State-of-the-art and emerging technologies for therapeutic monoclonal antibody characterization. Volume 3, Defining the next generation of analytical and biophysical techniques

450 Pages·2015·8.08 MB·English

by  Borisov, Oleg, Davis, Darryl L., Schiel, John E

State-of-the-Art and Emerging
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In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
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In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
1202
ACS SYMPOSIUM SERIES
State-of-the-Art and Emerging
Technologies for Therapeutic
Monoclonal Antibody Characterization
Volume 3. Defining the Next Generation of
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1/ John E. Schiel, Editor
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AmericanChemicalSociety,Washington,DC
DistributedinprintbyOxfordUniversityPress
In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
LibraryofCongressCataloging-in-PublicationData
State-of-the-artandemergingtechnologiesfortherapeuticmonoclonalantibody
characterization/JohnE.Schiel,editor,NationalInstituteofStandardsandTechnology,
Gaithersburg,Maryland,DarrylL.Davis,editor,JanssenResearchandDevelopment,LLC,
SpringHouse,Pennsylvania,OlegV.Borisov,editor,Novavax,Inc.,Gaithersburg,
1
0 Maryland.
0
w volumescm.-- (ACSsymposiumseries;1202)
02.f Includesbibliographicalreferencesandindex.
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1 Contents:v.3.definingthenextgenerationofanalyticalandbiophysicaltechniques
15- ISBN978-0-8412-3031-6(v.3)
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2 1. Monoclonalantibodies.2. Immunoglobulins--Therapeuticuse. I.Schiel,JohnE.,editor.
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b II.Davis,DarrylL.,editor.III.Borisov,OlegV.,editor.
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2 QR186.85.S732014
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0.1 616.07′98--dc23
oi: 1 2014040141
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ber ThepaperusedinthispublicationmeetstheminimumrequirementsofAmericanNational
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In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
Foreword
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sponsoredsymposiabasedoncurrentscientificresearch. Occasionally,booksare
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In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
Preface
The line between where we are, and where we are going often blur.
Developmentofnovelanalyticalandbiophysicaltechnologyaredescribedwellby
thisnotion,asadvancesevolveinrealtime. Definitionof“emergingtechnology”,
however, is often associated with a continuous uptick in industry acceptance.
1 Thismayincludepromisingmodifications,orinsomecasesdrasticaccelerations,
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pr of state-of-the-art technology. The following volume of the book series is titled
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0 “Defining the Next Generation of Analytical and Biophysical Techniques” and
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5- contains 15 original chapters, authored by scientists from the biotechnology
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20 industry, academia, government agencies, and instrument-manufacturing firms
bk- thatspanmethod,technology,andinformaticsplatforms. Thisvolumedescribes
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2 novel and emerging analytical technologies for analysis of proteins with the
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0. emphasis on technologies aimed to address characterization “knowledge gaps”
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5 | selectivity,sensitivity,resolution,andthroughput.
01 HigherorderstructureofproteinsisarecognizedimportantattributeofmAbs,
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5, with potential implications on stability, safety, and biological function of these
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er large molecules. X-ray crystallography, NMR, hydrogen-deuterium exchange
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cto mass spectrometry (Chapter 2) and covalent labeling techniques (Chapter 3) are
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b): describedinlightoftheirapplicationtoexaminehigherorderstructureofmAbs.
e Ionmobilitymassspectrometry,inChapter4,providesstructuralinformationby
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e ( examining the collisional cross-sections of proteins in a gas phase under native
Dat ionizationconditions,theinformationbeingparticularlyusefulforcomparability
on investigations, including development of biosimilars. Chapter 5 summarizes
cati the current knowledge on the nature of protein aggregation (at nanometer-sized
Publi scale) of mAb formulations. This chapter further emphasizes the need for
more sophisticated and high-resolution techniques to replace conventional
lower resolution biophysical approaches for probing structure and molecular
interactions. Chapter 6 introduces a novel tool to study protein aggregation
simultaneouslyundermultipleconditionsbylightscatteringtoenableexpedited,
controlled, and reliable formulation screening. Chapter 7 discusses specifics of
applications of modern bioinformatics tools for the analysis of biotherapeutic
proteins,anissuethathasbeenlargelyunderrepresentedintheliterature. Inthis
regard,Chapter14continuesthediscussionbyintroducingseveralnewsoftware
tools for the analyzing peptide mapping data and enabling trending attributes
by comparing multiple data sets. Chapter 8 describes newer nucleic acid-based
polymerasechainreaction(PCR)methodsforthedetectionofadventitiousagents
during biopharmaceutical manufacturing. Microfluidic technologies such as
lab-on-a-chip and high-performance liquid chromatography (HPLC)-chip mass
ix
In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
spectrometrytools,inChapter9,simplifyintegrationofmultiplesteps,enabling
higherthroughputandtheeaseofuseofcomplexanalyticalprotocols. Analysis
of large proteins, such as intact IgG, by state-of-the-art mass spectrometry, with
the emphasis on extracting useful sequence information from the top-down
fragmentation data, are presented in Chapter 10 and Chapter 11, respectively,
usingESIOrbitrapandMALDImassspectrometrytechnologies. Automationof
manual processes of sample extraction, cleaning, and preparation for analysis is
describedinChapter12,whichtargetstheimprovementofreliability,consistency,
andthroughputofanalyticalworkflows. Chapter13describesnovelapproaches
foridentificationandquantitationofHCPsinbiotherapeuticproducts.
The compilation of data and willingness of scientists throughout the
biopharmaceuticalindustrytosharetheirmostrecentinnovationsinthisvolume
is a testament to the collaborative nature and interest in furthering a mission to
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0 quality therapies. At the time of the first mAb approved for human use, it was
pr
2. unthinkablethatonedayanimageofasinglemAbmoleculemightbeattainable.
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1 Such astonishing developments have now become a reality, and the excitement
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1 only continues to grow. Many of novel and exciting technologies are rapidly
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k- advancinganddemonstratethatasavillage,wewillsucceedinattaininganeven
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doi: JohnE.Schiel
15 | ResearchChemist
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[email protected](e-mail)
OlegV.Borisov
AssociateDirector
Novavax,Inc.
Gaithersburg,Maryland20878,UnitedStates
[email protected](e-mail)
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In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
Editors’ Biographies
John E. Schiel
Dr. John E. Schiel received his B.S. (2004) and Ph.D. (2009) in Chemistry
from the University of Nebraska-Lincoln, and is currently a research chemist
in the NIST Biomolecular Measurement Division. He is leading the LC- and
MS-based biomanufacturing research efforts at NIST; developing a suite of
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0 fundamental measurement science, standards, and reference data to enable
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ot more accurate and confident characterization of product quality attributes. Dr.
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20 Schiel is also the technical project coordinator for the recombinant IgG1κ NIST
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5- monoclonal antibody Reference Material (NISTmAb) program. He is an author
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2 of over 20 publications and recipient of numerous awards, including the ACS
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02 Award,andUNLEarlyAchieverAward.
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2 Dr. Darryl L. Davis holds a doctorate in Medicinal Chemistry from the
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1 Philadelphia College of Pharmacy and Science. His thesis focused on the use
ber of MS in the characterization and quantitation of peptide phosphorylation.
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b): glycan linkages found on Remicade. Upon receiving his doctorate he accepted
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e ( aJ&Jcompany. SincejoiningJ&Jhehasheldawidevarietyofresponsibilities
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andhigh-throughputanalysiswhichcontinuestobeacurrentfocus. Currentlyhe
leadsananalyticalgroupwithinthediscoveryorganizationatJanssenR&D.

