What You Need to Know About Cell-Based Therapy Regulations in the United States

David O’Neill, MD, Medical Director and Director, Analytical Development | April 23, 2018

From helping prepare clients' cell therapy products for commercial-scale manufacturing to troubleshooting test methods for compliance with cGMP and cGTP regulations, HCATS has been assisting cell therapy developers for years. Knowledge of U.S. FDA cell-based therapy regulations is essential for filing for an investigative new drug (IND) application or planning for the commercialization of a cell therapy product in the United States.

Which Regulations Apply to Your Cell Therapy Product?

Minimally manipulated human cells, tissues, and cellular and tissue-based products (HCT/Ps) fall under U.S. FDA current Good Tissue Practices (cGTP) regulations, 21 CFR 1271. Meanwhile, cellular therapies that are more than minimally manipulated fall under regulations for pharmaceutical or biologic products: 21 CFR 210 or 21 CFR 211.

When is 21 CFR 1271 the sole set of regulations that applies to a therapy product? A cell therapy would be governed by 21 CFR 1271 if it meets all of the following criteria:

  1. The therapy is minimally manipulated, meaning that the cells have not had their characteristics “significantly” altered prior to administration. An example of a minimally manipulated cell might include a hematopoietic stem cell transplant that has been concentrated and stored frozen.
  2. The therapeutic cells are intended for homologous use—i.e. they perform the same function in the donor that they do in the recipient.
  3. It is not combined with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the combination does not raise additional safety concerns.
  4. Either:
    1. Does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
    2. Has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and is for autologous use, or allogeneic use in a first or second-degree blood relative, or reproductive use.

If your cell therapy product doesn’t match all of the above criteria, then it will fall under both 21 CFR 1271 and 21 CFR 210/211.

Who Can Answer My Questions Regarding Jurisdiction for My Cell Therapy?

The FDA formed the Tissue Reference Group (TRG) to answer questions regarding jurisdiction and applicable regulations of HCT/Ps for cell therapy developers/manufacturers.

What Constitutes “Minimal Manipulation?”

The FDA has stated that the following processes are all considered “minimal manipulation” under their guidelines:

Meanwhile, cell expansion in culture is considered more than “minimal” manipulation.

How Long Does an IND Application Take?

The time it takes for an investigative new drug application to be approved can vary greatly depending on several factors. If the cell therapy developer has the results of IND-enabling studies already in place, including animal pharmacology and toxicology studies, manufacturing information, as well as clinical protocols and investigator information, then an IND application could take less than a year. Typically, however, applying for an IND is not a fast process, since it requires the generation of pre-clinical data in animal models as well as manufacturing quality data, which are included in the Chemistry, Manufacturing and Controls (CMC) portion of the IND application.

Why Should I Work with a Third-Party Cell Therapy Manufacturing Partner?

One of the primary reasons that cell therapy developers work with service providers like HCATS is that an experienced third-party cell therapy manufacturing partner can help to smooth the process for getting an FDA approvals, and HCATS has years of experience in supporting cell therapy manufacturing from IND-enabling studies to manufacturing for large clinical trials.

Need help with your own cell therapy’s regulatory compliance in preparation for the next phase of your development cycle? Contact HCATS today to request a strategic manufacturing assessment that can help identify opportunities to increase your chances of success!

Manufacturing Cell Therapies 

David O’Neill, MD, Medical Director and Director, Analytical Development

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