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June 2015

INTERNATIONAL

The Science amp Business of Biopharmaceuticals

e B O O K S E R I E S

wwwbiopharminternationalcom

OUTSOURCING RESOURCES

ContentsBioPharmINTERNATIONAL

eBook Supplement to


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BioPharm International does not verify any claims or other information appearing in any of the advertisements contained in the publication and cannot take responsibility for any losses or other damages incurred by readers in reliance of such content

BioPharm International welcomes unsolicited articles manuscripts photographs illustrations and other materials but cannot be held responsible for their safekeeping or return

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Outsourcing Resources 2015

QUALITY RISK MANAGEMENT

QRM Tools for Contract BiomanufacturingBikash ChatterjeeQuality-risk-management tools can assist biopharma

companies in mitigating risks when outsourcing crucial

elements of the drug-development process 4

VIDEO INTERVIEW

Biologics Development and Manufacturing Trends Part IAn Interview with Eric Langer BioPlan Associates 10

CROCMO VIEWPOINTS

Biopharma Advances Demand Specialized ExpertiseContract service providers share insights

on biopharma market developments and

the implications of biosimilar drug approvals 12

FILLFINISH

FillFinish TrendsEric LangerAutomation and disposables

continue to reduce human error 20

VIDEO INTERVIEW

Biologics Development and Manufacturing Trends Part IIAn Interview with Eric Langer BioPlan Associates 25

CELL THERAPY

Taking a ldquoDevelopment-by-Designrdquo Approach to Cell TherapiesAgnes ShanleyWhether outsourcing or developing cell therapies

in-house success demands a focus on quality

cost of goods and sustainability from the start 26

INTELLECTUAL PROPERTY

Protecting Intellectual Property in Engagements with CMOsJennifer L CollinsImportant IP contractual provisions

should be included when working with CMOs 32

Ad Index 35

Cover Scott Tysick Getty Images Dan Ward

EDITORIAL

Editorial Director Rita Peters rpetersadvanstarcom

Senior Editor Agnes Shanley ashanleyadvanstarcom

Managing Editor Susan Haigney shaigneyadvanstarcom

Science Editor Randi Hernandez rhernandezadvanstarcom

Science Editor Adeline Siew PhD asiewadvanstarcom

Community Editor Ashley Roberts arobertsadvanstarcom

Art Director Dan Ward dwardmediaadvanstarcom

Contributing Editors Jill Wechsler Jim Miller Eric Langer Anurag Rathore Jerold Martin Simon Chalk and Cynthia A Challener PhD Correspondent Sean Milmo (Europe smilmobtconnectcom)

ADVERTISING

Publisher Mike Tracey mtraceyadvanstarcom

WestMid-West Sales Manager Steve Hermer shermeradvanstarcom

East Coast Sales Manager Scott Vail svailadvanstarcom

European Sales Manager Chris Lawson clawsonadvanstarcom

European Sales Manager Wayne Blow wblowadvanstarcom

Direct List Rentals Tamara Phillips tphillipsadvanstarcomReprints 877-652-5295 ext 121 bkolbwrightsmediacom Outside US UK direct dial 281-419-5725 Ext 121

PRODUCTION

Production Manager Jesse Singer jsingermediaadvanstarcom

AUDIENCE DEVELOPMENT

Audience Development Rochelle Ballou rballouadvanstarcom

UBM LIFE SCIENCES

Joe Loggia Chief Executive Officer Tom Ehardt Executive Vice-President Life Sciences Georgiann DeCenzo Executive Vice-President Chris DeMoulin Executive Vice-President Rebecca Evangelou Executive Vice-President Business Systems Julie Molleston Executive Vice-President Human Resources Mike Alic Executive Vice-President Strategy amp Business Development Tracy Harris Sr Vice-President Dave Esola Vice-President General Manager PharmScience Group Michael Bernstein Vice-President Legal Francis Heid Vice-President Media Operations Adele Hartwick Vice-President Treasurer amp Controller

UBM AMERICASSally Shankland Chief Executive Officer Brian Field Chief Operating Officer Margaret Kohler Chief Financial Officer

UBM PLCTim Cobbold Chief Executive Officer Andrew Crow Group Operations Director Robert Gray Chief Financial Officer Dame Helen Alexander Chairman

wwwbiopharminternationalcom June 2015 BioPharm International eBook 2

PHARMACEUTICAL n HEALTH SCIENCES n FOOD n ENVIRONMENTAL n CHEMICAL MATERIALS

With great detection power comes great possibility To eliminate the unknown find out how Waters ACQUITY QDareg Mass Detector is making heroes out of chromatographers like you Visit waterscomPRESSON

copy2015 Waters Corporation Waters ACQUITY QDa and The Science of Whatrsquos Possible are registered trademarks of Waters Corporation

4 BioPharm International eBook June 2015 wwwbiopharminternationalcom

Outsourcing Resources Quality Risk Management

QRM Tools for

Contract Biomanufacturing

Quality-risk-management tools can assist biopharma companies in mitigating risks when outsourcing crucial elements

of the drug-development process

BIKASH CHATTERJEE

Well-defined well-executed risk man-

agement is a central component of

any clinical strategy and there are

many steps in the drug-development

lifecycle where risk management

brings value For decision making and overall program

risk reduction a quality-risk-management (QRM) pro-

gram is an effective means for biotech companies to

mitigate the risks associated with outsourcing crucial

elements of the drug-development lifecycle Risks only

get larger when activities typically performed inter-

nally during the development process are outsourced

to a contract service provider

The role of contract service providers has grown

over the past decade as the industry has worked to

shrink time-to-market by outsourcing major pieces

of the drug-development lifecycle Today because of

this heightened responsibility for a programrsquos success

organizations tend to rely on contract service provid-

ers as partners

Selecting an outsourcing partner is more complex

than simply comparing factors like on-time-in-full

BIKASH CHATTERJEE is president and CSO of Pharmatech Associates

Mic

ha

el H

Ge

ttyim

ag

es



(OTIF) delivery performance right-

the-first-time (RTF) cycle-time etc

The complexity of the global sup-

ply chain and global compliance

warrants some form of structured

evaluation tool QRM provides this

framework

Production risks are not lim-

ited to time-to-market concerns

Emerging biotherapeutics such as

antibody drug conjugates (ADCs)

and chimeric antigen receptorT

cel l technology (CAR-T) pro -

vide the potential for significant

advances in cancer treatment

but also bring with them a new

level of risk in terms of charac-

terization and quality assurance

Integrating QRM as part of the

program management process pro-

vides a mechanism for addressing

these risks and technical uncer-

tainties as the program progresses

QRM can be divided into two

major areas of application risk-

based decision-making and risk

analysis and management

QRM and Risk assessMent

QRM embodies a systematic pro-

cess for the assessment control

communication and review of

risks The core elements of QRM

are defined in the ICH Q9 guide-

line Quality Risk Management (1)

The principles of using risk as

part of a scientific approach to

drug development are captured

across ICH guidances ICH Q5

Quality of Biotechnological Products

(2) and ICH Q8 Pharmaceutical

Development (3) The European

Un ion a nd Ph a r m ac e ut ic a l

Inspec t ion Convent ion a nd

P h a r m a c e ut i c a l I n s p e c t io n

Co-operat ion Scheme (PICS)

have adopted these principles in

Annex 20 of the EU and PICS

GMP guides

Integ rat ing QR M elements

within the product development

process can raise organizational

FIG

UR

ES

CO

UR

TE

SY

OF

TH

E A

UT

HO

R

Figure 1 Product development risk analysis tools impacted by outsourcing (ADME is absorption distribution metabolism and

excretion PARNOR is proven acceptable rangenormal operating range AHP is analytic hierarchy process CDMO is contract

development manufacturing organization FMEA is failure mode and effects analysis RRD is risk ranking and fltering CMO is

contract manufacturing organization NPV is net present value)

Preclinical

De

ve

lop

me

nt

Ph

ase

Bio

log

ic Q

RM

Animal models ADME studies and

toxicology studies

AHP CDMO

selection

Decision-tree molecule selection

Pre-hazard analysis

Process cause-and

-effect analysis

AHP CMO selection

Process FMEA

RRF

Capital risk investment weighted

NVP calculation

Final RRF or FMEA

Intermediate scale up container-closure studies stability studies PARNOR

tech transfer method transfer fnal reference characterization

Final stability studies fll fnish PARNOR fnal control

strategy process performance

qualifcation lots attribute testing strategy

Ou

tso

urc

ing

QR

M

Phase 1 Phase 2 Phase 3

Quality target product profle formulation selection process design master and

working cell banks raw material characterization method development

initial critical quality attributes reference standard characterization

Figure 2 Preclinical analytical hierarchy process (AHP) structure

GOAL

Select the best

CDMO for

preclinical testing

CRITERIA

ALTERNATIVES

Experience with

route of deliverySchedule

Data analysis

capabilityCost

CDMO 3CDMO 2CDMO 1



visibility of program risks based

upon past program development

with long-term benefit For plat-

form products this means cap-

turing universal program risk

to learn from past risk analyses

and mitigation activities Mature

organizations link assessments to

program milestones moving the

context of risk management from

a supportive role to one of deci-

sion making and program man-

agement

QRM pRoduct developMent and outsouRcingThe principles of QRM can be use-

ful in almost every step of drug

development Risk analysis tools

are ideal as aids to evaluate cri-

teria leading to the selection of

a contract service provider One

important advantage of apply-

ing a QRM approach to product

development is the ability to

harness internal expertise from

across the organization and focus

decision-making using a com-

mon perspective The key process

development activities defined in

the Parenteral Drug Associationrsquos

Technical Report 42 (4) are not

the only development activities

and milestones that can leverage

a QRM framework The empha-

sis in biologic drug development

is predominantly on the drug

substance not the drug prod-

uct While both are important

to a successful drug filing drug

product activities often begin at

the fillfinish stage of the process

and are more standardized from a

design and execution perspective

Figure 1 illustrates which risk

analysis tools can assist in execut-

ing an outsourcing strategy in each

phase of product development

Similar risk analysis tools are color

coded and linked to each of the

four major phases of product devel-

opment prior to commercial manu-

facturing

analytic hieRaRchy pRocess The dec ision to outsource a

key program element to a con-

tract service provider may occur

regardless of the stage of product

development Early in the prod-

uctrsquos development in the preclin-

ical phase development activity

emphasis is on assessing the basic

characteristics of the molecule in

animal models Pharmacokinetic

and pha r macody namic mea-

surements and absorptiondis-

tributionmetabolismexcretion

(ADME) studies are typica l ly

conducted in rodent and non-

rodent mammalian animal mod-

els Selection criteria to assess an

appropriate service provider can

include route of delivery capabil-

ity and experience data analysis

capability schedule and budget-

ary considerat ions The r ight

service provider will contribute

to the success of a programrsquos

investigational new drug filing

and impact the overall program

schedule

One effective risk-analysis tool

to address this outsourcing deci-

sion is Analytic hierarchy process

(AHP) AHP allows the evaluation

to translate subjective opinions

or preferences into measurable

numeric relations to make deci-

sions in a rational way AHP uses

pairwise comparison for consis-

tency in the evaluation of each

criterion for each circumstance

Using AHP requires that the alter-

natives be structured as a hierar-

chy as shown in Figure 2

Figure 3 Preliminary hazard analysis

Attribute Key word Deviation Cause EffectCurrent

safeguardscontrolsHazard levels

ProductNumeric

level

Assay HighOutside tolerance

limitsFillfinish error

Possible hypoglycemia

Sampling manufacturing weight check

High Ampoules 3

Assay LowOutside tolerance


Possible hyperglycemia


Medium Ampoules 2

Sterility Low Non-sterilePoor aseptic

handlingInfection

Media fills and environmental monitoring

High Ampoules 3

Keyword Defnition

Low Low risk to patient

Medium Potential risk to form fit and function of drug which could do harm to patient

