The US Food and Drug Administration (FDA) published a press release earlier this week for manufacturers developing cell and gene therapies (CGTs). FDA expects manufacturers to verify that their products work as intended, from the time of approval through post-approval monitoring.
The guidance titled Potency Assurance for Cellular and Gene Therapy Products replaces the agency's previous recommendations issued in 2011. It focuses on a more comprehensive approach to potency testing.
The guidance recommends a science- and risk-based approach to potency assurance, covering different stages of product development and manufacturing. It is important to note that FDA guidance documents contain non-binding recommendations and do not independently create legally enforceable responsibilities. The underlying statutory and regulatory requirements continue to apply. For example, licensed biological products must meet applicable potency testing requirements for lot release.2
In 2011, cell and gene therapy was still an emerging field within medical research. At that time, researchers were still exploring the potential of cellular treatments and gene transfer technologies, and the range of products being developed was considerably small compared to today. However, in the last 15 years, there have been advances in biotechnology that have improved how these treatments are designed, manufactured and tested.
Cell and gene therapy now involves a range of sophisticated techniques.
For example, CAR T-cell therapy that uses a patient's immune cells, which are genetically modified to target and kill cancer cells. These cells must maintain their ability to target and kill their intended target after various manufacturing processes.
In vivo gene editing, such as using CRISPR technology, means that gene editing components are directly administered to the patient. This is a change from previous gene therapies, where cells were modified outside the body and then administered. This poses challenges in assessing whether the correct genetic modifications are taking place and if the desired biological response will occur.
Advanced viral vectors have been developed to deliver the genetic therapy to the target cells. These vectors are complex to manufacture and must be assessed for quality and consistency.
To address this, the recommendations previously made have had to develop further. Manufacturers must provide evidence that the product maintains biological activity that will achieve the desired therapeutic effect.
Potency is the ability of a biological product to produce the desired biological/therapeutic effect. It is an important quality attribute to ensure the treatment can offer the desired function.
The FDA defines potency as the specific ability or capacity of a product to produce a given result, as indicated by appropriate laboratory tests or adequately controlled clinical data obtained through its intended administration.2
For example, CAR-T therapy uses genetically modified immune cells that must be able to target and kill cancer cells. However, if they lose their biological activity during manufacturing, storage or transportation, the final product may not work as intended.
Therefore, potency testing is very important for cell and gene therapies. These products can be complex and contain live cells, meaning that they may be impacted by changes in the manufacturing processes.
A single test may not be sufficient to analyze all biological activity within complex therapies meaning multiple complementary tests may be required.
The selection of potency assays is product-specific because different cell and gene therapies have different mechanisms of action. Tests should measure biological activities relevant to the intended therapeutic effect. The FDA guidance also discusses assay suitability, reference materials, qualification, validation and acceptance criteria to ensure that testing methods provide reliable results.2
This updated guidance encourages manufacturers to develop an overall Potency Assurance Strategy(PAS) for their product. This means that rather than just performing a final potency assay, manufacturers are encouraged to consider factors that could impact the product’s biological activity.
What Are the Five Components of FDA's Potency Assurance Strategy?
The five components include:
Understanding how different aspects of the manufacturing process will impact the biological activity of a product. This encompasses monitoring processes that may have an impact on the cells, genetic materials or other active ingredients.
Control of manufacturing processes. This helps ensure conditions are controlled and minimize variability.
Understanding and controlling the quality of materials. This will ensure that variations in starting and raw materials are understood.
In process testing. Testing of a product throughout the manufacturing process.
Lot release potency assays. Ensure appropriate assays are in place to demonstrate that each batch meets the required potency.
The strategy is based on quality risk management. Manufacturers are encouraged to identify factors that could affect potency, assess the associated risks and establish appropriate manufacturing controls and testing methods. The strategy should also evolve as manufacturers gain more knowledge about the product and its manufacturing process.
This will ensure that cell and gene therapies maintain consistency in their biological activity.
