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Regulatory Focus – Groups Seek More FDA Flexibility in Early Cell Therapy Development

Regulatory Focus – Groups Seek More FDA Flexibility in Early Cell Therapy Development

A new white paper from the Friends of Cancer Research (FOCR) and the Parker Institute for Cancer Immunotherapy calls on the US Food and Drug Administration (FDA) to ease clinical and manufacturing requirements to speed early development of anti-cancer cell therapies.

In recent years cell therapies, including engineered T-cell receptor (TCR) and chimeric antigen receptor (CAR) T-cell therapies have shown promise in treating a wide range of cancers. To date, FDA has approved two CAR T-cell therapies to treat specific hematologic malignancies.

“To potentially help a much larger number of patients, in particular those patients with solid tumors and no remaining treatment options, it would be desirable to advance small, data-intensive clinical exploratory studies to differentiate which approaches warrant further focus,” the groups write, noting that solid tumors account for 90% of cancer cases.

Following typical IND requirements, the groups argue, limits the study of investigational T-cell therapies to a “select few product candidates.”

Specifically, the paper calls for FDA to revise its 2006 guidance on exploratory investigational new drug (IND) studies to provide recommendations for exploratory studies of cell therapies.

The paper also suggests the development of a “parent-child” IND framework to make it easier to rapidly test multiple cell therapy candidates based on a “parent” IND containing common information for multiple “child” candidates. For each child candidate, a new IND-containing candidate and process specific information would be submitted.

Similarly, the paper calls for more clarity on good manufacturing practice (GMP) requirements for early investigational production of cell therapies, as varying interpretations of GMP requirements can result in early investigational products being manufactured to GMP standards “more applicable for later stage clinical development.”

These stricter GMP requirements lead to higher costs, which the groups say hinders early stage development.

While FDA and the International Council for Harmonisation (ICH) provide guidance on clinical stage GMPs, “many of these documents were published at a time when cell therapy was in its infancy,” the groups write.

“Updated guidance specifically addressing the unique aspects of cellular therapies is needed. Due to the time required to manufacture most cellular therapies … early clarity in their development is needed regarding the acceptability of a more phase appropriate cGMP approach.”

Beyond those constraints, the paper also argues that new adaptive manufacturing technologies are needed to tailor production for different stages of development and allow for patient-specific product modifications.

The groups acknowledge, however, that these technologies would add new complexities to development “as current regulatory requirements and processes may not readily allow for patient-level modifications, especially when the understanding of the linkage among product quality attributes, manufacturing processes, clinical efficacy, and safety continue to evolve late in development or after licensure.”…