High Significant risk to a patient andor form fit and function of product

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Within the AHP hierarchy it is

important to establish the priori-

ties for each element Priorities

are the numbers associated with

the nodes to represent the rela-

tive weights of the nodes in any

group Similar to probabilities

priorities are absolute numbers

In executing the method criteria

are evaluated against the goal to

establish priority Similarly each

alternative is evaluated against

each criteria With these two ele-

ments complete the priority of

each alternative can be calcu-

lated against the goal to select

the appropriate contract develop-

ment and manufacturing organi-

zation (CDMO)

decision-tRee analysis

As a molecule passes the pre-

clinical development program

typically an organization will

evaluate the information to make

a gono-go decision to move the

program forward A tool that can

be useful in quantifying this

phase-gate decision is a decision

tree analysis a decision support

tool that uses a tree-like graph of

decisions and their possible con-

sequences including chance event

outcomes and resource costs

One area where a decision

tree has been a useful tool is in

biologic companies with a com-

bination-product development

program Some biologics may inte-

grate a device component such as

an auto-injector as opposed to

an IV delivery The advantage of

an auto-injector is that it is por-

table and able to deliver outside

a healthcare setting Quantifying

the organizat ionrsquos abi l ity to

develop and commercially support

a device component is a signifi-

cant program risk consideration

for many biotech companies

Choosing a contract manufacturer

with experience in devices and

drugs may drive down technical

and program risk but could com-

plicate the overall supply chain

With a decision-tree analysis an

organization can quantify the cost

of moving forward with each alter-

native while flagging uncertain-

ties One course of action may be

to address the uncertainties and

drive the likelihood of success to

an acceptable level before proceed-

ing with any program

AHP and decision-tree analy-

sis can be used anywhere in the

drug development process where

in-house manufacturing versus

outsourcing alternatives must be

evaluated

pReliMinaRy hazaRd analysis

In the United States Phase I

activities involve satisfying FDArsquos

latest expec tat ions in terms

of product design and process

under sta nd ing For mulat ion

selection is one of the first mile-

stones in a Phase I program A

pre l iminar y haza rd ana lysi s

(PHA) is typically performed early

in a program to identify known

hazards determine their causes

effects and probability and to

establish initial design and proce-

dural requirements to eliminate

or control them

While PHA can be used as an

early evaluation of any risk situ-

ation one effective application

of PHA is to evaluate the prod-

uct design from a patient safety

perspective as a precursor to pro-

Figure 4 Monoclonal antibody process train cause-and-effect matrix

Critical quality attributes (Risk level)

Preculture and expansion

Fermentation and harvest

CentrifugeCation exchange chromatography

Anion exchange chromatography

Viral filtrationConcentration

and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)

Immunoreactivity (H)

Purity (H)

Bioburden (H)

In-process controls

Fill weight check (M)

Visual Inspection (M L)

Risk Key None Low Med High



cess design The PHA can use a

simple heat map of low medium

and high-severity assessments

An example of a partial PHA is

shown in Figure 3 Any evalu-

ation that results in a hazard

level of medium or high should

be included as part of the control

strategy for the process

pRocess cause-

and-effect MatRix

As the program moves into the

process design and scale up or

technology transfer activities a

cause-and-effects (CampE) analy-

sis is a simple and effective tool

to determine which unit opera-

tions impact the drug productrsquos

final critical quality attributes

(CQAs) These unit operations

could then focus on determin-

ing if there are critical control

parameters (CPPs) that impact

the final productrsquos CQAs If there

are CPPs present a f inal con-

trol strategy should ref lect the

potential risk of straying from

the process design space for that

unit operation An example of a

simple CampE analysis for a sim-

ple monoclonal antibody (mAb)

process train is given in Figure 4

The CampE matrix can assign val-

ues descriptors or in this case

integrate a heat map to commu-

nicate potential risk

failuRe Modes

and effects analysis

Failure modes and effects analy-

sis (FMEA) is a systematic pro-

active method for evaluating a

process to identify where and

how it might fail and to assess

the relat ive impact of d i f fer-

ent failures It is used to iden-

tify the parts of the process that

represent the greatest risk to the

productrsquos performance FMEAs

are one of the most commonly

used risk analysis tools used in

the biopharma industry today

FMEAs are based upon risk rank-

ing tables that provide a com-

mon definition for ranking the

severity of a failure and the like-

lihood of occurrence These are

typically ranked on a scale of 1

to 10 then multiplied together

to give a r isk priority number

(RPN) For FMEAs that do not

intend to address potential fail-

ure modes dur ing the design

activity such as process FMEAs

an additional evaluation cate-

gorymdashProbability of Detectionmdash

is used It is not unusual for an

FMEA to generate a large num-

ber of potential failure modes

FMEAs can be effective as part of

deviation and corrective and pre-

ventive action (CAPA) root cause

investigations as a structured

tool for identifying and demon-

strating a true root cause for a

non-conformance

Risk Ranking and filteRing

Risk ranking and filtering (RRF)

is a common facilitation method

used for risk management and

is also known as relative r isk

ranking risk indexing and risk

matrix and filtering The intent

is to provide sharper focus to the

critical risks within a systemmdash

typically from a large and com-

plex set of risk scenarios RRF

works by breaking down overall

r isk into risk components and

evaluat ing those components

and their individual contribu-

tions to overall risk RRF is most

suited to comparing and manag-

ing a portfolio of complex risks

RRF like all risk-assessment tools

requires agreed-upon sets of risk

factors and evaluation criteria

RRF provides a means to priori-

tize and filter individual risks

by combining the evaluations of

risk components against set cri-

teria into a single risk score

Applying RRF requires identi-

fying the primary risk question

then defining the head topics

and subtopics An example of

a CDMO audit risk assessment

structure is shown in Figure 5

Figure 5 Risk ranking and fltering (RRF) outsourcing example structure

Risk question

Subtopics

Head topics

What should the audit frequency be at the CDMO to ensure GMP compliance

Engineering

Calibration Manufacturing

Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance

Operations ComplianceSupplychain



Biologics Development and Manufacturing Trends Part I

Eric Langer Managing Partner BioPlan Associates talks about the results from BioPlan Associatesrsquo 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production Trends in downstream processing protein A and single-use technology are discussed in Part I of this discussion For a discussion on productivity trends and biosimilars see Part II of the interview on page 25

With this structure in place

each risk can be assessed against

the probabil ity of occurrence

and severity impact and summa-

rized in a simple heat map

Risk-adjusted

net pResent value

For those decision milestones

that require investment in capi-

tal or resources a risk-adjusted

net present value (rNPV) is a

more acc urate method than

convent iona l N PV a na ly se s

for communicat ing the t r ue

cost of an investment decision

rNPV is sometimes referred to

as expected NPV (eNPV) rNPV

modifies the standard NPV cal-

cu lat ion of d iscounted cash-

f low analysis by mult iply ing

each cash flow by the estimated

probability that it occurs (the

estimated success rate) In the

language of probability theory

the rNPV is the expected value

rNPV is the standard valuation

method in the drug development

industry where sufficient data

exists to estimate success rates

for all RampD phases

conclusion

Biopharmaceutical products and

processes figure among the most

complex drug development life-

cycles within the industry A

structured QRM program that

integ rates s t anda rd i zed r i sk

assessment tools as part of the

overa l l product development

program can highlight the criti-

cal technical compliance and

regulatory risks when consider-

ing an outsourcing service pro-

vider The application of simple

QRM tools will provide structure

to the decision-making and eval-

uation process and when com-

bined with a simple knowledge

management framework provide

a foundation for all future prod-

uct programs Insight into the

risk and mitigation strategies can

reduce a programrsquos risk profile

significantly

RefeRences 1 ICH Q9 Quality Risk Management

(2005)

2 ICH Q5A-Q5E Quality of

Biotechnological Products

3 ICH Q8 Pharmaceutical Development

(2009)

4 Parenteral Drug Associates

Technical Report 42 Process

Validation for Protein Manufacturing

(2005) Bp

wwwtosohbiosciencecom

Tosoh Bioscience and TOYOPEARL are registered trademarks of Tosoh Corporation

Every mAb is unique

Your Protein A should be as well

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TOYOPEARLreg AF-rProtein A HC-650FHigh Capacity Protein A Resin for Monoclonal Antibody Purifi cation

0

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20

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40

50

60

70

80

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Residence time (minutes)

DBC

for I

gG (g

L)

1 gL

5 gL

10 gLResin TOYOPEARL AF-rProtein A HC-650FColumn size 5 mm ID times 5 cmMobile phase 002 molL sodium phosphate 015 molL NaCl pH 74Residence time 2 35 5 minDetection UV 280 nm (10 breakthrough)Sample human IgG 1 5 10 gL in mobile phase


Outsourcing Resources CROCMO Viewpoints

Biopharma Advances

Demand Specialized Expertise

Contract service providers share insights on biopharma market developments and the implications of biosimilar drug approvals

The ediTors of Biopharm international

The approval of the first biosimilar in the

United States as well as continuing consolida-

tion in the biopharma and contract develop-

ment and manufacturing markets are just

two indicators of the ongoing evolution of

biopharmaceutical development Representatives of

contract service providers shared observations trends

and projections with BioPharm International

Roundtable participants are Gary Chambers busi-

ness manager biopharma labs Europe SGS Bill

Hartzel director of strategic execution Catalent

Pharma Solutions Chris R Lively PhD director of

biopharmaceutical services PPD Scott Lorimer

VP Global Operations Patheon Biologics Eugene

McNally PhD executive director PPD Consulting

Rekha Patel global director large molecules devel-

opment and analytical solutions Catalent Pharma

Solutions and Mark Rogers vice-president SGS

Life Science Services USA

RegulatoRy and business tRends

BioPharm What regulatory changes have positively or

negatively impacted biopharmaceutical development

manufacturing processes

Ad

am

Ga

ult

Ge

tty Im

ag

es

info_contractmanufacturingebsicom | 1 800 441 4225 | emergentcontractmanufacturingcom

Aseptic FillFinish

Pre-Clinical Development

BDSManufacture

Clinical amp Commerical

Lyo CycleDevelopment

Emergent BioSolutions has a proven track record as a world-class provider of contract manufacturing services for both bulk drug substances and sterile injectable drug products Our team has successfully launched 20 commercial products and developedmanufactured over 200 clinical candidates for our clients

Emerging Capability

State-of-the art flexible single-use facility enables turnkey upstream and downstream solutions for clinical and commercial scale biopharmaceutical drug development

