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contents
Beyond SOPs page 4
Whats Trending in Pharma IT? page 10
All-Star Innovators 2014 page 18
Vials vs. Dual-Chamber Systems page 24
Compliance Management page 27
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AS THE philosophy and techniques enshrined in
Quality by Design (QbD) become second nature to the
pharmaceutical industry, their application is spread-ing. Analytical method development is a current area
o ocus. Te process o developing, validating and
deploying analytical methods closely parallels product
development and can similarly benefit rom the sys-
tematic and scientific approach that QbD promotes.
Te dependence o pharmaceutical development and
manuacture on robust analytical data intensifies
the need or rigor in analytical method development
and increasingly a QbD approach Analytical QbD
(AQbD) is seen as the way orward.
THE GOAL IS TO DEVELOP
In analytical method development the goal is to
develop, validate and deploy a method or making an
analysis that will deliver the inormation required,
in all the instances that it is required to do so. Te
starting point is to identiy exactly why the measure-
ment is being made; in the same way that the starting
point or conventional QbD is to identiy clinical
perormance targets or the product. Once this is
established, the process is one o understanding and
learning to control those aspects o the measurement
method that define critical elements o analyticalperormance. Tis closely mirrors the QbD model o
working toward a ully scoped design space.
INTRODUCING THE PRINCIPLES OF QBD
A useul starting point or examining AQbD is to
return to the generally accepted definition o QbD,which was originally presented in International Con-
erence on Harmonization document Q8(R2). Tis
states that QbD is:
A systematic approach to development that begins
with predefined objectives and emphasizes product
and process understanding and process control, based
on sound science and quality risk management
Figure 1 shows the QbD workflow that represents
this systematic approach. Te first step is to identiy
the Quality arget Product Profile (QPP), the
definition o what the product must deliver. Te
subsequent steps o QbD involve identification o
the variables that must be controlled to deliver the
defined product perormance, and the best way o
implementing that control.
CONTINUOUS IMPROVEMENT WRAPPER
Determination o perormance-defining Critical
Quality Attributes (CQAs), and the Critical Process
Parameters (CPPs) and Critical Material Properties
(CMAs) that control them, comes first. Definition o
the design space ollows. Te design space is the op-
erating envelope or the process. It encompasses thedefined ranges or the CPPs and CMAs that ensure
the CQAs will be achieved consistently. Defining the
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Figure 1: QbD workflows for product development and the analogous
workflow for analytical method development.
Figure 2: Laser diffraction analyzers determine particle size from the pat-
tern of scattered light produced as a collimated laser beam interacts with
particles in the sample.
Incident light
Incident light
Small angle scattering
Large angle scattering
control strategies needed to maintain operation within
the design space is the final step, but the entire workflow is
wrapped within a process o continuous improvement across
the liecycle o the drug. Indeed, a major attraction o QbD is
that its application permits ongoing optimization within thedesign space without requiring urther regulatory approval.
ICHQ8 (R2) does not specifically mention analytical
method development. However, the underlined phrases in
the original QbD definition (above) have direct resonance
when looking to apply a structured, rigorous approach to
developing analytical methods. Tis resonance has prompted
the evolution o Analytical Quality by Design (AQbD).
TRANSFERRING QBD TO ANALYTICAL METHOD
DEVELOPMENT
FDA guidance on the application o AQbD [1] highlights the
potential benefits o transerring QbD to analytical methoddevelopment. Te proposal is that AQbD will lead to the
development o a robust method that will be applicable
throughout the liecycle o the product. Just as with QbD,
being able to demonstrate adherence to AQbD will be associ-
ated with a certain degree o regulatory flexibility, providing
the reedom to change method parameters within a methods
design space, reerred to as the Method Operable Design
Region (MODR).
Te starting point or AQbD is an Analytical arget
Profile, or AP, which is directly analogous to a QPP
(Figure 1). Te AP defines the goal o the analytical method
development process, linking the output o the method to
the overall QPP. Identiying why the analytical inormation
is required, what it will be used or and when, helps to
ormulate the AP. Supplementary targets or perormance
characteristics, such as precision and reproducibility, stem
rom a more detailed analysis o these needs.
Te next step is to identiy a suitable analytical technique.
Tis must be done with reerence to the needs defined in
the AP. Once the technique is identified, AQbD ocuses on
method development and includes detailed assessment o the
risks associated with variability associated with:
Aayst metods Istumet couatio ad maiteace
Measuemet ad metod paametes
Mateia caacteistics
Eiometa coditios
Tis assessment identifies the CQAs, the parameters that
impact te ATP. A Desi of Epeimets (DOE) appoac
is then adopted to define the MODR. Tis is the operating
range or the CQAs that produces results that consistently
meet the goals set out in the AP. Once this is defined,
appropriate method controls can be put in place and method
validation carried out ollowing the guidance in ICH Q2.
Like QbD, AQbD works on the principle o recognizingand handling variability by understanding its potential
impact. By identiying an analytical design space, rather than
applying a fixed set o measurement conditions, it enables a
responsive approach to the inherent variability encountered
in day-to-day analysis throughout the liecycle o a
pharmaceutical product. Tis delivers an analytical method
that is robust in daily use and which also substantially
reduces the potential or ailure when the method is
transerred rom, or example, a research laboratory through
to QC. Te root causes o method transer ailure can usually
be traced back to insufficient consideration having been given
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Figure 3: Output of an assessment of the key parameters for a dry dispersion method. Items shown
in green are noise factors within the method; those in orange are control factors; whereas those in
red must be investigated experimentally to determine the MODR.
to the nature o the routine operating
environment and a ailure to capture
and transer the inormation needed to
ensure robust measurement. Applying
AQbD overcomes these issues and has the
potential to eliminate costly mistakes.
DEVELOPING A PARTICLE
SIZING METHOD
Addressing a specific analytical chal-
lenge helps to clariy what the applica-
tion o AQbD looks like in practice.
Consider the scenario o measuring the
particle size distribution o a micron-
ized active pharmaceutical ingredient
with the goal o assessing its suitability
or downstream processing and bio-
availability or a solid oral dose product.In this situation the AP is
the measurement o particle size
distribution at a defined point in the
process, in a way that is precise enough
to ensure the material will perorm to
expectations. In practice, the required
level o precision may exceed that
which is laid down in the US and
Euopea Pamacopoeias [2, 3], but
or simplicity we will assume that the
USP ad P. Eu. acceptace citeia
are adequate. Many techniques are
available or particle size distribution
measurement, but laser diffraction
is the method o choice or most
pharmaceutical applications. So we
will base this AQbD example on laser
diffraction particle size measurement.
INTRODUCING LASER
DIFFRACTION
Fast, non-destructive and amenable
to automation, particle sizing by laserdiffraction is a technique that has been
tailored in modern instrumentation or
high productivity, routine use. In a laser
diffraction particle size analyzer, the
particles in a sample are illuminated
by a collimated laser beam. Te light is
scattered by the particles present over
a range o angles, with large particles
predominantly scattering light with
high intensity at narrow angles, and
smaller particles producing lower in-
tensity signals over a much wider range
o angles. Laser diffraction systems
measure the intensity o light scattered
by the particles as a unction o angle
and wavelength. Application o an ap-
propriate light scattering model, such
as Mie theory, enables particle size dis-
tribution to be calculated directly rom
the measured scattered light pattern.
Laser diffraction involves relatively
little sample preparation, but it is
essential to present the sample in a
suitably dispersed state to generate
data that are relevant. In our example,
the need is to measure the primary
particle size distribution o the active
pharmaceutical ingredient. Tis
means that any agglomerated material
present must be dispersed, prior to
measurement, to ensure consistent
and relevant results. Here then the
parameters applied to ensure completedispersion are CQAs, variables that
have a direct impact on the quality o
the results. Investigating dispersion in
a systematic way is thereore a primary
objective when it comes to defining the
MODR or a laser diffraction method.
SCOPING THE MODR
When it comes to dispersing a sample
or laser diffraction particle size mea-
surement, there is a choice to be made
between dry powder or liquid disper-
sion. Dry dispersion is the preerred
option because it:
Eabes apid measuemet to be made,
Is we-suited to moistue-sesitie
materials,
Accommodates eatiey ae sampe
volumes, enabling reproducible mea-
surement o poly disperse materials,
and
Is environmentally benign, as the use
o organic liquid dispersants is avoided.
