Completing an investigational new drug (IND) application can be a long and tedious process, one known to bog down timelines and frustrate sponsors looking to take their cell or gene therapy (CGT) to the clinic. In a tight race to trials, program sponsors look for efficiencies from bench to bedside.
Using off-the-shelf materials such as plasmid DNA products and CRISPR-associated nucleases is one way to potentially speed things up — particularly if they come with a drug master file, or DMF.
What is a drug master file?
Drug master files are reference packages that report to the FDA information about the processes involved in new drug products. They’re not FDA-required — nor approved nor denied — but they can help supplement INDs and other applications as a way to cross-reference new processes with pre-filed submissions.
And as a concept, DMFs aren’t new. Download the DMF list and you’ll see tens of thousands of submissions, some dating to 1939. They’ve always been used to support various materials, even ibuprofen and acetaminophen. But as normalized as they’ve become, DMFs are still novel among CGTs, which only recently began using off-the-shelf materials that would benefit from a DMF.
With the growing standardization of cell and gene therapies, interest has emerged in DMFs as a tool to expedite the path to clinical trials. If you use an off-the-shelf reagent that has a DMF, the application links to that preexisting file without the filer having to provide redundant information.
Using DMFs for off-the-shelf products
As more off-the-shelf materials such as plasmids become available for cell and gene therapies, suppliers are submitting DMFs for those products as a benefit to customers. Doing so gives researchers a dual offering: They can not only access standardized materials at GMP-grade — with the cost and time savings that come with that — but they can also cross-reference their INDs to the already prepared DMF.
Two examples of these DMF-ready products are Aldevron’s SpyFi™ Cas9 nuclease and pALD-X80 helper plasmid, each available from research grade to GMP. When new cell and gene therapy products use these materials, users automatically get the benefit of a pre-filed DMF that references Aldevron’s manufacturing processes involved in making them.
Anticipated benefits of cell and gene therapy DMFs
The reason IND submissions have long embraced DMFs is the same reason DMFs are likely to rapidly expand among CGT applications in the months and years ahead: They’re not just efficient in saving time, but they’re also potentially more comprehensive with less of a risk of missed information.
If you use the SpyFi™ Cas9 nuclease, for example, or others offered from Aldevron, you can skip the drug substance part for the Cas9 product when filing the IND because Aldevron has already prepared the DMF.
And when linking to the DMF, the FDA gets complete access to manufacturing information without the filer having to do so. This avoids overlooking information the FDA might need, which can delay application review.
Moreover, translational medicine organizations may find particular value in DMF-ready products because they overcome resource barriers inherent to hospitals and academic institutions. Unlike big pharma or biotech companies, many such organizations may not have easy access to field experts. Turning to DMFs gives academic outfits the economies of scale they might not get otherwise.
Accelerating a new frontier of medicine
By 2025 — that’s just two years away — the FDA expects to approve up to 20 cell and gene therapy products per year. With all that IND activity in a crowded market, sponsors will need any differentiating efficiency they can get along the pathway to clinical trials and beyond.
By taking advantage of pre-filed DMFs, researchers benefit from the value, time savings and reduced complexities of having someone else do the heavy lifting for key components of the final drug product. After all, this concept isn’t new in drug development. However, the science in this so-called “new frontier of medicine” is. As it becomes more standardized, everyone wins — including future patients.
Looking for other ways to standardize processes and accelerate your path to market? Stay tuned for Aldevron’s next post, where we’ll explore how plasmid backbones can simplify development logistics and reach your goals faster.