569Bioanalysis (2015) 7(5), 569–572 ISSN 1757-6180

part of

Conference Report

10.4155/BIO.14.319 © 2015 Future Science Ltd

Bioanalysis

Conference Report7

5

2015

The 10th Annual Bioassays and Bioanalytical Method Development Conference was hosted in Boston, MA, USA on 20–22 October 2014. This meeting brought together scientists from the biopharmaceutical and life sciences industries, the regulatory agency 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

11 Amgen Center Dr., Thousand Oaks,

CA 91320, USA 2Lovelace Respiratory Research Institute,

2425 Ridgecrest Drive SE, Albuquerque,

NM 87108, USA 3Institute 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

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Conference report Ma, Tudan & Koltchev

Bioassay & bioanalytical method development strategiesStrategies 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 perspectivesWith 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

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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 & technologiesNovel 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.

ConclusionThe 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 have a wealth of knowledge to share and a variety of topics 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.

DisclaimerD Koltchev was the conference producer for the Annual

Bioassays and Bioanalytical Method Development Conference,

and developed the program.

572 Bioanalysis (2015) 7(5) future science group

Conference report Ma, Tudan & Koltchev

Financial & competing interests disclosureThe 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.

References1 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.