Although dry dispersion offers
these advantages, it is not suitable
or all sample types. Dry dispersion
involves entraining the sample within
a high-velocity air stream. Te process
o entrainment subjects the particles
to substantial shear energy and
promotes particle-particle/particle-wall
collisions, dispersing any agglomerates.
Friable materials may be damaged bythis process. It may also be hazardous
to handle highly active ingredients in
this way because o the risks associated
with aerosolization. Some samples are
thereore better suited to liquid-based
measurement.
Fiue 3 sows some of te CQAs
associated with a dry method or
a micronized API powder. In dry
dispersion, the air pressure applied
during entrainment o the sample is the
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Figure 4: Pressure titration data for a lactose formulation. A comparison of liquid (blue) and dry
measurement shows close agreement at a compressed air pressure of 3 bar with the standard
venturi (upper plot) and at 1 bar with the more aggressive venturi (lower plot).
Figure 5: Plotting measured particle size as a function of air pressure for each venturi disperser.
Shaded region shows where the results are in agreement with the reference method to within
USP guidance. The standard venturi disperser delivers a wider MODR.
VolumeDensity(%)
VolumeDensity(%)
Size Classes (m)
Size Classes (m)
Dv50/m
Air Pressure / Bar
lever that is used to control the input
o energy into the dispersion process.
Tis identifies it as a CQA. Another
consideration is the sample eed rate, as
this determines the amount o material
which passes through the venturiduring the dispersion process and
thereore the efficiency o dispersion.
It also defines the concentration o
a sample, which in turn can have an
impact on the measurement process
itsel. I particle number/density is
too low, then the signal to noise ratio
during measurement may be unreliable.
Conversely, a high particle density
increases the risk o multiple scattering,
where the light interacts with more
than one particle prior to detection,a phenomenon that complicates the
calculation o particle size. Feed rate,
thereore, tends to be the other CQA
when using dry dispersion or laser
diffraction particle size measurements.
So, working on the basis that dry
dispersion is suitable or our model
sample, and that the above assessment
is realistic in terms o identiying
the CQAs or the method, one o the
steps needed to scope the MODR is to
determine how air pressure influences
the results o the analysis. Te
experiment that delivers the necessary
data is commonly reerred to as a
pressure titration.
Figure 4 shows results rom two
pressure titrations. Tese were carried
out usi te Mastesize 3000,
which has a number o modular dry
dispersion units that allow the intensity
o dry dispersion to be matched to the
sample. Te upper o the two plotswas measured using a dry dispersion
unit fitted with the systems standard
venturi disperser, while the lower plot
was generated using a venturi designed
to provide high dispersion energies.
Te aim with dry dispersion is to
completely break up any agglomerates
present, without causing damage
to the primary particles. Te results
show that with each venturi increasing
pressure decreases particle size. Tis
raises the question o how to determine
whether a given pressure is breakingup agglomerates as required, or is
causing damage to primary particles.
A comparison with a reerence liquid
dispersion measurement helps to answer
this question since liquid dispersion
very rarely results in particle damage.
Results rom liquid measurements
are shown in blue in Figure 4. Tese
indicate that the standard venturi
disperser delivers complete dispersion
at a compressed air pressure o around
3 ba, weeas usi te i eey
venturi disperser an air pressure oaround 1 bar is required.
Tese data suggest that it would be
possible to use either o the venturi
tested. However, by plotting particle
size as a unction o air pressure or
each venturi (Figure 5) it can be seen
that the standard venturi is the better
option. Tis plot shows that the MODR
is larger with the standard venturi than
with the high energy disperser.
Tese results show that with the
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Figure 6: Mastersizer 3000 measurement manager, showing a dispersion trend. Figure 7: Measurement data quality advice
provided in the Mastersizer 3000 software.
high energy disperser any variation in air pressure will have
a significant effect on particle size, compromising the ability
o the method to meet the AP. Using the standard venturi,
on the other hand, the particle size results are reasonably
cosistet acoss te pessue ae 3 to 4 ba. is etui
will thereore deliver an inherently more robust measurement.
Te MODR associated with its use can be determined, in
terms o suitable air pressure, on the basis o these data.
METHOD VALIDATION
Te data shown in Figure 5 enable the selection o a dispersion
pressure which would be expected to deliver robust results. o
ensure that a proposed method meets the AP, it is essential
to veriy that any variability in the way the method is applied
does not shif the precision o the results outside the intended
limits. Tis requires the method to be validated, ollowing the
guidance outlined in ICH Q2.
wo concepts are central to confirming that a particle sizing
method is fit or purpose: repeatability and reproducibility.
Assessing repeatability involves duplicate measurements o the
same sample. It thereore tests the precision o the instrument,
and the consistency o the sampling and dispersion process.
Reproducibility is a broader concept that also encompassesmultiple operators or even multiple analytical system
installations.
Bot te USP [2] ad EP [3] ecommed acceptace citeia
or reproducibility testing. A Coefficient o Variability (COV)
of ess tat 10% is suested as acceptabe fo te media
(D50) patice size o ay simia aue wic is cose to
the center o the particle size distribution. Tis figure rises
to 15% o aues towads te ede of te distibutio, suc
as D10 ad D90, te patice size beow wic 10 ad 90%
o the population lies on the basis o volume. Tese limits
ae doubed fo sampes cotaii patices smae ta 10
microns because o the difficulties associated with dispersing
such fine powders.
In our example then, where the acceptance criteria or
the results are based on pharmacopoeial guidance, robust
definition o the MODR requires that any source o variability
does not take data reproducibility outside these limits.
For example, the precision o air pressure control during
dispersion is a unction o the analyzer. I air pressure, a CQA,
is cotoed to witi +/-0.1 ba, it is ecessay to coduct
experiments to determine the level o variability that this
introduces in terms o the repeatability and reproducibility o
the measured data. All potential sources o variability must be
investigated in this way.
TOOLS TO EASE AQBD
As with QbD, AQbD places the emphasis on ully understand-
ing a process, rather than simply ocusing on a set o condi-
tions that work or certain sample types. Te potential rewards
o this approach have already been highlighted, but gaining
the necessary understanding is inextricably linked with more
extensive experimentation. ools that can alleviate the burden
associated with this research are thereore to be welcomed.
Fiue 6 sows a scee sot fom te Mastesize 3000illustrating the Measurement Manager tool. Tis is a sofware
eature that provides real-time eedback which indicates the
impact o changing an analytical parameter. Parameters
can either be modified by the user in real-time as part o a
manually controlled measurement or they can be set within
pre-defined measurement sequences within the sofwares
SOP-player tool. Tis tool provides the first step towards ull
automation o the method development process.
In addition to aiding with the process o method
development, there is also a requirement to ensure that
the data collected are reasonable and thereore reflect the
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9
capabilities o the analytical technique in terms o both
resolving product changes and delivering reproducible results.
Here, tools to assess the quality o the data are extremely
valuable, helping to guide the user towards the definition o a
good method.
Figure 7 shows the output o the Data Quality assessmenttoo poided i te Mastesize 3000. Adice is ie eati
the measurement process (e.g. instrument cleanliness and
alignment) and also the analysis process (e.g. the goodness o
fit between the light scattering data acquired by the instrument
and the optical model selected to calculate a size distribution
rom these data). Tis helps to address many o the method
control issues highlighted in Figure 4. Sofware advances such
as these can thereore make a big difference when it comes
to the application o AQbD, and they substantially ease the
analytical burden associated with its implementation.
LOOKING AHEAD
A decade or so ago the introduction o standard operating
procedures (SOPs) was groundbreaking, but analytical method
development is now moving beyond simply defining a fixed set
o measurement parameters. AQbD invites analysts to estab-
lish a robust MODR, a sae analytical working space. Work-
ing within the MODR ensures that results consistently meet
defined quality criteria while at the same time providing the
flexibility to respond to routinely encountered variability.
