Laboratory cold chain quality performance

an exploratory study
Joye Dixon
Auckland Distract Health Board, Auckland City Hospital, LabPlus Microbiology, Auckland
New Zealand, joyed@adhb.govt.nz

Nihal P. Jayamaha, Nigel P. Grigg

School of Engineering & Advanced Technology, Massey University, Palmerston North, New Zealand,
N.P.Jayamaha@massey.ac.nz, N.Grigg@massey.ac.nz

Abstract
Assuring quality in a medical laboratory requires, among other things, acceptable levels of
quality of the incoming goods. The objective of this prospective study was to examine the
performance of the delivery process of cold chain laboratory products through to the end
user and to identify opportunities for improvement. Temperature and delivery lead-time
were chosen as the desired quality characteristics. Pre-programmed temperature loggers
were used to log the data. The study was undertaken in New Zealand over the seasons of
winter, spring and summer: June 2012 February 2013. By using control charts and other
quality tools that facilitate "statistical thinking" it was found, in the District Health Board
(DHB) studied, that the process of transporting cold chain products did not maintain the
cold chain specifications. During the study it was discovered that products have a stability
budget, which is the number of hours that a product can be outside its normal storage
temperature before it should be discarded because its quality is compromised and its shelf
life shortened. Recommendations have been suggested that may enable the institution to
improve its handling of the cold chain products that it purchases.
Key words: Laboratory Cold Chain, Statistical Thinking (ST), Control Charts, Process
Capability Analysis
Topic: Quality and Performance
Methodology: Empirical work

Introduction
Globalisation of world trade has made supply chains very efficient and effective. However,
the resulting complexity of the supply chain can result in undesirable consequences on the
suppliers and the customers in the supply chain (Parker & Anderson.jr., 2002). It is not
uncommon for New Zealand healthcare providers to procure pharmaceutical products and
laboratory products from as far away places as the USA and UK. The resulting supply
chain involves many inland and offshore logistics services providers sharing information
through an integrated information system. While the quality of pharmaceutical and
laboratory products that can be supplied at ambient temperature levels (i.e. products whose
1

temperature specifications are within the ambient temperature levels that exist across the
supply chain) do not get affected by supply chain inefficiency and ineffectiveness, the same
cannot be said about products whose cold chain has to be maintained (typically between
2oC to 8oC).
There is a general consensus among practitioners that laboratory cold chain products do
not receive the same treatment as the pharmaceutical cold chain products do, even though
the quality of the former (e.g. the quality of HIV AIDS test kits, reagents) can have as
significant an effect on the patients as the quality of the latter (Rodrigue, 2013; Walsh,
2013).
This paper empirically examines the current state of the delivery process of laboratory
cold chain products in terms of two quality characteristics temperature and delivery lead
time and provides short term recommendations to improve the quality performance of
the supply chain, based on the said quality characteristics.
The literature supports the notion that the processes upstream of the local distributor
(e.g. long haul flights) tend to preserve the cold chain and that only when the goods are
repacked and transported locally (via a specialised company) through to the final customer
(laboratory) that breaches to the cold chain tend to occur (Department.of.Health.Victoria,
2014; Rodrigue, 2013). Being an exploratory study, only the weaker link of the supply
chain (the specialised delivery company inwards goods department of the district health
board laboratory) was analysed by the lead researcher. Moreover, this is the link that the
final customer the laboratory has the greatest control over to effect process
improvements in the short term.
Literature Review
Laboratory Cold Chains
As medicine developed through the centuries the advances created the basis for diagnostic
discoveries. In the latter part of the 19th century the clinical laboratory started to be
established. By the turn of the century many specific chemical, haematological and
bacteriological tests had been developed due to innovations in basic science (Berger,
1999a) enabling the clinical laboratory to be used for diagnostic purposes.
Different types of laboratories started to emerge, including physiological,
pharmaceutical, forensic, public health, clinical chemistry and microbiological (Berger,
1999b). Laboratories developed similarly in Britain and the United States of America
(USA) due to the influences of medical faculties in Europe (Petts, 2012; Race, Tillery, &
Dysert, 2004).
The number of laboratory tests available increased dramatically over the 20th century.
The first half of the century was involved in developing individual biochemical methods for
the variety of parameters that medical professionals were interested in such as ion
concentration of elements in serum (Berger, 1999b). Because the refrigerator was not
invented until the late 1910s to early 1920s these methods did not require refrigeration.
Today the range of different analyses available is now well over 3000, and still increasing,
although not all will be available at each laboratory (Wians, 2009).
Requests for laboratory investigations increased as medical professionals found the data
useful in establishing diagnoses. The desire to have this data prior to treatment led to the
expectation of faster turnaround times for testing (Seligson, 1966), so more efficient
methodologies needed to be introduced. The first convenient and accurate kit-type
diagnostic test, Clinitest, was introduced in 1941 and measured reducing sugars in urine
2

