-hour segments. The PM-2.5 overnight sampling data are condensed
into one graph and shown in Figure 3-21. Please note carefully that the Y-axis is adjusted from
graph to graph based on the concentrations within the particular time segment shown, in order
to show relative levels of PM within each time segment.
The position of the identifier text and notes seemed to be dependent on airflow within the
pharmacy, the position of the sampling tube with respect to the dispensing cell in the robot, the
type and number of pills dispensed, and the location to which the prescription was delivered.
35
Photo 3-1. Phase IV 24-hr Sampling at Pharmacy S
(Filter samples were present only during the overnight hours.)
36
12
10
8
6
4
2
2
Manual counting
4
Potassium Chloride ER 10 mEq
Furosemide 20 mg
Plavix 75 mg
Delivery of supplies near Parata Max
6
14
12
Emptying trash cans near Parata Max
Started APS Sampling
8
Manual counting
8:58
8:59
9:00
9:01
9:02
9:03
9:04
9:05
9:06
9:07
9:08
9:09
9:10
9:11
9:12
9:13
9:14
9:15
9:16
9:17
9:18
9:19
9:20
9:21
9:22
9:23
9:24
9:25
9:26
9:27
9:28
9:29
9:30
9:31
9:32
Mass Concentration (µg/m3)
10
Pantoprazole Sodium 40 mg
Manual counting
Potassium Chloride 10 mEq
Lexapro 20 mg
Emptying trash cans near Parata Max
14
9:28
9:29
9:30
9:31
9:32
9:33
9:34
9:35
9:36
9:37
9:38
9:39
9:40
9:41
9:42
9:43
9:44
9:45
9:46
9:47
9:48
9:49
9:50
9:51
9:52
9:53
9:54
9:55
9:56
9:57
9:58
9:59
10:00
10:01
10:02
Mass Concentration (µg/m3)
20
18
16
0
Time (hr:min)
Figure 3-1. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 9:10 to 9:30 AM - Parata Max
20
18
16
0
Time (hr:min)
Figure 3-2. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 9:30 to 10:00 AM - Parata Max
37
80
70
60
50
40
30
20
10
Fluoxetine 40 mg
Trazodone HCl 100 mg
Pantoprazole Sodium 40 mg
Meloxicam 15 mg
Simvastatin 40 mg
Manual counting
Manual counting
Manual counting
Manual counting
Manual counting
Manual counting
Manual counting
40
Manual counting
Metoprolol Tartrate 100 mg
Alprazolam 0.25 mg
Levothyroxine Sodium 100 Mcg
Fluoxetine 20 mg
Cefdinir 300 mg
Glipizide ER 5 mg
Heat turned on
Clarinex 5 mg 5
Fluoxetine 20 mg
Amitriptyline HCl 25 mg Amlodipine Besylate 10 mg
Carvedilol 6.25 mg
Diovan 320 mg
Manual counting
35
Unloading supplies near Parata Max
10
Hydrochlorothiazide 50 mg
Fexofenadine HCl 180 mg
Metoclopramide 10 mg
30
Manual counting
15
Fexofenadine HCl 180 mg
20
Fluoxetine 20 mg
Carisoprodol 350 mg
Folic Acid 1 mg
Levothyroxine Sodium 100 Mcg
9:58
9:59
10:00
10:01
10:02
10:03
10:04
10:05
10:06
10:07
10:08
10:09
10:10
10:11
10:12
10:13
10:14
10:15
10:16
10:17
10:18
10:19
10:20
10:21
10:22
10:23
10:24
10:25
10:26
10:27
10:28
10:29
10:30
10:31
10:32
Mass Concentration (µg/m3)
25
10:28
10:29
10:30
10:31
10:32
10:33
10:34
10:35
10:36
10:37
10:38
10:39
10:40
10:41
10:42
10:43
10:44
10:45
10:46
10:47
10:48
10:49
10:50
10:51
10:52
10:53
10:54
10:55
10:56
10:57
10:58
10:59
11:00
11:01
11:02
Mass Concentration (µg/m3)
50
45
0
Time (hr:min)
Figure 3-3. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 10:00 to 10:30 AM - Parata Max
0
Time (hr:min)
Figure 3-4. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 10:30 to 11:00 AM - Parata Max
38
6
4
2
2
Manual counting
4
Zolpidem 10 mg
Manual counting
6
Manual counting
10:58
10:59
11:00
11:01
11:02
11:03
11:04
11:05
11:06
11:07
11:08
11:09
11:10