Te understanding that comes with scoping the MODR
secures robust application o an analytical method across the
product liecycle and substantially eases method transer.
As with QbD, AQbD holds out the attraction o greater
understanding, but brings with it the burden o a broader
research remit. However, advances in instrumentation, mostespecially in sofware, can make a major contribution when
it comes to efficient scoping o the MODR. Features such as
real-time eedback on the stability o a measurement and the
impact o changes, or example, and the ability to automatically
step through a series o SOPs, can help to substantially lighten
the analytical burden, enabling analysts to reap the benefits o
AQbD more easily.
References
[1] QbD Considerations for Analytical Methods FDA Perspective.
Presentation by Sharmista
Chatterjee at IFPAC Annual Meeting, Jan 25th 2013. Available for
download from
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedi-
calProductsandTobacco/CDER/UCM359266.pdf
[2] General Chapter , Light Diffraction Measurement Of Particle
Size, United States Pharmacopeia, Pharmacopoeial Forum (2005), 31,
pp1235-1241
[3] General Chapter 2.9.31, Laser Diffraction Measurement of
Particle Size, European Pharmacopeia.
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ChAllEngIng PhArMACEUTICAl
manuacturers everywhere, every day are the myriad is-
sues surrounding the acquisition, disposition and analysis
o the huge amounts o data their operations create around
the clock. Any Pharma producer worth its salt these days
is likely investing a great deal o time, resources and effort
to create or maintain a comprehensive inormation tech-
nology (I) inrastructure to support compliant opera-
tions, process quality and efficiency, and ultimately assure
product saety, effectiveness and affordability.
Accodi to eseac m Compute Ecoomics,
which provides benchmarking metrics to aid I
operations management, lie science organizations
have some unique attributes. In its study, Comparative
Analysis o I Spending in the Lie Sciences, Computer
Ecoomics compaed i-ee spedi metics fo ife
science companies against a broad sample o organizations
in all industries. Te study delivered our key findings:
1. Lie science companies have high I intensity. Tey
spend considerably more than the composite sample,
as measured by total I spending per user and spend-
ing as a percentage o revenue.
2. Lie science companies spend a higher portion o
their I budgets on data center and network inra-
structure than the average company, and they spend
a correspondingly smaller portion on business ap-
plication sofware.
3. Te sie of te appicatio suppot staf f ad
spending on application sotwa re per user is typi-
cal, indicat ing that high data center and network
inrastructure costs are the actors that drive I
spending in this sector.
4. Te staffing mix or lie science companies is simi-
lar to other organizations. I staffing headcount,
thereore, can be benchmarked against similar-size
organizations rom all sectors.
Within the context o a typical drug manuacturing
environment and its incumbent data volume, it makes
sense that Pharmas spending may be proportionately
higher than other industries to und its high-capacity
data adi eeds. recet, gate Becma
Aatics eeased its IT Metics Data 2014 epot
which revealed that Pharmaceuticals, Lie Sciencesad Medica Poducts compaies sped 3.2 pecet of
revenues on their I inrastructure a level higher
ta Idustia Eectoics ad Eectica Equipmet
(2.5 percent), Industrial Manuacturing (1.7 percent),
ad iteesti eou, Cemicas at 1.3 pecet.
What these figures seem to reflect is the reality on the
ground; that is, Pharma is spending more (generally)
now than peer counterparts because those industries
are urther along the curve when it comes to integrating
a modern, enterprise-wide I inrastructure to support
operations and business goals.
OPErATIOnAl TrAnSPArEnCy AnD OPTIMIzED PrOCESSES FrOM lAB TOPlAnT FlOOr TO ExECUTIvE SUITE AnD BACk ArE DrIvIng IT InvESTMEnTS
I N F O R M A T I O N T E C H N O L O G Y A L M A N A C I T PA N E L
BEST OFPHARMACEUTICAL M ANUFACTURING www.pharmamanufacturing.com
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Wheres I spending heading or Pharma and Lie
Science companies? Analytics firm Inorma Ovum
orecasts global lie sciences technology spending toeac $40.8 bi io b te ed of 2017. Accodi to
Ovums research, spending will increase at a cumula-
tie aua owt ate (CAgr) of 3.6 pecet to eac
the predicted figure. Ovum says its study reveals that
the increase in I spending will be ueled in large
part by the growth in data analysis and related tech-
nologies, the acquisition o systems to comply with
new regulatory requirements, and increased spending
on applications that advance operating efficiency and
automatio. Esewee, Oums dis sow tat
value chain ragmentation caused by new entities
being spun out o Big Pharma and rapid growth in emerging markets will see strong I spending growth
of 9.4 pecet CAgr i te sma pama/biotec sub
secto, totai $10.5 biio i 2017.
he actors driving I spending in the lie
sciences industry continue to be complex, with
payers o healthcare demanding greater value in
the ace o increasing costs, technological advances
enabling new types o research that are changing
societal expectations, and opportunities arising rom
the emerging markets, explains Andrew Brosnan,
senior analyst, healthcare and lie sciences at Ovum.
We expect much o this predicted growth to come
rom investment in business intelligence (BI) and
analytics, as institutions look to collect, clean,
manage and analyze the vast amount o data rom
sources such as social media, electronic medical
records and genetic sequencing.
Ovum expects total I spending as a percentage
of tota eeues to decease to 3.4 pecet i 2017,
even though overall I spending will be higher as
total revenue increases, largely due to I-related cost
efficiencies and the increased use o generics, which are
less I-intensive to develop than novel medications.Te improvement o I-related cost efficiencies
will be achieved through systems simplification and
inrastructure consolidation, urther cloud adoption,
alling component prices and increased external
souci, epais Bosa. geate eteaiatio
o what were once in-house resources and capabilities
is occurring globally across all sub-sectors (biotech,
small- to mid-sized pharma, and Big Pharma). Te
centralization o externalized services reduces the
total cost o ownership by stripping out duplicate
investments and realizing greater economies o scale.
Pharma manuacturers and prominent members o the
pharmaceutical supply chain are certainly looking to
make sure their I investments yield value. Te efficientflow o process/machine data and inormation rom
production line to executive suite and back is dependent
on a well-organized, modern data/inormatics inra-
structure. Tis is also unflinchingly true or the reams
o data streaming rom laboratory operations espe-
cia tose i suppot of cgMP maufactui ad its
incumbent quality regimes.
In discussions with customers trying to integrate more
unctionality and value into their existing I inrastruc-ture, inormation technology suppliers and integrators are
witnessing first hand where customers are ocusing their
I investments as well as the priorities they assign with
tei sped. Pomiet Maufactui Eecutio Sstems
(MES) suppie Weum IT Soutios seio diecto rof
Blumenthal explains, Our customers are asking us to
fill the gap between the business level and automation
level. On this operational level, the first ocus in pharma
manuacturing is the replacement o paper batch record-
ing with an electronic system. O course, this doesnt just
entail mere paper replacement, says Blumenthal, because
customers are taking a broader approach to many business
unctions including material flow, quality control and
process automation. Using this unctionality across the
complete liecycle o a pharmaceutical product, rom lab
to maet, e sas, is positioi MES as a too fo pocess
development, clinical trials production and commercial
manuacturing. During the last three years customers
are looking more or strategic products in manuactur-
ing than or customized [bespoke] sofware. Using an
out-o-the-box product with a strategic roadmap or the
next decade, customers can achieve long-term investment
protection and lower total cost o ownership.Te notion that Pharma customers are looking or
a transcendental experience as they integrate new
I unctionality and capacity is echoed by Termo
Fisher Scientifics rish Meek, director o strategy
Inormatics: Our customers today are looking at how
inormatics can go beyond driving their processes to
really transorm their business, says Meek. o push the
boundaries o innovation, [companies] are monitoring
their perormance and quality and actively looking or
opportunities they can capitalize on to improve their
operations. Tis is due, in part, says Meek, to
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At the end of the day, people are looking for solutions to eliminatepaper, to become more compliant, and to increase efciencies in
and around [their] labs.
