Embed Size (px)
Citation preview
Issue 3 - April 2012 www.pall.com/biopharm
bioprocess
vision
Pall�Life�Sciences�will�showcase�itsnewest�lineup�ofleading-edgeproducts�and�services�to�enhancebioprocessingworkflows�at�two�upcoming
international�conferences.�The�companywill�demonstrate�how�its�technologies�forupstream�and�downstream�processingcan�be�"Your�Path�to�BioprocessSuccess"�in�drug�development�andproduction�at�Interphex�and�Achema.Interphex�takes�place�May�1-3�in�New�York,�USA;�Achema�will�be�held�June�18-22�in�Frankfurt,�Germany.
Visitors�to�Pall’s�booths�will�explorecritical�steps�in�bioprocessing�anddiscover�fast�and�flexible�solutions�atevery�stage�of�the�process:�Flexibility�in�Media�Prep,�Reliability�in�Cell�Culture,Simplicity�in�Cell�Clarification�and�CellHarvest,�Scalability�in�DownstreamProcessing,�Safety�in�ContaminantControl�and�Polishing,�and�Consistencyin�Formulation,�Filling,�and�Pharma�QC.We�are�happy�to�explore�all�this�together�with�you.
On�the�following�pages�you�will�findnumerous�new�products�worthconsidering�for�existing�or�new�processes.At�Interphex�and�Achema,�all�these�will�be�featured�together�with�othergroundbreaking�innovations,�amongstthem�new�bioreactor�technologies,�new�chromatography�sorbents,�newmembrane�filters�and�new�disposabledevices�such�as�single-use�needles�and�plastic�and�transportation�totes.
We�are�happy�to�provide�reliable�and�fully�integrated�solutions�for�the�design,manufacturing,�and�service�of�ourproducts.�All�these�will�help�you�toensure�timely�biopharmaceutical�processdevelopment�and�procurement�ofproduction�capacity.�We�are�lookingforward�to�seeing�you�soon�at�Interphex,Achema,�or�one�of�the�many�otherevents�we�attend�all�over�the�world!
Page
Market Trends 1Interphex and Achema 2012
Product News 2-4
AllegroTM Single-use TFF System: Fullyautomated with disposable manifolds
KleenpakTM Sterile Disconnectors: New variants for separation of single-use systems
Allegro Bioprocessing Workstations:Supporting flexible single-use systems
Palltronic® AquaWIT IV System: Automated preparation/testing ofhydrophobic/hydrophilic filters
Fluorodyne® EX Sterilizing Grade Filters: 5 in. configurations for smaller filter systems
PegasusTM SV4 Filters:For small virus removal
Mustang® XT Acrodisc® Units: Membrane adsorbers for scale-downprocess development
SentinoTM Microbiology Pump: Smallperistaltic pump with disposable fluid path
Acrodisc MS Syringe Filter: Certified for low extractables for LC/MS
Application 5
ISPE Facility of the Year Awards 2012
Interview 5
Two filters better than one? Jerold Martin, Pall Life Sciences, about recent discussions with regulators
Internet Highlights 6
Pall Biopharm Webinars: Online presentations of industry leadersand experts – live and on-demand
Contents
Dirk Sievers, Editor
Market Trends
1Further Information.
Your Path to Bioprocess Success
bioprocess
vision
The system combines the advantages of
Allegro single-use manifolds with an
engineered automated system design,
providing reliable control of key parameters
and ease-of-use in manufacture.
Adopting a single-use approach for TFF can provide reductions in:
System�preparation�and�cleaning�time�and�costs
Downtime�in�the�production�area
Risk�of�batch�or�cross�contamination�
Validation�time�and�costs��
The system has 1⁄2-in. tubing and a
feed pump capacity of 1000 L/hour.
It can be run with 20 L or 100 L feed
biocontainers, and run in fed batch
mode for processing larger volumes.
Single-use TFF manifolds:
Are�supplied�gamma-irradiated
Incorporate�pre-calibrated�single-use�instruments
Require�simple�installation�(15�minutes)
The�addition�of�two�smaller�diameterversions�of�the�Kleenpak�steriledisconnector,�¼�in.�and�⅜ in.�hose�barbformats,�provides�users�with�a�widerrange�of�application�potential.�
Typical�applications�include:
Sample biocontainer separation
for QC testing
Separation of fluid handling assemblies
around bioreactors
Disconnection of sterile filters for
offline integrity testing
Removal of sterile filtration sets from
filtered buffer or media
The Kleenpak sterile disconnector allows
for the separation of single-use systems,
whilst maintaining the sterility of, or
managing the general bioburden levels
within, the separated sections. The
demand for single-use systems integrating
sterile disconnectors is increasing at a fast
rate and the new size variants facilitate
wider application of these enabling
technologies, to further simplify operations
and improve process safety.