Emergent Contract Manufacturing

Enhancing Life in Every Single Dose



McNally (PPD Consulting) FDA

establ ished a new Off ice of

Pharmaceutical Quality in 2014

which we anticipate will have major

impacts on the biopharmaceuti-

cal development and manufactur-

ing process This reorganization

was designed to enhance quality

drug assessment by realigning sev-

eral elements of the preapproval

and surveillance inspection pro-

cess Integrating risk-based review

GMP inspection implementation

of quality by design and the new

FDA process validation guidance

within one office is expected to

significantly change the biophar-

maceutical development and manu-

facturing process

H a r t z e l ( C a t a l e n t P h a r m a

Solutions) In todayrsquos market there

are significant manufacturing

challenges in traditional glass vial

filling applications These chal-

lenges manifest in quality issues

with the final container closure

and may be related to microbial

contamination glass particulates

and foreign materials that lead to

necessary market action causing

supply issues

Lorimer (Patheon Biologics) The

greatest regulatory change in recent

times is the acceptance and approval

of biosimilars

BioPharm What business trends

have posit ively or negatively

impacted biopharmaceutical devel-

opmentmanufacturing processes


Solutions) Today there is a stronger

emphasis in the development life-

cycle on the delivery of the mol-

ecule to the patient and not just

the molecule itself Deliverydevice

experts are being added to teams

at Phase II to improve the delivery

beyond the traditional vial

Lively (PPD) Growing interest

in biopharmaceutical drug devel-

opment necessitates partnering

between clients and contractors to

increase industry capacity breadth

of capabilities expertise and

the experience required to bring

these drugs to market The client

will receive the most benefit by

selecting a high-quality contract

research organization (CRO) lab

that is able to meet its needs and

work collaboratively with the cli-

ent to ensure timely development


trend of small biotech partner-

ing with large pharma for clinical

manufacturing and development

has certainly facilitated the full

development of more novel mol-

ecules Also the increasing trend

toward outsourcing of GMP biolog-

ics manufacturing ensures biopro-

cessing and testing is performed

by expert manufacturers with

proven track records in quality and

biomanufacturing This helps to

reduce the risk to clinical programs

and product safety

technicalscientific tRendsBioPharm Can you describe pro-

ductivity improvements your com-

pany has experienced from new

technologies

Patel (Catalent Pharma Solutions)

Catalent Pharma Solutions has sig-

nificant ongoing investments in

enhancing our large-molecule ana-

lytical capabilities and productiv-

ity to meet and advance current

industry needs Recent invest-

ments include the updatednew

technologies new assay strategies

and updated electronic systems

and processes

Lively (PPD) Evolving character-

ization expectations for biologics

have driven improvements in ana-

lytical equipment processes and

systems Ultra performance liquid

chromatography (UPLC) systems

have improved resolution and sen-

sitivity while reducing run times

In addition 2D high-performance

liquid chromatography (HPLC)

high-resolution mass spectrom-

etry (MS) allows for analysis of

samples incompatible with tradi-

tional MS Reporter gene bioassays

apply genetically engineered cell

lines both to directly model mech-

anisms of action and to amplify

assays for improved performance

with shorter incubations and

increased signalnoise relative to

standard bioassays


main productivity improvement

has been increasing the through-

put of products in Patheonrsquos mul-

tiproduct biopharmaceutical GMP

facilities Single-use disposable

bioreactors and similar single-use

bioprocess equipment minimize

plant downtime which is tradi-

tionally required for line clearance

and product changeover The com-

plexity of product changeovers is

reduced by single-use technology

which decreases the need for clean-

in-place steam-in-place and qual-

ity control testing Typically line

Approval of the first

biosimilar in the

United States as well

as consolidation in

the biopharma and

contract development

and manufacturing

markets are just

two indicators of the

ongoing evolution of

biopharmaceutical

development

YOUR PARTNER FROM CONCEPT TO COMMERCIAL

1

42

5

3CELL LINE DEVELOPMENT

bull Cell line development amp selection

bull Cell line characterization amp optimization

bull Subcloning

bull Suspension adaptation

PROCESS DEVELOPMENT

bull Upstream development amp optimization

bull Media optimization feeding strategyamp design including DoE approach

bull Downstream development ampoptimization

bull Process optimizationprocess scale-up

bull Viral inactivationremoval study design

bull Formulation development amp screening

bull Up to 100L controlled bioreactors

bull Process validation

ANALYTICAL METHODS DEVELOPMENT

bull Development feasibility optimizationtransfer qualification amp validation of methods

bull Identity purity potency safety ampcharacterization

cGMP BIOMANUFACTURING

bull Commercially-licensed facility

bull Flexible manufacturing capabilities

bull Stainless steel amp single-use systemsfrom 100L-1000L

bull FDA EU amp ANVISA inspected

QUALITY AND REGULATORY SERVICES

bull Regulatory strategy amp submissions

bull cGMP CMC Section 7 support

bull In-process amp release testing

bull Stability testing

bull Reference standard generation

For more information please visit us at wwwavidbiocom or

e-mail businessdevelopmentavidbiocom

THE AVID

ADVANTAGE



clearance time is reduced by sev-

eral days

R o g e r s ( S G S L i f e S c i e n c e

Services) As an analytical ser-

vice provider SGS is constantly

in search of means to improve

its laboratory efficiencies partic-

ularly those that enhance turn-

around time without adversely

effecting quality With this in

mind substitution of HPLC for

UPLC rapid microbiolog ica l

screening methods and invest-

ment in automated approaches to

complex analytical problems such

as protein sequencing are now

being used within the SGS labora-

tory network

Chambers (SGS) From a CRO

point of view the main produc-

tivity improvements in analytics

have been from higher through-

put systems and data analysis The

move to these faster systems with

semiautomated data processing has

allowed us to improve turnaround

times which are passed on to cli-

ents in terms who win on faster

to market times and faster gono

decisions

BioPharm What additional tech-

nology improvements are needed

to improve the efficiency of bio-

processing

Lorimer (Patheon Biologics)

Process analytical technology

(PAT) for continuous monitoring of

bioprocesses is helping reduce the

variability on biopharmaceutical

manufacturing

Also biopharmaceutical devel-

opment and process validation

have been accelerated by the use

of mini-bioreactor systems which

enable a large amount of process

development data to be gener-

ated within a very short timeline

These multi-bioreactor systems

can reduce process develop -

ment timelines by months when

applied to early-stage or late-stage

bioprocesses

Rogers (SGS Life Science Services)

The development of many tech-

nologies follows a common path

from academia to commercial

application and nowhere is this

more evident than in the field of

bioprocessing In almost all exam-

ples the key to this progression

lies in the ability to simplify opera-

tional aspects of the technology

and improve throughput This has

in the past been clearly demon-

strated in for example the field of

mass spectrometry and is currently

evolving with techniques involved

in biophysical characterization

BioPharm What is the greatest

technical challenge facing biophar-

maceutical companies today

Hartzel (Catalent Pharma Solutions)

Cost to manufacture will continue

to be a major challenge for the

industry especially with the rise

of biosimilars and market pressures

to drive down the cost of medi-

cines However the products that

are coming to market are more

targeted which leads to smaller

batch sizes This is counter to the

manufacturing adage of being able

to leverage economies of scale to

drive out costs hence the need to

focus on alternatives technologies

and innovation to reduce the man-

ufacturing costs versus economies

of scale

Lively (PPD) Application of ana-

lytical techniques to better char-

acterize innovator and biosimilar

or follow-on products by physico-

chemical and functional methods

are required and will continue to

be driven by the complexity of

biologics development For exam-

ple changes in formulations may

cause different leachable profiles

requiring increasing emphasis on

extractablesleachables techniques

(ie high-resolution MS) to sup-

port characterization of formu-

lation effects identification of

degradation and impurities and

determination of their potential

impact through application of

potency bioassays

Lorimer (Patheon Biologics) Most

of the technical challenges for

manufacturing have been over-

come and the technologies for

development and manufactur-

ing have been widely adopted

Perhaps the greatest challenge is in

clinical development of novel and

originator molecules where in-vitro

model systems are still not a great

predictor of clinical performance


To highlight one technical chal-

lenge above all others in todayrsquos

biopharmaceutical industry is

very difficult The complexity of

biotherapeutics often results in

considerable technical difficul-

ties as for example in the area

of impurities recognition of host-

cell proteins (HCPs) and identi-

fication of structural variants at

trace levels are certainly high on

the list of technical concerns The

necessary inclusion of relatively

elaborate analytical techniques

such as sedimentation velocity

analytical ultracentrifugation (SVndash

AUC) within a traditional qual-

ity control release environment is

also not without problems

BioPharm What are the pros-

pects for continuous manufac-

turing to be firmly established in

bioprocessing What are the road-

blocks to implementation


Continuous product ion f rom

mammalian cell cultures has been

operated in perfusion bioreactors

for many years The main road-

block for continuous processing is

downstream processing of proteins

which currently demands discrete

and distinct unit operations for

removal of impurities removal

of contaminants concentration

of the products and formulation

each in separate controlled steps

Introducing a next generation chemically-defined CHO fed-batch media platform from SAFC Developed across a range of widely used industrial CHO cell lines this newest portfolio media delivers exceptional titers and economic efficiencies Adaptation is simple Celebrate performance and accelerate your bio-development process

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EX-CELLreg ADVANCEDtrade CHO FED-BATCH SYSTEM

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NEXT GENERATION MEDIA PLATFORM



and which are not currently ame-

nable to continuous processing

the Rise of biosimilaRs

BioPharm What impact w i l l

biosimilar drugs have on bio-

pharma businesses bioprocessing

approaches and the contract ser-

vices market


The European biopharma land-

scape has already experienced

impact of the biosimilar drug mar-

ket leading to rapid expansion of

traditional small molecule generic

manufactures into the bio arena

Recent FDA approval of the Sandoz

biosimilar Zarixo may be the seed

for similar changes in the US pro-

viding a potential new line of busi-

ness for established pharmaceutical

companies Contract service pro-

viders such as SGS who already

have considerable experience with

biosimilars are able to offer exper-

tise to businesses new to this mar-

ket and will no doubt benefit from

such expansion in the US

Lively (PPD) Increased invest-

ment in biosimilars is driving

interest in improving and stream-

lining the development processes

as well as the sensitivity and scope

of characterization assays used to

compare biosimilars and innova-

tor drugs The expanding capac-

ity needs result in partnerships

between clients and their contrac-

tors with the systems experience

and expertise to achieve the qual-

ity and speed required while meet-

ing all regulatory expectations for

product approval

Chambers (SGS) With nearly

20 years exper ience perform-

ing biosimilar analysis the big-

gest impact had been the massive

increase in the characterization

needed for biosimilars compared

to innovators (although higher

standards are now needed for new

innovators too) This has resulted

CMOs Add Capabilities

Consolidation in the contract development and manufacturing market has resulted in new capabilities and facility expansions

In May 2015 CMC Biologics announced that it is expanding its Copenhagen Denmark facility to increase its manufacturing capacity through the installation of six 2000-L bioreactors The bioreactors can be run singly or in groups simultaneously or sequentially and are part of the companyrsquos signature Bioreactor 6Pack single-use program The Copenhagen installation will begin initial GMP production in November 2015 and will feature three bioreactors to start Three bioreactors will be added at a later date to complete the configuration Meanwhile the Bioreactor 6Pack at CMCrsquos Seattle facility will complete its first GMP run in mid-2015 and will be ready for commercial launch by the end of the year Through its recent expansions CMC plans to expand its global capacity by more than 30000 liters in the United States and Europe