(Chemical Heritage Foundation, 2010). This was followed by Clinistix in 1956, the first
dipstick which measured glucose in urine (Chemical Heritage Foundation, 2010).
Although Clinitest has long been discontinued in modern laboratories dipsticks continue
today with up to 10 parameters being measured by one dip in the urine. These types of tests
did not require refrigeration.
Mechanisation followed with the first clinical autoanalyser being introduced in 1959
(Berger, 1999b) and it was around this time that sub-ambient storage of some reagents
became essential. Such analysers could perform multiple tests on much smaller samples of
the patients blood (Seligson, 1966). In the 1960s culture media became more
sophisticated with antibiotics included as selective agents (Smith, 2005) necessitating
storage at sub-ambient temperatures. The sixties also saw computers introduced into
laboratories in Europe, Britain and the USA but they did not become mainstream until the
1970s-1980s (Keller, 1982). Miniaturisation of laboratory techniques began in the 1970s
with microbiology and immunoassays being the initial beneficiaries and this has
progressed through all disciplines (Fung, 2002; Hansen, Hardesty, & Myers, 1974;
McGlennen, 2001). The reagents for these kit/reagents needed to be stored at sub-ambient
temperatures (Ammann, 2011; Ramanujam, Koelbl, & Ting, 1993). An example of this
type of kit is the API range manufactured by bioMriuex Inc. More recently these
techniques have moved onto full automation especially in larger laboratories (Wu, 2006).
The molecular era started in 1943 when Oswald Avery (1877-1955) demonstrated that
deoxyribonucleic acid (DNA) played a significant role in the carriage of genetic
information (Bersch, 2006). Research into DNA moved forward on multiple fronts with
James Watson (b. 1928), Francis Crick (1916-2004), Maurice Wilkins (1916-2004) and
Rosalind Franklin (1920-1958) all working on defining DNAs structure in the early 1950s
(Bersch, 2006). In 1953 the peer reviewed academic journal Nature published this research
and the findings were widely accepted.
This along with further discoveries of critical enzymes and manipulation techniques led
to the development of new laboratory procedures. However, it was not until the invention
of the polymerase chain reaction (PCR) technique by Kary Mullis (b. 1944), in 1983, that
molecular methodologies moved from the research laboratory into the clinical laboratory
(Tang, Procop, & Persing, 1997) providing enhanced sensitivity and faster turnaround
times. Kits that use this technique require sub-ambient temperatures. Kits such as the Hain
Lifescience Genotype Mycobacterium CM/AS, Genotype MDR TBplus and Genotype
SL require a mix of temperatures for storage. The primers and probes need to be kept at
4oC and the master mix that contains the enzymes and dinucleotides at -20oC but are
provided together in the same kit.
Today, the diagnostic industry is starting to move towards "black box" type testing methods
(Bersch, 2006) that includes the three main phases of PCR, extraction, amplification and
detection. This type of testing often does not require specialised staff or sub-ambient
storage conditions for reagents. An example of this is the Gene Expert range of cartridges
manufactured by Cepheid.
To complicate matters the supply chain's national and international regulations are
moving towards "controlled room temperature" (CRT) requiring additional monitoring
steps for ambient temperature packages, and adding complexity to the transportation
process (Healthcare Commerce Media Corporation, April 09, 2010). Ultimately, even the
ambient temperature "black box" products being developed by the diagnostic industry will
come under the CRT auspices.
3

There is an abundance of literature and regulations on the development of drugs for

human use including stability, experimental design and data analysis for the pharmaceutical
industry but for the in vitro device (IVD) manufacturers, who manufacture kits for the
clinical laboratory, there are guidance documents but few regulations.
However, the need for regulation was reinforced by a study performed in 2011 that
showed that devices that had been deemed low risk and were not covered by regulations
had resulted in serious health problems or death for some patients (Zuckerman, Brown, &
Nissen, 2011). A draft document was issued by the Food and Drug Administration (FDA)
that covered companion diagnostic tests, with a deadline of 31 March 2013 but as late as
October 2013 the FDA were still talking about regulating but with no definitive action to
date (Novales-Li, 2013).
Currently, licenced laboratory developed tests (LDTs) and IVDs must be validated and
any reagents used, including calibrators, controls, and sample diluents, must undergo
stability testing so consumers know the temperature and storage limits of the product. In
order to deliver an accurate and precise result each of these components must be
functioning properly.
Stability studies cover the following: expected shelf life or expiration date, temperature,
humidity and photostability, stress testing and storage conditions (Food and Drug
Administration, 2003; International Conference on Harmonisation, 2003). Environmental
factors such as temperature, humidity and light can affect the quality and shelf life of a
product. Stability testing using the climatic zones helps establish a shelf life and the
recommended storage conditions for a product (Markens, 2009). The shelf life should be
based on the long term study at the recommended storage condition. The product should
also be subjected to elevated temperatures for an appropriate time period to emulate the
effect of short term excursions outside the recommended storage conditions which occurs
during shipping (World Health Organisation, 2009). The time-stress or excursion hours are
cumulative and includes all stages of the product's life from production to storage in the
central warehouse, then from the supplier to the distributor, which may mean exporting
overseas, customs or border processing, and lastly from the distributor to the customer. At
signed acceptance of the delivery the stress period is ended for the distributor company as it
has no control over what happens post-delivery.
All products of a temperature-sensitive nature should be labelled appropriately to alert
the customer of the packages storage requirements. The expectation is that the customer
would have procedures in place to manage the receipt of temperature-sensitive products.
However, no products are sold with the cumulative stress hours available making it all the
more essential that all parties involved in the transportation of goods monitor and ensure
that cold chain products are kept at the recommended temperature.
Knowledge of the stress hours originally available and how many have been used would
be useful to the purchaser. For most products the process of bringing a cold chain
kit/reagent to ambient temperature is a requirement before the test can be performed. The
speed of chemical reactions are altered at different temperatures therefore the prerequisite
of bringing a kit to room temperature is necessary because the kit/reagent will have been
designed to work in an ambient environment. These excursions should also be considered
as time-stress hours outside the recommended storage conditions. Consideration should be
given to how many times a kit/reagent is brought to, and left, at ambient temperature in the
laboratory environment and if consumption of the kit is slow then it should be discarded
prior to finishing or reaching its expiry date.
4

