[Federal Register Volume 85, Number 198 (Tuesday, October 13, 2020)]
[Notices]
[Pages 64444-64445]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-22620]


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DEPARTMENT OF COMMERCE

National Institute of Standards and Technology


Flow Cytometry Standards Consortium

AGENCY: National Institute of Standards and Technology, Department of 
Commerce.

ACTION: Notice of research consortium.

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SUMMARY: The National Institute of Standards and Technology (NIST), an 
agency of the United States Department of Commerce, in support of 
efforts to develop standards for regenerative medicine and advanced 
therapies, is establishing the Flow Cytometry Standards Consortium 
(``Consortium''). The Consortium will bring together stakeholders to 
identify and address measurement and standards needs related to flow 
cytometry used in the characterization and testing of cell and gene 
therapies. The Consortium efforts are intended to develop measurement 
solutions and standards to improve measurement confidence, establish 
measurement traceability, and enable comparability in flow cytometry 
measurements. Participation fees will be at least $25,000 annually or 
in-kind contributions of equivalent value. Participants will be 
required to sign a Cooperative Research and Development Agreement 
(CRADA).

DATES: The Consortium's activities will commence on December 1, 2020 
(``Commencement Date''). NIST will accept letters of interest to 
participate in this Consortium on an ongoing basis.

ADDRESSES: Completed letters of interest or requests for additional 
information about the Consortium can be directed via mail to the 
Consortium Manager, Dr. Lili Wang, Biosystems and Biomaterials Division 
of NIST's Material Measurement Laboratory, 100 Bureau Drive, Mail Stop 
8312, Gaithersburg, Maryland 20899, or via electronic mail to 
[email protected], or by telephone at (301) 975-2447.

FOR FURTHER INFORMATION CONTACT: J'aime Maynard, CRADA Administrator, 
National Institute of Standards and Technology's Technology 
Partnerships Office, by mail to 100 Bureau Drive, Mail Stop 2200, 
Gaithersburg, Maryland 20899, by electronic mail to 
[email protected], or by telephone at (301) 975-8408.