Gene Tetreault,BIOVIA
macro-trends like big data and predictive analytics that
ae cai IT acoss a idusties. goe ae te das
where we rely on statistics to take a sample o data that
is believed to represent the whole because analysis o the
entire data set is impossible. odays modern in-memorycomputing platorms offer organizations the ability to
look at their complete operation in real time or near
real time. Customers, explains Meek, want to achieve a
higher level o quality and efficiency and business agility,
but that ofen isnt possible i that data is siloed and inac-
cessible. Our customers are working with us to achieve
a connected inormatics inrastructure so that they can
achieve these higher-level organizational goals.
Citing the recent report, Product Innovation Requires
Laboratory Inormatics Systems to ranscend Phases,
Mee otes tat gate aast Micae Sae
recommends manuacturers prioritize end-to-end
inormatics investments and align metrics or innovation,
domain expertise, operational efficiencies and quality.
His recommendation, explains Meek, is based on an
observation that todays laboratories are, or the most
part, disconnected. By tightly integrating LIMS to other
etepise opeatio sstems suc as ErP, isits fom te
lab have the potential to be even more central to businesses
seeking true enterprise-wide agility. Businesses arent
simply capturing and collecting data, Meek contends, they
are making data actionable across the enterprise, putting
management in the position to transorm their businesses
into agile organizations capable o responding quickly to
market trends or new regulations and flexible enough torecognize and capitalize on cost-saving or margin-growing
opportunities in the uture.
gee Teteaut, BIOvIAs seio diecto of etepise
laboratory management, also knows that besides test
and development related data, inormatics are key to
managing lab operations effectively and holistically.
BIOVIAs customers, says etreault, are seeking a really
good capability to manage inventories and managing
all o the material flow in and out o the lab, as well as
specialized things like environmental monitoring. Tats
a manuacturing application typically included in the
LIMs, but its all about managing the [potential or]
microbial contamination in manuacturing. At the end
o the day, people are looking or solutions to eliminate
paper, to become more compliant, and to increase
efficiencies in and around their labs. Once you get allo those systems [on a common electronic technology]
platorm, people are asking: How do I connect other
systems together? How do I get the data out o them?
etreault explains that once a comprehensive lab
inormatics system is in place, discoverable inormation
becomes available and lab operations managers have
tremendous opportunity to gather and aggregate data
and then use it to look orward operationally creating
models and other visualizations to support quality
regimes in manuacturing.
GAPS TO CLOSE
Indeed, priorities have to be ordered and pursued to close
the gaps created by the complexities o Pharma manuactur-
ing environments and their supply chains. Business leader
Bia voe, fo rocwe Automatios goba life Scieces
business segment, finds Pharma needs to continue its e-
orts to organize I to serve the enterprise holistically. I
Inrastructure is a catch-all bucket that can include inorma-
tion and manuacturing sofware as well as hardware, says
Vogel. Most Lie Science manuacturers are moving in two
key areas. Beyond acquisition, there is a major movement to
shif capacity to more profitable locations. Tis is paralleled
with an emphasis on consolidating I-related systems while
improving and expanding access to shop-floor inormation.As this unolds, notes Vogel, Lie Science manuacturers
ae comi to te eaiatio tat, wie ErP is
absolutely undamental to driving the back end, there are
cosideabe aps at te sop oo. As suc, MES ae ow
being deployed in the context o an enterprise solution.
Rockwell Automation has a global customer base, so we see
a wide variety o approaches to addressing this. Developing
a commo MES coe to efoce quait, compiace ad
standard execution across all areas o manuacturing
irrespective o what type or where a product is being
manuactured is the leading trend.
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During the last three years customers are looking more for strategic productsin manufacturing than for customized [bespoke] software. Using an out-of-the-
box product with a strategic roadmap for the next decade, customers can
achieve long-term investment protection and lower total cost of ownership.
Rolf Blumenthal, Werum IT Solutions
Tere will still be areas o the world, says Vogel, where
the cost o energy and personnel will drive an approach
that is more centered on adding resources and lean
processes. However, most manuacturers are avoiding
the band-aid approach and are working to develop amoe sstematic, oba MES coe depomet mode.
Iauab, sas Jeife godsmit, vP, vaut r&D,
Veeva Systems, one the most data-driven areas in lie
sciences is manuacturing, which demands the ability to
sae ifomatio ad coaboate quic. godsmit
contends raw data ofen exists in multiple systems and
file ormats, making it difficult or people to access and
use. As a result, the data is ofen recreated in a document
or structured report ormat to provide context and
enable effective consumption. Content management
systems (CMS) have become the home or many o
these documents, and these systems typically lack the
capability to incorporate new data as they are updated.
Something as simple as a manuacturing specification
may require manual update and confirmation o values
as they change over time. Additionally, sharing this
inormation across geographies and between organizations
has also presented challenges. Cloud-based CMS allow
easy, secure sharing o valuable inormation with other
sstems ad a ae, eeat audiece, sas godsmit.
Users effortlessly collaborate with one another, while all
communication, content and versions are tracked and
stored. As cloud-based CMS evolve, they will challenge
traditional definitions o documents, enabling the storingand updating o structured data with unstructured content
such as descriptions in one document.
OPEX OR CAPEX?
When it comes to expensing operational necessities like
an I inrastructure, controlling that spend can be chal-
lenging, especially because it is so critical to operational
excellence and an efficient, compliant production environ-
ment. With Pharmas business models evolving quickly to
meet the needs o the swifly changing global marketplace,
the industry is shifing how it invests and maintains its
I inrastructure. Some are looking or alternative ways
to account or I expenditures and shifing unding rom
te capita epese (CapE) side of te baace seet to
te opeati epese (OpE) side i a attempt to bette
manage the rising and unavoidable cost o fielding a world-class I inrastructure. When it comes to managing I ex-
penses, each company may take an approach biased in one
direction or another depending on individual preerences
and financial exigencies, but theres no clear right answer
and Rockwells Vogel agrees. Tere is no right or wrong
answer here; manuacturers o all sizes are managing
expenditures as operating expenses and/or capital expenses
at both the corporate and site levels, observes Vogel.
Tough most customers/partners who are developing the
core model are treating the upront design and build as a
capital expense, and classiying the unding o the local
extensions and roll-out as an operational expense.
Werums Blumenthal offers this insight: Tere is a trend
on the radar that customers are expecting realistic solutions
beyond the cloud technology discussion in the I world. A
ew idea is to use a suppie-osted MES ad pa pe batc
record instead o purchasing complex I inrastructure
ad a MES sstem. at is a iteesti popositio ad
may offer very lean organizations an opportunity to stick to
core competencies and leave the heavy lifing to companies
whose core competency is in act I operations.
Speai of ea ii, veeas godsmit poits out
that the emergence o cloud applications has provided a new
alternative or financing projects, moving I inrastructurespend away rom capital expenditures and toward operating
epeses. new pojects tpica equie a siicat
amount o upront capital, and i the investment needed is
too high, it may deter organizations rom pursuing these
oppotuities at a, sas godsmit. e coud owes
the barrier to entry and supports a pay-as-you-go model,
enabling companies to try new ideas without long-term
commitment and easily scale as projects grow.
BIOVIAs etreault says that customers usually dont
include the company in the nitty-gritty o how they choose
to und I investments, but that when making I-related
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Gone are the days where we rely on statistics to take a sample of data that isbelieved to represent the whole because analysis of the entire data set is impos-
sible. Todays modern in-memory computing platforms offer organizations the
ability to look at their complete operation in real time or near real time.
Trish Meek, Thermo Fisher Scientifc
capital purchases, cost o ownership and time to value are
two key metrics, that help customers valuate the potential
return o their I investment. We are trying to deliver
sofware at the lowest cost. Were trying to make it so they
can basically get value [even i] it is rom one mapped outgoal. Cloud solutions, certificates o valuation, etc., all sorts
o things to deliver tangible value and to lower both o
those numbers. Tat opens up the world tremendously to
thousands o labs, as opposed to hundreds o labs.