Despite the numerous guidance documents surrounding the stability testing of

pharmaceutical products and IVDs, they do not extend to stability in transit. Below (Table
1) is a summary of the situation in 2011.
Table 1 An Overview of Guidance Availability for Cold Chain Products (Seevers, 2011)

Stability
Studies

ICH*
Q1A (R2)
(2003)

Long Term

Guidance

Accelerated

Guidance

Cold Chain Products

WHO
Parental Drug
TRS 953
Association
Annex 2 Technical Report 39
(2009)
(2007)
Guidance References ICH and
WHO
Guidance References ICH and
WHO
No
-20oC for 2 days
Guidance 40oC/75% RH for 2
days

Pharma Industry
Survey (2009)
Follow ICH
Follow ICH

-70oC for 36 months

-15oC to -25oC for 2
weeks to shelf life
0-2oC for 2 weeks to
24 months
30oC/65% RH or
30oC/75% RH for 2
weeks to 6 months
40oC/75% RH for
less than 2 weeks to 6
months
o
Temperature
No
No
-20 C for 2 days Temperature cycling
Cycling
Guidance Guidance followed
by and/or
freeze/thaw
o
25 C/60% RH for 2 for less than 2 weeks
days
to 1 month.
(Repeat for a total of
3 cycles)
* ICH: International Conference on Harmonisation
WHO TRS: World Health Organisation Technical Report Series
Temperature
Excursion

No
Guidance

While the product is being produced and then housed in the manufacturer's warehouse
controlling the cold chain is simple because the manufacturer will have highly controllable
internal systems in place. However, the aim is sell and distribute products and this activity
is difficult to control because it may involve several different organisations.
At the DHB studied pharmaceutical products such as drugs and vaccines which are
introduced into patients are transported in portable insulated containers (PICs) from
suppliers to the IGs department. In packages carrying a critical temperature-sensitive
product, such as vaccines which lose potency outside the recommended temperature range,
a data logger is included. Laboratory kits/reagents and culture media are "packed cold" 1
1

Products are removed from the 2-8oC cold room and packaged together and with paper to help retain the required
temperature.

and transported in boxes with appropriate labelling such as "Refrigerate" or "2oC to 8oC".
The box may or may not be labelled and/or insulated.
There is no time constraint on freighting non-urgent cold chain packages within the
industry. A courier company collecting a package from a supplier in the morning does not
guarantee that it will be delivered the same day. Packages picked up late in the day will
almost certainly be left at the depot overnight or possibly even in the courier van. Well
labelled packages may make it into a cold room at the depot but many will not. Some
depots may not have a cold room.
The cold chain industry has some concerns over "the last mile" or the end stage in the
logistics chain, where a shipment meets its ultimate destination. This may be a laboratory, a
pharmacy or it may be the patient. All temperature-sensitive products are at risk if handled
improperly.
The Inward Goods (IGs) department is the first step in the last mile. Before goods are
accepted for storage, quality control requirements need to be met. This involves ensuring
the product is in an undamaged condition and that temperature-sensitive products are
actually at the correct temperature (Learning and Skills Improvement (LSIS), 2013). If a
product has a 2oC-8oC temperature range then it should be close to or within that range on
delivery. In some countries probes can be used to check between products on a pallet. If
the truck is refrigerated then the vehicle temperature gauge reading should be recorded. The
products should have temperature-sensitive labels on the outside of the box.
On receipt the products should be divided into ambient, refrigerated or frozen. The
refrigerated and frozen products should be placed in a cold room as a matter of priority
until the paperwork has been processed.
Once processed the IGs department should have a standard operating procedure (SOP)
for delivery, which stipulates maintenance of the cold chain, to the relevant departments.
Records should be kept of the time that products are delivered to the various departments
and kept on file so that the last mile is monitored to the very end.
Prior Research on Pharmaceutical Cold Chains
The literature review indicated that most of research on cold chain risk management in the
medical industry has been on biopharmaceutical products. These studies included research
on quality risks associated with accidental freezing of vaccines (e.g. (Matthias, Robertson,
Garrison, Newland, & Nelson, 2007; Nelson et al., 2007; Nelson et al., 2004), quality risk
awareness assessment among medical staff (e.g. (Thakker & Woods, 1992), real time
temperature monitoring using state-of-the-art technology to predict cold chain performance
(e.g. (Chen & Shaw, 2011), review of policy documentation and cold chain management
best practices for transportation (e.g. (Bishara, 2006; Soeung et al., 2004)) and so on. Some
of these studies are discussed in turn.
Matthias et al (2007) conducted a systematic review on extant literature on risk
assessment of accidental freezing of vaccine to identify the prevalence of vaccine freezing
in the cold chain. They found that among studies that examined refrigerated transports,
between 14% to 35% (the figure varied from study to study) of the shipments were exposed
to accidental freezing, while among the studies that examined all segments of the supply
chaindepending on the study that they reviewedbetween 75% of 100% vaccine
shipments were exposed to accidental freezing (among the studies that they examined, they
found that the more rigorous studies reported higher figures). Nelson et al (2007)
monitored cold chain temperatures on a randomly selected sample of vaccine shipments
6

