SESSION 4: NEXT STEPS

Moderator: Sheng Lin-Gibson, NIST

• Meeting summary

• Key concepts / outline for whitepaper

• Other businesses

https://www.surveymonkey.com/r/CCW_idea_box
Workshop Goals Actions and potential 

solutions 

Raise awareness of the importance and 

challenges associated with cell counting 

measurements 

• Whitepaper 

• Additional NIST-FDA workshops 

Develop and document best practices for 

cell counting

• Whitepaper 

• Develop methods of general use 

through appropriate forums

Discuss options to address measurement 

challenges through collaborative studies 

(NIIMBL) 

• Send R&D topics to NIIMBL/TAC for 

funding to advance biomanufacturing

Workshop outcomes to support the 

development of international standards 

and more specific measurement 

challenges 

• Cell counting serves as a use case for 

upcoming ISO standard effort for cell 

characterization 
Recap

• Overarching theme: Counting is important 

• Many use cases, important considerations, 

lessons learned, opportunities/new 

technologies 

• FDA does not require prescriptive methods:

– fit for purpose 

– system suitability 

• Example of measurement assurance strategies 

for cell counting 
Terminology

• What is required during qualification, 

validation, and verification
Fit for purpose 

• I would like to count AA cells in media/matrix BB

using CC methods for DD purpose

• What is good enough – how to set specification using 

meaningful parameters

AA

MSC

iPSC

Car-T

...

CC

Manual

Automated

Impedance 

Imaging

Flow

...

CC

Release

Dose

In process

Compability

R&D

...

BB

Universal 

media

Cryopreservant

...
Various approaches

• General framework vs. individualized methods

• total cell count   various stages of cell 

health

• Improving the quality of “gold standard” 

methods   new counting technologies
3. ACCURACY 

The accuracy of an analytical procedure expresses the closeness of 

agreement between the value which is accepted either as a 

conventional true value or an accepted reference value and the value 

found. 

This is sometimes termed trueness. 

Ref: VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY Q2(R1) 

Role of reference material/reference standards

• Beads and their roles in calibration, comparability 

• Cells RM as an in process control, proficiency testing 

• Opportunities for new, better reference materials/what is NIST doing
Evaluating the quality of cell counting methods in the 

absence of a ground truth Cell Concentration (Cells/mL)

• Comparability between methods

• Accuracy

• Precision

• Linearity (proportionality)

• Reproducibility

Cell Counting Results for 4 methods 

Proportionality

Proportionality Index (PI)

ISO/WD 20391-2 [Under development: 20.60]

Biotechnology -- Cell Counting -- Part 2: Experimental 

design and statistical analysis to quantify counting 

method performance
Tools to get to “good enough”

- Strategies for better measurements

- Education materials 

- Reference materials/reference standards

- Bioprocessing control (equipment, reagent, etc.)

- Competency 

- Method standards 
What works well? 

(ripe for standardization / best practices / SOP) 
What are ongoing efforts

• Methods and funding to keep the discussions going

• NIST certified beads consortium 

• ISO Cell Counting Part 1– definitions and general 

considerations

• ISO Cell Counting Part 2 – method to evaluate the 

quality of cell counting 
What is needed?

(common understanding, methods, guidance, etc.)

• Deep dive on several case studies

• Best practices 

• Spike in or other methods 

• Minimum information for a specific method to 

provide confidence

• Inter-laboratory study / formation of 

consortium 
Additional Topics for NIST-FDA 

workshop
Use case for a hypothetical imaging based cell 

counting

Lin-Gibson, et al. Bioinsights 2016.
Working with NIST

Laboratory collaborations via joint studies, CRADA, 

consortium, post-doctoral opportunities, etc.

Participate in NIST workshops 

Participate in standards development efforts, 

including inter-laboratory studies 

Learn more @ www.nist.gov or search NIST 

Advanced Therapies

Contact: Sheng Lin-Gibson @ slgibson@nist.gov
Outline of a whitepaper

• Brief recap of workshop

• Key concepts 

– What works well

– What is ongoing 

• ISO Cell Counting Part 1– definitions and general 

considerations

• ISO Cell Counting Part 2 – method to evaluate the quality of 

cell counting 

– What is needed 

• Gaps in current guidance (communication, technical, 

guidance?)

• Additional tools to improve measurement assurance 
TC276 cell characterization standard effort

based on outcomes of Jan2017 US-Japan Workshop 

Cell characterization “umbrella” standard – to enable common 

understanding 

Cell characterization measurement process standard

Cell 

counting

1 & 2

Viability ??

...

Flow 

Cytometry

Gene 

therapy 

products

By attribute By technique

Imaging 

By purpose 

Drug 

discovery

Cell 

therapy 

products

...

By cell type 

??

??

c

Cell Counting Standards are under development; all others are listed as examples