Also in May 2015 SAFC announced an expansion to its St Louis MO facility to support the commercial-scale production of antibody-drug conjugates The facility which is expected to be online and operational in the third quarter of 2015 was designed to meet SafeBridge category 4 compound handling requirements for highly active or cytotoxic compounds The expansion of an existing Carlsbad CA location will enable SAFC to offer fillfinish capabilities of viral products to its clients in the gene therapy viral vaccine and immunotherapy sectors

Rentschler announced in March 2015 that a 2000-L bioreactor that the company commissioned and built in six months is up and running The bioreactor will be integrated into existing manufacturing suites containing two 1000-L single-use bioreactors according to a company statement The companyrsquos twin bioreactor systemmdashdesigned for running two main bioreactors in parallel with one shared downstream processing unitmdashwill be functional by 2017 The twin system is estimated to double the companyrsquos production capacities for cell culture-derived proteins

In December 2014 FUJIFILM Diosynth Biotechnologies USA (FDBU) acquired Kalon Biotherapeutics adding viral and cell-culture vaccine expertise and capabilities In other activity FDBU started construction of a three-story 62000-ft2 facility in Research Triangle Park NC in January 2015 to house the companyrsquos process and analytical research and development process sciences and stability groups The expected completion date is Q4 2015

In September 2014 PCI a provider of packaging services acquired Biotec Services International a provider of clinical-trial services and temperature-controlled pharmaceutical services headquartered in Bridgend Wales UK The addition expanded PCIrsquos presence in the European Union and added packaging storage and distribution capacity and consultative services for clinical-trial supplies In January 2015 Biotec announced the validation of its clinical supply facility expansion which added almost 50 to the companyrsquos clinical trial materials handling capacity



in challenges in data handling

interpretation and data presenta-

tion Biosimilars have also caused

the re-emergence of orthogonal

techniques like size exclusion

chromatographyndashmulti-angle laser

light scattering (SEC-MALL) and

SV-AUC for aggregation and cir-

cular dichroism (CD) and fourier

transform infrared spectroscopy

(FTIR) for higher-order structure

as critical analyses to understand

and compare and detect subtle

higher-order structural differences

between innovator and biosimilar

samples


The rise of biosimilar drugs will

dawn the next generation of bio-

logic manufacturing and force

the industry to look at new ways

of manufacturing to drive down

costs Therefore the industry will

seek new manufacturing partners

with strong technical expertise to

drive out costs through innovation

and operational excellence


Genera l ly b ios imi la r d r ugs

will encourage competitiveness

within the biopharma sector

Biomanufacturers expect increased

pressure on cost of goods and

pricing Biopharmaceutical con-

tract service providers with a flex-

ible multi-product operation and

proven track record in the indus-

try are well placed to ensure care-

ful control of manufacturing costs

and product quality Processing

approaches wonrsquot change in terms

of technology but there will be a

greater emphasis on operational

excellence to reduce costly inef-

ficiencies and improve yields from

bioprocesses As more biosimilars

come to the forefront and as the

industry trend for outsourcing

continues increasing operational

flexibility while maintaining the

highest quality standards will be

the keys to success

business challenges


business challenge facing biophar-


Lively (PPD) As with all phar-

maceutical drug development the

greatest challenge is getting new

life-changing and potentially life-

saving drug candidates to mar-

ket Biopharmaceuticals face more

challenges than traditional small-

molecule drug products because

the science of characterization

of such biologic drugs is rapidly

evolving along with the regulatory

landscape Those companies that

are best able to successfully char-

acterize and differentiate innovator

and biosimilar products for safety

and efficacy will have the greatest

opportunity to benefit

the knowledge gap

BioPharm In what areas do you

see knowledge or expertise gaps in

current biopharmaceutical compa-

nies Why do these gaps exist

Lorimer (Patheon Biologics) There

is a gap in translating good sci-

ence to industrial applications of

technologies that provide for reli-

able efficient cost effective man-

ufacturing at commercial scale

Maintaining a focus during early

development on eventual commer-

cial manufacturing requirements

while balancing limited develop-

ment resources requires a broad

base of coordinated organiza-

tional skillsets and a disciplined

approach


Devicedelivery expertise is an

area that has a potential gap For

biologics the historic default con-

tainer closure has been a tradi-

tional glass vial As the healthcare

industry seeks ways to improve

patient care and reduce costs the

delivery to the patient needs to

adopt new technologies and this

is why we have seen a rise of pre-

filled syringes and autoinjectors

These technologies will continue

to evolve and so will the demand

for devicedelivery experts

Lively (PPD) One of the chal-

lenges we see is the various levels

of knowledge and expertise that

exist between biopharmaceutical

RampD and the testing and regula-

tory industries That differential is

impacting those industriesrsquo ability

to fully consider and effectively

implement expectations and guid-

ance for physicochemical and

functional characterization expec-

tations of biologic drugs


commercial biopharmaceutical

industry demands global sourc-

ing of materials services supply

and ultimately distribution to each

patient This requires a robust inte-

grated supply chain to deliver high

value products to patients on-time

and at the right quality Doing this

reliably and efficiently with long

production lead times and uncer-

tain market sales forecasts is an

industry wide challenge

Speed-to-market remains a key

challenge to the development of

biopharmaceuticals Speedy first-

time-in-man clinical trials can be

a major hurdle for small biotech

companies and large pharma alike


I believe there continues to be a

significant problem in the level of

fundamental scientific expertise

within many biopharmaceutical

businesses In part this may be

attributed to the lsquokitrsquo and lsquoblack

boxrsquo approach of many modern

day technologies Due to the

complexity of many biopharma-

ceuticals their development and

success as therapeutics requires a

comprehensive range of scientific

disciplines and expertise which

can be difficult to fully realize

internally particularly for small

and mid-size companies bp


Outsourcing Resources FillFinish

FillFinish Trends

Automation and disposables continue to reduce human error

Eric s LangEr

Fillfinish operations continue to be domi-

nated by trends in automation and the adop-

tion of single-use equipment But these are

by no means the only factors affecting these

high-value operations according to BioPlan

Associatesrsquo latest biomanufacturing study (1) Fill

finish processes are among the most outsourced

activities in biomanufacturing today and a service

providerrsquos capacity for vialing pre-filled devices

and lyophilization is crucial In a recently pub-

lished whitepaper (2) BioPlan Associates determined

that there is sufficient global in-house capacity

for biologics but the need continues to grow for

greater access to specialized outsourcing competence

Whatrsquos trending is significant improvements in auto-

mation and operations

AutomAtion And single use defining Cmo strAtegy

The top trends today involve automation and devel-

opment of better disposable technologies As part of

the BioPlan study biomanufacturers were asked to

select the trends they believe to be the most impor-

tant in fill and finish today The top three trends

are single-use equipment automation in full isolator

units and facilities becoming multi-product ori-

ented (see Figure 1)

Other important trends were noted including

bull Increased serialization and product labeling for

anti-counterfeiting

Eric s LangEr is president and managing partner at BioPlan Associates Inc elangerbioplanassociatescom tel 3019215979 wwwbioplanassociatescom

Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es

WITH ALTHEA YOU HAVE THE POWER TO MAKE

You have the power to make a difference To make new therapeutics that improve quality of life and inspire a healthier world To do this you need a manufacturing partner who embraces your every challenge as its own who shares your unwavering tenacity and dedication from clinical studies through commercial success Thats The Power To Make

PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product

(D Al TH EA I THE POWER TO MAK A MEMBER OF THE AJINOMOTO GROUP



bull More f i l l f i n i sh fac i l i t ie s

o p e r a t i n g i n d e v e lo p i n g

regions

bull C o m p u t e r - b a s e d v i s u a l

i n s p e c t i o n a r t i f i c i a l

intelligence

bull Use of complex administration

systems

single-use equipment in fillfinish operAtionsT h e a d o p t i o n o f d i s p o s -

ab le e qu ipme nt i n f i l l f i n -

i s h o p e r a t i o n s e l i m i n a t e s

cross-contamination risks and

adds flexibility in process scale

While regulatory rest r ic t ions

may be increased by the adop-

tion of such equipment single-

use appl icat ions a lso enable

contract manufactur ing orga-

nizat ions (CMOs) to increase

fac i l i t y ut i l i z at ion t h rough

multi-product strategies which

can decrease their cost of goods

Experts in the f ield discussed

these trends

Peter Pekos CEO and president

of Dalton Pharma Services a fill

finish CMO says ldquoFor a CMO

disposables can be attractive hellip

For example a disposable isola-

tor can be packed and stored pre-

sterilized for use when needed

a f ixed isolator requires f ixed

space at all times Disposables

also allow a CMO to handle proj-

ects using specific systems for

non-typical project needs such

as disposable isolators without

going to the expense of buying

permanent isolator infrastruc-

ture Disposables do not obviate

the need for technical expertise

hellip so the need for a CMO isnrsquot

really reduced In fact CMOs

with expertise in single-use sys-

tems hellip can make them more

attractiverdquo

Mar t ina Fe r neman cor po -

rate development manager at

Recipharm bel ieves that the

adoption of single-usedispos-

able equipment is now impacting

f i l l and f inish ldquoIn mult ipur-

pose sites the cleaning proce-

dures will become more crucial

to avoid cross contamination

Single-use equipment [also] has

the advantage of shorter lead

t imes and lower procurement

costs Since no cleaning proce-

dure has to be established and

aseptic connections are easier to

be built-up the use of single-

use equipment is not only faster

but also safer than conventional

equipmentrdquo

AutomAtion in full isolAtor unitsW hi le s ing le -use equ ipment

adoption may be one of the hot-

test f i l lf inish trend automa-

tion technologies may actually

be experiencing more rapid rates

of implementation among bio-

manufacturers Indeed sepa-

rate results from BioPlanrsquos 12th

annual study suggest that the

industry wi l l be as l ikely to

implement automation technolo-

gies as they will use single-use

f i l l-f inish devices dur ing the

next 24 months

The removal of human factors

is a key to improving product

quality Isolators and automa-

tion are therefore key drivers

as facilities seek to improve their

i n f r a s t r u c t u r e I n nov a t io n

around equipment and facilities

able to handle multiple products

is going to continue Flexibility

is key as the reduced flexibility

of isolators (and higher cost) in

relation to traditional restricted

access barrier (RAB) systems may

deter some CMOs from adopt-

ing isolators The jury is st i l l

out because the decision fac-

tors between RAB and isolators

are complex and this tends to be

a high-cost decision often left

to the larger f illf inish CMOs

ldquoCMOs will adopt isolator tech-

nologies in their processes to

meet industry needs and reduce

r isk In some cases this wil l

also include disposable isolators

which can offer the benefits of

fixed isolators but add a degree

of f lexibil ity to the manufac-

turerrdquo Pekos notes

According to Ferneman adopt-

ing automat ion in ful l isola-

tor units to reduce the need for

operators is a trend seen in the

CMO market ldquoUse of barr ier

technology (RABS or isolators)

should ensure optimal protec-

t ion of ster i le areas Isolators

bear a better potential to prevent

biocontamination Since the iso-

lator is a closed system a lower

air quality than in RABS systems

can be usedrdquo For freeze-dried

products the RABS system is a

better choice because loading

has to be performed in class AB

surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r

Figure 1 selected bioprocessing fllfnish trends in 2015

Single-usedisposable equipment

adoption55

36

35Facilities becoming more multi-

product-use oriented

Automation in full isolator units

reduce need for operators

More compounds More accuratelyFaster than ever

Quantitation transformed

Todayrsquos range of possible therapeutic agents from small molecules to peptides to antibodies and

