Method Development, Qualification & ValidationInaugural

Method Development, Qualification & Validation

Developing Fit-for-Purpose Methods throughout Product Lifecycle

March 20-21, 2017 | Hyatt Regency | Bethesda, MD

Method development qualification and validation is a critical component in all stages of drug development from pre-clinical to commercial manufacturing. With an expanded portfolio of newer formats and non-mAbs in the pipelines, knowledge, experience and advanced techniques are critical to establish efficient, accurate and robust analytical methods that can be validated and transferrable, as well as to ensure that the methods are fit for their intended purpose, and will meet regulatory requirements at different phases of a product’s lifecycle.

The Inaugural Method Development, Qualification & Validation conference invites scientists with experience in developing, qualifying and validating methods for new and challenging molecules to share their case studies and discuss practical solutions.

Final Agenda

Monday, March 20, 2017

7:30 am Registration and Morning Coffee

8:30 Chairperson’s Opening Remarks

Kenneth R. Miller, Ph.D., Senior Scientist, Bioassay Development, Analytical Sciences Department, Biopharmaceutical Development, MedImmune

8:40 Featured Presentation: Open Innovation Reference Materials to Advance Characterization Technologies

John SchielJohn Schiel, Ph.D., Research Chemist, Bioanalytical Chemistry, NIST

Biopharmaceutical class-specific reference materials (rms) are key to proper evaluation of current characterization techniques and enabling disruptive technology development. Qualification, certification, and lifecycle management of the nistmab rm 8671 will be presented; a first-of-its-kind approach toward reference material development. The current and future direction fostered by this material include a new generation of therapeutic protein reference materials, an analytical sciences training program, and innovative cross-industry comparative studies oriented at accelerating biopharmaceutical development.


9:20 An Improved Method Lifecycle from Development through Point-of-Use Verification

John Gabrielson, Ph.D., President, Elion Labs

9:50 Potency Assays for Biotherapeutics Targeting T Cells: Issues to Consider

Shihua_LinShihua Lin, Ph.D., Senior Scientist, Bioassay Development, Analytical Sciences Department, MedImmune

10:20 Networking Coffee Break


10:50 Development of a High Throughput HILIC-CAD Method to Quantify Trisulfides in Monoclonal Antibodies

Christopher Cornell, MSc, Technical Development Scientist, Protein Analytical Chemistry, Genentech, Inc.

11:20 LC-MS Multi-Attribute Methods for Non-mAb Protein Therapeutics – Streamlined Method Development Aligned with Clone Selection

Matthew_TraylorMatt Traylor, Ph.D., Senior Scientist, Analytical Development, Shire

Multi-attribute LC-MS peptide mapping methods provide comprehensive characterization of protein therapeutics, and offer numerous benefits for the analytical support of process development. However, significant time and efforts are required to develop these methods. This talk will describe a case study where the development of a multi-attribute LCMS peptide map was simplified by aligning assay development with the analytical support of cell line development and clone selection.

11:50 A Streamlined Approach to Qualification of Platform Analytical Methods for Early-Phase Programs

Ruth Frenkel, Scientist I, Analytical Development, Biogen

Method qualifications in Biogen have historically followed a “one-size-fits-all” approach, closely adhering to the experiments recommended in ICH Q2(R1). A case study will be presented on how we have streamlined the qualifications for platform methods by leveraging the extensive data set generated from historical method qualification reports across multiple mAb programs, applying a phase-appropriate risk-based approach, and using Design-of Experiments (DOE) to minimize the number of experiments needed to demonstrate that the platform method is fit for purpose for a new mAb.

