The 10th Annual Bioassays and Bioanalytical Method Development Conference brought together scientists from industry, academia, and regulatory agencies to discuss trends in cell-based assays and bioanalysis. Presentations evaluated new technologies and their impact on bioassay methods and workflows. Regulatory perspectives on draft guidance were provided. Discussions focused on strategies to develop sensitive and reproducible bioassays, challenges in validating assays for clinical samples, novel technologies to expedite drug development, and ensuring continuity of data through assay transfers. The conference provided a forum for collaborative discussions around critical issues in bioanalytical method development.

1. 569Bioanalysis (2015) 7(5), 569–572 ISSN 1757-6180
part of
Conference Report
10.4155/BIO.14.319 © 2015 Future Science Ltd
The 10th Annual Bioassays and Bioanalytical Method Development Conference was
hosted in Boston, MA, USA on 20–22 October 2014. This meeting brought together
scientistsfromthebiopharmaceuticalandlifesciencesindustries,theregulatoryagency
and academia to share and discuss current trends in cell-based assays and bioanalysis,
challenges and ideas for the future of the bioassays and bioanalytical method
development. The experiences associated with new and innovative technologies
were evaluated as well as their impact on the current bioassays methodologies
and bioanalysis workflow, including quality, feasibility, outsourcing strategies and
challenges, productivity and compliance. Several presentations were also provided by
members of the US FDA, sharing both scientific and regulatory paradigms including
a most recent update on the position of the FDA with specific aspects of the draft
Bioanalytical Method Validation guidance following its review of the industry’s
responses. The meeting was jointly coincided with the 15th Annual Immunogenicity
for Biotherapeutics meeting, allowing for attendees to also familiarize themselves
with new and emerging approaches to overcome the effect of immunogenicity, in
addition to investigative strategies.
Keywords: analytical platforms • bioanalytical method development • bioassays • bioterapeutics
• method development strategies • method validation • regulatory perspectives
The complexity of developing effective biologic
therapeutics requires adequate analytical meth-
odology to characterize both their physico-
chemical properties and biological activity. In
contrast to small molecules, the final product
for every biologic is influenced by all steps in
the process of its production. Therefore, devel-
oping sensitive, reproducible bioassays and pre-
cise bioanalytical methods for their character-
ization (in preclinical and clinical studies) are
crucial for biologics. The cost for developing
innovative biologics is staggering. Biopharma-
ceutical research community is under pressure
to discover innovative therapeutics and move
them through the development pipeline faster
than ever before. Bioassays and bioanalytical
characterization of biologics are at the core of
the biopharma business.
The 10th Annual Bioassays and
Bioanawlytical Method Development
Conference [1] was designed to bring
together research (from discovery to clini-
cal) and regulatory scientists from across
the biopharmaceutical industry to discuss
their achievements, challenges and ideas for
the future of the bioassays and bioanalyti-
cal method development. During the con-
ference, a substantial amount of key bioas-
say and bioanalytical topics were presented
and practical experiences and case studies
were shared. The conference spanned over
two sequential days and one training course
covering major practical issues in bioanalysis
including method development strategies,
regulatory perspectives in bioanalysis, and
novel technologies and processes in biologic
drug development support. The twenty
conference topics chosen for discussions
were segmented in five sessions covering the
following areas.
The 10th Annual Bioassays and
Bioanalytical Method Development
Conference
Mark Ma*,1
, Christopher
Tudan2
& Dolly Koltchev3
1
1 Amgen Center Dr., Thousand Oaks,
CA 91320, USA
2
Lovelace Respiratory Research Institute,
2425 Ridgecrest Drive SE, Albuquerque,
NM 87108, USA
3
Institute for International Research,
708 Third Avenue, New York,
NY 10017, USA
*Author for correspondence:
mhma@amgen.com
For reprint orders, please contact reprints@future-science.com

2. 570 Bioanalysis (2015) 7(5) future science group
Conference report Ma, Tudan & Koltchev
Bioassay & bioanalytical method
development strategies
Strategies and considerations in cell-based assays and
bioanalytical method development and implementa-
tion were emphasized and discussed in-depth amongst
the attendees. During the conference, keynote speak-
ers (from Amgen, CA, USA and Pfizer, MA, USA)
outlined their perspectives on the past, present and
future of bioassays and bioanalysis. The diversity of
modern biotherapeutics compounds translates to a
variety of challenges when designing an appropriate
bioanalytical or bioassay strategy. For the past decade,
the evolution of innovative technologies has had a
major impact on many arenas of bioanalysis, including
quality, feasibility, compliance and productivity (the
number of samples that can be processed in a specified
impetus to harmonize bioanalytical method valida-
tion [BMV] period). At the same time, the regulatory
and industry expectations have become more rigorous,
resulting in drive for the harmonization of method
validation, sample analysis approaches and acceptance
criteria with a greater emphasis on respective fit-for-
purpose approaches to accommodate new analyti-
cal platforms, and therapeutics. For example, testing
for the immunogenicity potential is highly critical in
development of any biotherapeutics. While the indus-
try overall has made significant progress in developing
common and acceptable approaches associated with
the development of appropriate assays, many questions
still remain, such as:
• Given the immense diversity in biotherapeutic bio-
assay and bioanaltyical platforms, and the analytes
that are being assayed, what will the acceptable and
more dominant approaches be going forward?