The�new�Allegro�bioprocessing�workstationsfrom�Pall�provide�extreme�ease-of-usearound�operations�and�activities�that�utilize�disposable�or�single-use�systems.�The�typical�applications�that�theseworkstations�can�be�used�for�include:
Clarification�and�product�storage:�usingStax™�depth�filter�modules
Filter�and�single-use�system�support�forbuffer�filtration�and�storage.
Chromatography�fraction�collection�andstorage�around�downstream�operations
Sterile�filtration�support�with�in situintegrity�testing�and�product�storage
Available in two basic formats (single or
double column width) and with a range
of frame extensions, plastic trays and
supporting hardware (such as filter
supports and document holders), these
workstations can greatly assist in the safe
handling, protection and general flexibility
for a wide range of operations from small
scale development activities through to
full scale production.
Product News
2Further Information. 3Further Information. 4Further Information.
Water Intrusion Testing is the most
convenient in situ integrity test for
hydrophobic filters. However – reliable,
reproducible results can only be achieved
with suitable measurement methods and
tightly-controlled filling and temperature
conditions.
Pall’s new Palltronic AquaWIT IV system
utilizes the on-board Flowstar IV instrument
to control up to three pneumatic valves to
isolate the test filter, fill the housing/capsule
with water and perform the entire test
automatically. The system can also perform
a fully automated Forward Flow or Bubble
Point test for liquid filters.
Features
Fully�automated�preparation�and�testingof�hydrophilic�or�hydrophobic�filters
All�critical�test�parameters�controlled�to�ensure�reproducibility�of�test�results
Fully�supports�electronic�signaturesaccording�to�21�CFR�Part�11
Internal�open�process�control�(OPC)server�for�communication�with�processcontrol�systems
High capacity Fluorodyne EX filters with
built-in prefiltration are now available in
5 in. filter cartridge and filter capsule
configurations. These allow for the
downsizing of single 10 in. or dual stage
filter systems, and as a result, lower
filtration costs.
0.2 µm-rated Fluorodyne EX grade
EDF membrane filters are recommended
for the sterile filtration of cell harvest,
process intermediates, and for some
niche applications such as the filtration
of liposomal fluids in vaccine
manufacturing.
0.1 µm-rated Fluorodyne EX grade
EDT membrane filters combine high
capacity performance with additional
safety. With outstanding mycoplasma
removal efficiency for A. laidlawii and
M. orale (typically > 10 LRV), they are
a primary recommendation for filtering
cell culture media or growth media as
bioreactor feeds and used during
aseptic filling validation.
Coming soon: The new Pegasus SV4
small-virus removal filter offers constant,
stable flow-rate performance and
outstanding throughput capacity,
enabling maximum filtration economy.
It demonstrates highly-efficient clearance
of both small ‘non-enveloped’ viruses and
large viruses, even showing constant,
stable flow-rate performance when used
with either dilute or complex/concentrated
biological fluids. It also offers stable
pressure/flux capability in more complex or
concentrated feeds, helping improve virus
filtration economy in highly-concentrated
protein solutions, without unnecessary
product dilution. Flow decay caused by
unwanted membrane ‘plugging’ and gel
polarization is also kept to a minimum over
a wide range of process conditions and
extended process times. All of these
factors combine to ensure that Pegasus
SV4 virus removal filters can be established
as a platform technology enabling high
virus safety and significantly reducing
processing costs.
Product News
5Further Information. 6Further Information. 7Further Information.
Mustang XT Acrodisc units, the latest
addition to Pall’s membrane adsorbers,
are available in Q and S chemistries.
They have been designed to be fast, easy
to use, and ideal for scale-down process
development in a variety of applications.
These include protein purification and
sample preparation in research
laboratories, contaminant removal in
biotech and plasma fractionation as well
as contaminant removal and large molecule
capture in vaccines manufacturing.
The new units can be easily connected to
low pressure chromatography systems and
offer excellent performance over a broad
range of flow rates.
Features:
Device�volumes�<1�mL�to�minimizesample�requirements
Easy�scale�up�due�to�consistent�16�membrane�layer�format
Flow�rates�of�up�to�10�MV/min�at�low�pressure�drop
Female�Luer�Lock�inlet/outletconnections
The Sentino pump streamlines analysis by
replacing the traditional vacuum filtration
system with a small peristaltic pump that
channels fluid directly to drain. Simple
operation, compact design, and portability
make it easy to use in confined spaces and
frees valuable benchtop space for better
workflow efficiencies. The disposable fluid
path provides easy maintenance and
superior contamination control in a busy
microbiology laboratory - no more cleaning,
wrapping or autoclaving a bulky manifold.
