Try this Xcellerex bioreactor Get this bioprocess toolkit

54 Pages·2010·5.87 MB·English

Try this Get this
Xcellerex bioprocess
bioreactor toolkit
System Characterization
Process Modelling
Six Degrees of
Process Freedom
see reverse for details
Download the XDR toolkit paper today at:
www.xcellerex.com/toolbox
1.866.Xcellerex t
[email protected]
Proven single-use GMP bioreactors backed
by a team of bioprocess professionals
XDR bioreactors are engineered on the principles of stainless steel reactor design,
but with flexibility available only from single-use technology. XDRs offer a range of
mass transfer and C02 control capabilities that give process scientists the freedom
they need to achieve optimal cell culture conditions.
Together, XDR bioreactors, the Xcellerex team and ourr
bioprocess toolkit put you in control of
cell culture productivity.
XDR systems are available with maximum working volumes of 50, 200, 500, 1000 and 2000 liters.
Download the XDR toolkit paper today at:
www.xcellerex.com/toolbox • 1.866.Xcellerex • [email protected]
BioPharm
Supplement to:
INTERNATIONAL
November 2010 www.biopharminternational.com
Guide to
Disposables
Implementation

Guide to
Disposables Implementation
CONTENTS
EXTRACTABLES & LEACHABLES
Regulatory Expectations and Consensus Industry
Recommendations for Extractables Testing of
Single-Use Process Equipment
BPSA eases confusion over extractables and leachables
testing through guides.
6
Jerold Martin
BIOREACTORS: MABS
Evaluation of a Single-Use Bioreactor for the
Fed-Batch Production of a Monoclonal Antibody
Despite different material, agitation, and aeration, the performance of
the disposable bioreactor is similar to that of stainless steel bioreactors
Emmanuelle Cameau, Georges de Abreu, Alain Desgeorges,
12
Elodie Charbaut, Henri Kornmann
BIOREACTORS: VACCINES
Disposable Bioreactors for Viral Vaccine
Production: Challenges and Opportunities
Switching to single-use bioreactors can have fi nancial
and performance benefi ts.
Jean-François Chaubard, Sandrine Dessoy, Yves Ghislain,
22
Pascal Gerkens, Benoit Barbier, Raphael Battisti, Ludovic Peeters
ECONOMICS
An Economic Analysis of Single-Use Tangential
Flow Filtration for Biopharmaceutical Applications
Single-use TFF offers the greatest savings in clinical and
contract manufacturing, where the scale is low and
changeovers are frequent.
32
Michael LaBreck, Mark Perreault
FILTRATION
Implementing Single-Use Technology in Tangential
Flow Filtration Systems in Clinical Manufacturing
A case study evaluates the performance, control of operations,
productivity, and cost savings of a single-use system.
Keqiang Shen, Be Van Vu, Nikunj Dani, Bryan Fluke,
40
Lei Xue, David W. Clark
Cover credit: GLaxoSmithKline group of companies
November 2010 The BioPharm International Guide 3
BioPharm
INTERNATIONAL EDITORIAL ADVISORY BOARD
BioPharm International’s Editorial Advisory Board
comprises distinguished specialists involved in
Group Publisher Michael Tessalone the biologic manufacture of therapeutic drugs,
diagnostics, and vaccines. Members serve as a
[email protected]
sounding board for the editors and advise them on
Editor in Chief Laura Bush biotechnology trends, identify potential authors, and
[email protected] review manuscripts submitted for publication.
Managing Editor Chitra Sethi K. A. Ajit-Simh Denny Kraichely
[email protected] President, Shiba Associates Associate Director, CMC Team
Leader, Portfolio Management &
Associate Editor Haydia Haniff FVriceed Prriecs iGde. nBta, Pdreorcess Sciences TJoehcnhsnoicna Pl Ihnatremgraacteiounti,c Jaol hRn&sDon, I&nc .
[email protected] Centocor, Inc.