Cell and gene therapies can have some unique challenges when manufacturing.
Some of these therapies have a short shelf life. Autologous CAR-T therapies are made from cells taken from individual patients. Therefore, manufacturers will need to ensure there is good control of variability in the starting materials and manufacturing conditions.
With viral vector-based therapies, manufacturers will need to ensure the vectors remain consistent and maintain their biological activity during the manufacturing process.
The updated guide encourages developers to take into consideration these differences when developing their potency assurance strategy. It does, however, recognize that testing may need to be adjusted based on the characteristics and mechanism of action of the product.
The FDA guidance also addresses situations in which a product has an extremely short shelf life and there may not be sufficient time to complete a potency bioassay before lot release. In such cases, the guidance discusses using appropriate physicochemical assays for lot release, alongside in-process testing and post-release potency bioassays where appropriate. This helps manufacturers assess whether the manufacturing process consistently produces products with the required biological activity.2
The FDA guidance is specific to products regulated as biological products under Section 351 of the US Public Health Service Act. It does not automatically apply to manufacturers in India. However, its focus on potency assurance, manufacturing controls and product consistency is relevant to India's developing cell and gene therapy sector.2
India has also taken steps to strengthen its regulatory oversight of advanced therapies. On July 2, 2026, the Ministry of Health and Family Welfare announced amendments to the Drugs Rules, 1945, bringing cell-derived products, stem cell-derived products, gene therapeutic products and xenografts under the Centrally License Approving Authority (CLAA) framework. The framework provides for joint oversight by Central and State Licensing Authorities to promote uniformity in regulatory standards.5
India's regulatory framework for gene therapy development also includes the National Guidelines for Gene Therapy Product Development and Clinical Trials, 2019, issued by CDSCO, ICMR and DBT. These guidelines provide a framework for the development and clinical evaluation of gene therapeutic products in India.6
An example of India's progress in this field is NexCAR19, an indigenous CAR-T cell therapy developed through a collaboration involving IIT Bombay, Tata Memorial Centre and ImmunoACT. President Droupadi Murmu launched the therapy on April 4, 2024.7
The development of indigenous CAR-T therapies highlights the importance of manufacturing consistency and biological activity. Although the new FDA guidance does not govern NexCAR19's Indian manufacturing, its focus on potency assurance illustrates a quality consideration relevant to the wider cell and gene therapy sector.
References:
1. U.S. Food and Drug Administration. “FDA Provides Clarity to Support Cell and Gene Therapy Development and Quality.” November 2, 2026. https://www.fda.gov/news-events/press-announcements/fda-provides-clarity-support-cell-and-gene-therapy-development-and-quality.
2. U.S. Food and Drug Administration. Potency Assurance for Cellular and Gene Therapy Products: Guidance for Industry. November 2026. Official FDA guidance: https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
3. U.S. Food and Drug Administration. Potency Tests for Cellular and Gene Therapy Products: Guidance for Industry. January 2011. Official FDA guidance archive: https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
4. U.S. Food and Drug Administration. Potency Assurance for Cellular and Gene Therapy Products: Draft Guidance for Industry. December 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
5. Press Information Bureau, Ministry of Health and Family Welfare. “Centre Amends Drugs Rules, 1945 to Ensure Uniform Regulation of Advanced Cell and Gene Therapies.” July 2, 2026. https://www.pib.gov.in/PressReleasePage.aspx?PRID=2280408.
6. Press Information Bureau, Ministry of Science and Technology. “Parliament Question: Self-Reliance in CRISPR and Gene Editing.” March 19, 2026. https://www.pib.gov.in/PressReleasePage.aspx?PRID=2242411.
7. President of India. “President of India Launches India’s First Home-Grown Gene Therapy for Cancer.” April 4, 2024. https://www.presidentofindia.gov.in/press_releases/president-india-launches-indias-first-home-grown-gene-therapy-cancer.
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