ADCrsquos makes quantitative bioanalysis a challenge Quantify potential therapeutics faster and more

accurately with our new portfolio of LC-MS instruments sample prep solutions and software HRAM

solutions using Thermo Scienti ctrade Orbitraptrade MS enables selectivity for complex molecules while

triple quadrupole MS delivers SRM sensitivity and speed to detect targeted compounds more quickly

Meet todayrsquos challenges with us and together wersquoll transform quantitative bioanalysis

Thermo Scienti ctrade Orbitrap Fusiontrade MSUnprecedented depth of analysis and

throughput for biological discovery

Thermo Scienti ctrade TSQ Quantivatrade MSLeading SRM sensitivity and speed

in a triple quadrupole MSMS

Thermo Scienti ctrade Q Exactivetrade MSScreen and quantify known and unknown targets with HRAM Orbitrap technology

copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries

bull Discover more at thermoscienti ccomquan-transformed



Cmos stAying

AheAd of the Curve

In the whitepaper on in-house

fillfinish operations for recom-

binant therapeutics (2) BioPlan

found relatively low average in-

house capacity utilization rates

for lyophilization (55) pre-filled

devices (58) and vialing (70)

This finding suggests that for fill

finish CMOs the real value isnrsquot

necessarily in providing additional

flexible capacity but rather in posi-

tioning themselves as providing

highly sophisticated and novel

technologies and expertise in fill

finish services Indeed CMOs are

expected to have state-of-the-art

equipment As Pekos notes ldquoCMOs

who implement flexible and inno-

vative technologies to make man-

ufacturing or development more

efficient faster compliant or more

economical all serve to make them

more attractive to customersrdquo

For CMOs that make use of

innovative fillfinish technologies

there appears to be a good deal

of demand Results from BioPlanrsquos

annual studies indicate that fill

finish services are among the most

widely and heavily outsourced

biomanufacturing activities today

and are also among the activities

that biomanufacturers are most

likely to outsource at significantly

higher levels in the future

Biomanufacturers and CMOs are

actively looking to their fillfin-

ish equipment suppliers and are

beginning to demand additional

new technologies innovation and

product development In 2014 for

example when the top areas that

biomanufacturers wanted their

suppliers to focus their develop-

ment efforts on were measured

fillfinish services topped the list

cited by 23 of biomanufacturers

Not only did that figure represent

a substantial increase from years

past (13 in 2011) but it was also

ahead of other services including

upstream and downstream process

development services

Fillfinish will continue

to be an area of

growth for CMOs

There are a number of areas in

which suppliers can add value to

fillfinish innovation according

to industry experts Jim Agalloco

president of Agalloco amp Associates

in Belle Mead NJ says ldquovendors of

equipment and components to fill

finish must continue their roles as

technology leaders Innovation in

this market has always been sup-

plier driven because the operating

firms do not have the necessary

expertise Collaboration between

equipment manufacturers and

component suppliers is essential

for implementation of new con-

tainer systems single-use dispos-

ables and other advancesrdquo

Ronald Malone senior principal

scientist at Novartis Vaccines says

ldquoBlow-fill-seal containerclosure

systems are beneficial for small-

volume parenterals However over-

all cost may still be higher per unit

than traditional vialstopper fill-

ing Vaccines and biologicals can

benefit from single-dose disposable

systems that drive down the cost

of the containerclosure system

This will assist the global supply to

developing world countries where

these products are truly neededrdquo

W B W i e d e r s e i m o f

PharmaBioSource in Wayne PA

states ldquoWe see smaller higher

technical facilities inclusive of dis-

posables (isolators and not RABS)

and advanced aseptic work cell

technology as the wave of the

futurerdquo

WhAt does the future hold

BioPlanrsquos survey data and indus-

try interviews indicate that fill

f inish will continue to be an

area of growth for CMOs that

maintain the required technical

quality and regulatory expertise

in this segment Experts have

taken note of CMOsrsquo introduc-

tion of smaller filling machines

for syringes or vials a trend that

may be in response to the indus-

try-wide move towards smaller-

scale manufactur ing projects

This shift may be accelerated by

the advent of biosimilars which

should provide an increasing

number of projects for fillfin-

ish CMOs although likely on a

smaller scale This increase in

projects could lead to potential

mergers and acquisitions with

some experts noting that fillfin-

ish CMOs are already engaging

in this trend toward larger capac-

ity and global operations

Indeed within the past 18

months a number of acquisi-

tions have occurred including

Pfizerrsquos acquisitions of Hospira

a nd In noPha r ma Pat heonrsquos

mergers in the contract services

space IDT Biolog ika invest-

ments Vet ter invest ing USD

$100 million to upgrade fill-fin-

ish facilities in the United States

a nd Ger ma ny a nd Ba xte r rsquos

investment in German facilities

and numerous others (3)

For CMOs to stay ahead of the

curve they will likely need to

continue to adopt disposables

technologies and advance their

automation in full isolators Ray

Cardin of PharMax Consulting

says ldquoIncreased use of dispos-

able pre-sterilized f illing tech-

nologies [are future trends] The

combination of these pre-ster-

ilized units with the coming of

age of ster i le connectors that

provide high sterility assurance



Biologics Development and Manufacturing Trends Part II

Eric Langer Managing Partner BioPlan Associates talks about the results from BioPlan AssociatesOtilde 12th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production Langer discusses what respondents indicated as the number one trend in biologics manufacturing improving efficiencies and the biosimilars market

in less clean environments is

changing the way aseptic pro-

cesses are designedrdquo

Gordon Leichter PhD Eastern

r e g io n a l s a l e s m a n a ge r a t

Belimed in Charleston SC states

ldquoAutomat ion in fu l l i solators

wil l el iminate operator inter-

vention and laser-sealed vials

Automation will become more

integral to building automation

and enterprise systemsrdquo

Douglas Stockdale vice-presi-

dent CMCTechnical Operations

Hi l lhurst Biopharmaceut ica ls

Los Angeles CA says ldquoIndustry

will continue pushing the PAT

[process analytical technology]

envelope to f ind a lternat ive

methods to improve in-process

methodologies and processesrdquo

Fe r ne ma n add s ldquoCu r r e nt

trends in fillfinish innovation

will probably focus the market

authorization holders on a few

strategic products resulting in

outsourcing of a bigger share of

products overallrdquo

ConClusion

Until recently the handling of

ster i le l iquids in the pharma-

ceutical industry has relied on

relatively consistent techniques

during the past 100 years with

relatively slow changes in tech-

nologies and regulations result-

ing in incremental improvements

in safety efficiency and prod-

uct quality During the past 20

years however costly biologics

have taken a prominent indus-

try role The value of these drugs

can often be measured in tens of

thousands per dose This has put

greater pressure on these down-

stream fillfinish operations to

ensure quality safety and cost-

efficiency are not compromised

at this crucial late stage in manu-

facturing Trends in fillfinish for

recombinant therapeutics include

the increased use of isolator

technologies more high-speed

operations and other innovative

approaches including single-use

processing As a result of industry

research BioPlan expects more

outsourcing of fillfinish opera-

tions in coming years

referenCes 1 BioPlan Associates 12th Annual

Report and Survey of Biopharmaceutical

Manufacturing Capacity and Production

(Rockville MD April 2015) www

bioplanassociatescom

2 BioPlan Associates Trends in Aseptic

Bioprocessing Capacity for the Fill and

Finish of Recombinant Biologics An

Analysis of US and European In-house

Capacity and Capacity Utilization (BioPlan

Associates December 2014)

3 Information derived from BioPlan

Associatesrsquo BioFacilities Newsletters Bp


Outsourcing Resources Cell Therapy

Taking a ldquoDevelopment-by-Designrdquo

Approach to Cell Therapies

Whether outsourcing or developing cell therapies in-house success demands a focus on quality cost of goods

and sustainability from the start

Agnes shAnley

Cell therapies both autologous and allo-

geneic have come a long way in just a

few years Countries around the world

most recently Japan have passed regula-

tions designed to speed development of

these treatments which are now a big and growing

global business

In 2013 according to the Pharmaceutical Research

and Manufacturers Association 69 cell therapies six

of them autologous or patient-specific treatments

were in clinical trials or being reviewed in the United

States alone 15 of them in Phase III trials (1)

The road is littered with failures however often

in clinical stages This has been traced to problems

with manufacturing and failure to understand pro-

cess requirements earlier in the development process

Table I outlines manufacturing issues

As a growing number of Big Pharma companies

explore the potential for immune regenerative and

other cell therapies equipment manufacturers includ-

Agnes shAnley is senior editor of BioPharm International

SC

IEP

RO

GE

tt

y Im

aG

ES

wwwcytovancecomResponsive Reliable Resourceful

Your partner in biopharmaceutical contract manufacturing of therapeutic proteins and antibodies from mammalian cell culture and microbial fermentation



ing Pall Corp EMD Millipore

and GE Biosystems have set up

centers of excellence to focus on

developing equipment for this

new market Engineering compa-

nies such as Invetech and Instrom

are developing equipment specific

to this niche

More CDMos are entering

Cell therapy Market niChe

Demand for spec ia l i zed ce l l

t he rapy ma nu fac t u r ing a nd

development serv ices is a lso

growing and has attracted Lonza

Bioservices Cognate BioServices

WuXi AppTech and Roslin Cells

among others

NeoStem is fol low ing t wo

paths pursuing its own cel l

therapy pipel ine and explor-

ing contract services through

its contract development and

manufac t u r ing organ i zat ion

(CDMO) subsidiary Progenitor

Cell Therapy (PCT) With bases

in Irvine and Mountain View CA

and Allendale NJ PCT is cur-

rently working with Intrexon and

Fibrocell on connective tissue

treatments and with the United

K ingdomrsquos Adapt immune on

oncology treatments

A new CEO David Mazzo with

a doctorate in analytical chemis-

try and experience running both

private and public international

biopharma companies assumed

NeoStemrsquos leadership in January

He sees no conflict between grow-

ing a pipeline and a contract man-

ufacturing business

ldquoWe are not trying to be two

di f ferent companies and we

do not see the two competing

with each otherrdquo says Mazzo

in an interview with BioPharm

Inte rnat ionalrsquos s i ster publ ica-

tion Pharmaceutical Technology

during his second week on the

job ldquoInstead there is a symbi-

otic relationship between themrdquo

As he sees it the companyrsquos

track record in developing prod-

ucts should attract more spon-

sors ldquoProblems in development

usually occur at the interfaces

Our unique experience of having

lsquodone that beforersquo should be help-

fulrdquo he says

In January PCT entered a

partnership with Invetech an

equipment design firm based in

Australia with offices in San Diego

to develop automated equipment

for cell therapy manufacturing Fig

ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch

Figure 1 Part of an automated solution being developed by neostem and invetech Automating processes is key to reducing costs