Howard L. Levine
Art Director Dan Ward Rory Budihandojo President, BioProcess Technology
Manager, Computer Validation Consultants
[email protected] Boehringer-Ingelheim
Herb Lutz
Associate Pat Venezia, Jr. Edward G. Calamai Senior Consulting Engineer
Publisher [email protected] Managing Partner Millipore Corporation
Pharmaceutical Manufacturing
European James Gray and Compliance Associates, LLC HVPa, Innsn-oPveattioenr fMor eFyuteurre
Sales Manager [email protected] John Carpenter Technologies, Lonza, Ltd.
Professor, School of Pharmacy
Production Kim Brown University of Colorado Health K. John Morrow
Sciences Center President, Newport Biotech
Manager [email protected]
Suggy S. Chrai Wassim Nashabeh
Marketing Cecilia Asuncion President and CEO, Global Head, Technical Regulatory
Promotions Specialist [email protected] The Chrai Associates PAo Mliceym &b eSrt roaft ethgey, RGoecnheen Gtercohu,p
Janet Rose Rea
Vice President, Regulatory Barbara Potts
Affairs and Quality Director of QC Biology, Genentech
Poniard Pharmaceuticals Tom Ransohoff
John Curling Senior Consultant, BioProcess
President, Technology Consultants
John Curling Consulting AB Anurag Rathore
Rebecca Devine Biotech CMC Consultant
Biotechnology Consultant Faculty Member, Indian Institute of
Technology
Mark D. Dibner
President, Chief Executive Officer Joe Loggia; Vice President, BioAbility Tim Schofield
Director, North American
President, Finance & Chief Financial Officer Ted Leonard J. Goren Regulatory Affairs,
Alpert; Vice President, Information Technology Global Director, Genetic GlaxoSmithKline
Identity, Promega Corporation
J. Vaughn; Executive Vice President, Corporate Paula Shadle
Development Eric I. Lisman; Vice President, Electronic Uwe Gottschalk Principal Consultant,
Vice President, Purification Shadle Consulting
Media Group Mike Alic; Vice President, Media Technologies
Operations Francis Heid; Vice President, Human Sartorius Stedim Biotech GmbH Alexander F. Sito
President, BioValidation
Resources Nancy Nugent; Vice President, General Rajesh K. Gupta
Counsel Ward D. Hewins; Executive Vice President, Laboratory Chief, Gail Sofer
Division of Product Quality Consultant, Sofeware Associates
Healthcare & Pharma/Science Group Steve Morris; Office of Vaccines Research and S. Joseph Tarnowski
Vice President and General Manager, Pharma/ Review, CBER, FDA
Senior Vice President, Biologics
Science Group Dave Esola Chris Holloway Manufacturing & Process
Group Director of Regulatory Development,
Affairs, ERA Consulting Group Bristol-Myers Squibb
© 2010 Advanstar Communications Inc. All rights Ajaz S. Hussain William R. Tolbert
reserved. No part of this publication may be reproduced or VP, Biological Systems, R&D President, WR Tolbert & Associates
tinracnlusmdiinttge db iyn apnhyo ftoorcmo poyr ,b yr eacnoyr mdienagn,s ,o erl eicntfroornmica otri omne cshtoarnaicgael Philip Morris International Michiel E. Ultee
and retrieval without permission in writing from the publisher. Jean F. Huxsoll Chief Scientific Officer
Authorization to photocopy items for internal/educational or Senior Director, QA Compliance Laureate Pharma
personal use, or the internal/educational or personal use of Bayer Healthcare, Pharmaceuticals Krish Venkat
specific clients is granted by Advanstar Communications Inc. for Barbara K. Immel Principal, AnVen Research
libraries and other users registered with the Copyright Clearance President, Immel Resources, LLC Steven Walfish
C97e8n-te6r4, 62-2827 R00o.s e Fwoor ouds eDsr .b Deaynovnedr sth, oMsAe l0is1t9ed2 3a,b 9o7v8e-,7 p5l0ea-8s4e 0d0ir feacxt Stephan O. Krause President, Statistical Outsourcing
your written request to Permission Dept. fax [phone] or Principal Scientist, Analytical Services
email: [email protected]. Biochemistry, MedImmune, Inc. Gary Walsh
Steven S. Kuwahara Associate Professor
Principal Consultant University of Limerick, Ireland
www.biopharminternational.com GXP BioTechnology LLC Lloyd Wolfinbarger
Eric S. Langer President and Managing Partner
President and Managing Partner BioScience Consultants, LLC
BioPlan Associates, Inc.
