Characterization of Tissue 

Engineered Medical Products

Bao-Ngoc Nguyen, Ph.D.

CMC Reviewer/Biomedical Engineer

Tissue Engineering Branch

Division of Cellular and Gene Therapies

Office of Tissues and Advanced Therapies

FDA Center for Biologics Evaluation and Research

Workshop on Measurement Needs for Biofabrication of 

Tissue Engineered Medical Products 

December 1, 2022

www.fda.gov
Office of the Director

Peter Marks, MD, PhD, Director

Celia Witten, PhD, MD, Deputy Director

Office of Tissues and 

Advanced Therapies

Office of Blood 

Research and Review

Office of Vaccines 

Research and Review

Office of Management

Office of 

Communication, 

Outreach and 

Development

Office of Compliance 

and Biologics Quality

Office of Biostatistics 

and Epidemiology

Center for Biologics Evaluation

and Research (CBER)

www.fda.gov 2
• Stem cells/stem cell-derived

– Adult (e.g., hematopoietic, neural, cardiac, 

adipose, mesenchymal)

– Perinatal (e.g., placental, umbilical cord blood)

– Fetal (e.g., neural)

– Embryonic

– Induced pluripotent stem cells (iPSCs)

• Functionally mature/differentiated cells (e.g., 

retinal pigment epithelial cells, pancreatic islet cells, 

chondrocytes, keratinocytes)

• Products for xenotransplantation

• Tissues

• Devices

• Combination products

– Tissue-engineered and regenerative medicine 

products 

• Therapeutic vaccines and cellular immunotherapies 

including antigen-specific and active immunotherapies

• Gene therapies

– Genetically-modified cells

– Replication-competent vectors

– Non-viral vectors

– Viral vectors

– Genome editing products

– Genetically modified organisms

• Blood products

– Coagulation factors

– Fibrin sealants

– Fibrinogen

– Thrombin

– Plasminogen

– Immune globulin

– Venom antisera for snakes, scorpions, and spiders

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Examples of OTAT-Regulated Products

www.fda.gov
REGULATORY CONSIDERATIONS FOR

TISSUE-ENGINEERED MEDICAL 

PRODUCTS (TEMPs)

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• A product composed of different categories of regulated articles:

‒ Device-biologic, biologic-drug, drug-device, biologic-drug-device (not biologic-biologic, etc.)

• Constituents are:

‒ intended for use together

‒ required to mediate the intended therapeutic effect

• Can be:

‒ Physically or chemically combined

‒ Co-packaged; or packaged separately but cross-labeled

• Jurisdiction is assigned based on Primary Mode of Action (PMOA), 21 U.S.C.§ 503(g). PMOA is 

the primary reason for assignment.

• PMOA is defined as the single mode of action of a combination product that provides the most 

important intended therapeutic action of the combination product.

‒ Final Rule: http://www.fda.gov/OHRMS/DOCKETS/98fr/05-16527.pdf

‒ 21 CFR 3.2(k) and (m) 5

Combination Products

21 CFR 3.2(e)

www.fda.gov 5
Quality of reagents used to prepare cells

Cell bank safety testing

Use of feeder layer

Quality of manufacturing facility

Level of cell characterization 

Aseptic processing

Cell viability

Cell stability

Regulatory Concerns Related to Cells

www.fda.gov 6
Physical strength and integrity

Quality of materials used to synthesize scaffold

Residual reagents

Biocompatibility with cells and tissues

Scaffold sterilization 

Stability in vitro and in vivo

Equipment and facility used

Regulatory Concerns Related to Scaffolds

www.fda.gov 7
Impact of cells on properties of scaffold

Impact of scaffold on properties of cells

Testing of construct

Uniformity 

Reproducibility

Shipping

Construct stability

Handling at clinical site

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Regulatory Concerns Related to Combined

Cell-Scaffold Product
• Exist to set expectations for product safety and quality

• Lots that don’t meet these cut-offs should not be distributed and used 

Lot Release Specifications

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• Methods using clinical product

• Surrogate samples

• Sample product made using identical materials and manufacturing method, ideally 

manufactured at the same time as the clinical product.

• Requires additional data to demonstrate that surrogates are adequate representations of the 

final clinical product.

• Portion of clinical product

• Unused or extra part of clinical product used for testing prior to administration

• Must demonstrate that portion of clinical product is representative of whole clinical product.

• Separation of cells from scaffold to evaluate cell characteristics (viability, identity, 

potency) and scaffold parameters (porosity, strength, degradation)

• Impact of dissociation of cells from scaffold should be considered

• Utilization of entire product for lot release testing (sterility, potency, endotoxin, 

mycoplasma, identity, etc.)

• Lot release testing should be conducted on final product after all manufacturing 

steps. 

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Characterization Methods for TEMPs

www.fda.gov
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Summary

• Tissue engineered medical products are complex and require assessment of 

the cells, scaffold, and final cell-scaffold product.

• Depending on the TEMP, final product release testing may require use of 

parts or entire final product. When only parts of the final product or 

surrogate products are used, sufficient supporting data may be necessary to 

demonstrate that they adequately represent the clinical product. 

• Ensure product quality attributes (e.g., sterility) are not compromised when 

final product is tested prior to administration by utilizing non-destructive 

methods (e.g., visual assessment of cells, using portions of the product).

• Seek FDA advice early and throughout product development.

www.fda.gov
• References for the Regulatory Process for the Office of Tissues and Advanced Therapies 

(OTAT): 

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/OtherRecommendationsf

orManufacturers/ucm094338.htm

• Cellular & Gene Therapy Guidances: 

https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances

• Additive Manufacturing Guidance: https://www.fda.gov/media/97633/download

• Combination Products Guidances: 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/combination-products-guidance-doc

uments

• Interactions with Office of Tissues and Advanced Therapies: 

https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/interactions-office-tissues-and

-advanced-therapies

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Useful FDA Information
• Bao-Ngoc Nguyen, Ph.D.

Bao-Ngoc.Nguyen@fda.hhs.gov

• Regulatory Questions:

OTAT Main Line – 240 402 8190

Email: OTATRPMS@fda.hhs.gov and Lori.Tull@fda.hhs.gov

• OTAT Learn Webinar Series: 

http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

• CBER website: www.fda.gov/BiologicsBloodVaccines/default.htm

• Office of Combination Products (OCP): http://www.fda.gov/CombinationProducts/default.htm

• Phone: 1-800-835-4709 or 240-402-8010

• Consumer Affairs Branch: ocod@fda.hhs.gov

• Manufacturers Assistance and Technical Training Branch: industry.biologics@fda.hhs.gov

• Follow us on Twitter: https://www.twitter.com/fdacber

FDA Headquarters

Contact Information

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