Features
Compact�Size�-�takes�up�less�space
Portable�-�rechargeable�battery�or�use�astandard�electrical�outlet
Simple�Operation�-�no�programming�ordata�storage�to�validate
Peristaltic�Design�-�fluid�flows�in�onedirection
Disposable�Fluid�Path�-�replace�beforebiofilm�build-up�becomes�a�problem
The Acrodisc MS syringe filter is the first
syringe filter specifically designed and
certified for low extractables in high
performance liquid chromatography/mass
spectrometry (LC/MS) applications.
The filter improves the accuracy of testing,
enhances LC/MS performance, and
extends the longevity of sensitive testing
instrumentation. The low extractable levels
minimize interference with the ionization
process and reduce the need for re-testing.
These features lower costs while
minimizing instrumentation downtime
due to unexpected contamination.
Features
Certified�low�in�LC/MS�extractables
Low�in�ion�suppression�and�ionenhancement
Excellent�chemical�resistance�due�towater�wettable�PTFE�membrane
Low�protein�binding
Product News
8Further Information. 9Further Information. 10Further Information.
Regulatory�authoritiesaround�the�worldpromote�riskassessment�to�ensuredrug�product�safety.�We�interviewed�JeroldMartin�about�recentdiscussions�withregulators.
Jerry, how is the expectation of regulators changing with regard to drug products that cannot be sterilized in their final container?
Sterilizing filtration is still the norm for these
products. US FDA requires that sterilizing
filtration be validated under worst case
conditions (a service provided by Pall).
EMA accepts this, but European GMP
also recommends use of a second sterilizing
filter (usually 0.2 micron rated) for added
sterilization assurance.
Using two filters to do one job seems excessive, do the regulatorsmandate this?
Only selectively. It’s optional under US FDA
guidance and the European GMP guidance
is not universally mandated across Europe.
However, some European country
inspectors do expect it.
Is integrity testing of both filters required?
Post-use integrity testing of the final
sterilizing filter is always required. Testing of
“double” (serial) filtration schemes, however,
can vary. Where the first filter is used as a
prefilter, it is not required to integrity test it
because the product upstream of the final
filter must be sampled for bioburden
anyway. In a redundant scheme, if the
second (final) filter passes a post-use
integrity test, the
product can be
considered sterilized without
testing the first filter.
The benefit of redundancy is that
if the final filter fails the integrity
test, and the first filter passes,
the product is still considered sterile.
Where both filters are required for
sterilization, then both will need to
be integrity tested, at least post-use.
How about pre-use testing?
Although some EU Inspectors
are requiring pre-use testing after steam
sterilization, pre-use testing does not affect
patient safety and is primarily a business
decision to avoid loss of the batch or
rework in the event of a non-integral filter.
It can ensure that shipping, handling and
installation, as well as the sterilization
process, have been done correctly.
Lastly, can these test procedures be applied to single-use systems?
Certainly. For single use systems,
Pall provides standard and customized
designs suitable for use in compliance
with regulatory requirements, as well as
offering consultancy and training workshops
on filtration system design, installation and
integrity testing that many users find
extremely beneficial.
References:PDA Technical Report TR26 (2008)
FDA Guidance for Industry – Sterile Drug Products Produced
by Aseptic Processing – Current Good Manufacturing Practice
(September, 2004)
EC Guide to GMP - Revision to Annex I - Manufacture of Sterile
Medicinal Products (Revised Feb, 2008 - Effective March,
2009)
EMEA Committee for Proprietary Medicinal Products (CPMP).
Note for Guidance on Manufacture of the Finished Dosage
Form (CPMP/QWP/486/95) (April, 1996)
Every year, the International Society
for Pharmaceutical Engineering
(ISPE) makes awards in their Facility
of the Year competition. For 2012,
two category awards went to facilities
where Pall played an extensive role
in providing innovative equipment
and support.
For "Equipment
Innovation"1,
Rentschler
Biotechnologie
GmbH (Laupheim,
Germany) was the
winner, with the citation concluding
"Jointly developed was a highly
automated skid for virus filtration that
can accommodate a wide variety of
manufacturing protocols." Pall also
provided many other systems.
These systems
were discussed
by Rentschler at
a conference
hosted by the
National Institute
of Bioprocessing Research and Training
(NIBRT) in Dublin, who won the "Novel
Collaboration" category2. Pall’s work
with NIBRT was featured in a recent
press release3 describing the "master
class on the use of single-use systems
in the development and manufacturing
of biopharmaceuticals."
1.�www.facilityoftheyear.org/foyawinners2012#Rentschler
2.�www.facilityoftheyear.org/foyawinners2012#NIBRT
3.�news.pall.com/article_display.cfm?article_id=4614
Jerold Martin, Sr. VP of GlobalScientific AffairsPall Life Sciences
Application Interview
11Further Information.
bioprocess
visionBiopharmaceutical Webinar Series
Detailing�the�latest�industry�trends�and�providing�updates�on�newtechnologies,�Pall�Life�Sciences’�series�of�webinars�are�botheducational�and�informative.�The�presentations�are�given�bybiopharmaceutical�industry�leaders�and�experts.�Have�you�missedone�of�our�live�webinars?�Not�a�problem.�All�Pall�Biopharmaceuticalwebinars�are�also�made�available�on-demand�to�be�viewed�at�your�convenience.�See�information�on�right�for�the�content�of�our�most�recent�live�webinar.