4 The BioPharm International Guide November 2010
Evolution at work.
We believe that evolution is essential to delivering smarter single-use
technology. Our fully integrated solutions are backed by over 50 years of
expertise gained from close collaboration with our clients. Are you ready to
take your bioprocessing operations to the next level?
Mobius. Smart people, smart products, smart services.™

Learn more about Mobius
Single Use. Visit us at
www.millipore.com/smartmobius
© 2010 Millipore Corporation. All rights reserved.
DISPOSABLES EXTRACTABLES & LEACHABLES
Regulatory Expectations and
Consensus Industry Recommendations
for Extractables Testing of Single-Use
Process Equipment
BPSA eases confusion over extractables
and leachables testing through guides.
Jerold Martin
Abstract systems, the absence of specific regulatory
The demand for single-use bioprocess guidance for process equipment extract-
systems in biotech and pharmaceutical ables and leachables has many drug
manufacturing has expanded significantly manufacturers unsure of what data must
over the past few years. Applications for be submitted.
I
single-use systems in biomanufacturing
n response to the interest in single-
range from upstream media preparation
use disposable manufacturing and to
single-use bioreactors, buffer preparation,
and intermediate processing, to storage of address the challenges of associated
active pharmaceutical ingredients (APIs), problems affecting the industry, the Bio-
bulk formulations, and filling of final dos- Process Systems Alliance (BPSA), the
age containers. Despite their
single-use biomanufacturing trade associ-
increased acceptance and
implementation, a pri-
mary concern with single-
use disposable polymeric
equipment continues to
be that of extractables
and leachables. In con-
trast with final dosage
container and closure
Jerold Martin is the senior
vice president of global scientifi c
affairs at Pall Life Sciences, Port
Wjies ratahslehd i_cnmhgataoirrnmt,i naN@nY ,po 5af 1ltlh.6ce.o8 Bm0o1. a.H9rde0 8aa6lns,do Corporation
TBeioc-hPnroolcoegsys C Soymstmemittse eA lalita nce. Pall
6 The BioPharm Intteerrnnaattiioonnaall GGuuiiddee NNoovveemmbbeerr 22001100
EXTRACTABLES & LEACHABLES DISPOSABLES
ation, has developed best practice educa- ables data submitted by biopharmaceutical
tional guides on a range of topics includ- manufacturers in drug product applications.
ing component quality tests, disposal For example, in an April 2008 prelicensing
issues, irradiation and sterilization, the inspection 483, the FDA stated, “Besides the
economics of single-use technology, and 0.22 μm sterilizing filters, there was no leach-
extractables and leachables. These guides able and extractable testing performed for the
tie together the expertise and leadership equipment and (--redacted--) materials used
of BPSA’s supplier and end-user member in (--redacted--) purification process includ-
companies to provide recommendations ing purification of (--redacted--).”
for industry best practices.
In December 2007 and January 2008, BPSA encouraged its member
BPSA published its fi rst white papers on ex-
companies to develop generic
tractables and leachables testing of single-
and comparable extractables
use process equipment.1,2 This was the fi rst
data to reduce the burden on
independent consensus guide that provided
basic concepts of extractables and leach- users for redundant testing.