11:11
11:12
11:13
11:14
11:15
11:16
11:17
11:18
11:19
11:20
11:21
11:22
11:23
11:24
11:25
11:26
11:27
11:28
11:29
11:30
11:31
11:32
Mass Concentration (µg/m3)
8
Manual counting
Manual counting
8
11:28
11:29
11:30
11:30
11:31
11:32
11:33
11:34
11:35
11:36
11:37
11:38
11:39
11:40
11:41
11:42
11:43
11:44
11:45
11:45
11:46
11:47
11:48
11:49
11:50
11:51
11:52
11:53
11:54
11:55
11:56
11:57
11:58
11:59
12:00
12:00
12:01
Mass Concentration (µg/m3)
20
18
16
14
12
10
0
Time (hr:min)
Figure 3-5. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 11:00 to 11:30 AM - Parata Max
20
18
16
14
12
10
0
Time (hr:min)
Figure 3-6. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 11:30 AM to 12:00 PM - Parata Max
39
5
8
6
4
2
Manual counting
Manual counting
30
Manual counting
35
Manual counting
Prednisone 5 mg
40
10
Manual counting
10
Manual counting
15
Naproxen 500 mg
11:58
11:59
12:00
12:01
12:02
12:03
12:04
12:05
12:06
12:07
12:08
12:09
12:10
12:11
12:12
12:13
12:14
12:15
12:16
12:17
12:18
12:19
12:20
12:21
12:22
12:23
12:24
12:25
12:26
12:27
12:28
12:29
12:30
12:31
12:32
Mass Concentration (µg/m3)
20
12:28
12:29
12:30
12:31
12:32
12:33
12:34
12:35
12:36
12:37
12:38
12:39
12:40
12:41
12:42
12:43
12:44
12:45
12:46
12:47
12:48
12:49
12:50
12:51
12:52
12:53
12:54
12:55
12:56
12:57
12:58
12:59
13:00
13:01
13:02
Mass Concentration (µg/m3)
50
45
25
0
Time (hr:min)
Figure 3-7. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 12:00 to 12:30 PM - Parata Max
20
18
16
14
12
0
Time (hr:min)
Figure 3-8. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 12:30 to 1:00 PM - Parata Max
40
40
20
80
60
Baclofen 10 mg Metformin HCl 1000 mg
Cephalexin 500 mg
Actos 45 mg
Metoprolol Succinate ER 100 mg
50
Loading Parata Cell 9H
60
Levaquin 500 mg
Prednisone 10 mg
Manual counting
Amlodipine/Benazepril 10/20 mg
Hydrocodone/APAP 5/500 mg
70
Manual counting
40
Clonidine HCl 0.1 mg
Cozaar 100 mg
80
Promethazine HCl 25 mg Bumetanide 1 mg 10
Manual counting
20
Amoxicillin 500 mg
12:58
12:59
13:00
13:01
13:02
13:03
13:04
13:05
13:06
13:07
13:08
13:09
13:10
13:11
13:12
13:13
13:14
13:15
13:16
13:17
13:18
13:19
13:20
13:21
13:22
13:23
13:24
13:25
13:26
13:27
13:28
13:29
13:30
13:31
13:32
Mass Concentration (µg/m3)
30
13:28
13:29
13:30
13:31
13:32
13:33
13:34
13:35
13:36
13:37
13:38
13:39
13:40
13:41
13:42
13:43
13:44
13:45
13:46
13:47
13:48
13:49
13:50
13:51
13:52
13:53
13:54
13:55
13:56
13:57
13:58
13:59
14:00
14:01
14:02
Mass Concentration (µg/m3)
100
90
0
Time (hr:min)
Figure 3-9. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 1:00 to 1:30 PM - Parata Max
120
100
0
Time (hr:min)
Figure 3-10. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 1:30 to 2:00 PM - Parata Max
41
25
20
15
10
5
Cyclobenzaprine HCl 10 mg
Amitriptyline HCl 10 mg Nexium 40 mg
200
Hydrocodone/APAP 5/500 mg
Hydrocodone/APAP 5/500 mg
Potassium chloride 10 mEq
300
Zolpidem 10 mg
250
Levothyroxine Sodium 100 Mcg
350
Prednisone 10 mg
50
Manual counting
100
Lisinopril 10 mg
13:58
13:59
14:00
14:01
14:02
14:03
14:04
14:05
14:06
14:07
14:08
14:09
14:10
14:11
14:12
14:13
14:14
14:15
14:16
14:17
14:18
14:19
14:20
14:21
14:22
14:23
14:24
14:25
14:26
14:27
14:28
14:29
14:30
14:31
14:32
Mass Concentration (µg/m3)
150
14:27
14:28
14:29
14:30
14:31
14:32
14:33
14:34
14:35
14:36
14:37
14:38
14:39
14:40
14:41
14:42
14:43
14:44
14:45