SOLUTIONS FOCUS
Its generally accepted that contemporary I and inor-
matics solutions must be adopted to effectively and profit-
ably manage Pharmas operations or ace the consequenc-
es. But just how are drug manuacturers working with
vendors and integrators to apply and implement such nec-
essary technologies? Rockwells Vogel offers this insight:
A hybrid-regulated consumer goods manuacturer with
oe 100k SkUs eeded to icease poductio tou-
put b 20 pecet (witout iceasi pesoe), ad
needed to meet increased market demand. Afer review-
ing its manuacturing process, it was determined that the
First ime Pass had to increase and the Quality Hold
Time ad to decease b moe ta 60 pecet. Moe
work orders per shif also needed to be executed to meet
te compas oas. Ae impemeti a ew MES
solution, the number o work orders per shif doubled,
First ime Pass increased by 85 percent, and quality hold
deceased b moe ta 90 pecet. now, adoptio of tesolution is underway in our additional plants.
Another o Rockwells customers, a global lie sciences
maufactue was oi out a ErP sstem to a its
manuacturing acilities, Vogel says, explaining that
the company needed to standardize its manuacturing
iteiece iteface wit ErP ad epace te miad of
eisti MES site-ee sstems wit a etepise-wide
solution. Te first challenge was the time rame, and
te secod was esui te MES sstem met eisti
unctional and regulatory needs at each site regardless
o what or how a product or ingredient was being made.
Te system was rolled out in stages, ocusing on core
aeas oe at a time. now, 17 pats ae ie, ad e wi
o ie i ou 30 mots sice te poam stated.
While each customer had different business drivers,
says Vogel, the need to standardize their manuacturingprocess and improve time-to-results was achieved
through Rockwells platorm.
Termo Fisher Scientifics Meek notes that with her
companys customer base, companies ofen take two
distinct approaches: Te first, one-stop shopping and the
second, integrated laboratory systems. Which approach
makes the most sense is largely based on the existing
systems investment and processes that are implemented
in those systems, says Meek. One major pharmaceutical
manuacturer has implemented a global deployment o
ou lIMS ad it is fu iteated wit etea lES ad
SDMS. By ocusing on strong integration between these
applications, they eel that they have optimized their
deployment and have a continuous flow o inormation
enabling them to make real-time decisions. Tey are
currently looking at predictive analytics tools to drive to a
more proactive environment.
Customers who have not made a significant investment
i lES ad SDMS capabiities aead, sas Mee, see te
value in a single solution that provides the unctionality
of a lIMS, lES ad SDMS i oe. e custome was
ooi at lab Eecutio ad lIMS ad we te
realized that they could get both in a single solution,
it made their decision or them. Teir comment wasthat, We never thought we would find a solution or lab
execution and management that is so tightly integrated,
why would we go with anything else?
veeas godsmit otes ood documetatio is essetia
or manuacturing acilities to ensure activities are executed
correctly and are in compliance. Most companies, she
says, rely on content management systems that were built
when companies were less impacted by globalization and
had ewer regulatory requirements. oday, customers
are looking or solutions that enable greater visibility and
flexibility, and collaboration across all parties. We have
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Most Life Science manufacturers are moving in two key areas. Beyond acqui-sition, there is a major movement to shift capacity to more protable locations.
This is paralleled with an emphasis on consolidating IT-related systems while
improving and expanding access to shop-oor information.
Brian Vogel, Rockwell Automation
customers that are in the early stages o adoption, having
built a single source o truth or SOPs accessible by both
documet oiiatos ad cosumes. gii moe pa-
ties visibility into document status accelerates edit, review
and approval cycles. Built-in read and understood tasksalso allow or real-time tracking o new SOPs as they are
rolled out across departments and sites.
godsmit epais tat e compas moe matue
customers understand that such systems deliver powerul
insights into the health o processes, departments and
partnerships. Most metrics monitor output, only
measuring what has happened. racking upstream
metrics, by contrast, provides leading indicators into
potential problems and can help identiy bottlenecks
befoe te damae is doe, sas godsmit. Compaies
that have developed a deeper understanding o their
business processes are using metrics to gauge perormance
across the organization, and drive continuous process
improvements and proactive decision-making.
Werums Blumenthal provides a closer look outlining
two solutions delivered to customers using their popular
platorm. A customer is using our [platorm] in process
development to develop a stable, best-fitting process or solid
dosage products, says Blumenthal. Te main business
goal is to be aster to market with a new product. By using
MES featues ie MBr ad EBr fo ceati ecipes ad
eauati best tti paametes ia Desi of Epeimets,
new processes will be continuously improved and stabilized.
Development with such tools and the transer o the gainedknowledge to the next production phase is much aster and is
the enabler to achieve expected business goals.
Another Werum customer is using the companys
technologies in the commercial production o a
biopharmaceutical product. Te main business goal is
to increase the yield o the actory, says Blumenthal.
Since production runs are very long, it is critical that
the process is stable without any contamination. Tis
can be achieved through our [platorm] by controlling
all process steps with additional checks o all material
and all equipment that is used. Both business goals,
he says, can be supported by the same system. Te
complete unctionality supported by Werums platorm,
says Blumenthal, is defined and controlled via recipes.
Te creation and change o recipes (MBRs) can be both
flexible (process development) or highly controlled withaccess rights (commercial manuacturing).
A PATH TO IMPROVED OPERATIONS
Many more parties are involved in the end-to-end pro-
duction o a product adding another layer o complexity to
te deeopmet pocess, epais godsmit. Suppoti
technologies are ofen deployed in a siloed model, limiting
the ability or parties to collaborate directly, thus orc-
ing the use o uncontrolled communication mechanisms,
such as email, she says. Mature companies are taking a
strategic approach to technology, creating a strong ounda-
tion or inormation sharing and collaboration to achieve
the biggest benefit. Companies that succeed in sharing
inormation with all parties involved and between systems
see significant improvements in all five areas.
Werums approach, says Blumenthal, is the
implementation o a recipe-driven system that leads the
operator through the business processes, enorcing the
right first-time principle and compliance with all pharma
regulations. Creating best practice recipes and ollowing the
guidance o the system along such recipes (like a navigation
system) will always result in best product quality, reduced
costs, saety, reduced risks and compliance, Blumenthal says.
Teteaut aees tat lES efoces it st time: Weyoure ollowing the process and doing QC testing on a
particular batch step one, prepare the agents and global
phase samples and so orth. Step two, do this. Step three,
do that. On step one, i you dont adhere to the process o
running that analytical test, i you dont adhere to all the
equipment being calibrated, all the materials being within
tolerance and o course not expired, all o the training
records [te lES is] efoci a of tat at te time
that youre doing the test. etreault notes test regimes,
independent o the quality control provided by an integrated
lab inormatics platorm can be problematic because any
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As cloud-based CMS evolve, they will challenge traditional denitions of
documents, enabling the storing and updating of structured data with
unstructured content such as descriptions in one document.
Jennifer Goldsmith, Veeva Systems
issues or mistakes may only be revealed afer a review.
somebody comes along and reviews it and finds that
tees a pobem. now tees a das wot of eot ito
doing something that was wrong on the first step. etreault
explains BIOVIAs platorm (as with others) electronicallyenorces process rubrics at the time they are being done.
It reduces costs. It increases quality. It decreases saety risk.
Termo Fisher Scientifics Meek knows that lab
inormatics platorms truly are the pointy end o the
spear when it comes to assuring quality when it counts.
Esui poduct quait, is eductio ad euato
compliance have always been among the top reasons to
deploy a LIMS, she says. est results rom suppliers are
checked to ensure they are fit or use beore time and
energy is wasted, all sample results or the batch including
environmental monitoring are collated beore product can
be released. Business processes are implemented in the
LIMS and the users are [systematically] stepped through
the organizations SOPs to ensure compliance. Hazard
warnings can be associated with any step in a workflow
ad, witi te lES, uses ae emided as te eecute
that step o the appropriate saety procedures including
saety images and videos i appropriate.