across Bolivia to identify which segment of the supply chain exposes the greatest risk to the
vaccine cold chain. They found that the greatest quality risk (exceeding the 2oC to 8oC
specification) occurs in the last leg of the shipment of goods to the customer.
Thakker and Woods (1992) studied the extent to which United Kingdom (UK) medical
staff adhere to departmental guidelines on vaccine cold chain maintenance, based on a
survey of 40 respondents representing 40 general practices (only the districts Manchester
and Bradford were covered). They found that only 16 out of 40 respondents were aware of
the correct guidelines on cold chain maintenance. Similar findings were reported by
Nelson et al (2004) on a cold chain elsewhere (Indonesia), although accidental freezing was
the main issue that they investigated. The researchers also encouraged other researchers to
conduct stability studies to determine whether maintaining a cold chain at an elevated
temperature (this reduces accidental freezing, energy costs, and waste) can be justified from
a health perspective.
Chen and Shaw (2011) showed how state-of-the art automated data collection methods
(e.g. radio frequency identification techniques) can be used to feed in cold chain product
temperatures to a central station which can take swift action based on temperature trends.
The quality tools that they used to monitor data were the exponentially weighted moving
average (EWMA) control chart and artificial neural networks.
Prior Research on Laboratory Cold Chains
In regards to temperature sensitive medical laboratory goods transportation and
distribution, it appears that current research is focused more towards robust product design
strategies (i.e. making products insensitive to temperature variation) (e.g. (Foo et al., 2012;
Hoizey et al., 2005) and point-of-care technologies (Lee et al., 2010; Shott, Galiwango,
& Reynolds, 2012).
Robust design refers to designing a product at a lower costfor example, by changing
the products design parameter settings rather than spending money on expensive design
components (e.g. raw material) or excessive maintenance costs (e.g. cold chain
maintenance over long haul overland transport)so that the products performance (in a
laboratory product context, the products efficacy) remains robust against the variations of
the environmental factors such as the temperature and the humidity (Montgomery, 2013;
Roy, 2010). Foo et al. (2012) as well as Hoizey (2005) argue that maintaining the cold
chain for long haul shipments in developing countries (e.g. across sub-Saharan Africa) is
costly and robust designs remain an attractive proposition. A similar argument is given for
bringing the laboratory to the patient (the term point-of-care technologies refer to the
collection of technologies that enable medical care, including laboratory services be
provided near to the patient).
New Zealand is a developed country and maintenance of the cold chain of laboratory
products is not cost prohibitive. Whilst alternative technologies such as robust designs and
point of care technologies should be explored, in the short term, efforts should be directed
to maintenance of the cold chain.
Statistical Thinking
There are numerous statistical methods involving number crunching, distributions and
control charting (Britz, 2000) used by statisticians on a daily basis but these are more
effective if used in conjunction with statistical thinking (ST). ST is about looking at time
series data to elucidate the process or phenomenon being observed: what has happened in
7

the past, what is happening currently and what should happen in the future (Ramsey &
Schafer, 1997; Wild & Pfannkuch, 1999).
W. Edwards Deming popularised ST among Japanese workers and managers from 1950s
through to 1970s when he was helping the Japanese industry to improve quality and
productivity to become a competitive industrial nation post World War II (JUCE, 2014). To
Deming, ST is a way of understanding what is happening to a process. He showed the
Japanese engineers and managers that on many occasions processes do show natural
(random) variation (he called this common cause variation), which do not warrant action.
He called such processes stable and predictable processes. Deming showed that a worker
ignorant of this important statistical property would make an unnecessary adjustment to a
process (thinking that an adjustment is needed to curb the variation) when leaving the stable
and predictable process alone would have been the right option. Deming showed that
unnecessary adjustments which he called tampering worsens process variation,
causing more loss to the organisation (more rework and waste) (Deming, 1982; Rao et al.,
1996). Deming identified two instances where action is necessary: (a) if the variation does
not look random (he showed that this occurs due a cause that is not normally part and
parcel of the system, which he called a special cause), and (b) if the natural variation of
the stable process (common cause variation) is so excessive that the process becomes
incapable of meeting the customer specifications (Deming, 1982; Rao et al., 1996). ST is
widely regarded as one factor that made Japanese products superior to (high quality at a
competitive price) the products manufactured in the west in the 1980s (Hoerl & Snee, 2012;
Snee, 1990). More recently an official definition was given to ST.
ST was defined by the American Society for Quality as a philosophy of learning
and action based on the following fundamental principles:
1) All work occurs in a system of interconnected processes.
2) Variation exists in all processes.
3) Understanding and reducing variation are keys to success. (American Society
for Quality, 1996).
The research reported in this paper uses ST to make recommendations to the
process owners to improve the cold chain delivery processes.
Research Questions
Given the background provided on cold chain management and the benefits of ST, the
following research questions are raised:
RQ1: Given the portion of the supply chain studied and the quality characteristics chosen,
does the delivery process remain stable and predictable?
RQ2: Given the portion of the supply chain studied and the quality characteristics chosen,
is the delivery process capable of meeting the requirements placed upon it?
RQ3: If the capability of the process needs to improved, what short term interventions
could be put in place to improve process capability?