14:46
14:47
14:48
14:49
14:50
14:51
14:52
14:53
14:54
14:55
14:56
14:57
14:58
14:59
15:00
15:01
Mass Concentration (µg/m3)
400
0
Time (hr:min)
Figure 3-11. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 2:00 to 2:30 PM - Parata Max
50
45
40
35
30
0
Time (hr:min)
Figure 3-12. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 2:30 to 3:00 PM - Parata Max
42
20
15
10
5
12
10
8
6
Loading Parata Cell 2T
Loading Parata Cell 5B
Loading Parata Cell 2T
Vacuuming in store area
Clonidine HCl 0.1 mg
Clonidine HCl 0.1 mg
Metoprolol ER 50 mg
Loading Parata Cell 7Z
Loading Parata Cell
Lexapro 20 mg
Lexapro 10 mg
Metoprolol Tartrate 50 mg
Meloxicam 15 mg
25
Budeprion XL 300 mg
14:58
14:59
15:00
15:01
15:02
15:03
15:04
15:05
15:06
15:07
15:08
15:09
15:10
15:11
15:12
15:13
15:14
15:15
15:16
15:17
15:18
15:19
15:20
15:21
15:22
15:23
15:24
15:25
15:26
15:27
15:28
15:29
15:30
15:31
15:32
Mass Concentration (µg/m3)
30
15:27
15:28
15:29
15:30
15:31
15:32
15:33
15:34
15:35
15:36
15:37
15:38
15:39
15:40
15:41
15:42
15:43
15:44
15:45
15:46
15:47
15:48
15:49
15:50
15:51
15:52
15:53
15:54
15:55
15:56
15:57
15:58
15:59
16:00
16:01
Mass Concentration (µg/m3)
50
45
40
35
0
Time (hr:min)
Figure 3-13. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 3:00 to 3:30 PM - Parata Max
20
18
16
14
4
2
0
Time (hr:min)
Figure 3-14. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 3:30 to 4:00 PM - Parata Max
43
25
20
15
10
5
35
Lisinopril 40 mg
Manual counting
60
Metoclopramide 10 mg
Metoprolol ER 50 mg
Manual counting
Metoprolol ER 50 mg
Loading Parata Cell 7Z
Clonazepam 1 mg
Estradiol 1 mg
Estradiol 1 mg
Fluconazole 100 mg
Manual counting
Clonazepam 1 mg
Prednisone 5 mg
Cephalexin 500 mg
20
Cefdinir 300 mg
Hydrocodone/APAP 7.5/500 mg
15:57
15:58
15:59
16:00
16:01
16:02
16:03
16:04
16:05
16:06
16:07
16:08
16:09
16:10
16:11
16:12
16:13
16:14
16:15
16:16
16:17
16:18
16:19
16:20
16:21
16:22
16:23
16:24
16:25
16:26
16:27
16:28
16:29
16:30
16:31
Mass Concentration (µg/m3)
40
Lorazepam 0.5 mg
Amlodipine Besylate 10 mg
30
16:27
16:28
16:29
16:30
16:31
16:32
16:33
16:34
16:35
16:36
16:37
16:38
16:39
16:40
16:40
16:41
16:42
16:43
16:44
16:45
16:46
16:47
16:48
16:49
16:50
16:51
16:52
16:53
16:54
16:55
16:55
16:56
16:57
16:58
16:59
17:00
17:01
Mass Concentration (µg/m3)
120
100
80
0
Time (hr:min)
Figure 3-15. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 4:00 to 4:30 PM - Parata Max
50
45
40
0
Time (hr:min)
Figure 3-16. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 4:30 to 5:00 PM - Parata Max
44
60
50
40
30
20
10
Doxazosin Mesylate 2 mg
Methotrexate 2.5 mg
Atenolol 50 mg Carbidopa/Levodopa 25/100 mg Nabumetone 750 mg
Fexofenadine HCl 180 mg
Vacuuming in store area
Prednisone 5 mg
Manual counting
Removed Parata Cell 9V
Furosemide 20 mg
Doxycycline Hyclate 100 mg
Lorazepam 0.5 mg
Sertraline HCl 100 mg
35
70
Hydrocodone/APAP 5/500 mg Warfarin 5 mg
Cyclobenzaprine HCl 10 mg
Isosorbide Mononitrate ER 30 mg Meloxicam 15 mg
Set up overnight filters by APS inlet
Bumetanide 1 mg Manual counting
25
Levothyroxine Sodium 200 Mcg
Atenolol 50 mg Metoprolol ER 50 mg
30
Amoxicillin 500 mg
5
Manual counting
10
Manual counting
Ciprofloxacin 500 mg
15
Methotrexate 2.5 mg
Manual counting
Nabumetone 500 mg
16:58
16:59
17:00
17:01
17:02
17:03
17:04
17:05
17:06
17:07
17:08
17:09
17:10
17:11
17:12
17:13
17:14