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

1:40 Chairperson’s Remarks

John Schiel, Ph.D., Research Chemist, Bioanalytical Chemistry, NIST


1:45 Method Development and Qualification for Antibody-Drug Conjugates

Jim_JiangJim Qingping Jiang, Ph.D., Principal Scientist, Bio-Therapeutics Analytical RD, Pfizer

Antibody-drug conjugates (ADCs) are complex molecules comprised of three components: a monoclonal antibody with targeting abilities, a linker, and a small-molecule payload with cytotoxicity. Various conjugation chemistry techniques, including conventional conjugations and site specific conjugations, have been commonly used. However, each technique and ADC imposes different challenges to analytical method development. This presentation examines analytical challenges encountered during development of ADCs, as well as the analytical strategy for the isolation and characterization of ADCs.

2:15 Development and Verification of a High Resolution LC-MS Method for Quantitation of Antigens and Known Host Cell Proteins in Vaccine Products

Tim Guo, Ph.D., Senior Scientist, Analytical Development, Novavax

Accurate protein quantitation is important for vaccine product development. Low protein concentration and presence of multiple components may limit the applicability of spectroscopic techniques such as A280 or binding methods such as SRID or ELISA which require the generation of specific antibody reagents. Here we present the development and verification of a high-resolution LC-MS method for quantitation of antigens and host cell proteins in vaccine products.

Unchained Labs2:45 Biologic Stability Cranked up to 11

Warner CandiCandi Warner, Field Application Scientist, Unchained Labs

Biologic stability characterization traditionally requires juggling disjointed data from multiple instruments. UNcle reduces these complications and conserves samples by combining fluorescence, SLS, and DLS detection modes in one instrument.This enables 11 different protein characterization applications, and allows for sizing, polydispersity, thermal melting, and aggregation data to be obtained at the same time from the same sample. We will demonstrate how UNcle can thoroughly characterize more biologics and formulations quickly and easily. 

3:15 Networking Refreshment Break

3:45 Km and Vmax, and O. Oh, My! Adventures in the Development and Qualification of Methods for Enzymes and Oxidized Proteins

Melissa Clague, Ph.D., Principal Research Scientist, Bioproduct Pharmaceutical R&D, Eli Lilly and Company

Complex products can require specialized assays. This talk will cover two case studies: the development and validation of a plate-based assay to determine the essential kinetic parameters, Km and Vmax for a therapeutic enzyme, and the development and qualification of an LC-MS method for quantitation of oxidation of a specific peptide in an antibody project.

4:15 Development of a Fast, Site-Specific Method for Monitoring Oxidation on a Complex Antibody-Based Fusion Protein

Fabio_CameriniFabio Camerini, MSc, Associate Researcher, Protein Chemistry, Analytical Method Development, Merck Serono S.p.A.

A fast LC-UV method to monitor oxidation in a site-specific way has been developed on a complex antibody-based fusion protein. After having identified protein’s sites prone to oxidation by characterizing artificially degraded samples, a peptide mapping method has been developed to monitor a specific Met residue. Mass spectrometry characterization confirmed the method specificity, while method robustness was studied by applying a DoE. The method developed has been successfully applied to support the process development and the selection of the final formulation.

4:45 Roundtable Breakout Session

Table 1: Validation of Research Test Kits for QC Lot Release

Moderator: Kenneth R. Miller, Ph.D., Senior Scientist, Bioassay Development, Analytical Sciences Department, Biopharmaceutical Development, MedImmune

  • How are ‘research test kits’ being used in a regulatory environment at your company?
  • Is this supported in quality systems at your company?
  • What challenges have you had with adopting ‘research test kits’ for regulated environments
  • What would you find helpful to include in a guidance document from a pharmacopeial organization?


Table 2: Lifecycle Management of Analytical Methods

Moderator: John Schiel, Ph.D., Research Chemist, Bioanalytical Chemistry, NIST

  • Implementation of novel technology
    • What mechanisms are used to de-risk novel technology for assimilation into a lifecycle management plan?
  • Assay suitability and lifecycle management
    • Are there differences/similarities between lifecycle management of validated versus characterization only assays? Are external system suitability metrics useful
  • Continuous improvement
    • What advantages are there to continuous analytical method improvement post-product commercialization? Are improvements proactively sought and/or are there advantages? What metrics are considered when evaluating a “better” method?
  • Method bridging
    • Bridging analytical methods is an inevitable requirement. Are open source class-specific materials (e.g. NISTmAb) potential avenues for assisting with product-specific method bridging?