Methodology
Demarcation of the System Boundaries and the Critical Control Points
As mentioned earlier, only the local movement of the cold chain goods that is, within
New Zealand transport from the New Zealand distributor through to the hospital medical
laboratory, the weaker link as far as preservation of the cold chain is concerned was
covered. Figure 1 shows the particular system studied (system 2).
When cold chain goods move through the system studied (System2 in Figure 1), the
temperature of the goods enclosed within a package rises due to exchange of heat with the
ambient. As such, the temperature of the product does not remain stable (there is an upward
trend in the temperature particularly in summer months) throughout the delivery process.

Figure 1: Demarcation of the system studied within the overall delivery system

However, given that the temperature of the goods entering the laboratory is expected to
be within the temperature range specified for cold chain products (2oC 8oC), it is possible
to assess the stability (predictability) and the capability of the system based on the
temperature of the goods at the point of arrival to the laboratory. Thus this point was taken
as a critical control point for data monitoring. Figure 2 depicts the critical control points
identified for the system studied, while Table 1 provides a description of these critical
points.

Figure 2: The subsystems of the system studied and the critical control points
Table 2: Definitions of the Critical Control Points
Description of the Critical Control Point
Critical
Control Point
A
Goods are packaged and wait for Courier pickup to leave the supplier
9

Goods enter Inward Goods department

Goods transported from Inward Goods department to laboratory

Goods delivered around laboratory via trolley

Goods unpacked in the laboratory

Note: (a) Please interpret this table in conjunction with Figure 2.

(b) Temperature and elapsed time monitoring was sporadic at critical points C

Given that the highest temperature occurs at control point E, a control chart was
constructed for the temperature at point E, based on the temperature of the incoming goods
in each trip. The I-MR (Individuals-Moving Range) chart was considered to be most
appropriate chart as the data of the variable were individual data (Wheeler & Chambers,
2010).
In addition to the I-MR chart for the temperature at point E, the stability/predictability of
the delivery process was also assessed in terms of the delivery lead time (from point A to
point E) using a run charts (each data point in run chart representing one trip). The control
charts, the run charts as well as process capability analysis was accomplished using the
Minitab 16 software package.
Selection of Participating Delivery Companies and Temperature Data Logging Equipment
A mix of companies were chosen to take part in the survey. They ranged from a family
firm, to companies that specialised in medical laboratory point-of-care kits to large
multinational companies. The large multinational companies included a pharmaceutical
company and two distributor companies involved in selling a wide range of products and
machinery. All the companies made regular deliveries to the laboratory.
Either the Warehouse Manager or the Operations Manager were contacted within each
company to explain that the research being undertaken was focusing on the 'last mile'.
Written instructions were left with each company. It was agreed by all parties that the
companies would remain anonymous.
Two companies were approached for the supply of loggers. Temprecord International
Ltd is an IANZ accredited company whose core competency is the production of a range of
temperature and humidity recording solutions for industry including software, calibration
and support. Six "scientific multi-use" Temprecord loggers were received, each of which
was already calibrated and with the correction factor built into the logger along with a
traceable calibration certificate. The loggers have a long life battery (two year guarantee), a
32K memory, are calibrated to within 0.2oC, readable to two decimal places and are
programmable between two seconds and 36 hours in two second increments. Each logger
has a start delay, start, stop and marker buttons, and inside and outside range indicators but
currently no LED display (Temprecord International Ltd, 2010).
Bell Technology Ltd is regarded as a leader in the supply of industrial process,
laboratory and portable instrumentation in New Zealand. Six "ESCORT Intelligent MINI
(Multi Trip)" loggers were received all of which were not calibrated. The loggers have a
long life battery (one to two year guarantee), memory sufficient for 1868 samples, internal
sensor accuracy 0.5oC, programmable between one and 255 minutes in one minute
intervals and readable to one decimal place. Each logger has a LED display with start and
10

stop buttons and time spent under or over specification (Escort Data Loggers Inc., 2010).
The ESCORT loggers were calibrated and found to have a correction factor of -0.5oC. This
correction could not be built into the logger therefore it had to be subtracted from each
reading.
Both companies have user-friendly software to download the loggers information.
Graphs and data were able to be produced for each trip. Temprecord data could be
exported to Excel for manipulation.
Results
Interpreting the I-MR Chart and Process Capability Analysis
Figure 3 depicts the control chart (I-MR) and process capability information. None of the
individual observations on the moving range (MR) chart fall outside the control chart
limits. There were several trips close to the upper and lower limits and a run of six
consecutive runs above the average but they were not rising or falling continuously.
Otherwise, the points displayed a random pattern. Since the variation (MR) chart was in
control the individual control chart (I chart) was examined. The Individual chart showed
two points outside the upper and lower control limits implying possible a special cause
variation that warrants further investigation.

Figure 3: The control chart and process capability information for the trips studied before
removing the unusual observations

The first trip (trip # 12) that implied instability (out of control) was from the
company that encased the logger in an ice slurry which is not the usual method of
11

transporting cold chain products! Consequently, this was treated as an assignable cause. It
is probable that because the shipment was being monitored with a logger the company
decided to ensure it remained between 2 o C-8 o C. Unfortunately, the temperature
reached well below 2 o C, and if this product had been a vaccine, it would have been
rendered inactive!
The second trip that implied instability was found to be the result of product being
stored overnight at the courier company's depot at ambient temperature. The trip took
place between 30-31 January 2013 when the ambient temperature averaged a high of
26 o C and a low of 16.5 o C (AccuWeather Inc., 2013). The trip from "supplier to
Inward Goods" took 18 hours.
The graphs were reproduced with the datum from the first unusual observation (trip #
12) removed as this was a special cause and not a normal practice but the datum from the
second trip was retained as this happens regularly and is an area that could be improved
upon. The I-MR chart and process capability information (Figure 4) reproduced by
Minitab showed little change in the indices. Although the estimated process mean
increased from 9.98 o C to 10.28 o C while the spread of data (standard deviation) was
reduced from 3.298 to 2.869 (2.9 o C to the 1dp). The normal probability plot in Figure 4
implies that the temperature data does not follow a strict normal distribution.