The two companies have already

been working together for a year

now honing the design and speci-

fications for the instrumentation

says NeoStemrsquos Chief Scientific

Officer (CSO) Robert Preti The

equipment will tackle cell therapyrsquos

most challenging side autologous

treatments where the manufactur-

ing lot is the patient dose adminis-

tered at the patientrsquos bedside

As Preti notes there really isnrsquot

much available today in the way

of automated equipment for cell

therapy especially on the autolo-

gous side The equipment will sep-

arate and wash cells among other

functions

labor-intensive

proCesses aDD Cost

So far Preti says the company

is evaluating the evolving equip-

ment in NeoStemrsquos own manu-

facturing efforts ldquoOne of the

largest commercial bottlenecks

is the heavy labor required by

processes especially for patient-

specific uses where one batch is

one patientrdquo

The cost of goods i s ver y

high Preti says ldquoSuccess long-

term will require a whole new

approach to development The

goal is to provide high qual-

ity and sustainabilityrdquo he says

Removing manual operat ions

and human error from the pro-

cess will be crucial

Invetech has been work ing

on cell therapy process scale-up

automation for more than 10

years and has successfully com-

pleted projects in North America

Europe and Asia for companies

that include Argos Therapeutics

Aa s t rom CCR M Hu mac y te

Innovacell Janssen kSep Systems

MolMed Organovo and ViaCyte

accord ing to R ichard Grant

global VP of the companyrsquos bio-

pharma operations who has been

with the company for more than

14 years

ldquoThe goal is to develop a mix

of equipment and manufactur-

ing st rateg ies that maximize

quality scalability and sustain-

ability with an eye toward cost-

effect iveness and commercial

viabilityrdquo Grant says Invetechrsquos

solutions typically tailor a mix of

OEM and customized equipment

to the clientrsquos processes The com-

pany recently commercialized

equipment used to manufacture

Janssenrsquos macular degeneration

treatment

Costs of current manufactur-

ing processes for both autologous

and allogeneic therapies are dif-

ficult to peg Last year experts

at University College London

attempted to pinpoint the cost and

overall economics of allogeneic

cell therapy using single-use tech-

nologies (2)

What is clear for both alloge-

neic and autologous systems is

that cell therapy development

Table I Manufacturing scenarios for cell therapies

Attributes Off-the-shelf therapiesPatient-specifc

therapies

Source material Always allogeneic Autologous or matched allogeneic

Batch size Many patients One patient

Business model Similar to pharmabiopharma New

Scaling Scale up (Increased lot size) Scale out (Increased number of lots)

Comparability vs scale Higher concern Lower concern

Manufacturing design drivers

Mission critical success + +++

Optimized process yield +++ +

Dimensional efficiency ++ +-

Integration +- ++

Automation + ++

source invetech

Table II Measuring comparability risk

Risk level Example Timing

None Automated sterility test Before biologics license application

Low Change in process unit op and cell journey is the same

Before 50 accrual in pivotal trials

Medium Change in process unit op and cell journey is similar

Before initiation of pivotal clinical trials

High Change in process unit op and the cell journey is matched

Some Phase II clinical data

source invetech



and manufacturing costs are cur-

rently prohibitive ldquoThe starting

points can vary dramaticallyrdquo

Grant says He recalls one cus-

tomer whose autologous process

ran to $80000 per patient in early

stage clinical trials Automation

he says could reduce costs by

40ndash90 depending on the ther-

apy involved

DevelopMent by Design

But before one can automate any

process one must understand it

NeoStem and PCT like a growing

number of companies are taking

the principle of quality by design

(QbD) to heart in their work

Mazzo arguably one of few

life-science company CEOs to

even articulate the QbD concept

explains that the company has

gone a step further and broadened

the International Conference on

Harmonization guidances adopted

by FDA into ldquodevelopment by

designrdquo (DbD)

ldquoWe say first consider the end-

point then take process as is and

understand its unit operations

Develop inputs and outputs and

discrete steps and define the pro-

cess in a way that promotes under-

standingrdquo he says

ldquoThis is challenging given prod-

uct complexity but there is a need

to understand the mechanism of

action very well so you put each

process in this overall envelope

of DbD and consider the cost of

goods scalability and sustainabil-

ityrdquo Preti adds ldquoYou consider the

process from the end only this

time each batch is an individual

patientrdquo

The critical part is defining and

measuring process needs he says

ldquoProduct definition is very impor-

tant particularly the quality target

product profilerdquo explains Brian

Hampson VP of manufacturing

development and engineering at

PCT in an Oct 22 2014 webcast

for the International Society for

Cell Therapy (3)

have the enD in MinD

Such t h ings a s for mulat ion

issues dosage potency impu-

rities residuals and microbial

assurance need to be thought out

clearly from the start Hampson

says as well as indications for

use geographic market projec-

tions cost-of-goods targets and

IP issues

The profile needs to be a liv-

ing document that changes as the

product takes shape Hampson

says There is a tendency for peo-

ple in the industry to ignore the

product profile until they have

all the answers says Hampson

ldquoInstead it needs to be developed

really early even when you donrsquot

have all or even many of the

answers hellip you can leave them

as blanks and continue to review

add to and updaterdquo

The result is not only a tool for

better understanding the prod-

uct process and mechanism of

action but a communication tool

for stakeholders

When to start DbD for cell ther-

apies ldquoThe temptation is to begin

later in the game when you need

reasonable COGS and you need

to be sure of sustainable manu-

facturingrdquo says Hampson ldquoThe

key thing is comparability and

anticipating its implications early

in the clinical program It needs

to be flexible at the early stagesrdquo

Hampson says ldquoBut as you near

Phase III you need to lock in your

equipment evolves

In the bioreactor area there is great interest in moving from 2-D to 3-D processing to enable the processing of the cell volumes required something that companies such as Israelrsquos Pluristem have been doing for some time

Equipment designer Instrom is partnering with companies including BRTI Life Sciences to focus on 3-D cell matrix technologies developed by Dr John Brekke EMD Millipore has been partnering with PharmaCell BV to use its Mobius bioreactor platform to expand and harvest HepRG cells GE Sciences is also evaluating Wave and other systems and set up a center of excellence in Wales recently

In other equipment areas Pall Corp has been partnering with CMDG LLC on cord blood processing technology Following are some of the equipment manufacturers and systems applied in cell therapy development and manufacturing

bull Beckman Coulter bull Corning Cell Stacks and Cell Cube

bull EMD Millipore bull GE Biosciences

bull Thermo Scientificrsquos Nunc Cell Factories bull Pall Corp



processrdquo Table II summarizes issues

and points where changes will be

easier

Thus Hampson suggests that

companies whether work ing

with CDMOs or in house think

through such issues as cost of

goods scale and sustainabil-

ity much earlier than they typi-

cally do today ldquoYou donrsquot need to

spend money on these issues but

you do need to think about themrdquo

Hampson says ldquoQuality must be

a key issue even at Phase II trials

and early action pays off laterrdquo

In addition he suggests that

companies th ink about the

e nt i r e p r o c e s s c o mp r e he n -

sively ldquoThere is often a tendency

to focus on the core processing

stepsrdquo Hampson says ldquoBut you

really need to think about every-

thing from collection of mate-

rial through to administration

of product to the patient and all

steps in betweenrdquo

For ce l l therapies d ispos -

able equipment and closed pro-

cesses can be an effective way to

reduce costs and improve quality

and compliance ldquoThey can allow

you to isolate different processes

so that they can share a Class

100000 cleanroom environmentrdquo

Hampson says

ldquoInvesting in automated informa-

tion management can also pay offrdquo

he says ldquowhere an electronic batch

record system that is fully validated

can enable release-by-exception

reducing error documentation

time and overall quality assurance

costsrdquo Hampson says

In addition he notes it is

important to look at costs compre-

hensively an increase in one cost

can for example reduce overhead

improve process sustainability and

cost of goods Table III outlines the

issues

regulations evolve

Cell therapy is still a new area

for regulators and as Preti says

some guidelines are clear and oth-

ers arenrsquot ldquoDevelopment by design

is needed throughout the pro-

cess but the piece we still struggle

with the most is mode of action

(MOA) and product characteriza-

tion Regulatory agencies under-

stand that it is difficult to pinpoint

MOArdquo

Preti emphasizes the importance

of working with regulators ldquoYou

can be in a position to inform and

influence regulations as products

are developedrdquo he says

For any company moving into

this brave new world top-level ques-

tions are needed Preti says empha-

sizing the following ldquoDo you have

an understanding of scale Can you

scale up from very small Can you

characterize the process and control

it for reliability and qualityrdquo

In the stem cell area in particu-

lar this is crucial Preti said since

the product relies heavily on the

process ldquoManufacturing can be

thought of as patient administra-

tion It cannot be separated in

the same way that it can for tra-

ditional medicinesrdquo For contract

suppliers he adds demonstrated

success will be important and

sponsors should consider whether

a prospective partner will be able

to stay with them for the long run

referenCes 1 P Hourd et al Regulatory Challenges

for the Manufacture and Scale-

Out of Autologous Cell Therapies

Massachusetts General Hospital

(Cambridge MA 2013)

2 S Farid et al Biotechnol Bioeng

111(1) 69-83 (January 2014)

3 R Grant Building Deliverable Cell

Therapeutics A Methodical Approach

to Manufacturing Development

(Webinar Oct 22 2014) bp

source invetech

Justifcation driversChange in cost

doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk

Quality COGs Scale Sustainability LaborMaterials outplant

Cost Time

P-2 Process change 1 Medium X X darr $ $$$ TT

P-3 Process change 2 High X X X darr $$$ $$$$ TTT

P-4 Process change 3 Low X X darr $$ $$ TTT

P-2 Process change 4 Low X $$ T

QC-4 In-house QC test None X TT

QA-1Electronic Batch

RecordNone X X X

darr $$$$

TTTT

Table III Process changes timing and comparability risks cogs is cost of goods Qc is quality control


Outsourcing Resources Intellectual Property

Protecting Intellectual Property

in Engagements with CMOs

Important IP contractual provisions should be included when working with CMOs

Jennifer L CoLLins

Biotechnology and pharmaceutical companies

often engage contract CMOs to assist with

the development of their drugs This type

of arrangement naturally involves the devel-

opment of intellectual property (IP) so it is

important for both the CMO and the sponsor to iden-

tify pre-existing intellectual property and also define

how rights to new IP will be allocated protected and

enforced by and between the companies

If the arrangement with the CMO is a traditional fee-

for-service arrangement where the company pays the

CMO service fees to perform development work on its

behalf then generally all new IP (other than improve-

ments to the CMOrsquos manufacturing technology) will be

owned by the biotechnology or pharmaceutical com-

pany that engaged the CMO On the other hand if the

arrangement between the CMO and the biotechnology

or pharmaceutical company is more of a collaborative

arrangement where both parties share the costs of devel-

opment as well as any profits from the commercializa-

tion then IP concerns become much more complicated

In that case in addition to describing which party will

Jennifer L CoLLins is a technology and licensing attorney with Morningstar Law Group jcollinsmorningstarlawgroupcom

