How New FDA Guidelines Can Affect Cell Therapy Development, part 2

June 9, 2022 / by Max Sellman

The effect on autologous and allogeneic therapies projects

In my previous post on new draft FDA guidelines that concern cell therapies, I covered key control considerations for CRISPR reagents and the GMP manufacturing considerations for drug substances affected by that guidance. In this post, I’ll go over a couple approaches to consider when working with gene-modified cell therapies, and how they could be affected.

• Download the FDA document, Human Gene Therapy Products Incorporating Human Genome Editing, Draft Guidance for Industry

When discussing gene-modified cell therapies, there are two common categories to consider – autologous therapies derived from a patient’s own cells and allogeneic therapies derived from healthy donor cell populations. Unlike autologous treatments that require rapid characterization to reduce vein-to-vein turnaround time, gene-modified allogeneic therapies can be extensively characterized and screened for any off-target effects of CRISPR editing prior to administration. There has been much speculation in the field around possible differences in CMC scrutiny between autologous and allogeneic therapies.

Notably, the guidance does not make many distinctions between CMC requirements for allogeneic and autologous gene-modified cell therapies. Some developers have assumed that, due to the more extensive up-front characterization, there will be less scrutiny on quality of gene editing reagents.

This does not appear to be the case – in fact, the only distinction the guidance makes between these two therapeutic approaches is to note that “additional testing and establishment of acceptance criteria may be appropriate” for allogeneic drug products. According to the guidance, this additional testing could include:

“More extensive analysis of the GE events occurring at both on- and off-target sites, additional adventitious agent testing, establishment of stringent acceptance criteria for the number of alloreactive lymphocytes and absence of aberrant growth (i.e., if the DP is an allogeneic T cell product)...”

There are many more details in this guidance, including discussion around clinical trial study design, in-process manufacturing controls (i.e. quality control of CRISPR ribonucleoprotein formation step), and long-term follow-up requirements. Aldevron is well situated to support cell therapy clients at all phases of their clinical journey and beyond.

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