17:15
17:16
17:17
17:18
17:19
17:20
17:21
17:22
17:23
17:24
17:25
17:26
17:27
17:28
17:29
17:30
17:31
17:32
Mass Concentration (µg/m3)
20
17:28
17:29
17:30
17:31
17:32
17:33
17:34
17:35
17:36
17:37
17:38
17:39
17:40
17:41
17:42
17:43
17:44
17:45
17:46
17:47
17:48
17:49
17:50
17:51
17:52
17:53
17:54
17:55
17:56
17:57
17:58
17:59
18:00
18:01
18:02
Mass Concentration (µg/m3)
50
45
40
0
Time (hr:min)
Figure 3-17. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 5:00 to 5:30 PM - Parata Max
80
0
Time (hr:min)
Figure 3-18. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 - 5:30 to 6:00 PM - Parata Max
45
Time (hr:min)
Figure 3-20. Phase IV - Pharmacy S - PM-2.5 Concentration
2/23/09 to 2/24/09 - Overnight - Parata Max
46
10:00
9:00
8:00
7:00
6:00
5:00
4:00
3:00
2:00
1:00
5
0:00
10
23:00
15
22:00
Plavix 75 mg
Pantoprazole Sodium 40 mg
Methotrexate 2.5 mg
25
21:00
20
Lexapro 20 mg
Alprazolam 0.5 mg
30
20:00
35
Warfarin 5 mg
Started overnight filter sampling
40
19:00
17:58
17:59
18:00
18:01
18:02
18:03
18:04
18:05
18:06
18:07
18:08
18:09
18:10
18:11
18:12
18:13
18:14
18:15
18:16
18:17
18:18
18:19
18:20
18:21
18:22
18:23
18:24
18:25
18:26
18:27
18:28
18:29
18:30
18:31
18:32
Mass Concentration (µg/m3)
45
18:00
17:00
Mass Concentration (µg/m3)
50
0
Time (hr:min)
Figure 3-19. Phase IV - Pharmacy S - Concentration
2/23/09 - 6:00 to 6:30 PM - Parata Max
20
18
16
14
12
10
8
6
4
2
0
30
25
20
15
10
5
8:28
8:29
8:30
8:31
8:32
8:33
8:34
8:35
8:36
8:37
8:38
8:39
8:40
8:41
8:42
8:43
8:44
8:45
8:46
8:47
8:48
8:49
8:50
8:51
8:52
8:53
8:54
8:55
8:56
8:57
8:58
8:59
9:00
9:01
9:02
Mass Concentration (µg/m3)
14
12
10
8
6
4
2
Pharmacy staff arriving
Emptying trash cans near Parata Max
Stopped off overnight filter sampling
16
Heat turned off
Hydrochlorothiazide 25 mg
Potassium chloride 10 mEq
Propoxyphene/APAP 100/650 mg
Propoxyphene/APAP 100/650 mg
Metformin HCl 500 mg
Singulair 10 mg
Lisinopril 10 mg
35
8:58
8:59
9:00
9:01
9:02
9:03
9:04
9:05
9:06
9:07
9:08
9:09
9:10
9:11
9:12
9:13
9:14
9:15
9:16
9:17
9:18
9:19
9:20
9:21
9:22
9:23
9:24
9:25
9:26
9:27
9:28
9:29
9:30
9:31
9:32
Mass Concentration (µg/m3)
20
18
0
Time (hr:min)
Figure 3-21. Phase IV - Pharmacy S - PM-2.5 Concentration
2/24/09 -8:30 to 9:00 AM - Parata Max
50
45
40
0
Time (hr:min)
Figure 3-22. Phase IV - Pharmacy S - PM-2.5 Concentration
2/24/09 - 9:00 to 9:30 AM - Parata Max
47
20
16
10
8
6
4
2
Stopped APS sampling
Levothyroxine Sodium 50 Mcg
Simvastatin 20 mg
Clonazepam 0.5 mg
12
Seroquel 25 mg
14
Heat turned off
Mass Concentration (µg/m3)
18
9:28
9:29
9:30
9:31
9:32
9:33
9:34
9:35
9:36
9:37
9:38
9:39
9:40
9:41
9:42
9:43
9:44
9:45
9:46
9:47
9:48
9:49
9:50
9:51
9:52
9:53
9:54
9:55
9:56
9:57
9:58
9:59
10:00
10:01
0
Time (hr:min)
Figure 3-23. Phase IV - Pharmacy S - PM-2.5 Concentration
2/24/09 - 9:30 to 10:00 AM - Parata Max
3.4
Comparison of PM-2.5 Levels
As stated previously, Pharmacy S was the same pharmacy designated as Pharmacy P during
Phase III. The average and maximum PM-2.5 concentrations as measured using the APS
during both phases are compared in Table 2.2. The average PM-2.5 levels measured during
this phase of testing were within the same range as those measured previously. During the
previous Phase III testing, there were 105 prescriptions filled by the Parata Max compared with
the 121 filled during this phase.
