FDA removes barriers to cell, gene therapy development

The FDA has said it will reduce the regulatory requirements on the manufacturing of cell and gene therapies (CGTs) in order to make it easier for developers to bring them to market.

Specifically, the US regulator wants to amend its position on the chemistry, manufacturing, and controls (CMC) portion of marketing applications for CGTs, taking a more flexible approach that recognises they are produced very differently from other pharmaceutical products.

CGTs tend to be made in very small batches, often using complex and sophisticated processes that are under time constraints. For example, the manufacture of CAR-T therapies for blood cancers can involve an intricate process of harvesting cells from patients, modifying them and growing them up in culture, and then reinfusing them – generally in the space of a few days or weeks.

The FDA's Center for Biologics Evaluation and Research (CBER), which has responsibility for regulating CGTs, said that it is building on its experience of approving more than 50 CGTs to identify and implement flexibilities that can be introduced under its current regulatory framework to lighten the burden of CMC requirements without undermining quality control standards.

While there has been scope for flexibility on a case-by-case basis, the aim now is to communicate a more structured framework, proactively, to try to bring more CGTs to patients more quickly and easily.

"There has been tremendous enthusiasm amongst product developers resulting in an explosive growth of cell and gene therapy submissions, many of which target serious or life-threatening conditions with an unmet medical need," commented CBER director Vinay Prasad.

"CBER is eager for stakeholders to know that our effectiveness at exercising greater regulatory flexibility around chemistry, manufacturing and control requirements furthers innovative product development," he added.

Among the measures are leeway on manufacturing specifications that apply during the clinical testing, process validation, and commercial supply stages, including product release specifications. The changes grew out of a roundtable on cell and gene therapy regulation held by the FDA last year.

"Regulatory flexibility must be tailored for cell and gene therapies," commented FDA Commissioner Marty Makary. "These are common-sense reforms that will address the unique characteristics of cell and gene therapies and foster more innovation."

Last November, the FDA also proposed a new regulatory pathway for personalised therapies – such as gene-editing medicines – based on 'plausible mechanism', which could see therapies authorised after testing on a small number of patients.

It is working on new guidance covering the use of regenerative medicines and CGTs for serious conditions affecting small populations.