American Association of Pharmaceutical Scientists (AAPS) Flow Cytometry Action Programming Committee – leveraging industry leader experience to expand the field of flow cytometry

Founded by Virginia Litwin in 2007, the AAPS Flow Cytometry Action Programming Committee (APC) was formed to create a forum for in depth discussions of the strengths and specific challenges surrounding the technology of flow cytometry.  Some specific goals of the group are to discuss challenges in the development and validation of flow cytometry assays, proper interpretation of flow cytometry data; publish best practice papers on the application of flow cytometry in drug development; to sponsor roundtable session/symposiums at the AAPS Annual and other scientific meetings and symposia and promote flow cytometry education via webinars and workshops.  The membership of the AAPS Flow Cytometry APC hails from the companies, illustrated below representing a cross section of the large pharma, biotech and CRO sectors.

Recently, the American Association of Pharmaceutical Scientists (AAPS) has instituted a new Communities feature to consolidate new and existing focus groups into a cohesive community of scientists.  With this comes the creation of dynamic virtual laboratory to foster knowledge exchange, idea incubation and networking to advance the pharmaceutical industry.  The Flow Cytometry APC recognized this unique opportunity.  The creation of the Flow Cytometry Action Community – WG was spearheaded by Steve Eck and our formation documents became a template we shared to help several other groups form within the AAPS Community.  Right now, we operate as a closed group with approximately 20 members.

Jennifer J Stewart and Steve Eck – Co-chairs

Executive Committee:  Virginia Litwin, Cherie Green and David Lanham

Membership:  Ruth Barnard, Vilma Decman, Anka Ehrhardt, Jose Estevam, Cathy Fleener, Christele Gonneau, Christopher Groves, Michael (Nathan) Hedrick, Shuguang Huang, Nicholas Jones, Tom McIntosh, Tom McCloskey, Shibani Mitra-Kaushik, Maxime Moulard, Ulrike Sommer, Soren Sonder, Yongliang (Steve) Sun, Alessandra Vitaliti, Dave Williams, Sam Witherspoon, Yuanxin Xu and Qiong (Chelsea) Xue

Highlights of Past Accomplishments

In 2011 a two part series of manuscripts published in the Journal of Immunological Methods intended to provide step by step guidance on the validation of both instrumentation and flow cytometry assays.  These two manuscripts were followed in 2013 by a special issue in Cytometry Part B Clinical Cytometry Special Issue volume 84B dedicated to the validation of cell-based fluorescence assays.  One year later, a manuscript that offered the reader a roadmap for specimen stability assessment for assays to be used in clinical trials with centralized testing facilities or any other type of stability assessment for flow cytometric methods was published.

Green, C.L., Brown, L., Stewart, J.J., Xu, Y., Litwin, V. and McCloskey, T.W. (2011).  Recommendations for the Validation of Flow Cytometric Testing During Drug Development: I Instrumentation. JIM, 363:104-119.

O’Hara, D.M., Xu, Y., Liang, Z. Reddy, M.P. Wu, D.Y. and Litwin, V.  (2011). Recommendations for the Validation of Flow Cytometric Testing During Drug Development: II Assays. JIM 363:120-134.

Wood, B., Jevremovic, D., Bene, M.C., Yan, M., Jacobs, P. and Litwin, V. (2013).  Validation of Cell-Based Fluorescence Assays: Practice guidelines from the ICSH and ICCS – part V – assay performance criteria. Cytometry Part B: Clinical Cytometry Special Issue volume 84B.

Brown, L., Green, C.L., Jones, N., Stewart, J.J., Fraser, S., Howell, K., Xu, Y., Hill, C.G., Wiwi, C.A., White, W.I., O’Brien, P.j., Litwin, V. (2015). Recommendations for the Evaluation of Specimen Stability for Flow CytometricTesting During Drug Development. JIM, 418:1-8.

Another accomplishment, in 2016, a special issue in Cytometry Part B Clinical Cytometry Special Issue volume 84B was dedicated to Receptor Occupancy assays (ROA), with a manuscript focused on the validation of this assay type.  Assessment of Receptor Occupancy is useful in drug development to confirm physical target coverage and support dose selection during pre-clinical and clinical trials.  Flow cytometry is a technology that is well suited for performing these types of measurements, by employing immunophenotyping to identify multiple biomarkers simultaneously as well as identifying individual targets/receptors in specific lymphocyte subsets.

Green, C.L., Stewart, J.J., Hogerkorp, C.M., Lackey, A., Jones, N., H., Liang, M., Xu, Y., Ferbas, J., Moulard, M., Czechowska, K., McCloskey, T.W., van der Strate, B., Wilkins, D., Lanham, D., Wyant, T. and Litwin, V. (2016).  Recommendations for the development and validation of flow cytometry-based receptor occupancy assays. Special Issue: Receptor Occupancy by Flow Cytometry, Cytometry Part B: Clinical Cytometry, 90B; 141, 2016.

2018, a very active year

The Flow Cytometry APC members were involved in numerous opportunities to present at various meetings throughout the year.  Below is a summary of meetings, authors and presentations given.