Table 3.2. Comparison of PM-2.5 Particle Concentration
Aerosol Particle
Aerosol Mass
Dispensing Method
Concentration
Concentration
PPLAvg
PPLMax
µg/m3Avg
µg/m3Max
Phase III-Pharmacy P-Parata Max
21,986
725,223
2.55
240.9
Phase IV-Pharmacy S-Parata Max
18,141
1,371,927
2.03
356.8
PPL = Particles per liter of air, used to measure the number of particles in a volume of air.
µg/m3 = Micrograms per cubic meter of air, used to measure the weight (mass) of the
particles in a volume of air.
48
4.
Quantitation Results for Acetaminophen
________________________________________________________________________
All of the filter samples collected during Phase II through Phase IV of this program were
analyzed using high-performance liquid chromatography combined with an ultraviolet diode
array detection system (HPLC/DAD). All of these samples were analyzed further by mass
spectrometric analysis (HPLC/DAD/MS). During the analysis of the filters collected at
Pharmacy S, standard solutions of acetaminophen were prepared at 0.2, 1.0, 5.0, 25.0, and
124.8 ppm and were included in the analysis. With the inclusion of the acetaminophen
standards, it was possible to quantitate the acetaminophen in each of the filter samples.
It was also possible to use the calibration curve for the acetaminophen standards based on the
UV spectrum as a tool for quantitating the acetaminophen from the spectra of some of the
previous samples. The detection limit for the acetaminophen is approximately 0.1 µg/filter.
The results for all of the samples evaluated using these methods are shown in Table 4-1. Using
the air sample volumes collected, it was possible to calculate the air concentration of
acetaminophen determined by each filter. The technician wearing PEM-4D at Pharmacy R
worked in close proximity to the Parata RDS and performed cell restocking and cell cleaning
activities during the day.
Phase
IV
IV
IV
IV
IV
IV
III
III
Table 4-1. Acetaminophen Air Concentrations
Acetaminophen
Air
Sampled
Weight
m3
µg
Pharmacy
Filter ID
Pharmacy S
PEM-2B
0.5
3.20
Pharmacy S
PEM-3C
0.2
4.20
Pharmacy R
PEM-1A
79.0
6.67
Pharmacy R
PEM-2B
7.0
5.92
Pharmacy R
PEM-3C
12.0
6.64
Pharmacy R
PEM-4D
14.0
3.40
Pharmacy Q
Ref Filter
21.0
5.70
Pharmacy Q
Ref Filter
28.0
5.70
Air
Concentration
µg/m3
0.16
0.05
11.8
1.18
1.81
4.12
3.68
4.91
49
5.
Summary of Phase I through Phase IV Data
________________________________________________________________________
A summary of project results for the four phases of this work performed to date is included in
the following sections. Sampling with the APS was performed during Phase II through IV
using the same procedure established during the Phase I portion of this study. During each of
these Phases, an APS was used to sample the air near the dispensing areas to determine the
aerosol particle size distribution and concentration. The PM-2.5 mass and number
concentration results are summarized in Table 5-1.