Figure 4: The control chart and process capability information for the 36 trips studied after
removing the unusual observation

The estimated process mean (after removing trip # 12) was found to be 10.28o C
while the estimated process standard deviation was found to be 2.87o C (the figure
12

shown in the left had side box of the capability plot shown in Figure 4) . This standard
deviation was treated as the baseline figure for future process improvement (reducing the
variation and moving the target value towards 5o C).
Figure 4 shows that the capability indices Cp and Cpk values for the process studied
were 0.26 and 0.23 respectively. Cp and Cpk for a just capable process is treated as 1.00 (any
value below this shows incapability in meeting the specifications), whilst Cp and Cpk values (in
general Cpk < Cp) for a good process is (the industry standard) is considered to be > 1.33
(Montgomery, 2009; Rao, 1996). These figures indicate that the process under review was
not capable of meeting the expectations / requirements placed upon them by the
customers: laboratory scientists and technicians. One way to improve the capability of the
process is to improve the quality of packaging (e.g. provide better insulation, include a
refrigerant). When the quality of packaging is improved, the average temperature of the
goods arriving the laboratory does reduce, because less heat is exchanged with the
ambient. It is also possible to reduce the average temperature of the goods arriving the
laboratory if the average delivery lead time can be reduced.
Interpreting the Run Charts for Delivery Lead Time
For the purpose of data analysis, the delivery lead time, the time elapsed from critical
control points A to E (Figure 2), was partitioned into two elapsed times: elapsed time for
goods movement from point A to B (supplier to inwards goods department) and elapsed
time for goods movement from point B to E (inwards goods to the laboratory).

Figure 5: Minitab run chart for time elapsed "supplier to inward goods department

Both Figures 5 and 6 show that whilst there are no clustering, mixtures, trends and
oscillation of data (see Wheeler and Chambers, 2010 or Evans, 2013 for run chart rules)
there are a number of so called astronomically high elapsed times for cold chain goods
movement, which suggests that the delivery lead time is unstable and unpredictable.
Comparing Figure 6 with Figure 5, it becomes evident that most of the spikes of high
13

elapsed times occur when the goods move from the inwards goods department to the
laboratory. The normal probability plot shown in Figure 7 shows that there are about nine
astronomically high elapsed times out of 36 (25% of instances) trips (elapsed times)
studied. The root causes for the aforesaid spikes were investigated along the five Ms: Men
and Women, Money, Methods, Material, and Mileau (mother nature, surroundings, setting
etc.) (Rao et al., 1996; Wilson, Dell, & Anderson, 1993).

Figure 6: Minitab run chart for time elapsed "inward goods department to the laboratory
Probability Plot of Elapsed Time (min)
Assumed Distribution : Normal
99
95

Percent

80

Astronomically high values!

(9 of them)

50
20
5
1

500

1000

1500

2000

2500

Elapsed Time (min)

Figure 7: The normal probability plot to detect astronomically high elapsed times for delivery of
cold chain goods from the "inward goods department to the laboratory"
14

Figure 8 shows the cause and effects diagram drawn for the high delivery lead time and
temperature variation (since the two effects delivery lead time and temperature are
correlated, it was decided by the researchers that a single cause and effect diagram would
suffice).
Measurement

Materials

Method
Industry is bound by guidance
documents for laboratory
products rather than
regulations

Supplier packs products which

then wait for courier pickup at
room temperature

Product not delivered directly

to Inward Goods by Courier
van - may take many hours to
deliver

Packaging often has confusing

labels or no labels related to
Cold Chain

Inward Goods cold room does

not have its temperature
monitored

No specifications around lead

time for delivery of uninsulated
Cold Chain products

Cold Chain products may be

'packed cold' which does not
accommodate delays in
delivery

Cold Chain products may not

be packaged in insulated
containers

Product may spend overnight

at room temperature in Courier
depot

Inward Goods do not

accommodate varying
temperature requirements of
products
Products not packaged
adequately for delays in
delivery both by Courier and
from Inward Goods to

Data logging not performed on

laboratory cold chain products

Products vary in temperature

requirements

Laboratory leaves products at

room temperature all day 'just
in case' they need to be used

Products packed and left in

Supplier warehouses until
pickup can reach high
temperatures in summer

Laboratory delivery staff have

many tasks and may not be
available when product
delivered by Inward Goods

Courier vans do not have

refrigerated compartments

Warehouse type environments

such as Inward Goods
departments can reach high
temperatures in summer
Laboratory products are left in
a North facing foyer until
delivery to cold rooms within
laboratory
Packages left at room
temperature whilst being
delivered - delivery may take
a long time

Inward Goods staff not trained

in Good Distribution Practice

Inward Goods staff not aware

of the 'Cold Chain'

Inward Goods staff accept

cold chain products regardless
of condition

Problem
Statement
Excessive
Delivery Lead
Time and High
Temperature
Variation

Inward Goods department

hasn't been refurbished for 38
years.