Fa

na

tic S

tud

ioG

ett

y Im

ag

es



own the new IP the contract should

sort out which party will be respon-

sible for obtaining and maintaining

patents on the new IP controlling

litigation against infringers and

defending the IP against challenges

In addition the parties should agree

upfront on how the IP may be used

by each party following various ter-

mination events so that the parties

are not left fighting about such mat-

ters at a time when they may not be

inclined to agree to anything

In both arrangements without

specific contractual provisions to

define and protect the new IP a

biotechnology company or phar-

maceutical company that uses a

CMO for development is at risk of

losing control of and possibly own-

ership of important improvements

to its drugs This article discusses

IP contractual provisions that

should be included in each type of

arrangement

Fee-For-service

development work

Traditionally CMOs perform fee-for-

service development work where

a biotechnology or pharmaceutical

company engages the CMO to per-

form this work for a fixed fee In this

type of arrangement the CMO is a

service provider and typically takes

no ownership interest in the drug or

product that is being developed or

in improvements to an existing drug

or product that is being tested or

developed The contract governing

the relationship nevertheless must

be clear about the IP rights that are

owned and licensed by each party

If the contract does not provide

for proper assignments of IP to the

biotechnology or pharmaceutical

company then it is likely that the

CMO will own any improvements

or other inventions that it develops

in the performance of the develop-

ment services even if that is not the

intent of the parties

Without signed written contracts

that state otherwise under United

States patent law the inventor of

a patentable invention or improve-

ment will own the invention or

improvement even if the inventor

is engaged to develop the invention

or the improvement for a customer

or other third party To ensure

that the biotechnology company or

pharmaceutical company obtains

all the patent and other IP rights

in developments inventions and

improvements created in the per-

formance of services by the CMO

the governing contract between the


maceutical company and the CMO

must include written present assign-

ments of those IP rights from the

CMO to the company Indeed based

on recent cases it is crucial that the

assignment clause in the contract

be a ldquopresentrdquo assignment mean-

ing that it must state specifically

that the CMO ldquohereby assignshelliprdquo

rather than a clause stating that the

CMO ldquoagrees to assignrdquo rights in the

future Otherwise the contract will

be interpreted as a promise to assign

rights in the future and the bio

pharmaceutical company will have

to go back to the CMO at some later

point in time for a separate writ-

ten assignment of rights to obtain

all patent and other IP rights in the

developments

While it sounds logical and

straightforward that the CMO

would assign all inventions created

in the development work to its cus-

tomer it is not always that simple

in practice What if the CMO devel-

ops an improvement to its manu-

facturing process in the course of

the development work Most CMOs

will want to reserve ownership of

any improvements to the CMOrsquos

existing IP and confidential infor-

mation This position is not unrea-

sonable as long as the customer

ultimately has the rights it needs in

all new inventions including those

owned by the CMO to take the drug

forward through further develop-

ment and commercialization One

must sort out IP allocation by sub-

ject matter To achieve this allo-

cation the development contract

typically will state that each party

retains ownership of all IP that it

owns as of the date of the contract

(all pre-existing intellectual prop-

erty) It will also state that the cus-

tomer owns its proprietary drug

and all improvements to the drug

or the customerrsquos confidential infor-

mation developed by either or both

parties The development contract

also may state more generally that

the customer owns all inventions

improvements and IP rights related

to the customerrsquos drug With respect

to the CMO and its IP the develop-

ment contract may state that the

CMO owns all improvements to the

CMOrsquos manufacturing process and

to its other pre-existing intellectual

property Again this reservation is

not unreasonable The customer

however should determine whether

it requires access to those improve-

ments or inventions to complete the

development and commercialization

of its drug If such access is necessary

the customer should either negotiate

a license (which may be royalty-free

or royalty-based depending on the

circumstances) to use such improve-

ments or inventions to develop and

commercialize the drug or the cus-

tomer should negotiate the terms

under which the CMO will continue

to use the improvements or inven-

tions to perform development work

andor manufacture the drug for the

customer

In the fee-for-service arrange-

ment the assignment and licensing

of IP rights in new inventions and

improvements is the key intellectual

property issue Intellectual property

considerations become much more

complicated when the biotechnol-



ogy or pharmaceutical company

partners with a CMO in the devel-

opment of a new drug or product

where the parties share development

costs and profits from commercial-

ization of the drug or product

cmo as collaborator

Although not as common as the

fee-for-service arrangement a CMO

may partner with a biotechnology

or pharmaceutical company in the


of a drug or product Generally both

parties are bringing pre-existing IP

to the collaboration such as a drug

from a biopharmaceutical com-

pany and proprietary drug delivery

technology from the CMO In this

scenario the CMO is taking a long-

term interest and often a part-own-

ership interest in the success of the

drug product

Instead of getting paid an hourly

rate or fixed fee for development

work on the drug product the CMO

may share the cost of development

work with the biotechnology or

pharmaceutical partner in exchange

for a share of the profits when the

drug or product is commercialized

Other costs involved in the develop-

ment and commercialization of the

drug or product that may be shared

include the cost of patent prosecu-

tion and the cost of patent litigation

if the drug product is challenged or

if it is misappropriated or infringed

To secure its interest in the profits

from commercialization of the drug

product the CMO may want to take

an ownership interest in the intel-

lectual property rights in the drug

product All of these issues must be

carefully addressed in the develop-

ment contract to avoid both finan-

cial and IP disputes

As with the fee-for-serv ice

arrangement the parties must

allocate ownership of intellectual

property rights pertaining to the

drug product to be commercialized

These rights include both pre-exist-

ing IP rights and new inventions

and improvements developed in

the course of the development con-

tract As with the fee-for-service

arrangement the parties typically

will retain rights to their respec-

tive pre-existing IP Intellectual

property rights to new inventions

and improvements however may

be shared by giving each party a

co-ownership interest in the intel-

lectual property Alternatively such

rights may be allocated by inventor-

ship with each party taking owner-

ship of developments that it invents

and with the parties jointly own-

ing jointly developed inventions

As another alternative the IP rights

may be allocated by subject matter

as in the fee-for-service arrangement

with each party owning improve-

ments and inventions related to its

pre-existing IP regardless of which

party invents those improvements

and inventions

Depending on how the pat-

ent applications are drafted the

IP rights may be ldquosliced and dicedrdquo

more finely One party for example

could own patent rights for a drug

product for one indication while the

other party owns patent rights for

the same drug product for another

indication Decisions about how

to allocate the IP rights should be

made in consultation with intel-

lectual property counsel and must

take into account the manner in

which the drug will be commercial-

ized If one party for example is

to commercialize the product in

North America and Europe and

the other party is to commercialize

the product in the rest of the world

then either the patent ownership

should be allocated by territory or

the development contract should

include exclusive cross-licenses of

each partyrsquos rights in all the intel-

lectual property necessary to com-

mercialize the product with the first

party having an exclusive license to

commercialize the product in North

America and Europe and the second


commercialize the product in the

rest of the world

If the parties are going to share

ownership of the IP related to the

drug product then the develop-

ment contract also should specify

which party is responsible for pros-

ecuting and maintaining patents

on the drug product Regardless of

which party is responsible for patent

prosecution and maintenance the

other party should be consulted and

involved in key decisions regard-

ing patent prosecution and main-

tenance Unless there are multiple

patents for different indications that

will be commercialized exclusively

by one party and unless each party

has exclusive rights to commercial-

ize the drug product in particular

geographic areas it generally makes

sense for one party to take the pri-

mary responsibility for patent pros-

ecution and maintenance globally

with the other party consulting and

sharing in the cost of the prosecu-

tion and maintenance in accordance

with the profit sharing The party

that is not responsible for prosecu-

tion and maintenance should have

a contractual right to approve patent

counsel and review and approve pat-

ent filings office action responses

and other communications with

patent registries before they are filed

or submitted so that the parties

agree on the proper prosecution and

maintenance strategy

Likewise the development con-

tract should allocate the rights and

responsibilities for asserting and

defending the patents pertaining to

the product in litigation Often these

rights and responsibilities are allo-

cated by territory according to com-

mercialization rights If one party

for example has the exclusive right

to commercialize the drug product



in the US then that party would

have the first right and responsibil-

ity to assert the patents on the drug

product against potential infringers

and defend the patents on the drug

product against infringement claims

in the US Likewise if one party has

the exclusive right to commercial-

ize the drug product for a particular

indication then that party would

have the first right and responsibility

to assert or defend the patents per-

taining to the product with respect

to that indication Both scenarios

can present challenges First some

courts will not recognize an exclu-

sive licensee as having standing to

assert a patent That court might

only allow the owner of the patent

(and not the exclusive licensee) to

bring a lawsuit asserting the patent

It is crucial therefore that contrac-

tual provisions relating to patent liti-

gation require the party that owns

the patent to cooperate in any litiga-

tion and to join the suit as a party if

necessary

Another potential problem is that

any litigation that asserts the pat-

ent is likely to draw a counterclaim

that the patent is invalid thus put-

ting the patent itself at risk of invali-

dation While one party might be

threatened by a potential infringer

in a particular market or for a partic-

ular indication and therefore might

want to assert the patent against the

potential infringer the other party

might not want to put the patent at

risk as to other markets and other

indications For these reasons the

contractual provisions pertaining

to patent litigation must be care-

fully drafted in consultation with

intellectual property counsel who

understands standing issues and

the potential areas for dispute The

contractual provisions also should

include dispute resolution provi-

sions for situations when the parties

do not agree on whether a patent

should be asserted

Finally while the parties may

want and expect their relationship

to continue for the full term of the

patents and the development con-

tract the parties must carefully

consider the IP ramifications of an

early termination of the develop-

ment contract and the relationship

particularly if the development con-

tract is terminated for breach If the

parties are sharing in the ownership

commercialization and profits gen-

erated by the drug product devel-

oped by the collaboration then

all of that must be unwound upon

termination The development

contract should be as specific as

possible with respect to the effect of

various types of termination on the

intellectual property and contin-

ued commercialization of the drug

product In particular the parties

may agree that if the development

contract is terminated due to breach

by one party then that breaching

party must relinquish and transfer

all of its rights with respect to the

drug product to the other party to

allow the non-breaching party to

continue the commercialization of

the drug product post-termination

Whether the necessary rights are

assigned or licensed whether the

terminated party should receive a

royalty for the transfer or license of

those rights and what if any pre-

existing IP is licensed to enable the

non-breaching party to continue

commercializing the drug product

are all key factors for negotiation

The development contract should

also address other types of termi-

nation such as termination for

insolvency and termination with-

out cause (ie if one party decides

it no longer wants to commercial-

ize the drug product) In each case

the effect of termination on the IP

rights should be carefully analyzed

and a competent IP counsel should

carefully draft post-termination

assignments and licenses

conclusion

While IP lawyers are not equipped

with crystal balls they can be

extremely helpful in analyzing par-

ticular development commercializa-

tion and post-termination scenarios

all of which affect IP in a drug devel-

opment arrangement Contractual

provisions related to IP must be

carefully drafted to align with the

strategic business objectives of any

relationship and particularly one

whose purpose is the development

and commercialization of intellec-

tual property Without a clear con-

tract each collaborator is at risk of

losing important rights bp

Ad Index

AJINOMOTO ALTHEA 21

AVID BIOSERVICES INC 15

CYTOVANCE BIOLOGICS 27

EMERGENT BIOSOLUTIONS 13

EUROFINS LANCASTER LABORATORIES 7

SAFC BIOSCIENCES SIGMA ALDRICH 17

THERMO FISHER SCIENTIFIC 23

TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page

ContentsBioPharmINTERNATIONAL

eBook Supplement to


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Outsourcing Resources 2015

QUALITY RISK MANAGEMENT

QRM Tools for Contract BiomanufacturingBikash ChatterjeeQuality-risk-management tools can assist biopharma

companies in mitigating risks when outsourcing crucial

elements of the drug-development process 4

VIDEO INTERVIEW

Biologics Development and Manufacturing Trends Part IAn Interview with Eric Langer BioPlan Associates 10