Table 5-1. Summary of APS Monitoring Results for all Phases II through IV
Aerosol Particle
Aerosol Mass
Timesd
e
Concentration
Concentration
Dispensing
>15
Method
µg/m3
PPLAvg
PPLMax
µL/m3Avg µL/m3Max
Phase II
A
Parata RDS
72,916
487,368
4.46
854
135
B
SP 200
4,638
12,654
0.58
8.32
0
C
Manual
13,374
114,648
1.92
64.3
135
D
Parata RDS
4,438
381,726
1.06
451
54
E
Parata RDS
8,458
554,682
1.56
253
41
F
Parata RDS
5,278
401,214
1.01
115
94
G
Parata RDS
24,198
607,272
4.52
567
427
H
SP 200
12,947
105,178
2.49
11.9
0
I
SP 200
9,483
42,557
1.76
15.1
1
J
SP 200
9,077
23,787
1.57
8.71
0
K
SP 200
8,100
32,675
2.14
16.4
1
L
Manual
2,468
9,174
0.47
13.0
0
M
Manual
3,378
11,442
0.59
12.7
0
N
Manual
36,612
60,785
4.94
35.8
5
O
Manual
1,874
8,964
0.57
11.1
0
Average Manual
11,541
41,002
1.70
27.4
Average SP 200
8,849
43,370
1.71
12.1
Average Parata RDS
23,057
486,452
2.52
448
Phase III
P
Parata Max
21,986
725,223
2.55
241
82
a
Q
Parata Max
31,633
1,699,244
7.01
1,193
586
Average Parata Max
26,809
1,212,234
4.78
717
Phase IV
Rb
Parata RDS
11,557
543,577
2.52
527
98
c
S
Parata Max
18,141
1,371,927
2.03
357
129
a
Test Q was performed in the same pharmacy as Test G. Pharmacy had installed newer
Parata Max between tests.
b
Test R was performed in the same pharmacy as Test A.
c
Test S was performed in the same pharmacy as Test P.
d
15 µg/m3 is the USEPA annual average National Air Quality Standard for PM-2.5.
e
The mass concentration was calculated from the number concentration as measured using the
APS by estimating a unit density for all particles.
PPL = Particles per liter of air, used to measure the number of particles in a volume of air.
µg/m3 = Micrograms per cubic meter of air, used to measure the weight (mass) of the particles
in a volume of air.
50
5.1
Phase I—Survey of Dispensing Methods
Pharmacy A used a McKesson/Parata RDS Robotic Dispensing System (which uses
compressed air to dispense pills). An increase in the concentration of airborne respirable
particles was detected by the APS during the dispensing of many drugs by the
McKesson/Parata RDS, including Hydrocodone/APAP (narcotic analgesic), Alprazolam (antianxiety), Bisoprolol/HCTZ (antihypertensive), Fluoxetine (antidepressant), Metoprolol
(antihypertensive), Torsemide (diuretic), Coumadin (blood thinner), Lorazepam (anti-anxiety),
and Trazodone (antidepressant).
Pharmacy B used a ScriptPro SP 200 Robotic Prescription Dispensing System (which does not
use compressed air to dispense pills). An increase in the concentration of airborne respirable
particles was not detected by the APS during the dispensing of any drugs by the ScriptPro
SP 200.
Pharmacy C did not use a robotic dispensing system. A slight increase in the concentration of
airborne respirable particles was detected by the APS during the manual dispensing of certain
drugs, including Cefuroxime (antibiotic), Methadone (narcotic analgesic), and Amlodipine
(antihypertensive).
5.2
Phase II—24-Hour Sampling
Subsequently, 24-hr sampling was repeated at Pharmacies A, B, and C, this time for full 24-hr
periods. The ScriptPro SP 200 again did not exhibit any observable emissions of pill dust
correlated with drug dispensing. The McKesson/Parata RDS did exhibit emissions of pill dust
correlated with drug dispensing during the 24-hr sampling. In order to confirm our
observations regarding the McKesson/Parata RDS, we conducted observations at four
additional pharmacies using this machine (D, E, F, and G) for a total of five such pharmacies.
Particle concentration peaks were closely associated with the dispensing of certain drugs by the
robot and with the cleaning of the robot’s dispensing cells using canned compressed air as
recommended by the manufacturer. A slight increase in respirable particles was observed at
Pharmacy C (manual dispensing site). Following these tests, testing was performed at four
additional ScriptPro SP 200 sites (Pharmacies H, I, J and K) for a total of five such pharmacies.
Again, the testing indicated no observable emissions of pill dust correlated with drug
dispensing. Four additional non-robotic sites (Pharmacies L, M, N, and O), for a total of five,
were also tested, making a total of 15 pharmacies visited or revisited during this phase for 24hr sampling. Slight increases in respirable particles were observed at the non-robotic
pharmacies.
In Phase II, an APS was used to sample the air near the dispensing areas to determine the
aerosol particle size distribution and concentration. The PM-2.5 mass and number
concentration results were presented previously in Table 5-1.
Fifty-four dust samples were collected from air filters placed at each of the pharmacy sites
during the 24-hr sampling period. The samples were analyzed using HPLC/DAD/MS and
showed hundreds of peaks indicating the presence of likely active pharmaceutical ingredients
at varying air concentrations. Seven of the largest peaks were identified by their exact ionic
masses, showing that active pharmaceutical ingredients, including acetaminophen, atenolol,
51
ibuprofen, isosorbide, pentoxifylline, trazodone, and trimethoprim were present in the air at
various pharmacies.