Its important, says Meek, to remember that todays
LIMS are ar more than just lab inormation systems. It
is also a laboratory resource planning system. Method
execution, scientific data visualization, instrument
calibration and maintenance, and detailed resource
planning and allocation can al l be done through the
LIMS. ypically, notes Meek, LIMS are on an upgradecycle o around every five years, and the first thing Termo
Fisher Scientific does with its customers is demonstrate
how much the unctionality o its platorms have evolved
since initial implementation and work with them to
leverage the new capabilities o the system. Te ocus,
she says, is to deliver on high-level organizational goals
by leveraging their existing investments in laboratory
instrumentation, inormatics and enterprise systems. And
while the concept o a truly paperless lab has been hotly
debated or many years, it is really only now coming into
its own. Te latest Inormatics solutions are capable o ully
integrating the lab to the rest o the business, eliminating
or the most part many o the paper-based processes that
have caused bottlenecks in workflow or contributed to
errors in transcribing results and generating reports.
Because LIMS are tightly integrated with otheretepise opeatio sstems suc as ErP, isits fom te
lab have the potential to be even more central to businesses
seeking true enterprise-wide agility says Meek. Businesses
arent simply capturing and collecting data; they are
making data actionable across the enterprise, putting
management in the position to transorm their businesses
into agile organizations capable o responding quickly to
market trends or new regulations and flexible enough to
recognize and capitalize on cost-saving or margin-growing
opportunities in the uture.
Rockwells Lie Science manuacturing customers, notes
Vogel, are moving to maximize their operating options by
standardizing the underlying recipe and execution process
around five imperatives: product quality, cost control,
saety, risk reduction and compliance. Tis will maximize
quality adherence, reduce risk and minimize cost
variations rom plant to plant. o ensure product quality,
fo eampe, etepise MES couped wit adaced EMI
sofware is being used by manuacturing and I teams.
Reports are produced throughout the day by aggregating
data rom machine, plant, enterprise and third-party
applications to produce real-time dashboards with unique
situational and historical context or different users.
o improve compliance, contends Vogel, companies
are selecting inormation technologies that go beyondcollection and archiving o data. odays manuacturers
are looking to inormation technology to automatically
gather required data, drive regulatory compliance, and
enorce execution standards while having robust security
capabiities. Depoi a Maufactui Eecutio Sstem
(MES) wit adaced ifomatio tecooies suc
as these has been proving to be a plus to profitability.
It greatly increases quality adherence coupled with the
ability to shif the production o a single product or a group
rom under-perorming plants to locations that are more
advantageous to the bottom line.
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BEST OFPHARMACEUTICAL M ANUFACTURING www.pharmamanufacturing.com
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_ ll i _ _ i
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Pharmas tech bench gets deeper with an All-Star lineup
ready for the big leaguesBY STEVEN E. KUEHN, EDITOR-IN-CHIEF
HOME RUNS are getting harder to come by in the phar-
maceutical industry and drug makers know it. Innovation
writ large or Pharma used to mean unneling, stadium-
filling amounts o money into research and development
(r&D) eots tied to di te et bocbuste teapy
and aferwards, reaping the rewards o its patent-protected
profitability. For most o Pharmas history, those successes
ueled even more profligate research spending, dollars which
not only financed the development o new winners, but also
plenty o losers as well. But in the wake o patent expiries
(and an ever-shrinking pool o large-class disease catego-
ries), this Blockbuster Quest business models being traded
fo a eae, moe cost-eectie r&D ad maufactui
strategy designed to ocus drug discovery efforts and acceler-
ate the time it takes to get a solid hit, take it around the bases
and score a run.gaii suc competitie aiity is iceasiy comi
rom the Pharma industrys technology and system
suppliers. Tese companies are fielding some pretty
impressive players to support big-league Pharma-style
innovation. Fortunately, innovation is a competitive driver
fo Pama tecooy poides as we, ad tei r&D
efforts continue to deliver game-winning solutions ready
to drive costs out and efficiencies in to drug manuacturing
operations. Tese innovators deserve to be recognized. What
ollows are this years All-Star Innovators: technologies and
systems introduced within the last 12 months that, based
on their relative applicational and technical merits, were
selected by Pharmaceutical Manufacturings editors and
reviewers to be on this years All-Star Roster. Just like in
the big leagues, each player, er, product is highlighted by its
own card, complete with perormance and other stats. What
ollows are excerpts rom those cards, but to view them in
their entirety visit PharmaManuacturing.comand click on
the All-Star Innovators logo. For now, though, take your
seat, grab some peanuts and find out which ones might have
the potential to be on your team.
ANALYTICAL AND MONITORING DEVICES
Cobalt Light Systems RapID developed its competitive edge
via its patented Spatially Offset Raman Spectroscopy (SORS)
technology, which permits a high-quality Raman spectrumto be measured through the thick, unopened layers o pack-
aging. Most players know significant time and resources
can be spent on veriying the identity o raw materials.
Accurate ID o these materials is essential, but time consum-
ing, expensive and resource intensive. RapID allows ID
through unopened plastic containers or growth media
and brown glass bottles or sterile liquids. According to
Cobalt, sacks o lactose can now be identified through a
mutiaye pape sac i 20-30 secods witout eedi
to open or sample the sack.
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RapID
COBALT LIGHTSYSTEMS
Most understand that i you have a player who can execute
on undamentals a little bit aster and more accurately, its
likely it can make a winning contribution to an optimizedpocess statey. gE Powe & Wates ot oe, te Siees
M9 Tota Oaic Cabo (TOC) Aayze. Desied to
measure OC in a broad range o samples rom ultrapure
wate to pocess wates, te M9 is abe
to measure OC and conductivity
simultaneously, and provide accurate
results in only two minutes.
Prozess echnologie developed an
interesting approach that drives a bit
o complexity and a lot o cost out o
spectroscopic measurement with its
rEvEAl Measuemet Appiaces.Tis in-process spectroscopic
measurement tool confirms blend
conormity in real time and is easily
deployable at a price that is well below
industry norms. Te company reers
to its devices as appliances because
unlike other measurement platorms,
the unit is a single measurement
device, eliminating the need or labs
and scientists while delivering an
accurate measurement or batch-based and continuously
pocessed compouds. rEvEAl is desied to wo
in virtually any manuacturing environment including
hazardous materials and provides data that is accessible
anytime via wired and wireless methods.
need a paye wo ca deie mateia ID weee its
needed? Rigaku Raman echnologies has one ready to run
the base line. Its Progeny Material ID Handheld system offers
bench top analytical perormance in a rugged, ergonomic
and IP-68 sealed enclosure. Progenys ully customizable
workflow sofware is 21 CFR Part 11 compliant, and its
ast quad-core processor manages demanding search and
quantification algorithms without requiring remote desktopwo outies. A ioatie 512-pie IgaAs detecto
delivers improved resolution, analytics and signal to noise,
handling the most challenging mixture analyses.
Improving HPLC/UHPLC method development
productivity is an optimal strategy to speed drug
development operations. Shimadzu Scientific Instruments
itoduced its neea Metod Scouti System at Pittco
2014, wee it was ecoized as a stad-out pefome.
Equipped wit two pumps eac wit a quateay ae
Shimadzus system allows analysts to run binary gradients
with 16 different solvent pairs. When combined with a robust,
high-pressure resistant column selection valve, which holdsup to six conventional or UHPLC columns, the system can
iestiate up to 96 uique sepaatio coditios pe sampe.
A transer program allows ultra-high-speed conditions to be
transerred to conventional conditions,
mai te system suitabe fo bot r&D
and QA/QC applications.
Wates iokey/MS System iteates
UPLC separation into the mass
spectrometer or improved sensitivity
and unparalleled compound separation
and detection something that reduces
solvent consumption and costs andsimplifies the user experience. Containing
uidic coectios, eectoics, ESI
interace, a column heater, eCord
Intelligent Chip echnology and 1.7
micron UPLC grade particles packed
iside a 150 mico I.D. cae, te
iokey/MS System was Mec Beta tested
eeai a >60-fod icease i sesitiity
fo glP-1.
AUTOMATION CONTROL AND SENSING
Edess+hause cotiues to iteee at citica poits
in manuacturing and process control and data environ-
ments, and its CM44x Liquiline Multichannel ransmit-
ter is a strong individual contributor to processing trains
ia Etenet/IP. Oe CM44 tasmitte i pay aows
access to many parameters and accepts inputs down to the
sensor level, including sensor condition and diagnostics.
raditionally, devices measuring and controlling process
variables rely on a process instrumentation network to
transer data, while other devices within the plant work
on a completely different network. By improving this
complex, multi-tier networking strategy with one stan-dad etwo acitectue Etenet/IP uses ae
better access to real-time inormation. Tis improves the
ability to monitor overall perormance, troubleshoot out-
o-margin conditions and minimize downtime.
