THE REGULATORY CONTEXT FOR STERILITY 

STANDARDS IN CELL-BASED THERAPIES

NIST, April 19, 2022 Margaret Foster Riley J.D. (Virtual)
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• Originates with FDA regulation of gene therapy and 

tissue products in the 1980s

• FDA could have gone in a number of directions—but 

opted for a scheme that fit into the existing statutory 

framework and allowed flexibility as the agency 

gained experience with the technology

EVOLUTION OF FDA REGULATION OF CELLBASED THERAPIES
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• Overlapping authority of the Food Drug and Cosmetic 

Act (FDCA) and Public Health Service Act (PHSA)

– [this is true of Biologics generally]

• Congress has added additional aspects statutorily—mostly through the 

21st Century Cures Act (2016)

HUMAN CELLS, TISSUES OR CELLULAR OR TISSUEBASED PRODUCTS—HCT/Ps
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• All HCT/Ps are subject to registration and good tissue practice requirements under §361 of the Public 

Health Service Act (PHSA): 

– The Surgeon General, with the approval of the Secretary, is authorized to make and enforce such 

regulations as in his judgment are necessary to prevent the introduction, transmission, or spread of 

communicable diseases from foreign countries into the States or possessions, or from one State or 

possession into any other State or possession. For purposes of carrying out and enforcing such 

regulations, the Surgeon General may provide for such inspection, fumigation, disinfection, 

sanitation, pest extermination, destruction of animals or articles found to be so infected or 

contaminated as to be sources of dangerous infection to human beings, and other measures, as in his 

judgment may be necessary.

– Gives the (FDA) broad powers because of expansive (and sparse) language

PHSA § 361
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• Cells that undergo more than “minimal manipulation,” are combined with 

non-cell/non-tissue components, or used for non-homologous functions 

are regulated under §351 of the PHSA and the FDCA as biological drugs or 

devices that require premarket approval 

• Good Tissue Practices and for products that qualify as biologic drugs or 

devices under §351 adds additional requirements for cGMPs

PHSA § 351
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• 21 CFR Part 1271 - Human Cells, Tissues, And Cellular and Tissue-Based 

Products applies to both 361 and 351 products [developed by FDA in 2005 

after some years of experience—superseded 1270.]

• “§ 1271.145 Prevention of the introduction, transmission, or spread of 

communicable diseases.

– “You must recover, process, store, label, package, and distribute HCT/Ps, and screen and 

test cell and tissue donors, in a way that prevents the introduction, transmission, or 

spread of communicable diseases.”

• These requirements do not require a specific methodology—the broad 

wording allows for significant flexibility

REGULATIONS
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• 21 CFR Part 610 –Sterility Requirements that apply to all Biologic Products

– Due to the nature of cell therapy products, FDA allows the sponsor to 

propose tests that are appropriate for their product.

– The sponsor will be required to establish equivalence of these test 

methods to those described in 21 CFR 610 for licensure. 

REGULATIONS
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• Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human 

Somatic Cell Therapy Investigational New Drug Applications (INDs) (2008)

• Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: 

Minimal Manipulation and Homologous Use; Guidance for Industry and Food and Drug 

Administration Staff (2017)

• Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based 

Products; Guidance for Industry (2007)

GUIDANCE
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ENFORCEMENT DISCRETION
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• Biologics introduce numerous complexities that do not exist with small 

molecule drugs

• FDA has consistently resisted mandatory standards (e.g. USP monographs)

– Tests themselves are complex

– Patents may block other products

A FOCUS ON FLEXIBILITY
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