Mechanism of action, potency and efficacy: considerations for cell therapies. 2024

Carl G Simon, and Erich H Bozenhardt, and Christina M Celluzzi, and David Dobnik, and Melanie L Grant, and Uma Lakshmipathy, and Thiana Nebel, and Linda Peltier, and Anthony Ratcliffe, and James L Sherley, and Glyn N Stacey, and Rouzbeh R Taghizadeh, and Eddie H P Tan, and Sandrine Vessillier
Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA. carl.simon@nist.gov.

One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be "potent but not efficacious" or "not potent but efficacious" are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product's MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs.

UI MeSH Term Description Entries
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014481 United States A country in NORTH AMERICA between CANADA and MEXICO.
D014486 United States Food and Drug Administration An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc. Food and Drug Administration (U.S.),USFDA,Food and Drug Administration,United States Food, Drug Administration
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D064987 Cell- and Tissue-Based Therapy Therapies that involve the TRANSPLANTATION of CELLS or TISSUES developed for the purpose of restoring the function of diseased or dysfunctional cells or tissues. Cell Therapy,Tissue Therapy,Therapy, Cell,Therapy, Tissue,Cell and Tissue Based Therapy

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