Table 3: Platform Approach for Method Development during Early Clinical Phases

Moderator: Claire Davies, Ph.D., Head, Bioanalytics, Sanofi

Topic: Method Development and Qualificaion for Novel, Non-Platform Molecules

Moderator: Jim Jiang, Ph.D., Principal Scientist, Bio-Therapeutics Analytical R&D, Pfizer, Inc.

 5:45 End of Day / Short Course Registration

6:00-8:30 pm Dinner Short Courses*

*Separate Registration Required.

Tuesday, March 21, 2017

8:00 am Morning Coffee

8:30 Chairperson’s Opening Remarks

Steven Walfish, MS, MBA, Principal Science & Standards Liaison, Global Science and Standards Division, United States Pharmacopeia



8:40 Use of Design of Experiment (DoE) for Optimization of ADC Potency Assays

Ken_MillerKenneth R. Miller, Ph.D., Senior Scientist, Bioassay Development, Analytical Sciences Department, Biopharmaceutical Development, MedImmune

The first stage in an analytical procedure lifecycle approach is procedure design. A design of experiment (DOE) study is a useful tool during procedure design to evaluate multiple variables systemically. One can perform a DOE study to identify optimal assay conditions allowing for the establishment of robust fit-for-purpose potency assays. In this talk, examples of DOE studies performed during the development of ADC potency assays will be presented.

9:10 Statistically Based Methods for Determining Target Measurement Uncertainty (TMU)

Steven_WalfishSteven Walfish, MS, MBA, Principal Science & Standards Liaison, Global Science and Standards Division, United States Pharmacopeia

The analytical target profile states the acceptable error in the measurement. In other words, it states the allowable target measurement uncertainty (tmu) associated with the reportable value of an analytical method. This talk will focus on the statistical methods used to determine the fraction of future results that could be expected to be outside a prespecified specification at a given level of confidence.

9:40 Overcome Soluble Target Interference in Developing Immunogenicity Assays

Dong Geng, Ph.D., Principal Scientist, Biologics and Vaccine Bioanalytics, Merck

Soluble target posts special challenge for immunogenicity assay. Soluble target may result in elevated false positive, sometimes false negatives if ADA assay is not developed properly. This applies to both ADA binding and Nab assay. The presentation will propose couples of approach on how to manage the target interference with case studies.

PerkinElmer NEW 200910:10 PerkinElmer Solutions to Facilitate the Development, Qualification & Validation of Biotherapeutics

Roger_BosseRoger Bosse, Ph.D., Sales Development Team Lead, North-America, Life Sciences & Technology, PerkinElmer

Accurate and reproducible technologies are essential for the development of robust methods that can be validated and easily transferred within the biotherapeutics workflow. We will present some of our capabilities that are applicable to the different stages of Biotherapeutics drug development ranging from pre-clinical to commercial manufacturing. Representative applications and distinct customer cases will be reviewed.

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

11:20 Phase Appropriate Approach for Bioassay Development, Validation, and New Technology Implementation in Quality Control Laboratories

Elena Belitsky, Ph.D., Director, QC Clinical Operations, Biogen

There are different requirements for Bioassays developed for early stage clinical programs compared to late stage programs. Phase appropriate approach for method development, qualification and validation for Bioassay will be presented. Introduction of new technology in GMP environment (Quality Control) is a challenging task requiring special considerations. Major points to consider before implementing a new technology based method in QC will be discussed.

11:50 Platform Approach for Method Development and Qualification during Early Clinical Phases

Claire_Davies Claire Davies, Ph.D., Head, Bioanalytics, Sanofi

In early drug development it is important to reduce costs and move quickly from candidate selection to the clinic. Approaches to streamline method development and qualification using risk based and QbD approaches will be presented.



 12:20 pm Close of Method Development, Qualification & Validation