Insufficient staff in Inward

Goods department to turn
product around rapidly

Inadequate training of Inward

Goods staff in Good
Distribution Practice and
awareness of the Cold Chain

Cost of portable insulated

containers relative to the cost
of the product

Courier drivers do not adhere

to cold chain requirements

Supplier staff do not

accommodate cold chain
products once packaged for
delivery

Supplier staff rely on 'stability

budget' for out of specification
deliveries.

Mileau (Environment)

Men and Women

Money (Capital)

Figure 8: The cause and effects diagram

The delivery goods from the inwards goods department to the laboratory are handled by
the inwards goods department. Therefore improvement of the work processes of the
inwards goods department stands out as a high leverage opportunity for process
improvement in order to reduce the delivery lead time (and the associated variation). When
15

the lead time is reduced and made stable, the average temperature (and its variation) of
goods arriving at the laboratory will also reduce and this will therefore improve the
capability of the goods movement process overall.
Discussion and Recommendations
If "Quality health care means doing the right thing, at the right time, in the right way, for
the right person and having the best possible results" (Agency for Healthcare Research
and Quality, 2007) then it is one of a DHBs core responsibilities to undertake risk
management for cold chain products, their processing through IGs and delivery to various
departments.
This study covered the delivery of product from suppliers to a large tertiary institution
laboratory via the IGs department. As can be seen from the results the cold chain is not
upheld during most trips. Cold chain products for the laboratory are not treated
similarly to pharmaceuticals by distributing companies. The cold chain around
pharmaceuticals is more stringent than for laboratory products and as a result drugs and
vaccines are transported in portable insulated containers (PICs) with the appropriate
refrigerant whereas laboratory products are packaged in boxes with 2o C 8o C labels
affixed. A refrigerant may or may not be present, the box may be or may not be insulated.
The IGs department did not record the delivery time of packages and as a result there
was no proof of delivery of a package. Neither did it separate cold chain and ambient
products to be independently processed, stored or delivered. Consequently, product sat at
ambient temperature for various time frames thereby adding to a products cumulative
excursion hours and shortening a products usable shelf life within the laboratory.
The question is why are laboratory cold chain products not treated similarly to
pharmaceuticals by suppliers? Although products are not being introduced into a patient,
the results of diagnostic testing are being used in up to 70% of diagnoses (Hallworth, 2011)
and therefore ensuring that the right result (i.e. lowest number of false positives and false
negatives) is obtained is essential. If the products have not been stored correctly during
transit, especially once they arrive at the IGs department, then the quality of the product
could be compromised.
Based on the lead authors experience and her own investigations on the potential root
causes for the reduced priority for laboratory cold chain products compared to
pharmaceutical cold chain products (in terms of maintaining the cold chain), the following
potential root causes are proposed:

Money - High Cost of Portable Insulated Containers (PICs) Relative to the Cost
of the Product Supplied: Reusable PICs could be used and a recycling
programme developed. When a new delivery is made the PICs from the
previous delivery to IGs could be picked up and returned to the company on
their next pick up. This would be made easier by companies having a
relationship with a courier or logistics company as suggested as Good
Distribution Practice (GDP). There could even be a city-or-countrywide
cycling of PICs where companies that receive PICs use them for the next trip.

Procedures - The industry is bound by guidance documents as opposed to

regulation. However, this is changing as governing bodies realise that
16

maintaining the cold chain is important and the logistics industry gathers
momentum to improve their service in this area.

Communication It appears that the IGs department has not necessarily kept up
with changes in the logistics area. At the very least such a department should
recognise the difference in the handling requirements of cold chain to ambient
temperature products and have access to a well maintained, monitored cold
room. This may mean a change to current practices. However, as well as
managing the cold chain, the future predicts such areas will have to be climate
controlled due to "controlled room temperature" guidance documents presently
in the pipeline.
The following short term process improvement recommendations were proposed to
the management of the DHB.
Recommendation #1
Health Alliance (hA) should notify their suppliers that packages should be labelled as to
the appropriate storage temperature on the outside of the box. Inappropriate labels
should be occluded on reused packaging and mixed packages should be discontinued.
IGs should not accept goods that have confusing storage condition labelling.
Recommendation # 2
Health Alliance should insist that all cold chain packages should be delivered in a
refrigerated vehicle or container. Such pressure would ensure that distribution
companies complied and the courier market would respond in kind. Also, the arrival of a
product in such a container would reinforce to the IGs staff that the product requires special
attention.
Recommendation # 3
The IGs department should record the delivery time of packages. This is common
practice in warehousing and is important for GDP. It also provides an audit trail for
deliveries. It may be as simple as writing on the box, in felt tip, the delivery date and time.
This information could then be entered into the supply chain computer software when the
product is receipted in.
Recommendation # 4
Packages need to be sorted on arrival onto ambient temperature and cold chain trolleys.
Cold chain trolleys would then be placed in the cold room until ready to be processed.
The cold chain trolleys need to be smaller so that only a limited number of packages are
removed for processing at any one time. Once processed the cold chain trolley would be
returned to the cold room until delivery to the laboratory was imminent. To make this a
lean process may require some reconfiguration of IGs so that there is a better work flow
between the staff and the cold room.
Recommendation # 5
Colour coding the packages as to the department they are to be delivered to within the
laboratory would assist the delivery staff, ensuring that they always deliver the products
17