ables from single-use equipment, summa-
rized the existing regulatory requirements, The drug manufacturer submitted a
and recommended a risk-based approach validation project plan defining require-
that could reduce the amount of testing re- ments for the evaluation of extractables
quired by users. As part of this initiative, and potential leachables from the prod-
BPSA also conducted a training seminar uct contact components of the process
in February 2008, at the headquarters of equipment, filters, and chromatography
the FDA and CBER near Washington, DC, media used to manufacture (the) drug
where we differentiated single-use process substances and products, and the risk
equipment from fi nal dosage container assessment. FDA’s subsequent 483 re-
and closures, discussed the BPSA recom- sponse review memo stated that the draft
mendations for extractables and leachables protocols and proposed corrective ac-
testing of single-use equipment, and the tions were considered to be adequate.1
proposed risk-based approach. BPSA also In a related inspection, the FDA similarly
has encouraged its supplier member com- observed, “There were no leachable and ex-
panies to develop more generic and compa- tractable testing performed for (--redacted--)
rable extractables data that would reduce materials used in buffer preparation.”
the burden on users for redundant testing. The drug manufacturer agreed to imple-
ment an extractables and leachables assess-
Regulatory Expectations for
ment policy that included risk assessment,
Extractables and Leachables Data
safety assessment, and model solvent study
In the ensuing period, BPSA has gotten design, along with generic family-approach
positive feedback from users and regulators studies for leachables and extractables for
about the risk-based approach. However, the storage of (--redacted--) used in buffer
FDA 483 observations and warning letters preparation activities.2 This is consistent
continued to cite insuffi ciencies in extract- with BPSA’s published recommendations.
November 2010 The BioPharm International Guide 7
DISPOSABLES EXTRACTABLES & LEACHABLES
At IBC’s 7th International Single Use be affected by potential leachables, studies
Applications for Biopharmaceutical Manu- may need to be performed to assess the ef-
facturing Conference, held in La Jolla, CA, fect on product quality, including effi cacy.”
on June 14, 2010, Destry M. Sillivan of the New products contacting single-use ma-
FDA provided an update and overview of terials often are reported in the product an-
types of data to be reviewed and specifi c nual report with no information regarding
areas of concern to the FDA. material composition, no extractables or
Sillivan stated that, “the responsibil- qualifi cation studies performed in support
ity for establishing that single-use ma- of use of the new material, and no written
terials selected for the manufacturing justifi cation of why the studies that were
process do not adversely impact the submitted were appropriate to support suit-
product falls on the manufacturer of the ability for use of the new materials with the
drug product under review,” and recom-
The FDA and CBER generally
mended that drug sponsors, “submit
recommend that the drug spon-
suffi cient information to provide evidence
that the product contacting material sor or the manufacturer demon-
does not introduce contaminants into the strate that the material is suitable
product so as to alter the safety, identity, for the submitted product.
strength, etc.”
Following closely the recommendations drug product. The FDA and CBER consider
made in BPSA’s 2008 Extractables Guide this level of information to be insuffi cient
and FDA CBER training seminar, Sillivan to determine if the change was submitted
stated that, “CBER recommends a risk- appropriately.
based approach be taken in evaluating ex- The FDA and CBER generally recom-
tractables and leachables where you take mend that either the drug sponsor or
multiple aspects into account (e.g., indica- the material manufacturer demonstrate
tion, safety issues, product characteristics, through suffi cient testing that the mate-
dosage, formulation, and stability profi le).” rial is suitable for the submitted processes
If there is no relevant risk associated with and product.
the (material in question), “vendor data can
BPSA Introduces
be cross referenced and a detailed justifi ca-
Updated Extractables Guide
tion for the applicability of these data and a
justifi cation for no additional testing should Recognizing the need for further education
be submitted,” he added. on extractables testing, including extrac-
According to Sillivan, “Where there is tion and analytical methods, BPSA began
relevant risk, the drug sponsor may have to develop a follow-up guide providing
to determine toxicity based on maximum more extensive information on methods
dosage of potential leachables based on ex- of extraction and extractables analysis in
tractables data. If the maximum dosage of 2009. The resulting BPSA 2010 Extractables
potential leachables presents a safety risk, Guide white paper, “Recommendations for
leachable evaluation and testing may be nec- Testing and Evaluation of Extractables
essary. Additionally, if product quality could from Single-Use Process Equipment”6 was
8 The BioPharm International Guide November 2010