Diverse pH and ORP sensing applications across
Pharma and chemical process system piping require
a tough and smart player to get the job done. With its
ued ryto body mateia, geo Fisce Pipi
Systems DryLoc Sensors deploy a positive connector
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DHXSINGLE-USEHEATEXCHANGER
ASILIFESCIENCES
system to indicate a solid, water-tight connection and
resist moisture/dirt intrusions. Te sensors mount into
stadad Siet 0.50-ic to 4-ic ttis as we as
ito gF tees ad educi tees of ic o ae. e
installation versatility makes v irtually any manuacturers
sensor simple and easy to replace when coupled with the
Siet 2760 Dyloc coecto, wic ca oo up to ote
manuacturers instruments.
BIO PROCESSING
Ofen innovation comes rom
understanding theres a gap andfilling it. ASI Lie Sciences engineers
understood that without an avail-
able high-capacity, single-use heat
exchanger, manuacturing engineers
were being orced to choose one o two
sub-optimal options: Insert a stain-
less-steel heat exchanger along with its
incumbent CIP/SIP inrastructure or
use a jacketed mixing tote or similar
technology as a stop-gap solution. Cer-
tai ot idea. ASIs Dhx Sie-Use
heat Ecae ow oes a pupose-
built solution by combining the heat
transer properties o a high-capacity
plate and rame heat exchangers with
the advantages users can leverage rom
its single-use configuration. ASIs sys-
tem offers advantages or cell culture at the manuactur-
ing scale, allowing engineers to build temperature control
into their process without having to sacrifice the benefits
o single-use.
On deck last September and already bringing
efficiencies to downstream single-stage clarificationae EMD Miipoes Caisoe Dept Fites. Wit
higher titers coming rom todays upstream bioreactors,
conventional approaches have posed a chal lenge to
clarification, that is, until now. Clarisolve depth filters
eliminate the need or centriugation, which enables
implementation o a ully single-use process train and
reduces pre-use flushing requirements. Tis technology
was developed to address the shortcomings o
traditional downstream clarification approaches when
processing high cell density and high-product titer
cell cultures.
Any process operation is likely well supported by
automating manual tasks. Parker domnick hunter
offers its SciLog SciFlex Filter and Dispense System, a
downstream solution that automates final bulk filtration
and container filling, a step previously perormed in a
manual ashion within a vertical laminar flow cabinet.
Te system can perorm manual filtrations, constant
pressure, constant flow rate or the companys R/P Stat
Method, a hybrid method that maximizes filtration
capacity. Playing or Fujifilm Diosynth Biotechnologies,
the installation o the SciFlex Filter
and Dispense System into thecompas cgMP maufactui
was a critical success actor in
achieving compliant, right-the-
first time manuacture o biologic
pharmaceuticals, according to the
biotech firm.
Single-use systems rely most on
the disposable vessels at their heart,
and Sartorius Stedim Biotech has
developed its Flexsae Single-Use
Family o scalable range bags to
perorm better. Flexsae enables
the implementation o single-use
bioprocessing throughout all steps
o drug manuacture using a single
polyethylene film. Te innovative
concept addresses key industry
requirements or uture-proo single-use manuacturing
o commercial vaccines and drugs. Te optimization
o the resin ormulation, the complete control o raw
materials, the extrusion process and the bag assembly
guarantee lot-to-lot consistent cell growth perormance.
Furthermore, batch-to-batch consistent extractablesand leachables profiles support drug manuacturers
throughout the entire liecycle o modern biological
treatments.
PACKAGING AND HANDLING
gass ampoues, ias ad ote esses ae bee o
Pharmas team a long time and possess many superior
qualities. However, commercial-scale handling o glass in
Pharma filling and handling operations is prone to create
contamination issues rom (relatively) rough handling.
gaey Cop.s Iity rx 36 Tabe Top Accumuato is a
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21
544SeriesIntelliSwitchIIv
CONCOAINFINITYRX36TABLE TOPACCUMULATOR
GARVEYCORP.
MANESTYTPR500TABLETPRESS
BOSCHPACKAGINGTECHNOLOGY
potential trade or traditional rotary table or turntable ac-
cumulators in product-handling environments. Te Infinity
rx 36 ca out-feed poducts faste ta a taditioa otay
table and with less pressure and no damage, says the com-
pany, and requires the same ootprint as a traditional rotary
table while greatly reducing the pressure and noise associ-
ated with rotary table accumulators.
hamito Stoae Tecooies labEite Bectop lie
offers users end-to-end, automated liquid sample processing,
decapping, recapping and high-speed barcode reading. Tis
innovator rom Hamilton provides the market with the first
system where users have the ability to positively identiy the
tube chosen or decapping/recapping and track it throughout
te woow. e labEite I.D. cappe eabes abs to combie
decapping/recapping and high-speed barcode reading within
one device without additional user interaction. When sample
taci is ot equied, te labEite DeCappe is eady fo
decappi ad ecappi tubes i 48-cyoia o 96-micotube
racks. A new eature can automatically move the racks romportrait to landscape ormats.
PROCESS HARDWARE
Process gas handling is ofen a critical control parameter, and
te 544 Seies IteiSwitc II fom COnCOA is desied to
routinely switch between two gas sources without interrup-
tion. Tis team player offers reliable high-flow, high-pressure
switching in the most demanding applications and environ-
mets. Ecoomizatio sowae ituay eimiates iquid
cylinder vent loss and substantially reduces residual return.
Switching is actuated as inlet pressure alls below a user-defined
point by means o a Web interace or a serial port. A server al-
lows or remote monitoring and e-mail notification o events.
SOLIDS HANDLING
Conveying ragile, riable products to and rom an opera-
tion along the line takes a player with a gentle touch. Flexicon
Corp.s Flexi-Disc ubular Cable Conveyors have that touch
able to move delicate pharmaceutical products gently, quietly
and dust-ree, horizontally, vertically or any angle with
minimal space requirements. Te conveyors are designed to
integrate with upstream and/or downstream equipment that
sources material rom single or multiple locations and deliver
it selectively to storage vessels, filling machines or other pro-
cessing equipment. Flexi-Disc conveyor moves materials
using high-strength polymer discs in 4- and 6-inch diameters
affixed to a stainless-steel or galvanized cable. Systems can
have single or multiple inlets and outlets, and convey over
short distances or hundreds o eet/meters.
TABLETING
Attention to detail provides Bosch Packaging echnologys
Maesty TPr 500 Tabet Pess a ioatie ede. Buit
or commercial, high-volume line duty, Boschs press can
poduce moe ta 400,000 tabets pe ou ad featues we-
integrated components and an advanced HMI to deliver high
throughput as well as reduced maintenance requirements. For
instance, filling parameters can be reproduced to consistently
support high-quality yields. o ensure the smooth delivery o
tablets, its rue Flow tablet discharge chute eatures a pneu-
matic gate mechanism and an optimized take-off angle, which
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22
SmartDose
WESThMTS
3MACCELRYSCAPTURE
BIOVIA
the company says reduces product damage and increases
output, especially with shaped/riable tablets.
DRUG DELIVERY
Dosing compliance is an issue both Pharma and health care
pofessioas ae seei aswes fo, ad 3M is appyi
its vast materials and manuacturing experience to solve
them. Its Hollow Microstructured ransdermal System is a
patient-riendly intradermal delivery solution designed or
difficult-to-deliver biologics and other therapies. Human
facto eemets to te 3M MTS icude a tetued ip
and the capability or non-specific actuation. A cap protects
the microneedle array, which patients simply remove, adhere
to the skin o the thigh or abdomen, then press down to
begin dosing. An audible click assures activation. Te FDA-
approved device is capable o delivering liquid ormulations
fom 0.5 ml to 2 ml.