to the correct department. This would help prevent "lost packages" that may not be
handled correctly by the receiving department if it is a product they do not normally
receive. It would also help when there is more than one box per picking slip.
Recommendation # 6
A cold chain trolley for "Frozen" products should also be available and separate to the
products to be refrigerated. Such products are usually packaged in dry ice which is
regarded as a dangerous good. As a result the package will be labelled with the appropriate
category labels making it obvious it is a cold chain product. Dry ice will keep the product
frozen but it would be useful to separate such products so that it is not left in the cold
room over a weekend as the dry ice will dissipate leaving the product at 4o C rather than 20o C. "FROZEN" stickers should be used on these products.
The "REFRIGERATE" or "FROZEN" stickers on the picking slip are useful to the
staff unpacking the products and should remain but it may also be useful to put another
sticker, in plain sight, on the package especially if the package does not have any other
indication that it is a cold chain product.
Recommendation # 7
The cold room should have temperature spatials 2 done six monthly to ensure that it is
running at the correct temperature range.
Recommendation # 8
Staff should be trained in all aspects of warehousing so that they can troubleshoot when
there are problems. This training would also give them an insight into the logistics of the
cold chain and their role in ensuring it is not broken. It would also give them the ability to
recommend changes that would result in quality improvement of the process.
Recommendation # 9
The delivery venue at the laboratory is unacceptable for cold chain products. Not only are
products left in a public space but it is a north facing glass fronted foyer which becomes
very hot in summer. The foyer area should have a small cold room installed, perhaps under
the stairs, where the cold chain trolleys could be stored until delivery staff are available to
distribute the products to the departments. Whilst in this cold room the packages could be
sorted into departments using the department colour coding placed on the package by IGs.
Then the products could be delivered directly to each department and placed in the different
cold rooms.

Recommendation # 10
Cumulative excursions need to be managed. An example of a possible method follows
(Table 2).
2

Spatials data loggers are placed at various points around the cold room and the temperature logged over a specific time
frame to give an indication as to any hot or cold spots in the cold room and whether the temperature remains within the
correct range.

18

Table 2: Example of Check Sheet for Temperature Excursions on Product

Grouping Kit
Batch #: C1234
Received:
17/1/13 Opened:
15/2/13

Date and Time

Removed from Cold
Returned to Cold
Room
Room
15/2/13
0800
15/2/13
1500
16/2/13
0800
16/2/13
1300
17/2/13
0800
17/2/13
1600

Hours at
Ambient
Temperatur
7
5
8

Accumulate
d Hours
7
12
20

The practice of removing a product from the cold room in the morning and leaving it at
ambient temperature all day may need to be adjusted. Labels could be affixed to each
product which can be used to monitor the excursions. If the requisite excursion hours are
not available to the laboratory an average arbitrary figure could be used such as 120 hours.
This label could then be photocopied or scanned and stored as an audit trail for that
particular product.
Recommendation # 11
The laboratorys mission statement and values should be displayed in each department
and staff reminded of them regularly. All staff, no matter what their role, should be
treated with respect by other staff and only then will the laboratorys and the DHBs
values be upheld.
Staff need to be reminded by senior management that as personnel of the laboratory
they are all on the same team and that no one person is superior to another. For the
laboratory to fulfil its mission statement people should be treated with respect regardless
of their role. Staff need to remember that the delivery staff are essential as they supply
products to the laboratory staff to ensure testing is done in a timely manner.
Conclusion
Customers of the laboratory services such as clinicians rely on true and accurate results.
Companies supply laboratories with products to perform tests and investigations using both
cold chain and ambient products. Cold chain product packages need to meet the
challenging temperature specification of 2oC to 8oC, the target being 5oC. Breaches of the
upper specification limit over prolonged periods can have an adverse impact on the quality
of laboratory services through inaccurate test results.
This study was undertaken to determine whether the portion of the supply chain studied,
and using the quality characteristics chosen, was able to provide a stable and predictable
delivery system which met the requirements of the products being transported. If capability
needed to be improved what short term interventions could be put in place?
The study found that the ambient product process was stable, predictable and met the
transport requirements the same could not be said about the delivery of cold chain products.
Based on the I-MR charts, the cold chain delivery process was almost always found to be
stable but the process means were way off-target and the variation was too high, given the
temperature specification.
19

The cold chain problem arises because distributing companies transport pharmaceutical
products differently to laboratory kits and reagents (IVDs). This is due to the regulation
surrounding pharmaceuticals compared to the guidance documents for products used in
laboratories. Despite the fact that the kits and reagents are not used to treat patients they
are used to help diagnose patients conditions and treatment so it is essential that their
quality is not compromised. Data loggers are the most efficient way of logging
temperatures as they are reusable and their data can be downloaded to a computer or the
cloud, stored indefinitely and provide an audit trail.
According to the literature the last mile is of concern to the transportation and
distribution companies as they no longer have control of the product and it is at this point
that the cold chain often breaks down.
It is hoped that the results will stimulate a larger and more comprehensive survey with
all of the critical control points being monitored through co-operation between distributors,
courier companies and the DHB. With a trip defined by these critical control points,
moving ranges could be calculated for each part of the trip creating the opportunity to
generate key performance indicators (KPIs) and it would also define the times when the
product was sitting in a warehouse as opposed to being transported. This would give
increased information by clearly showing which areas of the transportation process require
modification thereby strengthening the need for change in various areas of the supply chain
either within the hospital, courier depots or by the supplier.
The study showed how statistical process control can help in identifying delivery
performance gaps of cold chain products to a laboratory and uncovered the need to identify
industry best practices related to delivery of laboratory cold chain products.
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