• Will ligand-binding assays (LBA) continue to be
the most predominant approach to use?
• How can new and emerging bioanalytical applica-
tions address typical concerns for the bioanalysis of
biotherapeutics?
Presenters discussed strategies on how to bridge
discovery to development to leverage technology for
accelerated bioassay development. Bioanalytical scien-
tists are taking different approaches in this endeavor,
including the use of the fully automated discovery assay
platforms for reagent and sample processing and assay
execution (BMS, NJ, USA), practical solutions for
confirmatory assays, cut point calculations and ways to
reduce variability (Eurofins BioAnalytics, MO, USA),
using a dynamic cut point in a 384-well cell-based neu-
tralizing antibody Assay (Bioagilytix Lab, NC, USA),
and optimization of critical assay parameters using
design of experiments to develop gene therapy potency
assays (Genzyme, CA, USA).
Antibodies are critical reagents for biotherapeutics
analysis. A case study that demonstrates how anti-
body quality and performance dictates the robust-
ness of LBA was presented (Amgen). The systematic
multitiered approach at Amgen to generate and select
anti-idiotypic antibodies as reagents for the bioanaly-
sis of therapeutic antibodies was thoroughly discussed.
Scientist from AbD Serotec (Bio-Rad, London, UK)
also demonstrated new tools for PK and ADA assay
development – Recombinant Antibodies Binding to
Therapeutic Drugs with using the HuCAL®
technol-
ogy for fast development of fully human Fab and Ig
anti-idiotypic antibodies that demonstrated high-
affinity binding and specifically to well-known drugs,
such as adalimumab, trastuzumab and cetuximab.
Regulatory perspectives
With limited regulatory guidance available pertaining
to bioassay practices and respective reporting of data,
and the BMV guidance still in its draft form, regulatory
perspectives and considerations pertaining to the cur-
rent and new analytical technologies and biotherapeutic
entities, was shared.
The Revised US FDA Guidance on Quantitative
Bioanalytical Methods Validation and Implementation
was presented by a speaker from FDA. A revised ‘Draft
Guidance’ was posted in September 2013 for the 90-day
comment period. During the comment period, AAPS/
FDA Workshop Crystal City V was held in Decem-
ber 2013 to give representatives from FDA, industry
and international regulatory bodies an opportunity to
discuss the new sections of the revised guidance. New
sections were added to target special validation con-
siderations, such as the following: additional details
regarding reference standards, matrix effects, failed
validation runs, calibration curves and stability for chro-
matographic assays; advances in LBAs and the inherent
differences between chromatographic assays and LBAs;
incurred sample reanalysis; biomarkers, diagnostic kits,
endogenous products and other new technologies; chain
of custody; documentation.
The presenter from Lovelace Respiratory Research
Institute shared his review on adopting the bioanalytical
Method Validation Guidance’s to Clinical Samples in a
GCP Environment. In the efforts to interpret the accept-
able practices for validating bioanalytical methods with
the intended use for the analysis of human clinical sam-
ples in accordance to GCP’s, the 2012 EMA on BMV
directed that the validations be performed following the
principles of GCP. Outside of the UK, most institutions
and corporations have adopted principles of GLPs to the
bioanalysis of clinical samples, but it is being recognized

3. www.future-science.com 571future science group
The 10th Annual Bioassays & Bioanalytical Method Development Conference Conference report
that the principle of GCPs or GCLPs will need to apply
to clinical study sample bioanalysis (and respective
method validation). The presentation and subsequent
roundtable discussion highlighted the approaches for
how to bridge this gap from a global bioanalytical per-
spective through adopting the BMV Guidance’s to clini-
cal samples in a GCP environment. A heated roundtable
discussion followed when many shared their own related
challenges and concerns.
Future perspective: novel bioanalytical
approaches & technologies
Novel technologies to speed up the lead selection and
early drug development were discussed (Genentech,
CA, USA). A case study was presented on advantages
of Gyros technology and its utility in expediting lead
selection in early drug development. There are several
advantages of Gyros platform in supporting early drug
development: one PK method is suitable for multiple
drug candidates and lead selection; one PK assay is suit-
able for multiple nonclinical matrices; enable serial sam-
pling for PK/Tox studies to reduce animal numbers and
data variability; enable multiple read out from sample
with limited volume (e.g., CSF, PK/ATA/Biomarkers);
greater number of samples that can be analyzed per hour.
