Speed Can Kill: In Biotech Too!
Our industry is obsessed with speed to first in human trials. We all know the mantra – push to make the “first in man” milestone at all cost. This driver has caused companies to seek FDA’s Fast-Track designation for their development projects. Since July 2012, 516 projects have been granted this designation as companies seek to meet investor expectations and patient needs. This interest in seeking this designation is not surprising since such accelerated programs may reduce a typical development program from start to BLA from five to eight years to two and a half years. This focus on speed has also been encouraged by the emergence of platform technologies. This blog highlights some of the key elements from my presentation entitled: “The Pressures in Developing Fast Track Products”, given at CHI, Bioprocessing Summit, Boston, MA, August 21-25th, 2017.
Accelerated early development timelines often leave gaps in CMC development, i.e., process understanding and scalability. Problems due to these gaps can include:
- Unstable cell culture processes that don’t scale up well
- Suboptimal purification with irreproducible performance
- Lack of process understanding leading to poor process characterization
Many biomolecules don’t lend themselves to accelerated development programs. A standardized MAb platform doesn’t work for all MAbs, and Fc fusion proteins often exhibit non-MAb-like properties and behaviors. Other macromolecules, such as enzymes, blood factors, cytokines, hormones, and cell/gene therapy modalities, etc., requiring the development of unique upstream and downstream strategies.
If you are starting a Phase 1 process with the intention of seeking Fast Track designation, you need to consider the following factors. First, your Phase 1 process must be as close as possible to the process you will use in pivotal studies. Ideally, an optimized process developed during Phase 1 should demonstrate:
- Product production (titer) sufficient to supply the market at the intended scale
- Product purity to meet pivotal expectations
- Robust and scalable process
- Viral studies on all steps that may contribute to viral clearance
By meeting the above goals, you are ready to begin process characterization immediately after receiving Fast-Track designation. Remember that characterization will typically take one to one and a half years.
The FDA established the Fast-Track designation as part of the Orphan Drugs regulations to provide an incentive to our industry to develop therapies for disease indications having small patient populations. In recent years, BPTC has helped a number of companies navigate the Fast-Track product development compressed timelines.
However, one needs to remember that FDA didn’t change any of the regulatory expectations for these Fast-Track designated products. I’d be interested in learning more about your experiences with Fast-Track product development programs.
Blog article by: Frank Riske
The following three blogs written by my colleagues addressing other issues related to accelerating early stage product development.
Speed to IND: Risks to Achieving Aggressive Breakthrough/Fast-Track Product Timelines
Multiplexing for Efficient Product Development
Why QbD Is Critical for Breakthrough Therapeutics