Oleg V. Borisov
Dr. Oleg V. Borisov earned a B.S. degree (with honors) in Chemistry at
Moscow State University (1992), and received his Ph.D. in Chemistry from
Wayne State University (1997), after which he completed his post-doctoral
studiesatLawrenceBerkeleyNationalLaboratories(2000)andPacificNorthwest
NationalLaboratories(2001). Hisbackgroundincludesexperiencewithanalytical
methods for characterization of biotherapeutic proteins and vaccine products,
with emphasis on liquid chromatography and mass spectrometry methods.
©2015AmericanChemicalSociety
In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
Dr. Borisov held positions at Genentech and Amgen with responsibilities that
included protein characterization, testing improvement, leading innovation and
CMC strategy teams. He is currently a Director at Novavax, Inc., developing
methodsandstrategiesforanalysisandcharacterizationofrecombinantvaccines,
based on nano- and virus-like particle technologies. His credits include several
studentawards,abookchapter,andover25scientificpublications.
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444
In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.
©2015AmericanChemicalSociety
characterizationneedsfortheseproducts.
emerging technologies to address unmet or under-met
analytical methods and the need for the development of
a snapshot on current perspectives on the state-of-the-art
biotherapeutic proteins. The aim of the survey was to capture
researchers associated with the development and testing of
this introductory chapter is based on the polled opinions of
complex biological products in greater detail. Discussion in
well as the development of new tools to characterize these
for improvement of existing analytical methodologies as
01 Collectively, these trends amplify the increasing demand
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ch establishment biosimilar and follow-on biologics pathways.
2.
0 as well as making existing therapies more affordable via the
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5- as bispecific and conjugated monoclonal antibody products,
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20 targeting new and increasingly sophisticated therapies, such
bk- thefieldisrapidlyexpandinginseeminglyorthogonaldirections
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2 inmodernscienceandclinicalexperiencewithbiotherapeutics,
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Publi OlegV.Borisov,*,1JohnE.Schiel,2andDarrylDavis3

Characterization Tools
of Next-Generation Biotherapeutic
Trends and Drivers for the Development
Chapter 1
In State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 3. Defining the Next Generation of Analytical and Biophysical Techniques; Schiel, et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2015.