SUPPLEMENTARY INFORMATION: Advances in cell and gene-based therapeutics 
as well as other regenerative medicine products have increased the need 
for high quality, robust, and validated measurements for cell 
characterization. Flow cytometry, including imaging cytometry, has 
emerged as an important platform due to its ability to rapidly and 
simultaneously characterize heterogeneous cell populations and 
subcellular analytes. For example, flow cytometry has been critical for 
establishing identity, purity, and potency for Chimeric Antigen 
Receptor (CAR)-T cell manufacturing; and associated data to support the 
approval of Biological License Applications (BLA) by the U.S. Food and 
Drug Administration (FDA) and the approval by the European Medicines 
Agency (EMA). In addition, multiparameter flow cytometric measurements 
are routinely carried out in vaccine, drug and cancer research, 
clinical diagnosis, and immunotherapies. However, challenges remain 
with respect to measurement confidence and comparability of measurement 
results from different instrument platforms, locations, and over time, 
hindering critical decision-making based on flow cytometry data in 
research and clinical settings.
    NIST has extensively engaged with stakeholders to identify 
measurement needs. These include hosting joint workshops with the U.S. 
FDA and with the International Society for Advancement of Cytometry 
(ISAC) that brought together experts and stakeholders from industry, 
academia and government to discuss unique challenges for cell and gene 
therapy. The workshops identified three common, pre-competitive 
measurement needs: (1) High-quality reference materials, (2) confidence 
in the procedures from standardization/inter-laboratory studies, and 
(3) uncertainty associated with specimen quality and/or pre-analytical 
processes.
    This Consortium aims to develop measurement solutions and standards 
for flow cytometry, including improving measurement confidence by 
establishing traceability and assisting measurement comparability. 
Measurement applications to be addressed may include the use of flow 
cytometry for the characterization and testing for cell identity, 
purity, count, activity, potency, and biomarker expression. The working 
cell types will be determined based on the collective input of the 
Consortium members and can start with common immunotherapy cell types, 
e.g., T cells, iPSCs, and NK cells. To fulfill the objectives of the 
Consortium, associated critical reagents, such as antibodies, plasmids, 
and viral vectors pertaining to the development of the high-quality 
measurements and reference materials, will be characterized using 
orthogonal measurement capabilities, e.g., ddPCR, qPCR, NGS, Flow-FISH, 
nanoflow cytometry, and mass spectrometry, most of which are available 
at NIST as a part of the NIST Advanced Therapy Program. NIST may also 
leverage current capabilities such as the state-of-the-art flow 
cytometry and automation capabilities and expertise, ERF measurement 
service, blood cell characterization, cell counting expertise, as well 
as existing collaborations with calibration bead and cytometer 
manufacturers, international metrological institutions, and Standards 
Development Organizations (SDOs) such as CLSI to advance the goals of 
this Consortium.
    The Consortium is expected to form several Working Groups to 
continuously identify and address needs and gaps in quantitative 
cytometry through workshops, public meetings, and other collaborative 
efforts. The scope of Working Groups can include:
    (1) Equivalent Number of Reference Fluorophores (ERF) Measurement 
Service:
    a. Develop reference standards including reference materials, 
reference data, reference methods, and measurement service for 
assigning the ERF to calibration microspheres and assessing the 
associated uncertainties and utilities. This is the first step towards 
reliable quantitative measurements in flow cytometry.
    (2) Reference Material Selection and Design:
    a. Develop candidate reference standards including biological 
reference materials, reference data, reference methods;
    b. Evaluate common reagents and control materials including various 
types of compensation controls;
    c. Design and carry out interlaboratory testing to characterize and 
evaluate the reference materials using multiple methods, including 
orthogonal methods.
    (3) Assay and Protocol Selection and Design:
    a. Establish an inventory of existing protocols, shared data, 
existing standards;
    b. Generate standard operating procedures/methods for cross 
platform assay standardization and data analysis;
    c. Test the robustness of assays and associated uncertainties.
    No proprietary information will be shared as part of the 
Consortium.

[[Page 64445]]

    Participation Process: Interested parties with relevant flow 
cytometry associated capabilities (see below), products, and/or 
technical expertise to support this Consortium should contact NIST 
using the information provided in the ADDRESSES section of this notice. 
NIST will then provide each interested party with a letter of interest 
template, which the party must complete, and submit to NIST. NIST will 
contact interested parties if there are questions regarding the 
responsiveness of the letters. NIST will determine the eligibility to 
participate in the Consortium based on the requirements listed below. 
NIST will select participants based on information provided by 
interested organizations in their letter of interest and upon the 
availability of necessary resources to NIST.
    Requirements: Each letter of interest should provide the following 
information:
    (1) A description of the experience in flow cytometry/imaging 
cytometry, production and characterization of microparticles, 
antibodies, biological cells, other critical reagents of cytometric 
applications, and analysis of large data sets and related expertise to 
contribute to the Consortium.
    (2) Subgroups or topic areas of interest for participation.
    (3) List of interested party's anticipated participants.
    Letters of interest must not include business proprietary 
information. NIST will not treat any information provided in response 
to this Notice as proprietary information. NIST will notify each 
organization of its eligibility. In order to participate in this 
Consortium, each eligible organization must sign a CRADA for this 
Consortium. All participants to this Consortium will be bound by the 
same terms and conditions. Participants will be required to contribute 
at least $25,000 annually as participation fees or in-kind resources of 
equivalent value, as determined by NIST. NIST does not guarantee 
participation in the Consortium to any organization submitting a Letter 
of interest.

    Authority: 15 U.S.C. 272; 21 U.S.C. 356g.

Kevin Kimball,
Chief of Staff.
[FR Doc. 2020-22620 Filed 10-9-20; 8:45 am]
BILLING CODE 3510-13-P