CROCMO VIEWPOINTS

Biopharma Advances Demand Specialized ExpertiseContract service providers share insights

on biopharma market developments and

the implications of biosimilar drug approvals 12

FILLFINISH

FillFinish TrendsEric LangerAutomation and disposables

continue to reduce human error 20

VIDEO INTERVIEW

Biologics Development and Manufacturing Trends Part IIAn Interview with Eric Langer BioPlan Associates 25

CELL THERAPY

Taking a ldquoDevelopment-by-Designrdquo Approach to Cell TherapiesAgnes ShanleyWhether outsourcing or developing cell therapies

in-house success demands a focus on quality

cost of goods and sustainability from the start 26

INTELLECTUAL PROPERTY

Protecting Intellectual Property in Engagements with CMOsJennifer L CollinsImportant IP contractual provisions

should be included when working with CMOs 32

Ad Index 35

Cover Scott Tysick Getty Images Dan Ward

EDITORIAL

Editorial Director Rita Peters rpetersadvanstarcom

Senior Editor Agnes Shanley ashanleyadvanstarcom

Managing Editor Susan Haigney shaigneyadvanstarcom

Science Editor Randi Hernandez rhernandezadvanstarcom

Science Editor Adeline Siew PhD asiewadvanstarcom

Community Editor Ashley Roberts arobertsadvanstarcom

Art Director Dan Ward dwardmediaadvanstarcom

Contributing Editors Jill Wechsler Jim Miller Eric Langer Anurag Rathore Jerold Martin Simon Chalk and Cynthia A Challener PhD Correspondent Sean Milmo (Europe smilmobtconnectcom)

ADVERTISING

Publisher Mike Tracey mtraceyadvanstarcom

WestMid-West Sales Manager Steve Hermer shermeradvanstarcom

East Coast Sales Manager Scott Vail svailadvanstarcom

European Sales Manager Chris Lawson clawsonadvanstarcom

European Sales Manager Wayne Blow wblowadvanstarcom

Direct List Rentals Tamara Phillips tphillipsadvanstarcomReprints 877-652-5295 ext 121 bkolbwrightsmediacom Outside US UK direct dial 281-419-5725 Ext 121

PRODUCTION

Production Manager Jesse Singer jsingermediaadvanstarcom

AUDIENCE DEVELOPMENT

Audience Development Rochelle Ballou rballouadvanstarcom

UBM LIFE SCIENCES

Joe Loggia Chief Executive Officer Tom Ehardt Executive Vice-President Life Sciences Georgiann DeCenzo Executive Vice-President Chris DeMoulin Executive Vice-President Rebecca Evangelou Executive Vice-President Business Systems Julie Molleston Executive Vice-President Human Resources Mike Alic Executive Vice-President Strategy amp Business Development Tracy Harris Sr Vice-President Dave Esola Vice-President General Manager PharmScience Group Michael Bernstein Vice-President Legal Francis Heid Vice-President Media Operations Adele Hartwick Vice-President Treasurer amp Controller

UBM AMERICASSally Shankland Chief Executive Officer Brian Field Chief Operating Officer Margaret Kohler Chief Financial Officer

UBM PLCTim Cobbold Chief Executive Officer Andrew Crow Group Operations Director Robert Gray Chief Financial Officer Dame Helen Alexander Chairman







QRM Tools for




BIKASH CHATTERJEE




















ers as partners




Mic

ha

el H

Ge

ttyim

ag

es









framework









































GMP guides




FIG

UR

ES

CO

UR

TE

SY

OF

TH

E A

UT

HO

R





Preclinical

De

ve

lop

me

nt

Ph

ase

Bio

log

ic Q

RM


toxicology studies

AHP CDMO

selection


Pre-hazard analysis

Process cause-and

-effect analysis

AHP CMO selection

Process FMEA

RRF


NVP calculation

Final RRF or FMEA






Ou

tso

urc

ing

QR

M






GOAL

Select the best

CDMO for

preclinical testing

CRITERIA

ALTERNATIVES

Experience with


Data analysis

capabilityCost

CDMO 3CDMO 2CDMO 1















agement





































facturing



























schedule


















ProductNumeric

level





High Ampoules 3





Medium Ampoules 2


handlingInfection


High Ampoules 3

Keyword Defnition


































zation (CDMO)


















































evaluated
















or control them














and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)


Purity (H)

Bioburden (H)

In-process controls















pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page






QRM Tools for




BIKASH CHATTERJEE




















ers as partners




Mic

ha

el H

Ge

ttyim

ag

es









framework









































GMP guides




FIG

UR

ES

CO

UR

TE

SY

OF

TH

E A

UT

HO

R





Preclinical

De

ve

lop

me

nt

Ph

ase

Bio

log

ic Q

RM


toxicology studies

AHP CDMO

selection


Pre-hazard analysis

Process cause-and

-effect analysis

AHP CMO selection

Process FMEA

RRF


NVP calculation

Final RRF or FMEA






Ou

tso

urc

ing

QR

M






GOAL

Select the best

CDMO for

preclinical testing

CRITERIA

ALTERNATIVES

Experience with


Data analysis

capabilityCost

CDMO 3CDMO 2CDMO 1















agement





































facturing



























schedule


















ProductNumeric

level





High Ampoules 3





Medium Ampoules 2


handlingInfection


High Ampoules 3

Keyword Defnition


































zation (CDMO)


















































evaluated
















or control them














and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)


Purity (H)

Bioburden (H)

In-process controls















pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page









framework









































GMP guides




FIG

UR

ES

CO

UR

TE

SY

OF

TH

E A

UT

HO

R





Preclinical

De

ve

lop

me

nt

Ph

ase

Bio

log

ic Q

RM


toxicology studies

AHP CDMO

selection


Pre-hazard analysis

Process cause-and

-effect analysis

AHP CMO selection

Process FMEA

RRF


NVP calculation

Final RRF or FMEA






Ou

tso

urc

ing

QR

M






GOAL

Select the best

CDMO for

preclinical testing

CRITERIA

ALTERNATIVES

Experience with


Data analysis

capabilityCost

CDMO 3CDMO 2CDMO 1















agement





































facturing



























schedule


















ProductNumeric

level





High Ampoules 3





Medium Ampoules 2


handlingInfection


High Ampoules 3

Keyword Defnition


































zation (CDMO)


















































evaluated
















or control them














and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)


Purity (H)

Bioburden (H)

In-process controls















pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page















agement





































facturing



























schedule


















ProductNumeric

level





High Ampoules 3





Medium Ampoules 2


handlingInfection


High Ampoules 3

Keyword Defnition


































zation (CDMO)


















































evaluated
















or control them














and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)


Purity (H)

Bioburden (H)

In-process controls















pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page































zation (CDMO)


















































evaluated
















or control them














and diafiltration

Vial filling

Appearance (M)

Impurities (H)

Protein content (H)


Purity (H)

Bioburden (H)

In-process controls















pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page












pRocess cause-

and-effect MatRix


























failuRe Modes






































non-conformance


































Risk question

Subtopics

Head topics


Engineering


Labeling

Supplier

Storage

Changecontrol

Batch release

Deviations

Corrective and

preventive actions

Validation

Packaging

QC testing

Maintenance











Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page










Risk-adjusted

net pResent value
























conclusion























significantly


(2005)




(2009)




(2005) Bp



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



Every mAb is unique




0

10

20

30

40

50

60

70

80

2 35 5


DBC

for I

gG (g

L)

1 gL

5 gL




Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



Biopharma Advances



























Ad

am

Ga

ult

Ge

tty Im

ag

es


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page


Aseptic FillFinish


BDSManufacture




Emerging Capability
























facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page





















facturing process












supply issues




of biosimilars










































and product safety




technologies











and processes





















standard bioassays


















biosimilar in the


as consolidation in

the biopharma and


and manufacturing

markets are just



biopharmaceutical

development


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

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tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page


1

42

5




bull Subcloning


PROCESS DEVELOPMENT

























THE AVID

ADVANTAGE




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page




eral days
















tory network












decisions




processing






manufacturing












bioprocesses




































of scale



















potency bioassays




















































Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



Cat Nos 14366C 24366C 24367C 24368C














vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page










vices market


































product approval


































samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page


















samples




































the keys to success

business challenges





















the knowledge gap


















approach


































































FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



FillFinish Trends


Eric s LangEr




























anti-counterfeiting


Ma

ria T

ou

tou

da

ki

Ge

tty Im

ag

es



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



PLAY VIDEO

CONTRACT

MANUFACTURING

Q Development

Drug Substance

lj Drug Product






regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page





regions



intelligence


systems
















these trends






















attractiverdquo



















equipmentrdquo














next 24 months














































surrounding

Fig

ur

e 1

is

co

ur

te

sy

oF

th

e a

ut

ho

r



adoption55

36


















copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page














copy 2

014

Ther

mo

Fish

er S

cien

tifi c

Inc

All

right

s re

serv

ed A

ll tr

adem

arks

are

th

e pr

oper

ty o

f The

rmo

Fish

er S

cien

tifi c

and

its

subs

idia

ries




Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



Cmos stAying

AheAd of the Curve























































to be an area of

growth for CMOs








































futurerdquo





















































































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page

































ConClusion


















































Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page







Agnes shAnley







global business















SC

IEP

RO

GE

tt

y Im

aG

ES












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page












to this niche









among others















oncology treatments









ufacturing business


















fulrdquo he says







ur

e 1

is

co

ur

te

sy

oF

in

ve

te

ch





















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page




















functions

labor-intensive

proCesses aDD Cost









one patientrdquo
























14 years














treatment









nologies (2)






therapies










Integration +- ++

Automation + ++

source invetech










source invetech












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page












apy involved
















designrdquo (DbD)


















patientrdquo










Cell Therapy (3)










IP issues


















for stakeholders













equipment evolves











easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page





easier
































Hampson says















issues

regulations evolve











MOArdquo































(Cambridge MA 2013)


111(1) 69-83 (January 2014)





source invetech


doseDevelopment

estimate

Unit Op Ref

Change decription

Comparability risk


Cost Time







RecordNone X X X

darr $$$$

TTTT







Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page






Jennifer L CoLLins
























Fa

na

tic S

tud

ioG

ett

y Im

ag

es



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page



























arrangement

Fee-For-service

development work





























































developments




























































customer
















cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page









cmo as collaborator















drug product























































and inventions
































rest of the world











































































necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page





























necessary

























should be asserted





















































conclusion

















Ad Index

AJINOMOTO ALTHEA 21







TOSOH BIOSCIENCE 11

WATERS CORP 3

Company Page

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