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BEST OFPHARMACEUTICAL M ANUFACTURING www.pharmamanufacturing.com

22

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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4

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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5

www.pharmamanufacturing.com

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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6

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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7

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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8

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



9/31


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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10

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




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11

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




12/31


12

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.



13/31


1313

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



14/31


14

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



15/31


15

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



16/31


16

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.



17/31

17


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_ ll i _ _ i



18/31


18

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.

http://localhost/var/www/apps/conversion/tmp/scratch_4/PharmaManufacturing.comhttp://localhost/var/www/apps/conversion/tmp/scratch_4/PharmaManufacturing.com


19/31


19

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



20/31


20

www.pharmamanufacturing.com

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.



23/31

23


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.



24/31


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

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