Please�visit�www.pall.com/biopharmwebinars for�moreinformation�and�to�register.�
Biopharmaceutical Webinar Series (current topics)
Membrane�Chromatography�–�A�Flexible�Solution�to�High�Speed�Contaminant�Clearance
Thermal�Stability�and�Aggregation�Analysis�–�Clues�to�Better�Formulations
Determination�of�Extractables/Leachables�from�Single-use�Systems
Sterilization�of�Single-use�Systems�by�Gamma�Irradiation
Additional�webinar�topics�will�be�announced�several�weeks�inadvance�of�their�live�dates.�If�you�would�like�to�be�notified�or�have�suggestions�for�future�webinar�topics,�please�send�an�email�to��[email protected]
Upcoming�webinar�topics�include:
Post-Sterilization�/�Pre-Use�Integrity�Testing�of�Sterilizing�Grade�Filters:�Regulatory�Expectations,�Technical�Issues�and�Pall�Recommendations
Complex�Single-Use�Unit�Operations:�The�Process�andEconomic�Benefits�of�Replacing�Traditional�with�Single-UseTangential�Flow�Filtration
Webinar Series – Recently Held
Membrane Chromatography - A Flexible Solution to HighSpeed Contaminant Clearance
Continual�improvements�in�upstream�processing�have�led�tohigher�protein�expression�levels,�resulting�in�downstream�titers�in�excess�of�1g/L,�even�reaching�10g/L.�These�advances�directly�impact�the�downstream�process,�leading�to�potential�bottlenecks.�However,�trends�such�as�the�use�of�higher�capacity�chromatography�sorbents�with�improved�selectivity,�and�an�increase�in�the�use�of�single-use�technologies�such�as�membrane�chromatography,�are�gaining�momentum�in�thebiopharmaceutical�industry.
Efficient�contaminant�removal�from�such�processes�is�verychallenging�and�this�is�an�application�where�membranechromatography�is�proving�very�popular.�Its�ease�of�operation,speed,�and�efficiency�are�helping�to�reduce�processing�time�and�cost,�as�well�as�improve�overall�process�productivity.�This�webinar�will�provide�the�basic�principles�of�membranechromatography�and�illustrate�specific�customer�applications�of�how�this�technology,�when�incorporated�into�the�process,saves�time�and�cost.
The webinar is now available on-demand atwww.pall.com/biopharmwebinars.
For further information on any of the articles in this newsletter,
please visit www.pall.com/biopharm or email us, referring to the
respective article number, at [email protected]
Corporate HeadquartersPort Washington, NY, USA+1�800�717�7255��toll�free�(USA)+1�516�484�5400��[email protected]��e-mail
European HeadquartersFribourg, Switzerland+41�(0)26�350�53�00��[email protected]��e-mail
Asia-Pacific HeadquartersSingapore+65�6389�6500��[email protected]��e-mail
International OfficesPall�Corporation�has�offices�and�plants�throughout�the�world�in�locations�such�as:�Argentina,�Australia,�Austria,Belgium,�Brazil,�Canada,�China,�France,�Germany,�India,�Indonesia,�Ireland,�Italy,�Japan,�Korea,�Malaysia,�Mexico,�the�Netherlands,�New�Zealand,�Norway,�Poland,�Puerto�Rico,�Russia,�Singapore,�South�Africa,�Spain,�Sweden,Switzerland,�Taiwan,�Thailand,�the�United�Kingdom,�the�United�States,�and�Venezuela.�Distributors�in�all�major�industrial�areas�of�the�world.�To�locate�the�Pall�office�or�distributor�nearest�you,�visit�www.pall.com/contact.
The�information�provided�in�this�literature�was�reviewed�for�accuracy�at�the�time�of�publication.�Product�data�may�besubject�to�change�without�notice.�For�current�information�consult�your�local�Pall�distributor�or�contact�Pall�directly.�
© 2012, Pall Corporation. Pall, , Acrodisc, Allegro, Fluorodyne, Kleenpak, Mustang, Palltronic,Pegasus, and Sentino are trademarks of Pall Corporation. ® indicates a trademark registered in the USA andTM indicates a common law trademark. Filtration.Separation.Solution is a service mark of Pall Corporation.
4/12,�PDF,�GN12.5079
Visit us on the Web at www.pall.com/biopharmE-mail us at [email protected]
Internet Highlights