All of the pharmacies, including those equipped with robots, used manual counting for many
prescriptions. At the pharmacies using Parata RDS dispensing machines, active
pharmaceutical compounds found in the air are likely to be attributed to the particles shown to
be emitted by the robot during drug dispensing and also to particles generated by manual
counting. At the pharmacies using ScriptPro SP 200 dispensing machines, no particle
emissions were observed that correlated with drug dispensing by the robot, so active
pharmaceutical compounds found in the air there are attributed to those generated solely by
manual counting. At the pharmacies using manual counting, active pharmaceutical compounds
found in the air were attributed solely to manual counting.
5.3
Phase III—24-Hour Sampling at Pharmacies Using Parata Max Dispensing Machines
According to a Parata news release, the next generation pharmacy automation system referred
to as the Parata Max was released on July 28, 2008. (Parata, 2008) Subsequently, 24-hr
sampling was performed at Pharmacies P and Q for full 24-hr periods using the same
procedures employed during Phase II testing. The McKesson/Parata Max did exhibit
emissions of pill dust correlated with drug dispensing during the 24-hr sampling. Highly
elevated aerosol concentrations of PM-2.5 particles were observed in the vicinity of the
operating McKesson/Parata Max machines. At both pharmacies, the machines were located
within the pharmacy technicians’ work area. For example, maximum PM-2.5 particle
concentrations were 1,400% higher than concentrations previously observed and documented
in ScriptPro and manual dispensing pharmacies. These elevations were multiples greater than
even the 500% elevations previously observed and documented in pharmacies using
McKesson/Parata RDS dispensing machines. While the McKesson/Parata Max machines were
operating, maximum PM-2.5 aerosol mass concentrations increased to levels that were over
1,800% of concentrations observed and documented in pharmacies using ScriptPro SP 200
dispensing machines or manual dispensing only. Both of the pharmacies using
McKesson/Parata Max dispensing machines which were observed and studied showed
substantially higher levels of aerosol concentrations than were observed at any of the
pharmacies in the original study, including the pharmacies using McKesson/Parata RDS
dispensing machines. Interestingly, PM 2.5 concentrations increased when the Parata RDS
was replaced by a Parata Max between Phases III and IV in the same pharmacy (IIIG/IVR).
A summary of the APS results was included in Table 4-1.
As was done during Phase II, pharmaceutical residues were identified on reference filters used
to sample air near the McKesson/Parata Max machines. A greater number of different aerosol
drug residues were identified near these machines than in any of the pharmacies in the original
study. Table 5-2 shows the drugs that were identified. The chemical analyses were limited in
scope and there were indications that many other drug agents were present.
52
Table 5-2. Compounds in Filter Samples from Pharmacies Using
McKesson/Parata Max Dispensing Machines
Compound
Function
Acetaminophen
Analgesic
Atenolol
Antihypertensive
Baclofen
Muscle relaxer and antispasmodic
Benztropine
Anticholinergic
Butalbital
Sedative hypnotic
Caffeine
Stimulant
Carisoprodol
Muscle relaxant
Clonidine
Antihypertensive
Dicyclomine
Antispasmodic
Enalapril
Antihypertensive
Hydroxychloroquine
Antimalarial
Isosorbide
Vasodilator
Labetalol
Antihypertensive
Lansoprazole
Gastric acid inhibitor
Loratadine
Antihistamine
Metformin
Antihyperglycemic
Methadone
Opioid Analgesic
Niacin
Vitamin
Nifedipine
Antihypertensive
Nitrofurantoin
Antibiotic
Oxybutynin
Antispasmodic
Penicillin
Antibiotic
Phentermine
Appetite suppressant
Propranolol
Antihypertensive
Pseudoephedrine
Decongestant
Sulfamethoxazole
Antibiotic
Temazepam
Sedative hypnotic
Tramadol
Analgesic
Trimethoprim
Antibiotic
5.4
Phase IV—Personal Exposure Monitoring in Pharmacies Using McKesson/Parata RDS
and Max Dispensing Machines
One pharmacy included in the Phase II testing and one pharmacy included in the Phase III
testing were revisited during Phase IV for the purpose of determining exposure assessment by
collecting direct samples. At each pharmacy, four personal exposure monitoring (PEM)
samples were collected during one work shift while the McKesson/Parata RDS and
McKesson/Parata Max were in operation. The 24-hr sampling with the APS was repeated at
Pharmacies R and S for full 24-hr periods using the same procedures employed during Phase II
testing. Using analytical procedures employed during Phase II, pharmaceutical residues were
identified on PEM filters collected from pharmacy personnel working near the
McKesson/Parata Max machines. A greater number of different aerosol drug residues were
53
identified near these machines than in any of the pharmacies in the original study. Table 5-3
shows the drugs that were identified. The chemical analyses were limited in scope and there
were indications that many other drug agents were present.