Achieving better perormance per dose is something
gaoSmitkie wated fo its FDA-appoed type 2diabetes du ad noozymes vElTIS haf life Etesio
Platorm provided via its Veltis albiglutide technology that
helps diabetes therapies achieve an extended hal-lie; patients
are only required to inject their medication once a week.
Veltis hal-lie extension platorm is based on engineered
albumins that enable manuacturers to define and optimize
the therapeutic window o their drug candidate to help
control dose requency, dose quantity and improve drug
tolerability. Te platorm also offers the ability to provide
once-weekly, once two-weekly or once-monthly peptide or
protein dosing.
West designed the SmartDose patch injector system
technology to be a single-use system ready to deliver higher-
dose volumes by injecting therapies slowly over a period o
time. SmartDose can be pre-programmed and controlled
to provide the optimal dosing rate because many injectable
drugs currently on the market require repeated dosing
and are intended or sel-administration. Wests system is
delivered in a single package; patients insert the cartridge
into the devices injector and adheres the system to the body.
A push o a button inserts the needle and starts the injection,
which is delivered over time, based on instructions entered
by the drug company. Visible/audible indicators confirm
operation o the system.
INFORMATION TECHNOLOGIES
hitti te ed at Pittco, Bio-rad laboatoies kowItA
ATr/Ir ad rama ID Epet oe ew tecooies, says
the company, that combine years o accumulated knowledge
in the field o spectroscopy with advanced computationalpower to provide the astest, most accurate answers possible
to scientists identiying unknown inrared and Raman
specta. kowItA sowae oes uses compeesie
solutions or spectral analysis, identification, search, data
management and reporting. It supports multiple instrument
vendor file ormats and techniques including IR, Raman,
nIr, nMr, MS, Uv-vis. ready fo cgMP ad QbD-
compliant operations, the spectral intelligence built into
kowItA ATr/Ir ID Epet, combied wit te wods
largest spectral reerence collection, provides a high level o
expertise to any scientist.
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TERSUSCLEANROOMLAUNDERINGSOLUTION
CO2NEXUS
Increasingly, mobile devices are bringing efficiencies toPharma process and procedures, especially when it comes
to paper-based SOPs in the lab. o help run down this issue
and support mobile-device applications, BIOVIA, a brand o
Dassault Systmes (previously Accelrys) introduced Accelrys
Captue at Pittco 2014. ou a sma mobie deice,
users can enter data quickly, find procedures and make
instant procedural annotations at the bench without having
to document changes outside the lab.
BIOVIAs technology helps ensure
that laboratory data meets prerequisite
requirements beore being recorded,
thereby reducing review time andrework loops. Automated compliance
solutions include validation-ready
wireless inrastructure, validation-
ready handheld devices or tracking/
tracing process-linked data and
numerous instrument-to-procedure
integrations running on handheld
devices in regulated laboratory
environments.
A hit at Spring raining,
Biopharms BioSolve Process 5
process analysis and economic
modeling platorm provides
insight that enables biopharma
innovators to reduce manuacturing costs and make more
inormed process and operational decisions. Armed with
data rom a broad spectrum o sources, BioSolve Process can
analyze a range o scenarios to support operations business
planning, rom building a business case or a ully integrated
continuous biomanuacturing platorm to the development
o an integrated continuous purification process template or
monoclonal antibodies.
need a paye wo ca deie compete coto oemethods and SOPs rom a single source, and one that
combies SDMS, lIMS ad lES ito oe iteated patfom,
and obsoletes paper-based systems? Termo Fisher Scientific
eded its a-aoude lab Eecutio System lES at Pittco
2014 ad is eady to pay. e patfoms fuctioaity is buit
on the Termo Fisher Scientific SampleManager platorm
and is ully integrated with the newest SampleManager
LIMS. It combines all the unctionality and integration
capabilities necessary to move toward a truly paperless lab,
and lets lab managers automate their SOPs and methods, but
with much deeper integration.
SUPPLY CHAIN TRANSPARENCYruag echnologies ruag microtags are inert, edible
and can integrate into the abric o a product, independent
o packaging and labels, much like fingerprints. Millions o
optical patterns can be embedded into a ruag, which is
a dust-sized particle less than the width o a human hair. It
can be used or the authentication o ood, drugs and other
commercial/consumer products. A security platorm that
will help prevent countereiting, ruags technology etches
unique spectral barcodes into a porous
silicon waer. Te codes can be measured
via a portable spectrometer-based optical
reader and can reerence a label in a securedatabase, where more inormation about
the item (including lot number, expira-
tion date, date o manuacture, authorized
customer, or country o authorized sale) can
be stored as desired.
Imagine a labeling system that could
provide seamless, wireless, near-field
communications and data capture along
with temperature and time sensing.
i Fim Eectoics did, deeopi
te im nea Fied Commuicatio
Smart Label. Te platorm is designed to
handle a variety o sensing elements, both
printed and conventional, and depending
on the application, labels may be ully printed or eature
a combination o printed and surace-mounted elements.
Furthermore, Tinfilms Printed-dopant polysilicon logic
allows Tinfilm engineers to significantly compress the
cycle time or new designs.
WASTE STREAM AND SUSTAINABILITY
A solution that simplifies both resource management and a
necessary operational chore in an innovative way is sure tofind a spot on any team, in this case near a clean control zones
locker room. CO2neus Tesus Ceaoom laudei Sou-
tion enables simple, modular cleanroom laundry plants to be
deployed virtually anywhere, liberating cleanroom garment
end-users and service providers rom the uncertainties associ-
ated with water availability, permitting, cost, validation and
quality. Offering the worlds first CO2-based barrier (pass thru)
system and the companys cleanroom-specific process and
chemistry, ersus uses liquid carbon dioxide in place o water,
40-45 poud ceai capacity, 30-miute cyce times, ad
90-poud touput/ou ia a adaced coto system.
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24
BY THOMAS OTTO, MANAGING DIRECTOR, VETTER
FOR DRUG MANUFACTURERS, THE DUAL-
CHAMBER SYSTEM OFFERS AN ALTERNATIVEFOR SENSITIVE SUBSTANCES.
FREEZE-DRIED PRODUCTS are currently omnipres-
ent and gaining more and more ground in the pharma-
ceutical market. I international pharmaceutical and
biotech industries want to keep up, they are compelled to
reconsider their strategies. In the past ew years, no ewer
ta 30% of a FDA appoas fo paetea dus wee
given or lyophilized products. Market research is even
pedicti tat 50% of a paetea dus wi be opi-lized in the uture. For the manuacturers involved, the
major change lies in the challenges affecting the choice
o packaging.
Lyophilization is particularly advantageous or
complex and highly sensitive substances. For instance,
reeze-drying increases a drugs resistance to heat,
light and other external influences. Development,
manuacturing and delivery o such substances,
however, demands different requirements than with
iquid fomuatios. gaeic fomuatio, fo eampe,
requires other excipients, while manuacturing demands
efficient reeze-drying cycles. Also, the drug has to be
reconstituted completely and saely immediately prior
to administration.
A STRATEGY FOR THE LONG TERM
Lyophilized drugs require manuacturers to think care-
ully about what kind o packaging their product will
need; usually vials or dual-chamber systems, with the lat-
ter being either syringes or cartridges. Tese two systems
involve different manuacturing processes and later deliv-
e steps. Eac oes specic oppotuities tat deped
on the competitive situation. When determining the mostadapted packaging or the chosen system, companies
should take into consideration three critical actors:
e maet Wat ote dus ae aaiabe, ad i
what drug delivery system?
e use Wo wi be pefomi te ijectio, ad
will the user group be expanded to the homecare seg-
ment at a later date?
Pacai ow-ow Does te compa itsef o a
contract development and manuacturing organization
(CDMO) dispose o efficient production technologies
and innovative injection systems?
INNOVATORS FAVOR VIALS
Vials are a good option i the product is a genuine
innovation with no visible competition in the medium-
term. Tey are less complex than other options, and the
manuacturing processes are airly standard. Choosing
vials reduces t ime-to-market which, in turn, optimizes
the duration o patent protection.
At the same time, vials require experience orthe reconstitution o the drug and or producing an
accurate dosage. I the user group includes not only
doctors and nursing staff, but also patients and/or their
relatives, then