Regulatory Focus™ > News Articles > Draft Guidance on Cell, Gene Therapy Products Establishes General Framework

Draft Guidance on Cell, Gene Therapy Products Establishes General Framework

Posted 29 November 2012 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has release a new draft document aimed at providing guidance on the preclinical assessment of cellular, tissue and gene (CTG) therapy products.

CTGs are essentially used to make therapeutic changes to a person's cells, tissue or genes by injecting a patient with altered DNA, cells or implanted with organs. The products include cellular therapies, gene therapies, therapeutic vaccines, xenotransplantation and other drug products, including devices used in combination with them.

Such products are regulated by the Centers for Biologics Evaluation and Research (CBER) and Drug Evaluation and Research (CDER), and generally start their path to marketing approval through one of two approval pathways: An investigational new drug (IND) application and a biologics license application (BLA).

Those applications are intended to gauge the likely safety profile of a product before it is administered or consumed by human participants in clinical trials. For CTG products, though, preclinical testing clearance can often be difficult for both companies and regulators alike.

"The diverse biology and clinical indications and the rapid and fluid state of the evolving scientific research into these product areas pose unique scientific challenges in terms of regulatory review," FDA explained in its guidance. "As a consequence the regulatory review process for evaluation of investigational CGT products necessitates a careful risk-benefit analysis performed in the context of the particular clinical indication under study."

Because the composition of the products, as well as their mechanism of action, vary so greatly from chemical and biological drugs, standardized toxicology testing and other preclinical testing methods are often "not appropriate" for evaluating the products, FDA explained.

FDA's Office of Cellular, Tissue and Gene Therapies (OCTGT), the office in charge of regulating the products, said it uses a "flexible, science-driven" review approach to address preclinical safety issues to ensure a product is sufficiently safe to begin clinical testing. However, "Although flexible, such an approach incorporated the basic toxicological principles that underlie more traditional, standardized preclinical testing."

For sponsors, that amount of flexibility can be challenging. Therefore, a new guidance is born.

Preclinical Assessment of Investigational Cellular and Gene Therapy Products is a 32-page general framework for CTG products that also provides numerous detailed recommendations for designing preclinical studies for several types of products (transgenic proteins, ex vivo modified cells, etc).

The key to the entire approach, which FDA concedes can vary wildly among product types, is communication. The agency said it recommends "early and ongoing" communication with OCTGT staff to avoid any surprises or delays in approval. "These communications help to ensure that regulatory expectations related to safety, demonstration of potential activity, and understanding of possible MOA(s) are addressed," FDA explained.

The guidance will, when complete, supersede a 1998 guidance by a similar name (Guidance for Industry:  Guidance for Human Somatic Cell Therapy and Gene Therapy). It will not, FDA explained, apply to those products regulated under FDA's human cells, tissues and cellular and tissue-based product (HCT/P) regulation at 21 CFR 1271 or 21 CFR 820 in the case of devices. FDA's 28 November 2012 Federal Register posting on the guidance may be found here.


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