The opportunities and pitfalls in the development
and licensure of a next generation of engineered bio-
therapeutics - an approach with therapeutics by design
was revealed by a scientist from FDA laboratory. An
unprecedented number of second- and third-generation
therapeutic proteins, which have been engineered to
improve product attributes or to enhance process char-
acteristics, are entering the drug-development pipeline.
While the advantages of engineered therapeutic proteins
are considerable, the alterations can affect the safety
and efficacy of the drugs. The speaker focused on sev-
eral aspects of this topic, including the acknowledge-
ment that bioengineered therapeutic proteins are rapidly
becoming the norm for fast adoption of key platform
technologies used to improve product attributes or to
enhance process characteristics of therapeutic proteins,
and lessons learned from examples of engineered thera-
peutic proteins that have been successfully marketed as
well as those that have failed during drug development.
A cell engineering approach for quantification of
potency of multifunctional biotherapeitics was discussed
(Biomonitor, France). It utilizes a single assay platform
that allows simultaneous readout with a high degree of
sensitivity and precision.
Experiences associated with mammalian cell dis-
play systems for multiparameter selection of antibodies
designed for specific application was shared (AnaptysBio,
Inc., CA, USA). The natural mechanism of antibody
maturation, known as somatic hypermutation, has been
reproduced in vitro and coupled with a mammalian cell
display system to enable multiparameter selection and
optimization. This is enabled through the simultane-
ous cell surface display and secretion of the antibody
via alternative splicing of the heavy chain mRNA. A
number of novel examples was also presented for both
therapeutic and diagnostic applications.
The strategy for clinical biomarker discovery and
development was discussed (Merck, NJ, USA). Bio-
marker discovery takes place mainly in the lead opti-
mization space, whereas, fit-for-purpose assay validation
is normally established once a preclinical candidate is
approved for development in clinical studies. Certain
biomarkers, such as those used for patient selection
are naturally transitioned as companion diagnostics
assays in the clinic after a drug is approved. A case
study was provided to illustrate the development and
implementation of a novel clinical biomarker discovery
and assay validation to support late-stage clinical studies.
Bioassay and bioanaltyical assay transfer with focus
on confidence and continuity in the data chain was
reviewed by a scientist from Biogen Idec. (MA, USA)
The presentation highlighted some key considerations
when transferring LBA between laboratories, including
the need for a consistent supply (and Lot) of critical assay
reagents, harmonizing instrumentation and equipment
between laboratories and the need for clear, accurate
and unambiguous documentation. Case studies associ-
ated with practices that resulted in a successful transfer,
as well as lessons learned from assay troubleshooting
following a failed method transfer were also discussed.
Conclusion
The general impression of the conference is reflected in
the following thoughts: all good scientific endeavors can
be attributed to method development approaches that
are associated with critical thinking, scientific discus-
sion, continuous information sharing and transparency.
In the evolving fields of method development, scientists
haveawealthofknowledgetoshareandavarietyoftopics
to discuss within the bioanalytical community. Over the
past years, this conference has been the principle venue
for scientists from across the biopharmaceutical and life
sciences industries to meet. It has enabled the research-
ers who are discovering new approaches and solutions to
challenges in cell-based assays or bioanalytical method
development to collaborate, and it will continue to be
a principle forum for respective in-depth interactive
discussions in the future.
Disclaimer
D Koltchev was the conference producer for the Annual
Bioassays and Bioanalytical Method Development Conference,
and developed the program.

4. 572 Bioanalysis (2015) 7(5) future science group
Conference report Ma, Tudan & Koltchev
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial interest
in or financial conflict with the subject matter or materials
discussed in the manuscript. This includes employment,
consultancies, honoraria, stock ownership or options,
expert testimony, grants or patents received or pending, or
royalties.
No writing assistance was utilized in the production of this
manuscript.
Executive summary
Bioassay & bioanalytical method development strategies
• Innovative technologies and therapeutics modalities have deeply penetrated the bioanalytical field and the
pipelines.
• Focus on quality, feasibility, compliance and productivity.
• Rigorous regulatory requirements.
• Strategies to bridge discovery to development.
• Questions and concerns to be addressed in the future.
Regulatory perspectives
• Discussion on the Revised US FDA Guidance on Quantitative Bioanalytical Methods Validation and
Implementation.
• Review on adopting the Bioanalytical Method Validation Guidance’s to clinical samples in a GCP environment.
• Evaluation of the case studies and best practices within the industry.
Novel bioanalytical approaches and technologies
• Comparison of multiple technology platforms.
• Evaluation of the clinical biomarkers discovery, development and validation.
• Approaches to ensure successful bioassays and bioanalytical method transfer through the development pipeline.
References
1 Institute for International Research, BioPharma Knowledge
and Networking Group. 10th Annual Bioassays and
Bioanalytical Method Development. Boston, MA, USA ,
22 October 2014.
www.iirusa.com/cba/home.xml.