Presentations and Workshops:

WRIB workshop: Current Best Practices in Performing Flow Cytometry in a Regulated Bioanalysis Lab:  What’s new in this fast-evolving field? Speaker – Cherie Green

WRIB workshop: Flow Cytometry-based Biomarkers for Clinical Studies: Successes & Key Learnings in Biomarker Assay Development, Validation & Implementation. 12th WRIB Workshop on Recent Issues in Bioanalysis, April 9 – 13, 2018, Philadelphia, PA, Speaker – Yongliang (Steve) Sun

WRIB workshop: Flow Cytometry-based Immuno-Oncology Biomarkers: Successes and Challenges in Biomarker Assay Development and Validation. Speaker – Catherine Fleener

ICCS plenary: Advancing Transformational Therapies in Hematologic Malignancies Through Novel Flow Cytometry Biomarkers

ISAC C YTO2018 Workshop 3:  Dr. Reproducibility or: How I Learned to Stop Worrying and Love Validation.  Facilitators: Steven Eck, Chris Groves, Jennifer J. Stewart and Cherie Green

ISAC C YTO2018 Workshop 9:  Control Cells or Not

Facilitators: Yanli Liu, Paul Wallace, Virginia Litwin and Lili Wang

ISAC C YTO2018 Workshop 11:  Flow Cytometry Application in Multi-Center Global Clinical Studies: The Importance of Standardization and Harmonization. Is the Quality of Data Only as Good as the Weakest Control Planned?

Facilitators: Kamila Czechowska, Alessandra Vitaliti, Attila Tarnok, David Lanham, Ryan Brinkman and Paul Trampont

ISAC C YTO2018 Workshop 12:  Induced Biomarkers

Facilitators: Soren Ulrik Sonder, Jennifer J Stewart, Ruth Barnard and Maciej Cabanski

ISAC C YTO2018 Workshop 13:  Building Measurement Assurance in Flow Cytometry

Facilitators: Lili Wang, Stephen Perfetto, Robert Hoffman and Virginia Litwin

ISAC C YTO2018 Workshop 16:  Therapeutic Cell Sorting

Facilitators: Grace Chojnowski, Jeffrey Carrell and Christopher Groves

All of these workshop summaries have been accepted and will be featured in a special issue of Cytometry Part A to be published in early 2019.

ISAC CYTO University Webinars (available for download at cytou.org)

Validation, the Key to Translatable Flow Cytometry

Part 1: Method Validation- Overview, Concepts by Virginia Litwin

Part 2: Planning and Executing by Teri Oldaker

Part 3: Instrument Qualification by Cherie Green

Publications:

Selliah, N., Eck, S., Green, C., Oldaker, T., Stewart, J.J., Vitaliti, A., Litwin, V. (2018).

Cytometry Method Validation Protocols. Curr Protoc Cytom. Nov 12:e53. doi: 10.1002/cpcy.53. [Epub ahead of print]

Litwin V, Fleener CA, Green C, Sun Y. (2018) White Paper on Recent Issues in Bioanalysis: focus on flow cytometry, gene therapy, cut points and key clarifications on BAV (Part 3 – LBA/cell-based assays: immunogenicity, biomarkers and PK assays). Bioanalysis 10(24): 1973-2001

The Clinical and Laboratory Standards Institute (CLSI) is an organization that actively works to identify and develop new guidance on standards that raise laboratory testing quality, safety, and efficiency and are responsible for setting the bar for how that guidance is delivered. In December 2018, CLSI H62 – Validation of Methods Performed by Flow Cytometry was written and submitted with circulation for public comment occurring in early to mid 2019.  Stay tuned for details on when this document will be available.

Leadership:  Virginia Litwin – Chair, Teri Oldaker – Vice Chair, Raul Louzao – Secretary and Dave Sterry – CLSI Standards Director

Voting Members:  David Barnett, Jacqueline, Cleary, Tom Denny, Cherie Green, Wolfgang Kern, Natalia Kokorina, Jennifer J. Stewart and Lili Wang

Contributors and Reviewers:  Elena Afonina, Ahmad Al Samman, Tony Bakke, Fiona Craig, Bruce Davis, Lorella Di Donato, Steve Eck, Nancy Fine, Ben Hedley, Shuguang Huang, Jerry Hussong, Andrea Illingworth, Cassie Jiang, Mike Keeney, Natalia Kokorina, Sarah Maremont, Laura Marszalek, Kathy Muirhead, Andy Rawstron, John Schmitz, Alan Stall, Maryalice Stetler-Stevenson, Horacio Vall, Alessandra Vitaliti-Garami, Paul Wallace, Brent Wood and Yuanxin Xu.

2019, the agenda so far

2019 is shaping up to be another productive year for the committee.  Several members have been invited to present at the 2019 The 13th WRIB April 1-5, 2019 in New Orleans, LA.

The group also submitted two abstracts that have been accepted for Workshops at the ISAC CYTO2019 Meeting in Vancouver, BC.

The topics to be covered include:

• Flow Cytometry Data for Clinical Trials, Manual or Automated Analysis?

Join us

FCSL is a proud member if this organization and we believe that the discussions and outcomes that the AAPS Flow Cytometry Action Programming Committee engages in can improve the quality of our flow cytometry services.

If you are an expert in the field of flow cytometry and would like to share your expertise and contribute to the group, contact us for more information!