Table 5-3. Compounds in Filter Samples from Personal Exposure Monitoring Devices
from Pharmacies using McKesson/Parata Dispensing Machines
Compound
Function
Acetaminophen
Analgesic
Acetylsalicylic Acid
Analgesic
Amitriptyline
Antidepressant
Amoxicillin
Antibiotic
Atenolol
Antihypertensive
Carisoprodol
Muscle relaxant
Citalopram
Antidepressant
Clonidine
Antihypertensive
Colchicine
Antigout
Cyclobenzaprine
Muscle relaxant
Desloratadine
Antihistamine
Diclofenac
Anti-inflammatory
Enalapril
Antihypertensive
Hydrochlorothiazide
Diuretic
Hydromorphone
Opiod Analgesic
Meloxicam
Anti-inflammatory
Metformin
Antidiabetic
Methocarbamol
Muscle relaxant
Niacin
Vitamin
Oxybutynin
Anticholinergic
Paroxetine
Antidepressant
Penicillin
Antibiotic
Phenobarbital
Anticonvulsant
Phentermine
Appetite suppressant
Prednisone
Immunosuppressant
Prochlorperazine
Antiemetic
Propranolol
Antihypertensive
Sulfamethoxazole
Antibiotic
Tamsulosin
BPH treatment
Warfarin
Anticoagulant
54
6.
Conclusions
________________________________________________________________________
Through the use of direct monitoring methods, it was determined that personnel working in
pharmacies equipped with Parata RDS or Parata Max systems are exposed to aerosolized
active pharmaceutical compounds. In comparing the data with EPA established standards, the
following observations can be made—PM-2.5 emission peaks correlated with Parata RDS and
Parata Max dispensing frequently exceed the 15.0 µg/m3 level.
Other relevant factors to consider in evaluating the Parata RDS and Parata Max emissions:


Personnel in pharmacies are working indoors and are subject to proximity to source,
constant exposure, and constrained dispersion factors. Thus, a 1000× health impact
risk multiplier may apply as compared with outdoor exposure to the same source.
Active pharmaceutical compounds were determined to be present in these emissions.
Thus there is potential for allergic reactions, cross-contamination, and
synergistic/antagonistic reactions.
Conclusions and Recommendations for further study:




While extensive air quality studies have been performed with respect to personnel
safety in coal mines, cotton mills, etc. leading to workplace standards, our studies are
believed to be the first study addressing risks to workers and customers in pharmacies
arising from pill dust.
The data collected in these studies includes PM-2.5 and PM-10 measurements, and
could be further analyzed to predict health risks from exposure to aerosolized active
pharmaceutical compounds in the particle size ranges and concentrations observed.
This study raises serious issues relative to exposure risks for workers in pharmacies
using air pressure driven dispensing machines. It is important that further studies be
conducted by federal regulatory agencies. It is recommended that these studies assess
human health effects risk, set guidelines for these types of machines, and establish
procedures to monitor the health impact on pharmacy workers. Such studies could
include temporary total enclosures to enable determination of mass rate emissions from
the machines during operation; use of PEMs, as were employed during this phase of
testing, on pharmacy workers; health monitoring of exposed workers; and ongoing
blood and urinalysis monitoring of exposed workers.
If exposure is determined, engineering controls such as dedicated hooded ventilation
ducts equipped with HEPA filters could be recommended, or if engineering controls are
not feasible, personal protective equipment (PPE) for workers could be required.
55
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57
Acknowledgement
Mr. David S. Alburty and Mrs. Pamela S. Murowchick of AlburtyLab, Inc. were the principal
investigators and authors of this report.
Approved for:
ALBURTYLAB, INC.
David S. Alburty
President
July 27, 2009
About AlburtyLab, Inc.
AlburtyLab is an independent laboratory located in Drexel, Missouri, that serves the aerosol research,
development, and instrumentation communities. AlburtyLab has conducted independent studies for a range of
agencies and companies, including Boeing/US Navy, Boston Scientific, Northrop Grumman, US Postal Service,
US Department of Homeland Security, and the US Army Research Laboratory.
Technical questions may be directed to Mr. Alburty at (816) 619-3374 or via email to [email protected].
This study was funded by one of the technologies reviewed in the evaluation, ScriptPro LLC of Mission, Kansas.
58
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Missouri Engineering Labs
128 E. Main St.
Drexel, Missouri 64742
www.alburtylab.com
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