Applying an old concept to CRISPR applications
Historically speaking, drug master files (DMF) have been used in filing Investigational New Drug applications (IND). However, they’ve never been used for CRISPR because that’s a relatively new therapy. With new draft FDA guidance relating to cell therapies using CRISPR, we’re moving further ahead into a new frontier of genomic medicine. You can learn more about that in posts written by our Gene Editing Product Manager, Max Sellman.
- How New FDA Guidelines Can Affect Cell Therapy Development, Part 1
- How New FDA Guidelines Can Affect Cell Therapy Development, part 2
As CRISPR and gene editing reagents have not been heavily used in clinical settings, there have never been DMFs made for them. Due to the release of the new guidance, that’s now what we’ll be trying to accomplish at a high level as the number of projects having success with our enzymes increases.
When considering a market with clinical ambitions, there are a couple ways to increase the size of a user group. One is that you have material off-the-shelf so it's available and cost-effective from research grade to cGMP. But before you can start using that material for clinical trials, you must file an IND.
That’s an additional area where we can help, since filing can be substantially accelerated if there's an associated DMF referencing the critical reagents used in the therapy. Aldevron has been providing regulatory support on client clinical filings for some time and has leveraged this experience in preparing DMFs for off-the-shelf nucleases.
The benefit to researchers
What does that mean for our clients and researchers? When filing INDs, clients no longer need to prepare a standalone Drug Substance section in their filing for Cas9 when utilizing our SpyFiTM Cas9 nuclease. The IND application will directly link to the DMF, enabling the FDA to have full access to relevant manufacturing information while reducing burden on the client quality and regulatory experts.
The idea: we immediately provide one part of the solution with off-the-shelf GMP gene editing reagents and then coupled with the other part of our solution, to directly link to a DMF, making it much easier to complete an IND filing. This approach adds value, especially for translational medicine organizations, where hospitals may also have research institutes woven into their system.
In those settings, you don't often have large quality assurance and regulatory groups. But in dealing with first-in-human, Phase One clinical trials, these institutions want to demonstrate safety as well as some advocacy, yet do it in a cost-effective manner.
To demonstrate how welcome this one-two solution of providing DMFs with off-the-shelf CRISPR products can be, we were recently discussing the impact of the FDA guidance with an institution working in cell therapy. When this topic was raised, the researchers were absolutely thrilled that that we had a DMF available for their use, saying how it would help them in their IND filing and save them time. Based on that reaction, ability to access a master file for Cas9 will be an advantage for anyone in the cell and gene editing space.